1. A compound of formula I:
or a pharmaceutically acceptable salt thereof, wherein:
R1 and R2 are each independently hydrogen or a nitrogen protecting group;
one of R3 or R4 is \u2014R and the other one of R3 or R4 is \u2014Q1\u2014A\u2014Q2\u2014Y,
wherein Q1 is a valence bond, \u2014NRA\u2014, \u2014C(RA)2\u2014, \u2014S\u2014, \u2014O\u2014, \u2014SO2\u2014 or \u2014CO\u2014, wherein each occurrence of RA is independently hydrogen or optionally substituted C1-4aliphatic, or two occurrences of RA on the same carbon atom are taken together to form an optionally substituted 3\u20136-membered carbocyclic ring;
A is an optionally substituted group selected from a 5\u20137-membered monocyclic or 8\u201310-membered bicyclic aryl, heteroaryl, heterocyclic or carbocyclic ring;
Q2 is NRC, S, O, or C(RC)2, wherein each occurrence of RC is independently hydrogen or optionally substituted C1-4aliphatic;
Y is an optionally substituted group selected from a 5\u20137-membered monocyclic or 8\u201310 membered bicyclic aryl, heteroaryl, heterocyclic or carbocyclic ring;
R5 is \u2014R;
Z is CR6, wherein R6 is \u2014R; and
each occurrence of \u2014R is independently hydrogen, Q(n)halogen, Q(n)CN, Q(n)NO2, or Q(n)R7, wherein n is zero or one, Q is an optionally substituted C1-4alkylidene chain wherein one or more methylene units of Q is optionally replaced by \u2014O\u2014, \u2014S\u2014, \u2014NR7\u2014, \u2014NR7CO\u2014, \u2014NR7CONR7\u2014, \u2014NR7CO2\u2014, \u2014CO\u2014, \u2014CO2\u2014, \u2014CONR7\u2014, \u2014OC(O)NR7\u2014, \u2014SO2\u2014, \u2014SO2NR7\u2014, \u2014NR7SO2\u2014, \u2014NR7SO2NR7\u2014, \u2014C(O)C(O)\u2014, or \u2014C(O)C(R7)2C(O)\u2014, and each occurrence of R7 is independently hydrogen, an optionally substituted group selected from aliphatic, heteroaliphatic, aryl or heteroaryl, or two occurrences of R7 on the same nitrogen atom are taken together with the nitrogen atom to form an optionally substituted group selected from a 5\u20138-membered heterocyclic or 5\u20138-membered heteroaryl ring;
wherein one or more optional substituents on the unsaturated carbon atom of an aryl or heteroaryl group are independently selected from halogen \u2014R\xb0; \u2014OR\xb0; \u2014SR\xb0; 1,2-methylenedioxy; 1,2-ethylenedioxy, phenyl (Ph) optionally substituted with R\xb0; \u2014O(Ph) optionally substituted with R\xb0; \u2014(CH2)1-2(Ph), optionally substituted with R\xb0; \u2014CH\u2550CH(Ph), optionally substituted with R\xb0; \u2014NO2; \u2014CN; \u2014N(R\xb0)2; \u2014NR\xb0C(O)R\xb0; \u2014NR\xb0C(S)R\xb0; \u2014NR\xb0C(O)N(R\xb0)2; \u2014NR\xb0C(S)N(R\xb0)2; \u2014NR\xb0CO2R\xb0; \u2014NR\xb0NR\xb0C(O)R\xb0; \u2014NR\xb0NR\xb0C(O)N(R\xb0)2; \u2014NR\xb0NR\xb0CO2R\xb0; \u2014C(O)C(O)R\xb0; \u2014C(O)CH2C(O)R\xb0; \u2014CO2R\xb0; \u2014C(O)R\xb0; \u2014C(S)R\xb0; \u2014C(O)N(R\xb0)2; \u2014C(S)N(R\xb0)2; \u2014OC(O)N(R\xb0)2; \u2014OC(O)R\xb0; \u2014C(O)N(OR\xb0) R\xb0; \u2014C(NOR\xb0)R\xb0; \u2014S(O)2R\xb0; \u2014S(O)3R\xb0; \u2014SO2N(R\xb0)2; \u2014S(O)R\xb0; \u2014NR\xb0SO2N(R\xb0)2, \u2014NR\xb0SO2R\xb0; \u2014N(OR\xb0)R\xb0; \u2014C(\u2550NH)\u2014N(R\xb0)2; or \u2014(CH2)0-2NHC(O)R\xb0, wherein each independent occurrence of R\xb0 is selected from hydrogen optionally substituted C1-6aliphatic, an unsubstituted 5\u20136 membered heteroaryl or heterocyclic ring, phenyl, \u2014O(Ph), or \u2014CH2(Ph), or, two independent occurrences of R\xb0, on the same substituent or different substituents, taken together with the atom(s) to which each R\xb0group is bound, optionally form a 5\u20138-membered heterocyclyl, aryl, or heteroaryl ring or a 3\u20138-membered cycloalkyl ring having 0\u20133 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein one or more optional substituents on the aliphatic group of R\xb0 are selected from NH2, NH(C1-4aliphatic), N(C1-4aliphatic)2, halogen, C1-4aliphatic, OH, O(C1-4aliphatic), NO2, CN, CO2H, CO2(C1-4aliphatic), O(haloC1-4aliphatic), or haloC1-4aliphatic, wherein each of the foregoing C1-4aliphatic groups of R\xb0 is unsubstituted;
wherein one or more optional substituents on an aliphatic or heteroaliphatic group, or on a non-aromatic heterocyclic ring are independently selected from halogen; \u2014R\xb0; \u2014OR\xb0; \u2014SR\xb0; 1,2-methylenedioxy; 1,2-ethylenedioxy; phenyl (Ph) optionally substituted with R\xb0; \u2014O(Ph) optionally substituted with R\xb0; \u2014CH\u2550CH(Ph), optionally substituted with R\xb0; \u2014NO2; \u2014CN; \u2014N(R\xb0)2; \u2014NR\xb0C(O)R\xb0; \u2014NR\xb0C(S)R\xb0; \u2014NR\xb0C(O)N(R\xb0)2; \u2014NR\xb0C(S)N(R\xb0)2; \u2014NR\xb0CO2R\xb0; \u2014NR\xb0NR\xb0C(O)R\xb0; \u2014NR\xb0NR\xb0C(O)N(R\xb0)2; \u2014NR\xb0NR\xb0CO2R\xb0; \u2014C(O)C(O)R\xb0; \u2014C(O)CH2C(O)R\xb0; \u2014CO2R\xb0; \u2014C(O)R\xb0; \u2014C(S)R\xb0; \u2014C(O)N(R\xb0)2; \u2014C(S)N(R\xb0)2; \u2014OC(O)N(R\xb0)2; \u2014OC(O)R\xb0; \u2014C(O)N(OR\xb0)R\xb0; \u2014C(NOR\xb0)R\xb0; \u2014S(O)2R\xb0; \u2014S(O)3R\xb0; \u2014SO2N(R\xb0)2; \u2014S(O)R\xb0; \u2014NR\xb0SO2N(R\xb0)2; \u2014NR\xb0SO2R\xb0; \u2014N(OR\xb0)R\xb0; \u2014C(\u2550NH)\u2014N(R\xb0)2; or \u2014(CH2)0-2NHC(O)R\xb0, \u2550O, \u2550S, \u2550NNHR*, \u2550NN(R*)2, \u2550NNHC(O)R*, \u2550NNHCO2(alkyl), \u2550NNHSO2(alkyl), or \u2550NR*, where each R* is independently selected from hydrogen or an optionally substituted C1-6 aliphatic, wherein one or more optional substituents on the aliphatic group of R* are selected from NH2, NH(C1-4aliphatic), N(C1-4aliphatic)2, halogen, C1-4 aliphatic, OH, O(C1-4 aliphatic), NO2, CN, CO2H, CO2(C1-4 aliphatic), O(halo C1-4aliphatic), or halo(C1-4aliphatic), wherein each of the foregoing C1-4aliphatic groups of R* is unsubstituted;
