1. A compound comprising the Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from the group consisting of aryl, heteroaryl and aralkyl, each unsubstituted or substituted;
R2 is selected from the group consisting of hydrogen and unsubstituted or substituted C1-10alkyl;
R3 is selected from the group consisting of fluoro, chloro, bromo, iodo, C1-10alkoxy, nitro, haloC1-10alkyl, perhaloC1-10alkyl and unsubstituted or substituted C1-10alkyl;
each R4 is independently selected from the group consisting of halogen, nitro, C1-10alkyl, C2-10alkenyl, C2-10alkynyl, C1-10alkoxy, aralkyl, aryl, heteroaryl, cycloalkyl and heterocycloalkyl, each unsubstituted or substituted, or wherein R3 and an adjacent R4 together form a fused unsubstituted or substituted 5 or 6 membered cycloalkyl, aryl or heteroaryl ring;
R5 is selected from the group consisting of \u2014NH2, C1-10alkylamino, di(C1-10)alkylamino and aryl, each substituted or unsubstituted; and
m is 0, 1, 2, 3 or 4.
2. A compound according to claim 1: wherein:
R5 is selected from the group consisting of \u2014NH2, C1-10alkylamino, di(C1-10)alkylamino and aryl, each unsubstituted or substituted.
3. A compound comprising the Formula Ib:
or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from the group consisting of aryl, heteroaryl, and aralkyl and R16R17N\u2014, each unsubstituted or substituted;
R2 is selected from the group consisting of hydrogen and unsubstituted or substituted C1-10alkyl;
R3 is selected from the group consisting of hydrogen, halo, haloC1-10alkyl, perhaloC1-10alkyl, amino, cyano, nitro, hydroxy, thio, C1-20alkyl, C2-10alkenyl, C2-10alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted;
each R4 is independently selected from the group consisting of hydrogen, halo, nitro, haloC1-10alkyl, perhaloC1-10alkyl, amino, cyano, hydroxy, thio, C1-10alkyl, C2-10alkenyl, C2-10alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted, or wherein R3 and an adjacent R4 together form a fused unsubstituted or substituted 5 or 6 membered cycloalkyl, aryl or heteroaryl ring;
R16 and R17 are each independently C3-12cycloalkyl, aryl, heteroaryl, C1-10alkyl, each unsubstituted or substituted, or R16 and R17 together with the nitrogen atom to which they are attached form an unsubstituted or substituted 4, 5 or 6 membered ring; and
R18 is selected from the group consisting of C1-10alkyl, aralkyl, and heterocycloalkyl, each substituted or unsubstituted; and
m is 0, 1, 2, 3 or 4.
4. The compound of claim 3 comprising the Formula Ic:
or a pharmaceutically acceptable salt thereof, wherein:
R2 is selected from the group consisting of hydrogen, methyl and ethyl;
R3 is selected from the group consisting of hydrogen, halo, haloC1-10alkyl, perhaloC1-10alkyl, amino, cyano, nitro, hydroxy, thio, C1-20alkyl, C2-10alkenyl, C2-10alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted;
each R4 is independently selected from the group consisting of hydrogen, halo, nitro, haloC1-10alkyl, perhaloC1-10alkyl, amino, cyano, hydroxy, thio, C1-20alkyl, C2-10alkenyl, C2-10alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted, or wherein R3 and an adjacent R4 together form a fused unsubstituted or substituted 5 or 6 membered cycloalkyl, aryl or heteroaryl ring;
R6, R7, R8, R9 and R10 are each independently selected from the group consisting of hydrogen, halo, C1-10alkyl, C2-10alkynyl, C1-10alkoxy, aralkyl, cycloalkyl, arylC1-10alkyl and heteroarylC1-10alkyl; or R6 and R7, or R7 and R8, or R8 and R9, or R9 and R10 are taken together with the carbon atoms to which they are attached to form an unsubstituted or substituted fused 5 or 6 membered saturated, partially unsaturated ring, aryl or heteroaryl;
R18 is selected from the group consisting of C1-10alkyl, aralkyl, and heterocycloalky, each unsubstituted or substituted; and
m is 0, 1, 2, 3 or 4.
