1. A compound of Formula I, or a pharmaceutically-acceptable salt, tautomer or prodrug thereof:
wherein:
W is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano;
X is selected from the group consisting of \u2014OR1, \u2014NR1R10, and \u2014SR1;
Y is selected from the group consisting of hydrogen, \u2014N(R7)C(O)NR2R8, \u2014N(R7)C(O)OR2, \u2014N(R7)C(O)R2, \u2014N(R7)SO2R2, and \u2014NR2R7;
Z is selected from the group consisting of \u2014CH\u2550CH\u2014, \u2014CH2N(R9)\u2014, \u2014C(O)\u2014, \u2014C(O)N(R9)\u2014, and \u2014N(R12)C(O)N(R9)\u2014;
R1 is selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, and heteroarylalkyl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo;
R2 is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, cycloalkylalkyl, aralkenyl, arylcycloalkyl, and heteroarylalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo;
R3 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano;
R4 is selected from the group consisting of a bond, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, aralkyl, cycloalkylalkyl, aralkenyl, and heteroarylalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, alkoxycarbonyl, and halo;
R5 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R6 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R7 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano;
R8 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano, or R8 together with R2 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system;
R9 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R10 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano;
R11 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano; and
R12 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano.
2. The compound, pharmaceutically-acceptable salt or tautomer of claim 1, wherein:
W is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano;
R1 is selected from the group consisting of lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, aryl, lower aralkyl, heteroaryl, and lower heteroarylalkyl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo;
R2 is selected from the group consisting of lower alkyl, lower cycloalkyl, aryl, heteroaryl, lower aralkyl, lower cycloalkylalkyl, lower aralkenyl, lower arylcycloalkyl, and lower heteroarylalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo;
R3 is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano;
R4 is selected from the group consisting of a bond, lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, heteroaryl, lower aralkyl, lower cycloalkylalkyl, lower aralkenyl, and lower heteroarylalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, lower alkoxycarbonyl, and halo;
R5 is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R6 is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R7 is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano;
R8 is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano, or R8 together with R2 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system;
R9 is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R10 is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano;
R11 is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano; and
R12 is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano.
3. The compound, pharmaceutically-acceptable salt or tautomer of claim 2, wherein:
W is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano;
R1 is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro;
R2 is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, phenylcyclopropyl, phenylcyclobutyl, phenylcyclopentyl, phenylcyclohexyl, biphenylcyclopropyl, biphenylcyclobutyl, biphenylcyclopentyl, biphenylcyclohexyl, naphthylcyclopropyl, naphthylcyclobutyl, naphthylcyclopentyl, naphthylcyclohexyl, or R2 together with R8 and the nitrogen to which they are attached may form a ring selected from the group consisting of hexahydroisoindolyl, tetrahydroisoindolyl, dihydroisoindolyl, isoindolinyl, hexahydroindolyl, tetrahydroindolyl, dihydroindolyl, indolinyl, octahydroquinolinyl, hexahydroquinolinyl, tetrahydroquinolinyl, dihydroquinolinyl, and quinolinyl, wherein R2 or the ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro;
R3 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano;
R4 is selected from the group consisting of a bond, methyl, ethyl, propyl, butyl, pentyl, hexyl, ethenyl, propenyl, allyl, butenyl, pentenyl, acetylenyl, propynyl, butynyl, pentynyl, hexynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, or R4 together with R9 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, chloro, bromo, and fluoro;
R5 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano, or R5 together with R6 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring;
R6 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano, or R6 together with R5 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring;
R7 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano;
R8 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano, or R8 together with R2 and the nitrogen to which they are attached may form an isoindolinyl ring;
R9 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano, or R9 together with R4 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring;
R10 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano;
R11 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano; and
R12 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano.