wherein one or more optional substituents on a nitrogen of a non-aromatic heterocyclic ring are independently selected from \u2014R+, \u2014N(R+)2, \u2014C(O)R+, \u2014CO2R+, \u2014C(O)C(O)R+, \u2014C(O)CH2C(O)R+, \u2014SO2R+, \u2014SO2N(R+)2, \u2014C(\u2550S)N(R+)2, \u2014C(\u2550NH)\u2014N(R+)2, or \u2014NR+SO2R+; wherein R+ is hydrogen, an optionally substituted C1-6 aliphatic, optionally substituted phenyl, optionally substituted \u2014O(Ph), optionally substituted \u2014CH2(Ph), optionally substituted \u2014(CH2)1-2(Ph); optionally substituted \u2014CH\u2550CH(Ph); or an unsubstituted 5\u20136 membered heteroaryl or heterocyclic ring having one to four heteroatoms independently selected from oxygen, nitrogen, or sulfur, or, two independent occurrences of R+, on the same substituent or different substituents, taken together with the atom(s) to which each R+ group is bound, optionally form a 5\u20138-membered heterocyclyl, aryl or heteroaryl ring or a 3\u20138-membered cycloalkyl ring having 0\u20133 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein one or more optional substituents on the aliphatic group or the phenyl ring of R+ are selected from NH2, NH(C1-4 aliphatic), N(C1-4 aliphatic)2, halogen, C1-4 aliphatic, OH, O(C1-4 aliphatic), NO2, CN, CO2H, CO2(C1-4 aliphatic), O(halo C1-4 aliphatic), or halo(C1-4 aliphatic), wherein each of the foregoing C1-4aliphatic groups of R30 is unsubstituted.
2. The compound of claim 1, wherein either of R3 or R4 is \u2014Q1\u2014A\u2014Q2\u2014Y, wherein A is a substituted or unsubstituted aryl or heteroaryl moiety and compounds have the general formula IIa or IIb:
wherein Z1 is N or CRV, Z2 is N or CRW, Z3 is N or CRX and Z4 is N or CRY, wherein RV, RW, RX and RY are each independently R8, or RX and RY, or RV and RY are taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5\u20138 membered ring having 0\u20133 ring heteroatoms selected from oxygen, sulfur, or nitrogen, wherein any substitutable carbon on said fused ring formed by RX and RY or by RV and RY is substituted by oxo or R8, and any substitutable nitrogen on said ring formed by RX and RY or by RV and RY is substituted by R9;
wherein each occurrence of R8 is independently \u2014R; and
each occurrence of R9 is independently hydrogen, \u2014R\u2032, \u2014COR\u2032, \u2014CO2(R\u2032), \u2014CON(R\u2032)2, or \u2014SO2R\u2032, wherein each occurrence of R\u2032 is independently hydrogen, optionally substituted aliphatic, heteroaliphatic, aryl or heteroaryl, or two occurrences of R\u2032 on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted 5\u20138 membered heterocyclic or heteroaryl ring.
3. The compound of claim 2, wherein A represents one of the following moieties:
4. The compound of claim 3, wherein ring A is one of formulas i, ii, iii or x.
5. The compound of claim 2, wherein Ring A is one of groups II-A through II-DD, wherein Z1 is nitrogen or CRV, Z2 is nitrogen or CRW, and p is 0\u20134:
6. The compound of claim 5, wherein ring A is one of II-A, II-B, II-C, II-D, II-E, II-F, II-H, II-I, II-J, II-K, II-L, II-N, II-O, or II-DD.
7. The compound of claim 5, wherein ring A is one of II-A, II-B, II-C, II-D, II-E, II-H, or II-K.
8. The compound of claim 5, wherein ring A is one of II-A or II-B.
9. The compound of claim 5, wherein Z1 is CRV and Z2 is CRW.
10. The compound of claim 5, wherein Z1 is N and Z2 is N.
11. The compound of claim 5, wherein Z1 is N and Z2 is CRW.
12. The compound of claim 5, wherein Z1 is CRV and Z2 is N.
13. The compound of claim 2, wherein A is a monocyclic ring system and RX groups, when present, are selected from hydrogen, alkyl- or dialkylamino, acetamido, or a C1-4 aliphatic group; RY groups, when present, are selected from hydrogen, an optionally substituted group selected from C1-6 aliphatic, C1-6 heteroaliphatic, aryl, or heteroaryl, \u2014Q(n)N(R7)2, \u2014Q(n)OR7, \u2014Q(n)SR7, \u2014Q(n)(C\u2550O)O(R7), \u2014Q(n)C(O)N(R7)2, \u2014Q(n)NHC(O)R7, \u2014Q(n)NHSO2R7, or \u2014Q(n)SO2N(R7)2, wherein n is 0 or 1, and wherein Q is preferably \u2014(C(R\u2033)2)\u2014, wherein R\u2033 is hydrogen or C1-3alkyl, and wherein each occurrence of R7 is independently hydrogen, optionally substituted aliphatic, heteroaliphatic, aryl or heteroaryl, or two occurrences of R7 on the same nitrogen atom are taken together with the nitrogen atom to form an optionally group selected from a 5\u20138 membered heterocyclic or 5\u20138 membered heteroaryl ring.
14. The compound of claim 13, wherein RY is one of the following groups: optionally substituted 5\u20136 membered heteroaryl or heterocyclyl rings, optionally substituted aryl or cycloalkyl rings; optionally substituted C1-6 aliphatic; alkoxyalkylamino alkoxyalkyl; aminoalkyl; alkyl- or dialkylamino; alkyl- or dialkylaminoalkoxy; alkyl- or dialkylaminoalkoxyalkyl; or acetamido.