5. The compound of claim 1 comprising the Formula II:
or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from the group consisting of aryl, heteroaryl and aralkyl, each unsubstituted or substituted;
R2 is selected from the group consisting of hydrogen and unsubstituted or substituted C1-10alkyl;
R5 is selected from the group consisting of \u2014NH2, C1-10alkylamino, di(C1-10)alkylamino and aryl, each unsubstituted or substituted;
R19 and R20 are each independently selected from the group consisting of halo, cyano, nitro, halo(C1-10)alkyl, perhalo(C1-5)alkyl, aryl, heteroaryl, cycloalkyl, C1-10alkyl, aryl(C1-10)alkyl, cycloalkyl(C1-10)alkyl, hydroxy(C1-10)alkyl, amino(C1-10)alkyl, alkoxy(C1-10)alkyl, amino, hydroxyl, thio, C1-10alkoxy and C1-10alkylthiol; and
v and w independently are 0, 1, 2 or 3.
6. The compound of claim 1 comprising the Formula III:
or a pharmaceutically acceptable salt thereof, wherein:
R2 is selected from the group consisting of hydrogen and unsubstituted or substituted C1-10alkyl;
R3 is selected from the group consisting of fluoro, chloro, bromo, iodo, C1-10alkoxy, nitro, haloC1-10alkyl, perhaloC1-10alkyl and unsubstituted or substituted C1-10alkyl;
each R4 is independently selected from the group consisting of halogen, nitro, C1-10alkyl, C2-10 alkynyl, C 1-10alkoxy, aralkyl, aryl, heteroaryl, cycloalkyl and heterocycloalkyl, each unsubstituted or substituted, or wherein R3 and an adjacent R4 together form a fused unsubstituted or substituted 5 or 6 membered cycloalkyl, aryl or heteroaryl ring;
R5 is selected from the group consisting of \u2014NH2, C1-10alkylamino, di(C1-10)alkylamino and aryl, each unsubstituted or substituted;
R6, R7, R8, R9 and R10 are each independently selected from the group consisting of hydrogen, halo, C1-10alkyl, C2-10alkynyl, C1-10alkoxy, aralkyl, cycloalkyl, arylC1-10alkyl and heteroarylC1-10alkyl; or R6 and R7, or R7 and R8, or R8 and R9, or R9 and R10 are taken together with the carbon atoms to which they are attached to form an unsubstituted or substituted fused 5 or 6 membered saturated, partially unsaturated ring, aryl or heteroaryl; and
m is 0, 1, 2, 3 or 4.
7. The compound of claim 1 comprising the Formula IV:
or a pharmaceutically acceptable salt thereof, wherein:
R2 is selected from the group consisting of hydrogen and unsubstituted or substituted C1-10alkyl;
R3 is selected from the group consisting of fluoro, chloro, bromo, iodo, C1-10alkoxy, nitro, haloC1-10alkyl, perhaloC1-10alkyl and unsubstituted or substituted C1-10alkyl;
each R4 is independently selected from the group consisting of halogen, nitro, C 1-10alkyl, C2-10alkynyl, C1-10alkoxy, aralkyl, aryl, heteroaryl, cycloalkyl and heterocycloalkyl, each unsubstituted or substituted, or wherein R3 and an adjacent R4 together form a fused unsubstituted or substituted 5 or 6 membered cycloalkyl, aryl or heteroaryl ring;
R5 is selected from the group consisting of \u2014NH2, C1-10alkylamino, di(C1-10)alkylamino and aryl, each unsubstituted or substituted;
R6, R7, R8, R9 and R10 are each independently selected from the group consisting of hydrogen, halo, C1-10alkyl, C2-10alkynyl, C1-10alkoxy, aralkyl, cycloalkyl, arylC1-10alkyl and heteroarylC1-10alkyl; or R6 and R7, or R7 and R8, or R8 and R9, or R9 and R10 are taken together with the carbon atoms to which they are attached to form an unsubstituted or substituted fused 5 or 6 membered saturated, partially unsaturated ring, aryl or heteroaryl;
R11 is hydrogen or is an unsubstituted or substituted C1-10alkyl;
m is 0, 1, 2, 3 or 4; and
n is 0, 1, 2, 3, 4 or 5.
