A method of (i) increasing insulin secretion, and/or (ii) promoting insulin release into the blood stream, in an individual in need thereof comprising administering to the individual an effective amount of a compound of the formula (IA), (IB), (J-1) or (K-1), wherein formula (IA) is:
- or a salt, solvate or N-oxide thereof, wherein:
- R1 is H, hydroxyl, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, perhaloalkyl, acyl, acyloxy, carbonylalkoxy, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, C1-C8 perhaloalkoxy, alkoxy, aryloxy, thiol, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl or carbonylalkylenealkoxy, or R1 and R2a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety, or R1 and R3a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety, or R1 and R4a are taken together to form an ethylene (—CH2CH2—) moiety or a propylene (—CH2CH2CH2—) moiety;
- each R2a and R2b is independently H, substituted or unsubstituted C1-C8 alkyl, halo, cyano, hydroxyl, alkoxy, nitro or R2a and R2b are taken together with the carbon to which they are attached to form a carbonyl moiety or a cycloalkyl moiety, or R2a and R1 are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety, or R2a and R3a are taken together to form an ethylene (—CH2CH2—) moiety or a propylene (—CH2CH2CH2—) moiety, or R2a and R4a are taken together to form a methylene (—CH2—) moiety or an ethylene (—CH2CH2—) moiety;
- each R3a and R3b is independently H, substituted or unsubstituted C1-C8 alkyl, halo, and cyano, hydroxyl, alkoxy, nitro or R3a an R3b are taken together with the carbon to which they are attached to form a carbonyl moiety or a cycloalkyl moiety, or R3a and R1 are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety, or R3a and R2a are taken together to form an ethylene (—CH2CH2—) moiety or a propylene (—CH2CH2CH2—) moiety, or R3a and R4a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety;
- each R4a and R4b is independently H, substituted or unsubstituted C1-C8 alkyl, halo, cyano, nitro, substituted or unsubstituted amino, hydroxyl, alkoxy, acyloxy, acylamino, aryl, heteroaryl, cycloalkyl, heterocyclyl, or R4a and R4b are taken together with the carbon to which they are attached to form a carbonyl moiety or a cycloalkyl moiety, or R4a and R1 are taken together to form an ethylene (—CH2CH2—) moiety or a propylene (—CH2CH2CH2—) moiety, or R4a and R2a are taken together to form a methylene (—CH2—) moiety or an ethylene (—CH2CH2—) moiety, or R4a and R3a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety;
- each X1, X2, X3 and X4 is independently N, CH or CR6;
- Q is a substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted of unsubstituted aralkyl, wherein the aralkyl is a fused ring system where at least one cycloalkyl moiety is fused with at least one aryl moiety and wherein the aralkyl is attached to the parent structure via the cycloalkyl moiety or the aryl moiety;
- and
- R6 is hydroxyl, nitro, cyano, halo, C1-C8 perhaloalkyl, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, C1-C8 perhaloalkoxy, substituted or unsubstituted C1-C8 alkoxy, substituted or unsubstituted aryloxy, carboxyl, carbonylalkoxy, thiol, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl, carbonylalkylenealkoxy, alkylsulfonylamino or acyl,
- provided that:
- (1) at least one of X1, X2, X3 and X4 is CH or CR6;
- (2) when each X1, X2, X3 and X4 is independently CH or CR6, none of R1, R2a, R2b, R3a, R3b, R4a and R4b are taken together to form a ring and Q is an unsubstituted 6-membered aryl or an unsubstituted 6-membered heteroaryl, then Q is other than unsubstituted phenyl, unsubstituted pyridyl and unsubstituted pyrimidyl;
- (3) when each X1, X2, X3 and X4 is independently CH or CR6, none of R1, R2a, R2b, R3a, R3b, R4a and R4b are taken together to form a ring and Q is a substituted phenyl, then Q is a phenyl substituted with a substituent selected from the group consisting of substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocyclyl, and substituted or unsubstituted aralkyl;
- and
- (4) when each X1, X2, X3 and X4 is independently CH or CR6, and R2a and R3a are taken together to form an ethylene (—CH2CH2—) moiety, then Q is a substituted aryl or substituted heteroaryl, where the substituted aryl or substituted heteroaryl is substituted with at least one substituent selected from the group consisting of substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocyclyl, and substituted or unsubstituted aralkyl;
- formula (IB) is:
- or a salt or solvate thereof, wherein:
- R1 is H, hydroxyl, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, perhaloalkyl, acyl, acyloxy, carbonylalkoxy, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, C1-C8 perhaloalkoxy, alkoxy, aryloxy, thiol, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl or carbonylalkylenealkoxy, or R1 and R2a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety, or R1 and R3a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety, or R1 and R4a are taken together to form an ethylene (—CH2CH2—) moiety or a propylene (—CH2CH2CH2—) moiety;
- each R2a and R2b is independently H, substituted or unsubstituted C1-C8 alkyl, halo, cyano, hydroxyl, alkoxy, nitro or R2a and R2b are taken together with the carbon to which they are attached to form a carbonyl moiety or a cycloalkyl moiety, or R2a and R1 are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety, or R2a and R3a are taken together to form an ethylene (—CH2CH2—) moiety or a propylene (—CH2CH2CH2—) moiety, or R2a and R4a are taken together to form a methylene (—CH2—) moiety or an ethylene (—CH2CH2—) moiety;