15. The compound of claim 2, wherein A is a bicyclic ring system and the bicyclic ring system A may be substituted by one or more occurrences of oxo, R8 or R9, wherein R8 is \u2014R7, halo, \u2014O(CH2)2-4\u2014N(R7)2, \u2014O(CH2)2-4\u2014R7, \u2014OR7, \u2014N(R7)\u2014(CH2)2-4\u2014N(R7)2, \u2014N(R7)\u2014(CH2)2-4\u2014R7, \u2014C(\u2550O)R7, \u2014CO2R7, \u2014COCOR7, \u2014NO2, \u2014CN, \u2014S(O)R7, \u2014SO2R7, \u2014SR7, \u2014N(R7)2, \u2014CON(R7)2, \u2014SO2N(R7)2, \u2014OC(\u2550O)R7, \u2014N(R7)COR7, \u2014N(R7)CO2(optionally substituted C1-6 aliphatic), \u2014N(R7)N(R7)2, \u2014C\u2550NN(R7)2, \u2014C\u2550N\u2014OR, \u2014NHOR7, \u2014N(R7)CON(R7)2, \u2014N(R7)SO2N(R7)2, \u2014N(R7)SO2R7, or \u2014OC(\u2550O)N(R7)2, wherein each occurrence of R7 is independently hydrogen, an optionally substituted group selected from aliphatic, heteroaliphatic, aryl or heteroaryl, or two occurrences of R7 on the same nitrogen atom are taken together with the nitrogen atom to form an optionally substituted group selected from a 5\u20138 membered heterocyclic or 5\u20138 membered heteroaryl ring.
16. The compound of claim 15 wherein each occurrence of R8 is independently -halo, \u2014R7, \u2014OR7, \u2014COR7, \u2014CO2R7, \u2014CON(R7)2, \u2014O(C\u2550O)N(R7)2, \u2014CN, \u2014O(CH2)2-4\u2014N(R7)2, \u2014O(CH2)2-4\u2014R7, \u2014NO2, \u2014N(R7)2, \u2014NR7COR7, \u2014NR7SO2R7, \u2014SO2N(R7)2 wherein each occurrence of R7 is independently hydrogen, an optionally substituted group selected from aliphatic, heteroaliphatic, aryl or heteroaryl, or two occurrences of R7 on the same nitrogen atom are taken together with the nitrogen atom to form an optionally substituted group selected from a 5\u20138 membered heterocyclic or 5\u20138 membered heteroaryl ring.
17. The compound of claim 2, wherein Y is an optionally substituted heteroaryl moiety.
18. The compound of claim 2, wherein Y is selected from one of the following heteroaryl moieties a\u2013y:
wherein q is 0\u20134, R10 is \u2014R, and wherein each occurrence of R11 is independently hydrogen, \u2014R\u2032, \u2014COR\u2032, \u2014CO2(R\u2032), \u2014CON(R\u2032)2, or \u2014SO2R\u2032, wherein each occurrence of R\u2032 is independently hydrogen, an optionally substituted group selected from aliphatic, heteroaliphatic, aryl or heteroaryl, or two occurrences of R\u2032 on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted group selected from a 5\u20138 membered heterocyclic or 5\u20138 membered heteroaryl ring.
19. The compound of claim 18, wherein Y is one of the following heteroaryl moieties:
wherein q is 0\u20134, R10 is \u2014R, and wherein each occurrence of R11 is independently hydrogen, \u2014R\u2032, \u2014COR\u2032, \u2014CO2(R\u2032), \u2014CON(R\u2032)2, or \u2014SO2R\u2032, wherein each occurrence of R\u2032 is independently hydrogen, optionally substituted group selected from aliphatic, heteroaliphatic, aryl or heteroaryl, or two occurrences of R\u2032 on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted group selected from a 5\u20138 membered heterocyclic or 5\u20138 membered heteroaryl ring.
20. The compound of claim 18, wherein Y is a pyrazole moiety, h.
21. The compound of claim 18, wherein each R10 is independently hydrogen, C1-4aliphatic, alkoxycarbonyl, optionally substituted phenyl, hydroxyalkyl, alkoxyalkyl, aminocarbonyl, mono- or dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, phenylaminocarbonyl, or (N-heterocycle)carbonyl.
22. The compound of claim 18, wherein each occurrence of R10 is independently methyl, cyclopropyl, ethyl, isopropyl, propyl, t-butyl, cyclopentyl, phenyl, CO2H, CO2CH3, CH2OH, CH2OCH3, CH2CH2CH2OH, CH2CH2CH2OCH3, CH2CH2CH2OCH2Ph, CH2CH2CH2NH2, CH2CH2CH2NHCOOC(CH3)3, CONHCH(CH3)2, CONHCH2CH\u2550CH2, CONHCH2CH2OCH3, CONHCH2Ph, CONH(cyclohexyl), CON(Et)2, CON(CH3)CH2Ph, CONH(n-C3H7), CON(Et)CH2CH2CH3, CONHCH2CH(CH3)2, CON(n-C3H7)2, CO(3-methoxymethylpyrrolidin-1-yl), CONH(3-tolyl), CONH(4-tolyl), CONHCH3, CO(morpholin-1-yl), CO(4-methylpiperazin-1-yl), CONHCH2CH2OH, CONH2, or CO(piperidin-1-yl).
23. The compound of claim 18, wherein, Y is a pyrazole moiety, h\u2032, wherein the pyrazole is substituted with two occurrences of R10 (R10a and R10b)
wherein R10a is hydrogen, C1-4aliphatic, alkoxycarbonyl, optionally substituted phenyl, hydroxyalkyl, alkoxyalkyl, aminocarbonyl, mono- or dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, phenylaminocarbonyl, and (N-heterocycle)carbonyl; and R10b is hydrogen.
24. The compound of claim 23, wherein R10a and R10b taken together represent a substituted or unsubstituted cycloaliphatic, cycloheteroaliphatic, aryl or heteroaryl moiety and comprises one of the following groups:
wherein r is 0\u20134 and R12 is hydrogen, -halo, \u2014N(R7)2, \u2014C1-3 alkyl, \u2014C1-3 haloalkyl, \u2014NO2, \u2014O(C1-3 alkyl), \u2014CO2(C1-3 alkyl), \u2014CN, \u2014SO2(C1-3 alkyl), \u2014SO2NH2, \u2014OC(O)NH2, \u2014NH2SO2(C1-3 alkyl), \u2014NHC(O)(C1-3 alkyl), \u2014C(O)NH2, and \u2014CO(C1-3 alkyl), wherein the (C1-3 alkyl) is most preferably methyl, wherein each occurrence of R7 is independently hydrogen, an optionally substituted group selected from aliphatic, heteroaliphatic, aryl or heteroaryl, or two occurrences of R7 on the same nitrogen atom are taken together with the nitrogen atom to form an optionally substituted group selected from a 5\u20138 membered heterocyclic or 5\u20138 membered heteroaryl ring.
25. The compound of claim 2, wherein when R3 is \u2014Q1\u2014A\u2014Q2\u2014Y, R4 is hydrogen, C1-3aliphatic, hydroxy, hydroxyalkyl, alkoxy, amino, aminoalkyl, mono- or di-alkylamino, mono- or di-alkylaminoalkyl, or optionally substituted phenyl.