8. The compound of claim 3 comprising the Formula IVa:
or a pharmaceutically acceptable salt thereof, wherein:
R2 is selected from the group consisting of hydrogen, methyl and ethyl;
R3 is selected from the group consisting of hydrogen, halo, haloC1-10alkyl, perhaloC1-10alkyl, amino, cyano, nitro, hydroxy, thio, C1-20alkyl, C2-10alkenyl, C2-10alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted;
each R4 is independently selected from the group consisting of halogen, nitro, C1-10alkyl, C2-10alkynyl, C1-10alkoxy, aralkyl, aryl, heteroaryl, cycloalkyl and heterocycloalkyl, each unsubstituted or substituted, or wherein R3 and an adjacent R4 together form a fused unsubstituted or substituted 5 or 6 membered cycloalkyl, aryl or heteroaryl ring;
R6, R7, R8, R9 and R10 are each independently selected from the group consisting of hydrogen, halo, C1-10alkyl, C2-10alkynyl, C1-10alkoxy, aralkyl, cycloalkyl, arylC1-10alkyl and heteroarylC1-10alkyl; or R6 and R7, or R7 and R8, or R8 and R9, or R9 and R10 are taken together with the carbon atoms to which they are attached to form an unsubstituted or substituted fused 5 or 6 membered saturated, partially unsaturated ring, aryl or heteroaryl;
R11 is hydrogen or is an unsubstituted or substituted C1-10alkyl;
R18 is selected from the group consisting of C1-10alkyl, arylalkyl and heterocycloalkyl, each unsubstituted or substituted;
m is 0, 1, 2, 3 or 4; and
n is 0, 1, 2, 3, 4 or 5.
9. A compound comprising the Formula V:
or a pharmaceutically acceptable salt thereof, wherein:
R3 is selected from the group consisting of hydrogen, halo, haloC1-10alkyl, perhaloC1-10alkyl, amino, cyano, nitro, hydroxy, thio, C1-20alkyl, C2-10alkenyl, C2-10alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted;
each R4 is independently selected from the group consisting of hydrogen, halo, haloC1-10alkyl, perhaloC1-10alkyl, amino, cyano, nitro, hydroxy, thio, C1-20alkyl, C2-10alkenyl, C2-10alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted, or wherein R3 and an adjacent R4 together form a fused unsubstituted or substituted 5 or 6 membered cycloalkyl, aryl or heteroaryl ring;
R5 is selected from the group consisting of alkyl, amino, alkylamino, dialkylamino and aryl, each unsubstituted or substituted;
each R19 is independently selected from the group consisting of halogen, C1-10alkyl, C2-10alkynyl, C1-10alkoxy, aralkyl and cycloalkyl, each unsubstituted or substituted;
m is 0, 1, 2, 3 or 4; and
u is 0, 1 or 2.
10. The compound of claim 3 comprising the Formula Va:
or a pharmaceutically acceptable salt thereof, wherein:
R2 is selected from the group consisting of hydrogen and unsubstituted or substituted C1-10alkyl;
R3 is selected from the group consisting of hydrogen, halo, haloC1-10alkyl, perhaloC1-10alkyl, amino, cyano, nitro, hydroxy, thio, C1-20alkyl, C2-10alkenyl, C2-10alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted;
each R4 is independently selected from the group consisting of hydrogen, halo, haloC1-10alkyl, perhaloC1-10alkyl, amino, cyano, nitro, hydroxy, thio, C1-20alkyl, C2-10alkenyl, C2-10alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted, or wherein R3 and an adjacent R4 together form a fused unsubstituted or substituted 5 or 6 membered cycloalkyl, aryl or heteroaryl ring;
R16 and R17 are each independently C3-12cycloalkyl, aryl, heteroaryl, C1-10alkyl, each unsubstituted or substituted, or R16 and R17 together with the nitrogen atom to which they are attached form an unsubstituted or substituted 4, 5, or 6 membered ring;
R18 is selected from the group consisting of C1-10alkyl, arylalkyl, and heterocycloalkyl, each unsubstituted or substituted; and
m is 0, 1, 2, 3 or 4.
11. A compound comprising the Formula VI:
or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from the group consisting of aryl, heteroaryl, aralkyl and R16 R17N\u2014, each unsubstituted or substituted;
R2 is selected from the group consisting of hydrogen and unsubstituted or substituted C1-10alkyl;
R3 is selected from the group consisting of hydrogen, halo, haloC1-10alkyl, perhaloC1-10alkyl, amino, cyano, nitro, hydroxy, thio, C1-20alkyl, C2-10alkenyl, C2-10alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted;
each R4 is independently selected from the group consisting of halogen, nitro, C1-10alkyl, C2-10alkynyl, C1-10alkoxy, aralkyl, aryl, heteroaryl, cycloalkyl and heterocycloalkyl, each unsubstituted or substituted, or wherein R3 and an adjacent R4 together form a fused unsubstituted or substituted 5 or 6 membered cycloalkyl, aryl or heteroaryl ring;
R16 and R17 are each independently C3-12cycloalkyl, aryl, heteroaryl, C1-10alkyl, each unsubstituted or substituted, or R16 and R17 together with the nitrogen atom to which they are attached form an unsubstituted or substituted 4, 5, or 6 membered ring;
each R20 is independently selected from the group consisting of halo, cyano, nitro, halo(C1-10)alkyl, perhalo(C1-5)alkyl, aryl, heteroaryl, C1-10alkyl, aryl(C1-10)alkyl, alkoxy(C1-10)alkyl, amino, hydroxyl, thio and C1-10alkoxy and
m and p are each independently 0, 1, 2, 3 or 4.