4. The compound, pharmaceutically-acceptable salt or tautomer of claim 1, wherein X is \u2014OR1.
5. The compound, pharmaceutically-acceptable salt or tautomer of claim 2, wherein X is \u2014OR1.
6. The compound, pharmaceutically-acceptable salt or tautomer of claim 3, wherein X is \u2014OR1.
7. The compound, pharmaceutically-acceptable salt, tautomer or prodrug of claim 1, selected from the group of compounds consisting of
4-(3,4-dimethylphenyl)oxy-3-{(phenylamino)carbonylamino}-N-(2-(1-pyrrolidinyl)ethyl)benzamide,
4-(3,4-dimethylphenyl)oxy-3-(3-phenylpropanoyl)amino-N-(2-(1-pyrrolidinyl)ethyl)benzamide,
4-(3,4-dimethylphenyl)oxy-3-({(phenylmethyl)aminocarbonyl}amino)-N-(2-(1-pyrrolidinyl)ethyl)benzamide,
4-(phenyloxy)-N-(2-(1-pyrrolidinyl)ethyl)benzamide,
3-acetylamino-4-(3,4-dimethylphenoxy)-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
4-(3,4-dimethylphenoxy)-3-propionylamino-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
3-(3-cyclopentylpropionylamino)-4-(3,4-dimethylphenoxy)-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
4-(3,4-dimethylphenoxy)-3-phenylacetylamino-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
4-(3,4-dimethylphenoxy)-3-(3-phenyl-acryloylamino)-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
4-(3,4-dimethylphenoxy)-3-(2-phenyl-cyclopropanecarbonyl)amino-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
naphthalene-2-carboxylic acid 2-(3,4-dimethylphenoxy)-5-(2-pyrrolidin-1-yl-ethylcarbamoyl)phenylamide,
4-(3,4-dimethylphenoxy)-3-(3-ethylureido)-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
N-(2-aminoethyl)-4-(3,4-dimethylphenoxy)-3-(3-phenylpropionylamino)benzamide,
4-methoxy-3-(3-phenylpropionylamino)-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
4-(naphthalen-2-yl-oxy)-3-(3-phenylpropionylamino)-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
4-(3,4-dimethylphenoxy)-3-3-(2-methoxyphenyl)ureido-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
3-3-(2,4-dichlorophenyl)ureido-4-(3,4-dimethylphenoxy)-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
4-(3,4-dimethylphenoxy)-3-3-(4-phenoxyphenyl)ureido-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
3-(3-biphenyl-4-yl-ureido)-4-(3,4-dimethylphenoxy)-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
4-(3,4-dimethylphenoxy)-3-3-(4-isopropylphenyl)ureido-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
4-(3,4-dimethylphenoxy)-3-3-(2,6-dimethylphenyl)ureido-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
4-(3,4-dimethylphenoxy)-3-(3-naphthalen-1-yl-ureido)-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
3-3-(2,6-diisopropylphenyl)ureido-4-(3,4-dimethylphenoxy)-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
3-3-(4-bromophenyl)ureido-4-(3,4-dimethylphenoxy)-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
4-(3,4-dimethylphenoxy)-3-3-(3-fluorophenyl)ureido-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
4-(3,4-dimethylphenoxy)-3-3-(3-methoxyphenyl)ureido-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
3-3-(2-chlorophenyl)ureido-4-(3,4-dimethylphenoxy)-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
4-(3,4-dimethylphenoxy)-3-(3,3-diphenylureido)-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
4-(3,4-dimethylphenoxy)-3-(3-methyl-3-phenylureido)-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
1,3-dihydroisoindole-2-carboxylic acid 2-(3,4-dimethylphenoxy)-5-(2-pyrrolidin-1-yl-ethylcarbamoyl)phenylamide,
4-(4-fluoro-3-methylphenoxy)-3-3-(3-fluorophenyl)ureido-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
4-(3,4-dichlorophenoxy)-3-3-(3-fluorophenyl)ureido-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
4-(3,4-difluorophenoxy)-3-3-(3-fluorophenyl)ureido-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
4-(4-fluorophenoxy)-3-3-(3-fluorophenyl)ureido-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
4-(3-fluorophenoxy)-3-3-(3-fluorophenyl)ureido-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
3-3-(3-fluorophenyl)ureido-N-(2-pyrrolidin-1-yl-ethyl)-4-p-tolyloxybenzamide,
3-3-(3-fluorophenyl)ureido-N-(2-pyrrolidin-1-yl-ethyl)-4-m-tolyloxybenzamide,
3-3-(3,5-difluorophenyl)ureido-4-(3,4-dimethylphenoxy)-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
3-3-(3,5-dichlorophenyl)ureido-4-(3,4-dimethylphenoxy)-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
3-3-(3-fluorophenyl)ureido-4-phenoxy-N-(2-pyrrolidin-1-yl-ethyl)benzamide,
1-2-(3,4-dimethylphenoxy)-5-(2-pyrrolidin-1-yl-methylpyrrolidine-1-carbonyl)phenyl-3-phenylurea,
1-{2-(3,4-dimethylphenoxy)-5-(2-pyrrolidin-1-yl-ethylamino)-methylphenyl}-3-(3-fluorophenyl)urea,
1-2-(3,4-dimethylphenoxy)-5-(2-pyrrolidin-1-yl-methylpyrrolidine-1-carbonyl)phenyl-3-phenylurea, and
4-(3,4-dichlorophenoxy)-3-3-(3,5-difluorophenyl)ureido-N-(2-pyrrolidin-1-yl-ethyl)benzamide.