26. The compound of claim 25, wherein R4 is hydrogen, methyl, ethyl, cyclopropyl, hydroxy, phenyl or \u2014CH2NH2.
27. The compound of claim 2, wherein when R4 is \u2014Q1\u2014A\u2014Q2\u2014Y, R3 is hydrogen, C1-3aliphatic, hydroxy, hydroxyalkyl, alkoxy, amino, aminoalkyl, mono- or di-alkylamino, mono- or di-alkylaminoalkyl, or optionally substituted phenyl.
28. The compound of claim 27, wherein R3 is hydrogen, methyl, ethyl, cyclopropyl, hydroxy, phenyl or \u2014CH2NH2.
29. The compound of claim 2, wherein R5 is hydrogen, halogen, \u2014NO2, \u2014CN, hydroxy, optionally substituted C1-3alkyl, optionally substituted alkoxy, \u2014SO2NH2, or \u2014C(O)alkyl.
30. The compound of claim 29 wherein R5 is Cl, CF3, OCF3, CH3, \u2014CN, \u2014SO2NH2 or \u2014C(O)Me.
31. The compound of claim 2, wherein Q1 is NH and Q2 is NH, and compounds are defined by the general formula IIa(i) or IIb(i):
32. The compound of claim 2, wherein Q1 is S and Q2 is NH, and compounds are defined by the general formula IIa(ii) or IIb(ii):
33. The compound of claim 2, wherein Q1 is O and Q2 is NH, and compounds are defined by the general formula IIa(iii) or IIb(iii):
34. The compound of claim 2, wherein Q2 is NH, and compounds are defined by the general formula IIa(iv) or IIb(iv):
wherein Q1 is \u2014C(RA)2.
35. The compound of claim 2, wherein Q2 is NH and Y is an optionally substituted heteroaryl moiety, and compounds are defined by the general formula IIa(v) or IIb(v):
wherein Q1 is a direct bond.
36. The compound of any one of claims 31, 32, 33, 34 or 35, wherein:
(i) R1, R2, R4 and R5 are each hydrogen and wherein Z is CR6 and R6 is hydrogen; or R1, R2, R3 and R5 are each hydrogen and wherein Z is CR6 and R6 is hydrogen;
(ii) ring A is defined according to one of the following groups:
(a) a ring A is one of formulas
(b) ring A is one of formulas
(c) ring A is one of formulas II-A, II-B, II-C, II-D, II-E, II-F, II-H, II-I, II-J, II-K, II-L, II-N, II-O, or II-DD;
(d) ring A is one of the formulas II-A, II-B, II-C, II-D, II-E, II-H, or II-K;
(e) ring A is one of formulas II-A or II-B;
(f) ring A is II-A and Z1 is CRV and Z2 is CRW;
(g) ring A is II-A and Z1 is N and Z2 is N;
(h) ring A is II-A and Z1 is N and Z2 is CRW;
(i) ring A is II-A and Z1 is CRV and Z2 is N;
(j) ring A is an optionally substituted aryl or heteroaryl moiety of formula i, ii, i or x;
(k) ring A is a monocyclic ring system and RV and RW, when present, are hydrogen or amino; RX groups, when present, is hydrogen, alkyl- or dialkylamino, acetamido, or a C1-4 aliphatic group such as methyl, ethyl, cyclopropyl, or isopropyl; RY groups, when present, is hydrogen, an optionally substituted group selected from hydrogen, C1-6 aliphatic, C1-6 heteroaliphatic, aryl, or heteroaryl, \u2014Q(n)N(R7)2, \u2014Q(n)OR7, \u2014Q(n)SR7, \u2014Q(n)(C\u2550O)O(R7), \u2014Q(n)C(O)N(R7)2, \u2014Q(n)NHC(O)R7, \u2014Q(n)NHSO2R7, or \u2014Q(n)SO2N(R7)2, wherein n is 0 or 1, and wherein Q is preferably \u2014(C(R\u2033)2)\u2014, wherein R\u2033 is hydrogen or C1-3alkyl, and wherein each occurrence of R7 is independently hydrogen, an optionally substituted group selected from aliphatic, heteroaliphatic, aryl or heteroaryl, or two occurrences of R7 on the same nitrogen atom are taken together with the nitrogen atom to form an optionally substituted group selected from a 5\u20138 membered heterocyclic or 5\u20138 membered heteroaryl ring;
(l) ring A is a monocyclic ring system and RV, RW and RX groups, when present, are hydrogen or amino; RY groups include groups selected from optionally substituted 5\u20136 membered heteroaryl or heterocyclyl rings, such as 2-pyridyl, 4-pyridyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl; optionally substituted aryl or cycloalkyl rings such as phenyl, halogen substituted phenyl, alkoxy substituted phenyl, trifluoromethyl substituted phenyl, nitro substituted phenyl, methyl substituted phenyl; optionally substituted C1-6 aliphatic, such as methyl, ethyl, cyclopropyl, cyclopentyl, cyclohexyl, amino substituted cycloalkyl, acetamido substituted cycloalkyl, isopropyl, or t-butyl; alkoxyalkylamino such as methoxyethylamino; alkoxyalkyl such as methoxymethyl or methoxyethyl; aminoalkyl such as aminoethyl, dimethylaminoethyl; alkyl- or dialkylamino such as ethylamino or dimethylamino; alkyl- or dialkylaminoalkoxy such as dimethylaminopropyloxy; alkyl- or dialkylaminoalkoxyalkyl such as dimethylaminoethoxymethyl; and acetamido;
(m) ring A system is a bicyclic ring system and the ring formed when Rx and Ry are taken together may be substituted or unsubstituted;
(n) ring A system is a bicyclic ring system formed by RX and RY taken together and substituted by one or more occurrences of R8 or R9, wherein each occurrence of R8 is independently \u2014R7, halo, \u2014O(CH2)2-4\u2014N(R7)2, \u2014O(CH2)2-4\u2014R7, \u2014OR7, \u2014N(R7)\u2014(CH2)2-4\u2014N(R7)2, \u2014N(R7)\u2014(CH2)2-4\u2014R7, \u2014C(\u2550O)R7, \u2014CO2R7, COCOR7, \u2014NO2, \u2014CN, \u2014S(O)R7, \u2014SO2R7, \u2014SR7, \u2014N(R7)2, \u2014CON(R7)2, \u2014SO2N(R7)2, \u2014OC(\u2550O)R7, \u2014N(R7)COR7, \u2014N(R7)CO2(optionally substituted C1-6 aliphatic), \u2014N(R7)N(R7)2, \u2014C\u2550NN(R7)2, \u2014C\u2550N\u2014OR, \u2014NHOR7, \u2014N(R7)CON(R7)2, \u2014N(R7)SO2N(R7)2, \u2014N(R7)SO2R7, or \u2014OC(\u2550O)N(R7)2, wherein each occurrence of R7 is independently hydrogen, an optionally substituted group selected from aliphatic, heteroaliphatic, aryl or heteroaryl, or two occurrences of R7 on the same nitrogen atom are taken together with the nitrogen atom to form an optionally substituted group selected from a 5\u20138 membered heterocyclic or 5\u20138 membered heteroaryl ring; and each occurrence of R9 is independently hydrogen, \u2014R\u2032, \u2014COR\u2032, \u2014CO2(R\u2032), \u2014CON(R\u2032)2, or \u2014SO2R\u2032, wherein each occurrence of R\u2032 is independently hydrogen, an optionally substituted group selected from aliphatic, heteroaliphatic, aryl or heteroaryl, or two occurrences of R\u2032 on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted group selected from a 5\u20138 membered heterocyclic or 5\u20138 membered heteroaryl ring,