12. The compound of claim 6, wherein R8 is selected from the group consisting of C1-10alkyl, halogen, and C1-10alkoxy; and R6, R7, R9 and R10 are hydrogen.
13. The compound of claim 12, wherein R3 is selected from the group consisting of methyl, trifluoromethyl and chloro; and m is 0.
14. The compound of claim 1 that is:
2-Chloro-\u03b1-(4-cyanophenyl)aminomethylene\u2014N-ethyl-\u03b2-oxo-benzenepropanamide;
2-Chloro-N-ethyl-\u03b1-(4-iodophenyl)aminomethylene-\u03b2-oxo-benzenepropanamide;
2-Chloro-\u03b1-(4-iodophenyl)aminomethylene-\u03b2-oxo-N-(2-propynyl)-benzenepropanamide;
2-Chloro-\u03b1-(4-ethynylphenyl)aminomethylene-\u03b2-oxo-N-propyl-benzenepropanamide;
\u03b1-(4-Ethynylpheny)aminomethylene-2-methyl-\u03b2-oxo-N-propyl-benzenepropanamide;
\u03b1-(4-Cyanophenyl)aminomethylene-2-methyl-\u03b2-oxo-N-propyl-benzenepropanamide;
\u03b1-(4-Ethynylphenyeaminomethylene-2-methyl-\u03b2-oxo-N-(2- propynyl)-benzenepropanamide;
2-Chloro-\u03b1-(4-cyanopheny)aminomethylene-\u03b2-oxo-N-propyl-benzenepropanamide;
2-Chloro-N-ethyl-\u03b1(isoxazolyl-3-amino)methylene-\u03b2-oxo-benzenepropanamide;
\u03b1-(4-EthynylphenyDaminomethylene-\u03b2-oxo-N-propyl-1- naphthalenepropanamide;
2-Chloro-\u03b1-(isoxazolyl-3-amino)methylene-\u03b2-oxo-N-propyl-benzenepropanarnide;
2-Chloro-N-ethyl-\u03b2-oxo-\u03b1-(1,2,4-triazolyl-4-amino)methylenebenzene-propanamide;
\u03b1-(4Ethynylpheny)aminomethylene-\u03b2-oxo-N-propyl-1-naphthalenepropanamide;
2-Chloro-N-ethyl-\u03b2-oxo-\u03b1-(pyrazinyl)aminobenzenepropanamide;
\u03b1-(4-chlorophenyeaminomethylene-N-isopropyl-\u03b2-oxobenzenepropanamide;
2-chloro-a-(4-chlorophenypaminomethylene-N-isopropyl-\u03b2-oxobenzene-propanamide;
2-chloro-\u03b1-(4-chlorophenyl)aminomethylene-N-ethyl-\u03b2-oxobenzenepropanamide;
2-chloro-\u03b1-(4ethoxyphenyl)aminomethylene-N-ethyl-\u03b2-oxobenzene-propanamide;
2-chloro-\u03b1-(4chlorophenyl)aminomethylene-N-propyl-\u03b2-oxobenzene-propanamide;
2-chloro-\u03b1-(4-chlorophenypaminomethylene-N-(1-methylpropyl-\u03b2-oxobenzene-propanamide;
2-chloro-N-ethyl-\u03b1-(\u03b1-methyl-4fluorobenzyl)aminomethylene-\u03b2-oxobenzene-propanamide;
2-chloro-N-ethyl-\u03b1-(\u03b1-methylbenzyl)aminomethylene-\u03b2-oxobenzene-propanamide;
2-chloro-\u03b1-(4-iodophenyl)aminomethylene-N-methyl-\u03b2-oxobenzene-propanamide;
2-chloro-\u03b1-(4-chlorophenyl)aminomethylene-N-methyl-\u03b2-oxobenzene-propanamide; and 2-chloro-\u03b1-(4-chlorophenypaminomethylene-N-(\u03b1-methylbenzyl)-\u03b2-oxobenzene-propanamide.