8. A compound of claim 1, or a pharmaceutically-acceptable salt, tautomer or prodrug thereof, wherein the compound corresponds to Formula II
wherein:
W is selected from the group consisting of hydrogen, hydroxy, alkyl, and alkoxy;
X is selected from the group consisting of \u2014OR1, \u2014NR1R10, and \u2014SR1;
Y is selected from the group consisting of hydrogen, \u2014N(R7)C(O)NR2R8, \u2014N(R7)C(O)OR2, \u2014N(R7)C(O)R2, \u2014N(R7)SO2R2 and \u2014NR2R7;
Z is selected from the group consisting of \u2014CH\u2550CH\u2014, \u2014CH2N(R9)\u2014, \u2014C(O)\u2014, \u2014CH2N(R9)\u2014, and \u2014N(R12)C(O)N(R9)\u2014;
R1 is selected from the group consisting of alkyl, cycloalkyl, aryl, and heteroaryl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo;
R2 is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, cycloalkylalkyl, aralkenyl, and arylcycloalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo;
R4 is selected from the group consisting of a bond, alkyl, alkenyl, and cycloalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, and halo;
R5 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, and alkoxyalkyl, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R6 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, and alkoxyalkyl, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R7 is selected from the group consisting of hydrogen, alkyl, and aryl;
R8 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl, wherein R8 together with R2 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system;
R9 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R10 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl; and
R12 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl.
9. The compound, pharmaceutically-acceptable salt or tautomer of claim 8, wherein:
W is selected from the group consisting of hydrogen, hydroxy, lower alkyl, and lower alkoxy;
R1 is selected from the group consisting of lower alkyl, lower cycloalkyl, aryl, and heteroaryl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo;
R2 is selected from the group consisting of lower alkyl, lower cycloalkyl, aryl, heteroaryl, lower aralkyl, lower cycloalkylalkyl, lower aralkenyl, and lower arylcycloalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo;
R4 is selected from the group consisting of a bond, lower alkyl, lower alkenyl, and lower cycloalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, and halo;
R5 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, and lower alkoxyalkyl, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R6 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, and lower alkoxyalkyl, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R7 is selected from the group consisting of hydrogen, lower alkyl, and aryl,
R8 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl, or R8 together with R2 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system;
R9 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R10 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl; and
R12 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl.
10. The compound, pharmaceutically-acceptable salt or tautomer of claim 9, wherein:
W is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, butoxy, pentyloxy, and hexyloxy;
R1 is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, and benzodioxolyl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro;
R2 is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, phenylcyclopropyl, phenylcyclobutyl, phenylcyclopentyl, phenylcyclohexyl, biphenylcyclopropyl, biphenylcyclobutyl, biphenylcyclopentyl, biphenylcyclohexyl, naphthylcyclopropyl, naphthylcyclobutyl, naphthylcyclopentyl, naphthylcyclohexyl, or R2 together with R8 and the nitrogen to which they are attached may form a ring selected from the group consisting of hexahydroisoindolyl, tetrahydroisoindolyl, dihydroisoindolyl, isoindolinyl, hexahydroindolyl, tetrahydroindolyl, dihydroindolyl, indolinyl, octahydroquinolinyl, hexahydroquinolinyl, tetrahydroquinolinyl, dihydroquinolinyl, and quinolinyl, wherein R2 or the ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro;
R3 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano;
R4 is selected from the group consisting of a bond, methyl, ethyl, propyl, butyl, pentyl, hexyl, ethenyl, propenyl, allyl, butenyl, pentenyl, acetylenyl, propynyl, butynyl, pentynyl, hexynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, or R4 together with R9 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, chloro, bromo, and fluoro;
R5 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, and pentoxypentyl, or R5 together with R6 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring;
R6 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, and pentoxypentyl, or R6 together with R5 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring;
R7 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, phenyl, naphthyl, tetrahydronaphthyl, and biphenyl;
R8 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl, or R8 together with R2 and the nitrogen to which they are attached may form an isoindolinyl ring;
R9 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl, or R9 together with R4 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring;
R10 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl; and
R12 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl.