(iii) Y is defined according to one of the following groups:
(a) Y is an optionally substituted heteroaryl moiety;
(b) Y is selected from one of the heteroaryl moieties a\u2013y;
(c) Y is selected from one of the following heteroaryl moieties:
wherein q is 0\u20134, R10 is \u2014R, wherein \u2014R is defined generally above and in classes and subclasses herein, and wherein each occurrence of R11 is independently hydrogen, \u2014R\u2032, \u2014COR\u2032, \u2014CO2(R\u2032), \u2014CON(R\u2032)2, or \u2014SO2R\u2032, wherein each occurrence of R\u2032 is independently hydrogen, an optionally substituted group selected from aliphatic, heteroaliphatic, aryl or heteroaryl, or two occurrences of R\u2032 on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted group selected from a 5\u20138 membered heterocyclic or 5\u20138 membered heteroaryl ring;
(d) Y is a pyrazole moiety, h;
(e) Y is one of a, b, f, h or o, optionally substituted with one or more R10 groups, wherein each occurrence of R10 is independently hydrogen, C1-4aliphatic, alkoxycarbonyl, optionally substituted phenyl, hydroxyalkyl, alkoxyalkyl, aminocarbonyl, mono- or dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, phenylaminocarbonyl, and (N-heterocycle)carbonyl;
(f) Y is one of a, b, f, h or o, optionally substituted with one or more R10 groups, wherein each occurrence of R10 is independently hydrogen, methyl, cyclopropyl, ethyl, isopropyl, propyl, t-butyl, cyclopentyl, phenyl, CO2H, CO2CH3, CH2OH, CH2OCH3, CH2CH2CH2OH, CH2CH2CH2OCH3, CH2CH2CH2OCH2Ph, CH2CH2CH2NH2, CH2CH2CH2NHCOOC(CH3)3, CONHCH(CH3)2, CONHCH2CH\u2550CH2, CONHCH2CH2OCH3, CONHCH2Ph, CONH(cyclohexyl), CON(Et)2, CON(CH3)CH2Ph, CONH(n-C3H7), CON(Et)CH2CH2CH3, CONHCH2CH(CH3)2, CON(n-C3H7)2, CO(3-methoxymethylpyrrolidin-1-yl), CONH(3-tolyl), CONH(4-tolyl), CONHCH3, CO(morpholin-1-yl), CO(4-methylpiperazin-1-yl), CONHCH2CH2OH, CONH2, and CO(piperidin-1-yl).
(g) Y is a pyrazole moiety, h\u2032, wherein the pyrazole is substituted with R10a and R10b,
wherein each occurrence of R10a is hydrogen, C1-4aliphatic, alkoxycarbonyl, optionally substituted phenyl, hydroxyalkyl, alkoxyalkyl, aminocarbonyl, mono- or dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, phenylaminocarbonyl, and (N-heterocycle)carbonyl, and R10b is hydrogen;
(h) Y is a pyrazole moiety, h\u2032, wherein the pyrazole is substituted with R10a and R10b,
wherein each occurrence of R10a is hydrogen, methyl, cyclopropyl, ethyl, isopropyl, propyl, t-butyl, cyclopentyl, phenyl, CO2H, CO2CH3, CH2OH, CH2OCH3, CH2CH2CH2OH, CH2CH2CH2OCH3, CH2CH2CH2OCH2Ph, CH2CH2CH2NH2, CH2CH2CH2NHCOOC(CH3)3, CONHCH(CH3)2, CONHCH2CH\u2550CH2, CONHCH2CH2OCH3, CONHCH2Ph, CONH(cyclohexyl), CON(Et)2, CON(CH3)CH2Ph, CONH(n-C3H7), CON(Et)CH2CH2CH3, CONHCH2CH(CH3)2, CON(n-C3H7)2, CO(3-methoxymethylpyrrolidin-1-yl), CONH(3-tolyl), CONH(4-tolyl), CONHCH3, CO(morpholin-1-yl), CO(4-methylpiperazin-1-yl), CONHCH2CH2OH, CONH2, and CO(piperidin-1-yl, and R10b is hydrogen;
(i) Y is heteroaryl moiety substituted by at least two occurrences of R10 and where two occurrences of R10 taken together may represent an optionally substituted group selected from cycloaliphatic, cycloheteroaliphatic, aryl or heteroaryl;
(j) Y represents one of the following heteroaryl moieties:
wherein r is 0\u20134 and R12 is hydrogen, -halo, \u2014N(R7)2, \u2014C1-3 alkyl, \u2014C1-3 haloalkyl, NO2, \u2014O(C1-3 alkyl), \u2014CO2(C1-3 alkyl), \u2014CN, \u2014SO2(C1-3 alkyl), \u2014SO2NH2, \u2014OC(O)NH2, \u2014NH2SO2(C1-3 alkyl), \u2014NHC(O)(C1-3 alkyl), \u2014C(O)NH2, and \u2014CO(C1-3 alkyl), wherein the (C1-3 alkyl) is most preferably methyl;
(iv) for compounds of formula IIa(i), R4 is defined according to one of the following groups:
(a) R4 is hydrogen, C1-3aliphatic, hydroxy, hydroxyalkyl, alkoxy, amino, aminoalkyl, mono- or di-alkylamino, mono- or di-alkylaminoalkyl, or optionally substituted phenyl, or
(b) R4 is hydrogen, methyl, ethyl, cyclopropyl, hydroxy, phenyl or \u2014CH2NH2;
(v) for compounds of formula IIb(i), R3 is defined according to one of the following groups:
(a) R3 is hydrogen, C1-3aliphatic, hydroxy, hydroxyalkyl, alkoxy, amino, aminoalkyl, mono- or di-alkylamino, mono- or di-alkylaminoalkyl, or optionally substituted phenyl, or
(b) R3 is hydrogen, methyl, ethyl, cyclopropyl, hydroxy, phenyl or \u2014CH2NH2; and
(vi) R5 is defined according to one of the following groups:
(a) hydrogen, halogen, \u2014NO2, \u2014CN, hydroxy, optionally substituted C1-3alkyl, optionally substituted alkoxy, \u2014SO2NH2, or \u2014C(O)alkyl, or
(b) R5 is hydrogen, Cl, CF3, OCF3, CH3, \u2014CN, \u2014SO2NH2 or \u2014C(O)Me.