15. A pharmaceutical composition, comprising the compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from the group consisting of aryl, heteroaryl, aralkyl and R16R17N\u2014, each unsubstituted or substituted;
R2 is selected from the group consisting of hydrogen and unsubstituted or substituted C1-10alkyl;
R3 is selected from the group consisting of fluoro, chloro, bromo, iodo, C1-10alkoxy, nitro, haloC1-10alkyl, perhaloC1-10alkyl and unsubstituted or substituted C1-10alkyl;
each R4 is independently selected from the group consisting of halogen, nitro, C1-10alkyl, C1-10alkenyl, C2-10alkynyl, C1-10alkoxy, aralkyl, aryl, heteroaryl, cycloalkyl and heterocycloalkyl, each unsubstituted or substituted, or wherein R3 and an adjacent R4 together form a fused unsubstituted or substituted 5 or 6 membered cycloalkyl, aryl or heteroaryl ring;
R5 is selected from the group consisting of C1-10alkyl, C1-10alkoxy,\u2014NH2, C1-10alkylamino, di(C1-10)alkylamino and aryl, each substituted or unsubstituted;
R16 and R17 are each independently C3-12cycloalkyl, aryl, heteroaryl, C1-10alkyl, each unsubstituted or substituted, or R16 and R17 together with the nitrogen atom to which they are attached form an unsubstituted or substituted 4, 5, or 6 membered ring; and
m is 0, 1, 2, 3 or 4; with the proviso that when R5 is \u2014OEt, then R4 is not halogen, and the compound of Formula I is not the compounds ethyl \u03b1-(benzyl)aminomethylene- 2-chloro-\u03b2-oxobenzenepropionate and 1-(2,4-dichloro-5-fluorophenye-2-(2,4-difluorophenyl)aminomethylene-1,3-pentanedione; and
a pharmaceutically-acceptable carrier selected from the group consisting of excipients and auxiliaries.
16. A pharmaceutical composition comprising the compound of claim 14 and a pharmaceutically-acceptable carrier selected from the group consisting of excipients and auxiliaries.
17. A method for the treatment of a CNS disorder amenable to modulation of the GABAA receptor complex which comprises administering to a patient in need of such treatment a compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from the group consisting of aryl, heteroaryl, aralkyl and R16R17N\u2014, each unsubstituted or substituted;
R2 is selected from the group consisting of hydrogen and unsubstituted or substituted C1-10alkyl;
R3 is selected from the group consisting of hydrogen, halo, haloC1-10alkyl, perhaloC1-10alkyl, amino, cyano, nitro, hydroxy, thio, C1-20alkyl, C2-10alkenyl, C2-10alkyenyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted;
each R4 is independently selected from the group consisting of hydrogen, halo, haloC1-10alkyl, perhaloC1-10alkyl, amino, cyano nitro, hydroxy, thio, C1-10alkyl, C2-10alkenyl, C2-10alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted, or wherein R3 and an adjacent R4 together foam a fused unsubstituted or substituted 5 or 6 membered cycloalkyl, aryl or heteroaryl ring;
R5 is selected from the group consisting of C1-10alkyl, C1-10alkoxy, \u2014NH2, C1-10alkylamino, di(C1-10)alkylamino and aryl, each substituted or unsubstituted;
R16 and R17 are each independently C3-12cycloalkyl, aryl, heteroaryl, C1-10alkyl, each unsubstituted or substituted, or R16 and R17 together with the nitrogen atom to which they are attached form an unsubstituted or substituted 4, 5, or 6 membered ring; and
m is 0, 1, 2, 3 or 4;
wherein said CNS disorder is selected from the group consisting of anxiety disorder, insomnia, major depressive disorder, bipolar disorder, convulsions, withdrawal-induced convulsions from substance abuse, chronic pain, acute pain, neuroses, phobia, panic disorder, generalized anxiety disorder, obsessive-compulsive disorder, post traumatic stress disorder, acute stress disorder, migraine, depression, and epilepsy.