11. A compound of claim 1, or a pharmaceutically-acceptable salt, tautomer or prodrug thereof, wherein the compound corresponds to Formula III
wherein:
X is selected from the group consisting of \u2014OR1 and \u2014SR1;
Y is selected from the group consisting of hydrogen, \u2014N(R7)C(O)NR2R8, \u2014N(R7)C(O)OR2, \u2014N(R7)C(O)R2, \u2014N(R7)SO2R2, and \u2014NR2R7;
Z is selected from the group consisting of \u2014CH\u2550CH\u2014, \u2014CH2N(R9)\u2014, \u2014CH2N(R9)\u2014, and \u2014NHC(O)NR9\u2014;
R1 is selected from the group consisting of alkyl, cycloalkyl, aryl, and heteroaryl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo;
R2 is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, cycloalkylalkyl, aralkenyl, and arylcycloalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo;
R4 is selected from the group consisting of a bond, alkyl, alkenyl, and cycloalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, and halo;
R5 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, and alkoxyalkyl, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R6 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, and alkoxyalkyl, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R7 is selected from the group consisting of hydrogen, alkyl, and aryl;
R8 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl, or R8 together with R2 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system;
R9 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R10 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl; and
R12 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl.
12. The compound, pharmaceutically-acceptable salt or tautomer of claim 11, wherein:
R1 is selected from the group consisting of lower alkyl, lower cycloalkyl, aryl, and heteroaryl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo;
R2 is selected from the group consisting of lower alkyl, lower cycloalkyl, aryl, heteroaryl, lower aralkyl, lower cycloalkylalkyl, lower aralkenyl, and lower arylcycloalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo;
R4 is selected from the group consisting of a bond, lower alkyl, lower alkenyl, and lower cycloalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, and halo;
R5 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, and lower alkoxyalkyl, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R6 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, and lower alkoxyalkyl, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R7 is selected from the group consisting of hydrogen, lower alkyl, and aryl;
R8 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl, or R8 together with R2 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system;
R9 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R10 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl; and
R12 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl.
13. The compound, pharmaceutically-acceptable salt or tautomer of claim 12, wherein:
R1 is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, and benzodioxolyl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro;
R2 is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, phenylcyclopropyl, phenylcyclobutyl, phenylcyclopentyl, phenylcyclohexyl, biphenylcyclopropyl, biphenylcyclobutyl, biphenylcyclopentyl, biphenylcyclohexyl, naphthylcyclopropyl, naphthylcyclobutyl, naphthylcyclopentyl, naphthylcyclohexyl, or R2 together with R8 and the nitrogen to which they are attached may form a ring selected from the group consisting of hexahydroisoindolyl, tetrahydroisoindolyl, dihydroisoindolyl, isoindolinyl, hexahydroindolyl, tetrahydroindolyl, dihydroindolyl, indolinyl, octahydroquinolinyl, hexahydroquinolinyl, tetrahydroquinolinyl, dihydroquinolinyl, and quinolinyl, wherein R2 or the ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro;
R3 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano;
R4 is selected from the group consisting of a bond, methyl, ethyl, propyl, butyl, pentyl, hexyl, ethenyl, propenyl, allyl, butenyl, pentenyl, acetylenyl, propynyl, butynyl, pentynyl, hexynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, or R4 together with R9 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, chloro, bromo, and fluoro;
R5 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, and pentoxypentyl, or R5 together with R6 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring;
R6 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, and pentoxypentyl, or R6 together with R5 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring;
R7 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, phenyl, naphthyl, tetrahydronaphthyl, and biphenyl;
R8 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl, or R6 together with R2 and the nitrogen to which they are attached may form an isoindolinyl ring;
R9 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl, or R9 together with R4 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring;
R10 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl; and
R12 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl.
14. A compound of claim 1, or a pharmaceutically-acceptable salt, tautomer or prodrug thereof, wherein the compound corresponds to Formula IV
wherein:
X is selected from the group consisting of \u2014OR1 and \u2014SR1;
Z is selected from the group consisting of \u2014CH\u2550CH\u2014, \u2014CH2N(R9)\u2014, \u2014CH2N(R9)\u2014, and \u2014NHC(O)NR9\u2014;
R1 is selected from the group consisting of alkyl, cycloalkyl, aryl, and heteroaryl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo;
R2 is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, cycloalkylalkyl, aralkenyl, and arylcycloalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo;
R4 is selected from the group consisting of a bond, alkyl, alkenyl, and cycloalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, and halo;
R5 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, and alkoxyalkyl, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R6 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, and alkoxyalkyl, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R7 is selected from the group consisting of hydrogen, alkyl, and aryl,
R8 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl, or R8 together with R2 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system;
R9 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R10 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl; and
R12 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl.