37. The compound of claim 1, wherein either of R3 or R4 is \u2014Q1\u2014A\u2014Q2\u2014Y, wherein A is an optionally substituted cycloaliphatic or heterocycloaliphatic moiety and compounds have the general formula IIIa or IIIb:
wherein U is NR13, C(R14)2, or O; V is NR13, C(R14)2, or O; W is NR13, C(R14)2, or O, and X is NR13, C(R14)2, or O, and t is 0, 1 or 2, wherein each occurrence of R13 is independently hydrogen, \u2014R\u2032, \u2014COR\u2032, \u2014CO2(R\u2032), \u2014CON(R\u2032)2, or \u2014SO2R\u2032, wherein each occurrence of R\u2032 is independently hydrogen, optionally substituted group selected from C1-6 aliphatic, C1-6heteroaliphatic, aryl or heteroaryl, or two occurrences of R\u2032 on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted group selected from a 5\u20138 membered heterocyclic or 5\u20138 membered heteroaryl ring; and wherein each occurrence of R14 is independently \u2014R, with the proviso that when any one of U, V, W, or X is O or NR13, an adjacent group U, V, W or X is C(R14)2.
38. The compound of claim 37, wherein ring A is selected from the following group:
wherein R13 is hydrogen, \u2014R\u2032, \u2014COR\u2032, \u2014CO2(R\u2032), \u2014CON(R\u2032)2, or \u2014SO2R\u2032, wherein each occurrence of R\u2032 is independently hydrogen, optionally substituted group selected from aliphatic, heteroaliphatic, aryl or heteroaryl, or two occurrences of R\u2032 on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted group selected from a 5\u20138 membered heterocyclic or heteroaryl ring; R14 is oxo or \u2014R; and x is 0\u20134.
39. The compound of claim 38, wherein x is 0 or 1 and R14 is -halo, \u2014N(R7)2, \u2014C1-3 alkyl, \u2014haloalkyl, \u2014NO2, \u2014O(C1-3 alkyl), \u2014CO2(C1-3 alkyl), \u2014CN, \u2014SO2(C1-3 alkyl), \u2014SO2NH2, \u2014OC(O)NH2, \u2014NH2SO2(C1-3 alkyl), \u2014NHC(O)(C1-3 alkyl), \u2014C(O)NH2, and \u2014CO(C1-3 alkyl), wherein the (C1-3 alkyl) is most preferably methyl.
40. The compound of claim 38, wherein R13 is hydrogen or C1-4alkyl.
41. The compound of claim 38, wherein ring A is selected from one of xi, xii or xvi and x is 0.
42. The compound of claim 37, wherein Y is an optionally substituted heteroaryl moiety.
43. The compound of claim 37, wherein Y is selected from one of the following heteroaryl moieties a\u2013y:
wherein q is 0\u20134, R10 is \u2014R, and wherein each occurrence of R11 is independently hydrogen, \u2014R\u2032, \u2014COR\u2032, \u2014CO2(R\u2032), \u2014CON(R\u2032)2, or \u2014SO2R\u2032, wherein each occurrence of R\u2032 is independently hydrogen, an optionally substituted group selected from aliphatic, heteroaliphatic, aryl or heteroaryl, or two occurrences of R\u2032 on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted group selected from a 5\u20138 membered heterocyclic or 5\u20138 membered heteroaryl ring.
44. The compound of claim 43, wherein Y is one of the following heteroaryl moieties:
wherein q is 0\u20134, R10 is \u2014R, and wherein each occurrence of R11 is independently hydrogen, \u2014R\u2032, \u2014COR\u2032, \u2014CO2(R\u2032), \u2014CON(R\u2032)2, or \u2014SO2R\u2032, wherein each occurrence of R\u2032 is independently hydrogen, optionally substituted group selected from aliphatic, heteroaliphatic, aryl or heteroaryl, or two occurrences of R\u2032 on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted group selected from a 5\u20138 membered heterocyclic or 5\u20138 membered heteroaryl ring.
45. The compound of claim 43, wherein each R10 is independently hydrogen, C1-4aliphatic, alkoxycarbonyl, optionally substituted phenyl, hydroxyalkyl, alkoxyalkyl, aminocarbonyl, mono- or dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, phenylaminocarbonyl, or (N-heterocycle)carbonyl.
46. The compound of claim 43, wherein each occurrence of R10 is independently methyl, cyclopropyl, ethyl, isopropyl, propyl, t-butyl, cyclopentyl, phenyl, CO2H, CO2CH3, CH2OH, CH2OCH3, CH2CH2CH2OH, CH2CH2CH2OCH3, CH2CH2CH2OCH2Ph, CH2Ch2Ch2NH2, CH2CH2CH2NHCOOC(CH3)3, CONHCH(CH3)2, CONHCH2CH\u2550CH2, CONHCH2CH2OCH3, CONHCH2Ph, CONH(cyclohexyl), CON(Et)2, CON(CH3)CH2Ph, CONH(n-C3H7), CON(Et)CH2CH2CH3, CONHCH2CH(CH3)2, CON(n-C3H7)2, CO(3-methoxymethylpyrrolidin-1-yl), CONH(3-tolyl), CONH(4-tolyl), CONHCH3, CO(morpholin-1-yl), CO(4-methylpiperazin-1-yl), CONHCH2CH2OH, CONH2, or CO(piperidin-1-yl).
47. The compound of claim 43, wherein, Y is a pyrazole moiety, h\u2032, wherein the pyrazole is substituted with of R10a and R10b,
wherein R10a is hydrogen, C1-4aliphatic, alkoxycarbonyl, optionally substituted phenyl, hydroxyalkyl, alkoxyalkyl, aminocarbonyl, mono- or dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, phenylaminocarbonyl, and (N-heterocycle)carbonyl; and R10b is hydrogen.
48. The compound of claim 47, wherein R10a and R10b taken together represent a substituted or unsubstituted cycloaliphatic, cycloheteroaliphatic, aryl or heteroaryl moiety and comprises one of the following groups:
wherein r is 0\u20134 and R12 is hydrogen, -halo, \u2014N(R7)2, \u2014C1-3 alkyl, \u2014C1-3 haloalkyl, \u2014NO2, \u2014O(C1-3 alkyl), \u2014CO2(C1-3 alkyl), \u2014CN, \u2014SO2(C1-3 alkyl), \u2014SO2NH2, \u2014OC(O)NH2, \u2014NH2SO2(C1-3 alkyl), \u2014NHC(O)(C1-3 alkyl), \u2014C(O)NH2, and \u2014CO(C1-3 alkyl), wherein each occurrence of R7 is independently hydrogen, an optionally substituted group selected from aliphatic, heteroaliphatic, aryl or heteroaryl, or two occurrences of R7 on the same nitrogen atom are taken together with the nitrogen atom to form an optionally substituted group selected from a 5\u20138 membered heterocyclic or 5\u20138 membered heteroaryl ring.
49. The compound of claim 37, wherein when R3 is \u2014Q1\u2014A\u2014Q2\u2014Y, R4 is hydrogen, C1-3aliphatic, hydroxy, hydroxyalkyl, alkoxy, amino, aminoalkyl, mono- or di-alkylamino, mono- or di-alkylaminoalkyl, or optionally substituted phenyl.
50. The compound of claim 49, wherein R4 is hydrogen, methyl, ethyl, cyclopropyl, hydroxy, phenyl or \u2014CH2NH2.
51. The compound of claim 37, wherein when R4 is \u2014Q1\u2014A\u2014Q2\u2014Y, R3 is preferably hydrogen, C1-3aliphatic, hydroxy, hydroxyalkyl, alkoxy, amino, aminoalkyl, mono- or di-alkylamino, mono- or di-alkylaminoalkyl, or optionally substituted phenyl.