18. A method for the treatment of a sleep disorder involving reduced wakefulness comprising the steps of administering to a patient in need of such a treatment a compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from the group consisting of aryl, heteroaryl, aralkyl and R16 R17N\u2014, each unsubstituted or substituted;
R2 is selected from the group consisting of hydrogen and unsubstituted or substituted C1-10alkyl;
R3 is selected from the group consisting of hydrogen, halo, haloC1-10alkyl, perhaloC1-10alkyl, amino, cyano, nitro, hydroxy, thio, C1-20alkyl, C2-10alkenyl, C2-10alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted;
each R4 is independently selected from the group consisting of hydrogen, halo, haloC1-10alkyl, perhaloC1-10alkyl, amino, cyano, nitro, hydroxy, thio, C1-20alkyl, C2-10alkenyl, C2-10alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted, or wherein R3 and an adjacent R4 together form a fused unsubstituted or substituted 5 or 6 membered cycloalkyl, aryl or heteroaryl ring;
R5 is selected from the group consisting of C1-10alkyl, C1-10alkoxy, \u2014NH2, C1-10alkylamino, di(C1-10)alkylamino and aryl, each substituted or unsubstituted;
R16 and R17 are each independently C3-12cycloalkyl, aryl, heteroaryl, C1-10alkyl, each unsubstituted or substituted, or R16 and R17 together with the nitrogen atom to which they are attached form an unsubstituted or substituted 4, 5, or 6 membered ring; and
m is 0, 1, 2, 3 or 4.
19. The method of claim 18, wherein the sleep disorder involving reduced wakefulness is selected from the group consisting of narcolepsy and idiopathic hypersomnia.
20. The method of claim 17, wherein:
R5 is selected from the group consisting of \u2014C1-10alkyl, CH3O\u2014, C3-10alkoxy, \u2014NH2, C1-10alkylamino, di(C1-10)alkylamino and aryl, each unsubstituted or substituted.
21. A method for the treatment of a neurodegenerative disorder, which comprises administering to a patient in need of such treatment an effective amount of compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from the group consisting of aryl, heteroaryl, aralkyl and R16R17N\u2014, each unsubstituted or substituted;
R2 is selected from the group consisting of hydrogen and unsubstituted or substituted C1-10alkyl;
R3 is selected from the group consisting of hydrogen, halo, haloC1-10alkyl, perhaloC1-10alkyl, amino, cyano, nitro, hydroxy, thio, C1-10alkyl, C2-10alkenyl, C2-10alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted;
each R4 is independently selected from the group consisting of hydrogen, halo, haloC1-10alkyl, perhaloC1-10alkyl, amino, cyano, nitro, hydroxy, thio, C1-20alkyl, C2-10alkenyl, C2-10alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted, or wherein R3 and an adjacent R4 together form a fused unsubstituted or substituted 5 or 6 membered cycloalkyl, aryl or heteroaryl ring;
R5 is selected from the group consisting of C1-10alkyl, C1-10alkoxy, \u2014NH2, C1-10alkylamino, di(C1-10)alkylamino and aryl, each substituted or unsubstituted;
R16 and R17 are each independently C3-12cycloalkyl, aryl, heteroaryl, C1-10alkyl, each unsubstituted or substituted, or R16 and R17 together with the nitrogen atom to which they are attached form an unsubstituted or substituted 4, 5, or 6 membered ring; and
m is 0, 1, 2, 3, or 4.
22. A method for the treatment of senile dementia, which comprises administering to a patient in need of such treatment an effective amount of compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from the group consisting of aryl, heteroaryl, aralkyl and R16R17N\u2014, each unsubstituted or substituted;
R2 is selected from the group consisting of hydrogen and unsubstituted or substituted C1-10alkyl;
R3 is selected from the group consisting of hydrogen, halo, haloC1-10alkyl, perhaloC1-10alkyl, amino, cyano, nitro, hydroxy, thio, C2-10alkyl, C2-10alkenyl, C2-10alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted;
each R4 is independently selected from the group consisting of hydrogen, halo, haloC1-10alkyl, perhaloC1-10alkyl, amino, cyano, nitro, hydroxy, thio, C1-20alkyl, C2-10alkenyl, C2-10alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted, or wherein R3 and an adjacent R4 together form a fused unsubstituted or substituted 5 or 6 membered cycloalkyl, aryl or heteroaryl ring;
R5 is selected from the group consisting of C1-10alkyl, C1-10alkoxy, \u2014NH2, C1-10alkylamino, di(C1-10)alkylamino and aryl, each substituted or unsubstituted;
R16 and R17 are each independently C3-12cycloalkyl, aryl, heteroaryl, C1-10alkyl, each unsubstituted or substituted, or R16 and R17 together with the nitrogen atom to which they are attached form an unsubstituted or substituted 4, 5, or 6 membered ring; and
m is 0, 1, 2, 3 or 4.