15. The compound, pharmaceutically-acceptable salt or tautomer of claim 14, wherein:
R1 is selected from the group consisting of lower alkyl, lower cycloalkyl, aryl, and heteroaryl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo;
R2 is selected from the group consisting of lower alkyl, lower cycloalkyl, aryl, heteroaryl, lower aralkyl, lower cycloalkylalkyl, lower aralkenyl, and lower arylcycloalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo;
R4 is selected from the group consisting of a bond, lower alkyl, lower alkenyl, and lower cycloalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, and halo;
R5 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, and lower alkoxyalkyl, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R6 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, and lower alkoxyalkyl, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R7 is selected from the group consisting of hydrogen, lower alkyl, and aryl;
R8 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl, wherein R8 together with R2 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system;
R9 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R10 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl; and
R12 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl.
16. The compound, pharmaceutically-acceptable salt or tautomer of claim 15, wherein:
R1 is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, and benzodioxolyl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro;
R2 is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, phenylcyclopropyl, phenylcyclobutyl, phenylcyclopentyl, phenylcyclohexyl, biphenylcyclopropyl, biphenylcyclobutyl, biphenylcyclopentyl, biphenylcyclohexyl, naphthylcyclopropyl, naphthylcyclobutyl, naphthylcyclopentyl, naphthylcyclohexyl, or R2 together with R8 and the nitrogen to which they are attached may form a ring selected from the group consisting of hexahydroisoindolyl, tetrahydroisoindolyl, dihydroisoindolyl, isoindolinyl, hexahydroindolyl, tetrahydroindolyl, dihydroindolyl, indolinyl, octahydroquinolinyl, hexahydroquinolinyl, tetrahydroquinolinyl, dihydroquinolinyl, and quinolinyl, wherein R2 or the ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro;
R3 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano;
R4 is selected from the group consisting of a bond, methyl, ethyl, propyl, butyl, pentyl, hexyl, ethenyl, propenyl, allyl, butenyl, pentenyl, acetylenyl, propynyl, butynyl, pentynyl, hexynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, or R4 together with R9 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, chloro, bromo, and fluoro;
R5 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, and pentoxypentyl, or R5 together with R6 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring;
R6 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, and pentoxypentyl, or R6 together with R5 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring;
R7 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, phenyl, naphthyl, tetrahydronaphthyl, and biphenyl;
R8 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl, or R8 together with R2 and the nitrogen to which they are attached may form an isoindolinyl ring;
R9 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl, or R9 together with R4 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring;
R10 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl; and
R12 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl.
17. A compound of claim 1, or a pharmaceutically-acceptable salt, tautomer or prodrug thereof, wherein the compound corresponds to Formula V
wherein:
X is selected from the group consisting of \u2014OR1 and \u2014SR1;
Z is selected from the group consisting of \u2014CH\u2550CH\u2014, \u2014CH2N(R9)\u2014, \u2014CH2N(R9)\u2014, and \u2014NHC(O)NR9\u2014;
R1 is selected from the group consisting of alkyl, cycloalkyl, aryl, and heteroaryl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo;
R2 is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, cycloalkylalkyl, aralkenyl, and arylcycloalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R5 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo;
R4 is selected from the group consisting of a bond, alkyl, alkenyl, and cycloalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, and halo;
R5 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, and alkoxyalkyl, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R6 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, and alkoxyalkyl, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R7 is selected from the group consisting of hydrogen, alkyl, and aryl;
R8 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl, or R8 together with R2 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system; and
R9 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring.
18. The compound, pharmaceutically-acceptable salt or tautomer of claim 17, wherein:
R1 is selected from the group consisting of lower alkyl, lower cycloalkyl, aryl, and heteroaryl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo;
R2 is selected from the group consisting of lower alkyl, lower cycloalkyl, aryl, heteroaryl, lower aralkyl, lower cycloalkylalkyl, lower aralkenyl, and lower arylcycloalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo;
R4 is selected from the group consisting of a bond, lower alkyl, lower alkenyl, and lower cycloalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, and halo;
R5 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, and lower alkoxyalkyl, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R6 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, and lower alkoxyalkyl, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R7 is selected from the group consisting of hydrogen, lower alkyl, and aryl;
R8 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl, or R8 together with R2 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system; and
R9 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring.