52. The compound of claim 51, wherein R3 is hydrogen, methyl, ethyl, cyclopropyl, hydroxy, phenyl or \u2014CH2NH2.
53. The compound of claim 37, wherein R5 is hydrogen, halogen, \u2014NO2, \u2014CN, hydroxy, optionally substituted C1-3alkyl, optionally substituted alkoxy, \u2014SO2NH2, or \u2014C(O)alkyl.
54. The compound of claim 53, wherein R5 is Cl, CF3, OCF3, CH3, \u2014CN, \u2014SO2NH2 or \u2014C(O)Me.
55. The compound of claim 37, wherein Q1 is NH and Q2 is NH, and compounds are defined by the general formula IIIa(i) or IIIb(i):
56. The compound of claim 37 wherein Q1 is S, and Q2 is NH, and compounds are defined by the general formula IIIa(ii) or IIIb(ii):
57. The compound of claim 37 wherein Q1 is O and Q2 is NH, and compounds are defined by the general formula IIIa(iii) or IIIb(iii):
58. The compound of claim 37, wherein Q2 is NH, and compounds are defined by the general formula IIIa(iv) or IIIb(iv):
wherein Q1 is \u2014C(RA)2\u2014.
59. The compound of claim 37, wherein Q2 is NH, and compounds are defined by the general formula IIIa(v) or IIIb(v):
wherein Q1 is a direct bond.
60. The compound of any one of claims 55, 56, 57, 58, or 59 wherein:
(i) R1, R2, R4 and R5 are each hydrogen and wherein Z is CR6 and R6 is hydrogen; or R1, R2, R3 and R5 are each hydrogen and wherein Z is CR6 and R6 is hydrogen;
(ii) ring A is defined according to one of the following groups:
(a) ring A is selected from one of the groups:
wherein R13 is hydrogen, \u2014R\u2032, \u2014COR\u2032, \u2014CO2(R\u2032), \u2014CON(R\u2032)2, or \u2014SO2R\u2032, wherein each occurrence of R\u2032 is independently hydrogen, an optionally substituted group selected from aliphatic, heteroaliphatic, aryl or heteroaryl, or two occurrences of R\u2032 on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted group selected from a 5\u20138 membered heterocyclic or 5\u20138 membered heteroaryl ring; R14 is oxo or \u2014R; and x is 0\u20134; or
(b) ring A is selected from one of xi, xii or xvi and x is 0 or 1; R14 is -halo, \u2014N(R7)2, \u2014C1-3 alkyl, \u2014C1-3 haloalkyl, \u2014NO2, \u2014O(C1-3 alkyl), \u2014CO2(C1-3 alkyl), \u2014CN, \u2014SO2(C1-3 alkyl), \u2014SO2NH2, \u2014OC(O)NH2, \u2014NH2SO2(C1-3 alkyl), \u2014NHC(O)(C1-3 alkyl), \u2014C(O)NH2, and \u2014CO(C1-3 alkyl), wherein the (C1-3 alkyl) is most preferably methyl; and R13 is hydrogen or C1-4alkyl;
(iii) Y is defined according to one of the following groups:
(a) Y is an optionally substituted heteroaryl moiety;
(b) Y is selected from one of the heteroaryl moieties a\u2013y;
(c) Y is selected from one of the following heteroaryl moieties:
wherein q is 0\u20134, R10 is \u2014R, wherein \u2014R is defined generally above and in classes and subclasses herein, and wherein each occurrence of R11 is independently hydrogen, \u2014R\u2032, \u2014COR\u2032, \u2014CO2(R\u2032), \u2014CON(R\u2032)2, or \u2014SO2R, wherein each occurrence of R\u2032 is independently hydrogen, an optionally substituted group selected from aliphatic, heteroaliphatic, aryl or heteroaryl, or two occurrences of R\u2032 on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted group selected from a 5\u20138 membered heterocyclic or 5\u20138 membered heteroaryl ring;
(d) Y is a pyrazole moiety, h;
(e) Y is one of a, b, f, h or o, optionally substituted with one or more R10 groups, wherein each occurrence of R10 is independently hydrogen, C1-4aliphatic, alkoxycarbonyl, optionally substituted phenyl, hydroxyalkyl, alkoxyalkyl, aminocarbonyl, mono- or dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, phenylaminocarbonyl, and (N-heterocycle)carbonyl;
(f) Y is one of a, b, f, h or o, optionally substituted with one or more R10 groups, wherein each occurrence of R10 is independently hydrogen, methyl, cyclopropyl, ethyl, isopropyl, propyl, t-butyl, cyclopentyl, phenyl, CO2H, CO2CH3, CH2OH, CH2OCH3, CH2CH2CH2OH, CH2CH2CH2OCH3, CH2CH2CH2OCH2Ph, CH2CH2CH2NH2, CH2CH2CH2NHCOOC(CH3)3, CONHCH(CH3)2, CONHCH2CH\u2550CH2, CONHCH2CH2OCH3, CONHCH2Ph, CONH(cyclohexyl), CON(Et)2, CON(CH3)CH2Ph, CONH(n-C3H7), CON(Et)CH2CH2CH3, CONHCH2CH(CH3)2, CON(n-C3H7)2, CO(3-methoxymethylpyrrolidin-1-yl), CONH(3-tolyl), CONH(4-tolyl), CONHCH3, CO(morpholin-1-yl), CO(4-methylpiperazin-1-yl), CONHCH2CH2OH, CONH2, and CO(piperidin-1-yl);
(g) Y is a pyrazole moiety, h\u2032, wherein the pyrazole is substituted with R10a and R10b ,
wherein each occurrence of R10a is hydrogen, C1-4aliphatic, alkoxycarbonyl, optionally substituted phenyl, hydroxyalkyl, alkoxyalkyl, aminocarbonyl, mono- or dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, phenylaminocarbonyl, and (N-heterocycle)carbonyl, and R10b is hydrogen;
(h) Y is a pyrazole moiety, h\u2032, wherein the pyrazole is substituted with two occurrences of R10 (R10a and R10b as depicted),
wherein each occurrence of R10a is hydrogen, methyl, cyclopropyl, ethyl, isopropyl, propyl, t-butyl, cyclopentyl, phenyl, CO2H, CO2CH3, CH2OH, CH2OCH3, CH2CH2CH2OH, CH2CH2CH2OCH3, CH2CH2CH2OCH2Ph, CH2CH2CH2NH2, CH2CH2CH2NHCOOC(CH3)3, CONHCH(CH3)2, CONHCH2CH\u2550CH2, CONHCH2CH2OCH3, CONHCH2Ph, CONH(cyclohexyl), CON(Et)2, CON(CH3)CH2Ph, CONH(n-C3H7), CON(Et)CH2CH2CH3, CONHCH2CH(CH3)2, CON(n-C3H7)2, CO(2-methoxymethylpyrrolidin-1-yl), CONH(3-tolyl), CONH(4-tolyl), CONHCH3, CO(morpholin-1-yl), CO(4-methylpiperazin-1-yl), CONHCH2CH2OH, CONH2, and CO(piperidin-1-yl, and R10b is hydrogen;
(i) Y is heteroaryl moiety substituted by at least two occurrences of R10 and where two occurrences of R10 taken together may represent an optionally substituted group selected from cycloaliphatic, cycloheteroaliphatic, aryl or heteroaryl;
(j) Y represents one of the following heteroaryl moieties:
wherein r is 0\u20134 and R12 is hydrogen, -halo, \u2014N(R7)2, \u2014C1-3 alkyl, \u2014C1-3 haloalkyl, \u2014NO2, \u2014O(C1-3 alkyl), \u2014CO2(C1-3 alkyl), \u2014CN, \u2014SO2(C1-3 alkyl), \u2014SO2NH2, \u2014OC(O)NH2, \u2014NH2SO2(C1-3 alkyl), \u2014NHC(O)(C1-3 alkyl), \u2014C(O)NH2, and \u2014CO(C1-3 alkyl), wherein the (C1-3 alkyl) is most preferably methyl;
(iv) R4 is defined according to one of the following groups:
(a) R4 is hydrogen, C1-3aliphatic, hydroxy, hydroxyalkyl, alkoxy, amino, aminoalkyl, mono- or di-alkylamino, mono- or di-alkylaminoalkyl, or optionally substituted phenyl, or
(b) R4 is hydrogen, methyl, ethyl, cyclopropyl, hydroxy, phenyl or \u2014CH2NH2;
(v) R3 is defined according to one of the following groups:
(a) R3 is hydrogen, C1-3aliphatic, hydroxy, hydroxyalkyl, alkoxy, amino, aminoalkyl, mono- or di-alkylamino, mono- or di-alkylaminoalkyl, or optionally substituted phenyl, or
(b) R3 is hydrogen, methyl, ethyl, cyclopropyl, hydroxy, phenyl or \u2014CH2NH2; and
(vi) R5 is defined according to one of the following groups:
(a) hydrogen, halogen, \u2014NO2, \u2014CN, hydroxy, optionally substituted C1-3alkyl, optionally substituted alkoxy, \u2014SO2NH2, or \u2014C(O)alkyl, or
(b) R5 is hydrogen, Cl, CF3, OCF3, CH3, \u2014CN, \u2014SO2NH2 or \u2014C(O)Me.
61. A pharmaceutical composition comprising a compound of claim 1, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.
62. A method of inhibiting a PRAK, GSK3, ERK2, CDK2, MK2, SRC, SYK, or Aurora-2 kinase activity in a biological sample comprising the step of contacting said biological sample with:
a) a composition according to claim 61; or
b) a compound of claim 1.
63. The compound according to claim 1 selected from the following:
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
The invention claimed is:
1. A media release mechanism comprising:
a spindle having a fixed end, a free end, and an exterior surface,
a ramp on the exterior surface of said spindle, wherein said ramp slopes from said free end to said fixed end, and
a fin for engagement with said ramp, said fin having an outer surface and an inner surface.
2. A media release mechanism as defined in claim 1, wherein said inner surface of said fin is angled relative to said outer surface of said fin.
3. A media release mechanism as defined in claim 1, further including a back plate, and wherein said fixed end of said spindle is mounted to said back plate.
4. A media release mechanism as defined in claim 3, further including arms extending from said back plate and said spindle is mounted to said back plate by engaging said arms with said spindle.
5. A media release mechanism as defined in claim 4, wherein said arms further include ears extending from said arms, wherein said spindle includes apertures through a wall of said spindle, and wherein said ears engage with said apertures.
6. A media release mechanism as defined in claim 3, further comprising a spring having a first end and a second end, wherein said first end of said spring is attached to said fin and a second end of said spring is attached to said back plate.
7. A media release mechanism as defined in claim 1, further comprising a protrusion extending from said inner surface of said fin.
8. A media release mechanism as defined in claim 7, wherein said ramp includes a slot and said protrusion of said fin is positioned within said slot.
9. A media release mechanism as defined in claim 7, wherein said protrusion is T-shaped.
10. A media release mechanism as defined in claim 1, wherein said spindle further includes fingers extending from said exterior surface of said spindle on either side of said ramp.
11. A media release mechanism as defined in claim 1, wherein said spindle includes a rib extending from the exterior surface of said spindle.
12. A media release mechanism as defined in claim 1, wherein said fin further includes a finger grip.
13. A media release mechanism as defined in claim 1, wherein said fin further includes a body and a tab extending outwardly from said body proximate said fixed end of said spindle.
14. A media release mechanism as defined in claim 2, wherein a ramp angle is formed by said ramp and said exterior surface of said spindle, wherein a fin angle is formed by said inner surface of said fin and said outer surface of said fin, and said ramp angle corresponds to said fin angle.
15. A media release mechanism as defined in claim 1, further including a slot in said spindle through which a media can be positioned and retained.
16. A printer comprising:
a housing;
printhead means mounted in said housing;
media delivery means mounted in said housing for delivering a media to said printhead;
a media take-up and release mechanism mounted in said housing; and
wherein said media take-up and release mechanism includes;
a spindle having a fixed end, a free end, and an exterior surface,
a ramp on the exterior surface of said spindle, wherein said ramp slopes from said free end to said fixed end, and
a fin for engagement with said ramp, said fin having an outer surface and an inner surface.
17. A printer as defined in claim 16, wherein, said inner surface of said fin is angled relative to said outer surface of said fin.
18. A printer as defined in claim 16, further including a back plate mounted in said housing and said media release mechanism is mounted to said back plate.
19. A printer as defined in claim 16, wherein said media release mechanism further includes a protrusion extending from said inner surface of said fin, said ramp includes a slot, and said protrusion of said fin is positioned with in said slot.
20. A printer as defined in claim 16, wherein said media release mechanism further includes fingers extending from said exterior surface of said spindle on either side of said ramp.
21. A method of collecting and releasing media from a spindle assembly including the steps of:
providing a spindle having a fixed end, a free end, and an exterior surface,
providing a ramp on the exterior surface of said spindle, wherein said ramp slopes outward from said free end to said fixed end,
providing a fin for engagement with said ramp, said fin having an outer surface and an inner surface,
winding said media around said spindle and said fin,
sliding said fin toward said free end of said spindle, and
removing said media from said spindle and said fin.
22. A method of collecting and releasing media from a spindle as defined in claim 21, wherein said inner surface of said fin is angled relative to said outer surface of said fin.
23. A method as defined in claim 21, further including the steps of:
providing a slot in said spindle;
threading said media through said slot prior to winding said media around said spindle and said fin.
24. A spindle having an exterior surface and a slot provided in said exterior surface, and wherein said slot receives a media to be wound around said exterior surface.
25. A spindle as defined in claim 21, wherein said slot includes a first portion, a second portion and a third portion, said first portion being angled relative to said exterior surface, said second portion being angled relative to said first portion, and said third portion parallel to said exterior surface.