23. A method for the treatment of schizophrenia, which comprises administering to a patient in need of such treatment an effective amount of compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from the group consisting of aryl, heteroaryl, aralkyl and R16R17N\u2014, each unsubstituted or substituted;
R2 is selected from the group consisting of hydrogen and unsubstituted or substituted C1-10alkyl;
R3 is selected from the group consisting of hydrogen, halo, haloC1-10alkyl, perhaloC1-10alkyl, amino, cyano, nitro, hydroxy, thio, C1-20alkyl, C2-10alkenyl, C2-10alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted;
each R4 is independently selected from the group consisting of hydrogen, halo, haloC1-10alkyl, perhaloC1-10alkyl, amino, cyano, nitro, hydroxy, thio, C1-20alkyl, C2-10alkenyl, C2-10alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted, or wherein R3 and an adjacent R4 together form a fused unsubstituted or substituted 5 or 6 membered cycloalkyl, aryl or heteroaryl ring;
R5 is selected from the group consisting of C1-10alkyl, C1-10alkoxy,NH2, C1-10alkylamino, di(C1-10)alkylamino and aryl, each substituted or unsubstituted;
R16 and R17 are each independently C3-12cycloalkyl, aryl, heteroaryl, C1-10alkyl, each unsubstituted or substituted, or R16 and R17 together with the nitrogen atom to which they are attached form an unsubstituted or substituted 4, 5, or 6 membered ring; and
m is 0, 1, 2, 3 or 4.
24. A method for the treatment of a cognition deficit disorder, which comprises administering to a patient in need of such treatment an effective amount of compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from the group consisting of aryl, heteroaryl, aralkyl and R16R17N\u2014, each unsubstituted or substituted;
R2 is selected from the group consisting of hydrogen and unsubstituted or substituted C1-10alkyl;
R3 is selected from the group consisting of hydrogen, halo, haloC1-10alkyl, perhaloC1-10alkyl, amino, cyano, nitro, hydroxy, thio, C1-20alkyl, C1-10alkenyl, C2-10alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted;
each R4 is independently selected from the group consisting of hydrogen, halo, haloC1-10alkyl, perhaloC1-10alkyl, amino, cyano, nitro, hydroxy, thio, C1-20alkyl, C2-10alkenyl, C2-10alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C 1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted, or wherein R3 and an adjacent R4 together form a fused unsubstituted or substituted 5 or 6 membered cycloalkyl, aryl or heteroaryl ring;
R5 is selected from the group consisting of C1-10alkyl, C1-10alkoxy, \u2014NH2, C1-10alkylamino, di(C1-10)alkylamino and aryl, each substituted or unsubstituted;
R16 and R17 are each independently C3-12cycloalkyl, aryl, heteroaryl, C1-10alkyl, each unsubstituted or substituted, or R16 and R17 together with the nitrogen atom to which they are attached form an unsubstituted or substituted 4, 5, or 6 membered ring; and
m is 0, 1, 2, 3 or 4.
25. A method for the treatment of mild cognitive impairment, age related cognitive decline, or Alzheimer’s disease, which comprises administering to a patient in need of such treatment an effective amount of a compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from the group consisting of aryl, heteroaryl, aralkyl and R16R17N\u2014, each unsubstituted or substituted;
R2 is selected from the group consisting of hydrogen and unsubstituted or substituted C1-10alkyl;
R3 is selected from the group consisting of hydrogen, halo, haloCi1-10alkyl, perhaloC1-10alkyl, amino, cyano, nitro, hydroxy, thio, C1-10alkyl, C2-10alkenyl, C2-10alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted;
each R4 is independently selected from the group consisting of hydrogen, halo, haloC1-10alkyl, perhaloC1-10alkyl, amino, cyano, nitro, hydroxy, thio, C1-20alkyl, C2-10alkenyl, C2-10alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, C1-10alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, sulfinyl group, imino group, each unsubstituted or substituted, or wherein R3 and an adjacent R4 together foul a fused unsubstituted or substituted 5 or 6 membered cycloalkyl, aryl or heteroaryl ring;
R5 is selected from the group consisting of C1-10alkyl, C1-10alkoxy, \u2014NH2, C1-10alkylamino, di(C1-10)alkylamino and aryl, each substituted or unsubstituted;
R16 and R17 are each independently C3-12cycloalkyl, aryl, heteroaryl, C1-10alkyl, each unsubstituted or substituted, or R16 and R17 together with the nitrogen atom to which they are attached form an unsubstituted or substituted 4, 5, or 6 membered ring; and
m is 0, 1, 2, 3 or 4.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
What is claimed is:
1. A method of manufacturing a multilayer ceramic electronic part comprising:
providing a plurality of ceramic green sheets prepared by the method of
coating a ceramic slurry comprising a ceramic powder dispersed in a dispersion medium on a carrier film to form a sheet,
drying the sheet-formed ceramic slurry on the carrier film, and
pressing the dry sheet obtained by drying the ceramic slurry on the carrier film under conditions of a pressing surface temperature of about 0 to 150 C. and a pressing pressure of about 500 to 10,000 kgfcm2 to smooth the surface of the sheet,
coating an electrode paste on ceramic green sheets subjected to the smoothing process in a predetermined pattern;
coating a ceramic paste containing a ceramic powder, a binder and a solvent on a region of the electrode paste-coated surface on which the electrode paste was not coated,
subjecting the ceramic green sheet having the electrode paste and the ceramic paste coated thereon to a secondary smoothing process by pressing under conditions of a pressing surface temperature of about 0 to 150 C. and a pressing pressure of about 500 to 10,000 kgfcm2 to smooth the surface of the sheet;
laminating the sheets provided with electrodes to form a lamination, and
burning the lamination.