19. The compound, pharmaceutically-acceptable salt or tautomer of claim 18, wherein:
R1 is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, and benzodioxolyl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro;
R2 is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, phenylcyclopropyl, phenylcyclobutyl, phenylcyclopentyl, phenylcyclohexyl, biphenylcyclopropyl, biphenylcyclobutyl, biphenylcyclopentyl, biphenylcyclohexyl, naphthylcyclopropyl, naphthylcyclobutyl, naphthylcyclopentyl, naphthylcyclohexyl, or R2 together with R8 and the nitrogen to which they are attached may form a ring selected from the group consisting of hexahydroisoindolyl, tetrahydroisoindolyl, dihydroisoindolyl, isoindolinyl, hexahydroindolyl, tetrahydroindolyl, dihydroindolyl, indolinyl, octahydroquinolinyl, hexahydroquinolinyl, tetrahydroquinolinyl, dihydroquinolinyl, and quinolinyl, wherein R2 or the ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro;
R4 is selected from the group consisting of a bond, methyl, ethyl, propyl, butyl, pentyl, hexyl, ethenyl, propenyl, allyl, butenyl, pentenyl, acetylenyl, propynyl, butynyl, pentynyl, hexynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, or R4 together with R9 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, chloro, bromo, and fluoro;
R5 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, and pentoxypentyl, or R5 together with R6 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring;
R6 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, and pentoxypentyl, or R6 together with R5 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring;
R7 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, phenyl, naphthyl, tetrahydronaphthyl, and biphenyl;
R8 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl, or R8 together with R2 and the nitrogen to which they are attached may form an isoindolinyl ring; and
R9 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl, or R9 together with R4 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring.
20. A compound of claim 1, or a pharmaceutically-acceptable salt, tautomer or prodrug thereof, wherein the compound corresponds to Formula VI
wherein:
X is selected from the group consisting of \u2014OR1 and \u2014SR1;
Z is selected from the group consisting of \u2014CH\u2550CH\u2014, \u2014CH2N(R9)\u2014, \u2014CH2N(R9)\u2014, and \u2014NHC(O)NR9\u2014;
R1 is selected from the group consisting of alkyl, cycloalkyl, aryl, and heteroaryl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo;
R2 is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, cycloalkylalkyl, aralkenyl, and arylcycloalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo;
R4 is selected from the group consisting of a bond, alkyl, alkenyl, and cycloalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, and halo;
R5 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, and alkoxyalkyl, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R6 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, and alkoxyalkyl, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R7 is selected from the group consisting of hydrogen, alkyl, and aryl; and
R9 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring.
21. The compound, pharmaceutically-acceptable salt or tautomer of claim 20, wherein:
R1 is selected from the group consisting of lower alkyl, lower cycloalkyl, aryl, and heteroaryl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo;
R2 is selected from the group consisting of lower alkyl, lower cycloalkyl, aryl, heteroaryl, lower aralkyl, lower cycloalkylalkyl, lower aralkenyl, and lower arylcycloalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo;
R4 is selected from the group consisting of a bond, lower alkyl, lower alkenyl, and lower cycloalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, and halo;
R5 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, and lower alkoxyalkyl, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R6 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, and lower alkoxyalkyl, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R7 is selected from the group consisting of hydrogen, lower alkyl, and aryl;
R8 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl, or R8 together with R2 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system; and
R9 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring.