2. A method of producing a ceramic green sheet according to claim 1, wherein the pressing is effected by a pair of pressing plates.
3. A method of producing a green sheet according to claim 2, wherein plate pressing is performed under conditions of a pressing plate surface temperature of about 20 to 100 C. and a pressing pressure of about 1,000 to 6,000 kgfcm2.
4. A method of producing a ceramic green sheet according to claim 1, wherein the pressing is hydrostatic pressing.
5. A method of producing a ceramic green sheet according to claim 4, wherein hydrostatic pressing is performed by under conditions of a pressing temperature of about 20 to 100 C. and a pressing pressure of about 1,000 to 6,000 kgfcm2.
6. A method of producing a ceramic green sheet according to claim 1, wherein the pressing comprises:
calendering the dry sheet obtained by drying the ceramic slurry on the carrier film by using a calender roll comprising at least a pair of nip rolls under conditions of a pressing pressure (linear pressure) of about 500 to 1,000 kgfcm to smooth the surface of the sheet.
7. A method of producing a ceramic green sheet according to claim 6, wherein calendar roll processing is performed under conditions of a nip roll surface temperature of about 20 to 100 C. and a pressing pressure (linear pressure) of about 100 to 600 kgfcm.
8. A method of producing a ceramic green sheet according to claim 1, wherein the smoothing process is performed such that the surface roughness (Ra value) of the resulting ceramic green sheet is 100 nm or less.
9. A method of producing a ceramic green sheet according to claim 1, wherein the ceramic green sheet is separated from the carrier film, and a plurality of such separated sheets are laminated.
10. A method of manufacturing a multilayer electronic part according to claim 1, wherein the electrode paste for forming an internal electrode comprising a base metal powder as a conductive component so that the internal electrode formed after burning the lamination comprise a base metal.
11. A method of manufacturing a multilayer ceramic electronic part according to claim 1, wherein the smoothing process is performed by a calendar roll pressing, plate pressing or a hydrostatic pressing.
12. A method of manufacturing a multilayer ceramic electronic part according to claim 1, wherein the secondary smoothing process is performed by a calendar roll pressing, plate pressing or hydrostatic pressing.
13. A method of producing a multilayer ceramic electronic part according to claim 12, wherein the secondary smoothing process is performed by under conditions of a pressing temperature of about 20 to 100 C. and a pressing pressure of about 1,000 to 6,000 kgfcm2.
14. A method of producing a multilayer ceramic electronic part according to claim 13, wherein the secondary smoothing is effected by a pair of pressing plates.
15. A method of producing a multilayer ceramic electronic part according to claim 13, wherein the secondary smoothing is effected by hydrostatic pressing.
16. A method of producing a multilayer ceramic electronic part according to claim 13, wherein the secondary smoothing comprises:
calendering the dry sheet using a calender roll comprising at least a pair of nip rolls under conditions of a pressing pressure (linear pressure) of about 50 to 1,000 kgfcm to smooth the surface of the sheet.
17. A method of producing a multilayer ceramic electronic part according to claim 16, wherein calender roll processing is performed under conditions of a nip roll surface temperature of about 20 to 100 C. and a pressing pressure (linear pressure) of about 100 to 600 kgfcm.