22. The compound, pharmaceutically-acceptable salt or tautomer of claim 21, wherein:
R1 is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, and benzodioxolyl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro;
R2 is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, phenylcyclopropyl, phenylcyclobutyl, phenylcyclopentyl, phenylcyclohexyl, biphenylcyclopropyl, biphenylcyclobutyl, biphenylcyclopentyl, biphenylcyclohexyl, naphthylcyclopropyl, naphthylcyclobutyl, naphthylcyclopentyl, naphthylcyclohexyl, or R2 together with R8 and the nitrogen to which they are attached may form a ring selected from the group consisting of hexahydroisoindolyl, tetrahydroisoindolyl, dihydroisoindolyl, isoindolinyl, hexahydroindolyl, tetrahydroindolyl, dihydroindolyl, indolinyl, octahydroquinolinyl, hexahydroquinolinyl, tetrahydroquinolinyl, dihydroquinolinyl, and quinolinyl, wherein R2 or the ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro;
R4 is selected from the group consisting of a bond, methyl, ethyl, propyl, butyl, pentyl, hexyl, ethenyl, propenyl, allyl, butenyl, pentenyl, acetylenyl, propynyl, butynyl, pentynyl, hexynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, or R4 together with R9 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, chloro, bromo, and fluoro;
R5 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, and pentoxypentyl, or R5 together with R6 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring;
R6 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, and pentoxypentyl, or R6 together with R5 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring;
R7 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, phenyl, naphthyl, tetrahydronaphthyl, and biphenyl;
R8 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl, or R8 together with R2 and the nitrogen to which they are attached may form an isoindolinyl ring; and
R9 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl, or R9 together with R4 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring.
23. A compound of claim 1, or a pharmaceutically-acceptable salt, tautomer or prodrug thereof, wherein the compound corresponds to Formula VII
wherein:
R1 is selected from the group consisting of cycloalkyl and aryl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, and halo;
R2 is selected from the group consisting of alkyl, aryl, aralkyl, cycloalkylalkyl, aralkenyl, and arylcycloalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, aryloxy, and halo;
R5 is selected from the group consisting of hydrogen and alkyl, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R6 is selected from the group consisting of hydrogen and alkyl, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring; and
R8 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, and aryl, or R8 together with R2 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system.
24. The compound, pharmaceutically-acceptable salt or tautomer of claim 23, wherein:
R1 is selected from the group consisting of lower cycloalkyl and aryl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, and halo;
R2 is selected from the group consisting of lower alkyl, aryl, lower aralkyl, lower cycloalkylalkyl, lower aralkenyl, and lower arylcycloalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, aryloxy, and halo;
R5 is selected from the group consisting of hydrogen and lower alkyl, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring;
R6 is selected from the group consisting of hydrogen and lower alkyl, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring; and
R8 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, and aryl, or R8 together with R2 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system.
25. The compound, pharmaceutically-acceptable salt or tautomer of claim 24, wherein:
R1 is selected from the group consisting of cyclopentyl, cyclohexyl, phenyl, naphthyl, and biphenyl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, hydroxy, methoxy, ethoxy, propoxy, chloro, bromo, and fluoro;
R2 is selected from the group consisting of methyl, ethyl, propyl, butyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, phenylethyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, phenylethenyl, phenylpropenyl, phenylcyclopropyl, biphenylcyclopropyl, and naphthylcyclopropyl, or R2 together with R8 and the nitrogen to which they are attached may form a ring selected from the group consisting of dihydroisoindolyl, dihydroindolyl, tetrahydroisoquinolinyl, and tetrahydroquinolinyl, wherein R2 or the ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, hydroxy, methoxy, ethoxy, propoxy, phenoxy, naphthyloxy, biphenylyloxy, chloro, bromo, and fluoro;
R5 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, and hexyl, or R5 together with R6 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring;
R6 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, and hexyl, or R6 together with R5 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring; and
R8 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, and biphenyl, or R8 together with R2 and the nitrogen to which they are attached may form a ring selected from the group consisting of dihydroisoindolyl, dihydroindolyl, tetrahydroisoquinolinyl, and tetrahydroquinolinyl.
26. The compound, pharmaceutically-acceptable salt or tautomer of claim 25, wherein:
R1 is selected from the group consisting of phenyl, and naphthyl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of methyl, chloro, and fluoro;
R2 is selected from the group consisting of methyl, ethyl, phenyl, naphthyl, biphenyl, benzyl, phenylethyl, cyclopentylethyl, phenylethenyl, phenylcyclopropyl, or R2 together with R8 and the nitrogen to which they are attached may form a dihydroisoindolyl ring, wherein R2 or the ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of methyl, propyl, methoxy, phenoxy, chloro, bromo, and fluoro;
R5 is hydrogen or R5 together with R6 and the nitrogen to which they are attached form a pyrrolidinyl ring;
R6 is hydrogen or R6 together with R5 and the nitrogen to which they are attached form a pyrrolidinyl ring; and
R8 is selected from the group consisting of hydrogen, methyl, and phenyl, or R8 together with R2 and the nitrogen to which they are attached may form a dihydroisoindolyl ring.
27. A pharmaceutical composition comprising a compound, pharmaceutically-acceptable salt, tautomer or prodrug according to any one of claims 1, 7, 8, 11, 14, 17, 20, and 23 and a pharmaceutically acceptable carrier, adjuvant, or diluent.
28. A method of treating or preventing a melanin concentrating hormone-mediated disorder in a subject, the method comprising administering to a subject in need of such treatment or prevention a compound, pharmaceutically-acceptable salt, tautomer or prodrug according to any one of claims 1, 7, 8, 11, 14, 17, 20, and 23.
29. A method of treating or preventing a condition selected from the group consisting of feeding disorders, sexual disorders, reproductive disorders, depression, anxiety, epileptic seizure, hypertension, cerebral hemorrhage, congestive heart failure, and sleep disturbances, comprising administering to a subject in need of such treatment or prevention a compound, pharmaceutically-acceptable salt, tautomer or prodrug according to any one of claims 1, 7, 8, 11, 14, 17, 20, and 23.
30. The method of claim 29 wherein the condition being treated or prevented is a feeding disorder.
31. The method of claim 30 wherein the feeding disorder is selected from the group consisting of obesity, bulimia and bulimia nervosa.
32. A method of treating or preventing obesity, comprising administering to a subject in need of such treatment or prevention a compound, pharmaceutically-acceptable salt, tautomer or prodrug according to any of claims 1, 7, 8, 11, 14, 17, 20, and 23.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A semiconductor laser comprising:
a semiconductor substrate;
a semiconductor stacking body including a waveguide core formed on said semiconductor substrate, a cladding layer formed above said waveguide core, and a contact layer;
a diffraction grating with a period determining an oscillation wavelength and formed in a manner that does not impart a change in oscillation direction to an output wavelength; and
an electrode;
wherein said diffraction grating is formed along said waveguide core so as to appear in the surface of said cladding layer,
said contact layer is formed along said waveguide core on a region other than a region where said diffraction grating appears in the surface of said cladding layer,
each of a period direction of said diffraction grating and a longitudinal direction of said contact layer is in parallel in a longitudinal direction of said waveguide core,
said electrode is provided on said contact layer, and
said diffraction grating is formed right above a current injection region of said waveguide core, the current injection region being a region where current injection is performed through said electrode to amplify light.
2. The semiconductor laser according to claim 1, wherein said semiconductor laser is configured as a buried type semiconductor laser which comprises an electric-current constriction structure.
3. The semiconductor laser according to claim 2, wherein said electric-current constriction structure is a pnpn thyristor structure.
4. The semiconductor laser according to claim 2, further comprises a semi-insulating planar buried hetero-structure, wherein said electric-current constriction structure includes a semi-insulating semiconductor layer.
5. The semiconductor laser according to claim 2, further comprises a semi-insulating buried hetero-structure, wherein said electric-current constriction structure is constituted of a semi-insulating semiconductor layer.
6. The semiconductor laser according to claim 1, wherein said semiconductor laser is configured as an inner stripe type semiconductor laser which comprises an electric-current constriction structure.
7. A semiconductor laser comprising:
a semiconductor substrate;
a semiconductor stacking body including a waveguide core formed on said semiconductor substrate and a contact layer formed above said waveguide core;
a diffraction grating with a period determining an oscillation wavelength and formed in a manner that does not impart a change in oscillation direction to an output wavelength; and
an electrode;
wherein said diffraction grating is formed along said waveguide core so as to appear in the surface of said contact layer,
said electrode is formed along said waveguide core on a region other than a region where said diffraction grating appears in the surface of said contact layer,
each of a period direction of said diffraction gating and a longitudinal direction of said electrode is in parallel in a longitudinal direction of said waveguide core, and
said diffraction grating is formed right above a current injection region of said waveguide core, the current injection region being a region where current injection is performed through said electrode to amplify light.
8. The semiconductor laser according to claim 1, further comprises a protection film covering the region in which said diffraction grating is formed.
9. The semiconductor laser according to claim 8, wherein said protection film is a dielectric film.
10. The semiconductor laser according to claim 1, further comprises a dielectric film covering the region in which said diffraction grating is formed, wherein said dielectric film is formed so that a part thereof is interposed between said contact layer and said electrode.
11. The semiconductor laser according to claim 8, wherein a metal is deposited on the surface of said protection film.
12. The semiconductor laser according to claim 1, further comprises a metal film covering the region in which said diffraction grating is formed.
13. The semiconductor laser according to claim 1, wherein each of said diffraction grating and said electrode is formed in parallel along said waveguide core.