- each R3a and R3b is independently H, substituted or unsubstituted C1-C8 alkyl, halo, cyano, hydroxyl, alkoxy, nitro or R3a and R3b are taken together with the carbon to which they are attached to form a carbonyl moiety or a cycloalkyl moiety, or R3a and R1 are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety, or R3a and R2a are taken together to form an ethylene (—CH2CH2—) moiety or a propylene (—CH2CH2CH2—) moiety, or R3a and R4a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety;
- each R4a and R4b is independently H, substituted or unsubstituted C1-C8 alkyl, halo, cyano, nitro, substituted or unsubstituted amino, hydroxyl, alkoxy, acyloxy, acylamino, aryl, heteroaryl, cycloalkyl, heterocyclyl, or R4a and R4b are taken together with the carbon to which they are attached to form a carbonyl moiety or a cycloalkyl moiety, or R4a and R1 are taken together to form an ethylene (—CH2CH2—) moiety or a propylene (—CH2CH2CH2—) moiety, or R4a and R2a are taken together to form a methylene (—CH2—) moiety or an ethylene (—CH2CH2—) moiety, or R4a and R3a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety;
- each X1, X2, X3 and X4 is independently N, CH or CR6;
- Q is a substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted aralkyl, wherein the aralkyl is a fused ring system where at least one cycloalkyl moiety is fused with at least one aryl moiety and wherein the aralkyl is attached to the parent structure via the cycloalkyl moiety or the aryl moiety;
- and
- R6 is hydroxyl, nitro, cyano, halo, C1-C8 perhaloalkyl, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, C1-C8 perhaloalkoxy, substituted or unsubstituted C1-C8 alkoxy, substituted or unsubstituted aryloxy, carboxyl, carbonylalkoxy, thiol, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl, carbonylalkylenealkoxy, alkylsulfonylamino or acyl;
- provided that:
- (1) at least one of X1, X2, X3 and X4 is CR6;
- (2) when none of X1, X2 and X3 is N, and none of R1, R2a, R2b, R3a, R3b, R4a and R4b are taken together to form a ring, then Q is other than an unsubstituted phenyl;
- (3) when none of X1, X2, X3 and X4 is N, and R2a and R2b are taken together with the carbon to which they are attached to form a carbonyl moiety, then Q is other than a 4-substituted phenyl group;
- and
- (4) when each X1, X3 and X4 is CH, X2 is CR6 where R6 is fluoro, and each R2a, R2b, R3a, R3b, R4a and R4b is H, then Q is other than 4-fluorophenyl;
- formula (J-1) is:
- or a salt or solvate thereof, wherein:
- R1 is H, hydroxyl, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, perhaloalkyl, acyl, acyloxy, carbonylalkoxy, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, C1-C8 perhaloalkoxy, alkoxy, aryloxy, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl or carbonylalkylenealkoxy;
- each R2a, R2b R3a, R3b, R4a, R4b, R10a and R10b is independently H, hydroxyl, nitro, cyano, halo, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, perhaloalkyl, acyl, acyloxy, carbonylalkoxy, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, C1-C8 perhaloalkoxy, alkoxy, aryloxy, carboxyl, thiol, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl, alkylsulfonylamino, or carbonylalkylenealkoxy, or is taken together with the carbon to which it is attached and a geminal R2(a/b), R3(a/b), R4(a/b) or R10(a/b) to form a carbonyl moiety or a cycloalkyl moiety;
- each X1, X2 and X3 is independently N, CH or CR6;
- Q is a substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted aralkyl, wherein the aralkyl is a fused ring system where at least one cycloalkyl moiety is fused with at least one aryl moiety and wherein the aralkyl is attached to the parent structure via the cycloalkyl moiety or the aryl moiety;
- and
- R6 is hydroxyl, nitro, cyano, halo, C1-C8 perhaloalkyl, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, C1-C8 perhaloalkoxy, substituted or unsubstituted C1-C8 alkoxy, substituted or unsubstituted aryloxy, carboxyl, carbonylalkoxy, thiol, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, thioalkyl, —S(O)-alkyl, —S(O)-aryl, —S(O)-aralkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl, carbonylalkylenealkoxy, alkylsulfonylamino or acyl;
- provided that at least one of X1, X2, X3 and X4 is CH or CR6;
- and formula (K-1) is:
- or a salt or solvate thereof, wherein:
- R1 is H, hydroxyl, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, perhaloalkyl, acyl, acyloxy, carbonylalkoxy, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, C1-C8 perhaloalkoxy, alkoxy, aryloxy, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl or carbonylalkylenealkoxy;
- each R2a, R2b R3a, R3b, R4a, R4b, R10a and R10b is independently H, hydroxyl, nitro, cyano, halo, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, perhaloalkyl, acyl, acyloxy, carbonylalkoxy, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, C1-C8 perhaloalkoxy, alkoxy, aryloxy, carboxyl, thiol, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl, alkylsulfonylamino, or carbonylalkylenealkoxy, or is taken together with the carbon to which it is attached and a geminal R2(a/b), R3(a/b), R4(a/b) or R10(a/b) to form a carbonyl moiety or a cycloalkyl moiety;
- each X1, X2 and X3 is independently N, CH or CR6;
- Q is a substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted aralkyl, wherein the aralkyl is a fused ring system where at least one cycloalkyl moiety is fused with at least one aryl moiety and wherein the aralkyl is attached to the parent structure via the cycloalkyl moiety or the aryl moiety;
- and
- R6 is hydroxyl, nitro, cyano, halo, C1-C8 perhaloalkyl, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, C1-C8 perhaloalkoxy, substituted or unsubstituted C1-C8 alkoxy, substituted or unsubstituted aryloxy, carboxyl, carbonylalkoxy, thiol, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, thioalkyl, —S(O)-alkyl, —S(O)-aryl, —S(O)-aralkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl, carbonylalkylenealkoxy, alkylsulfonylamino or acyl;
- provided that at least one of X1, X2, X3 and X4 is CH or CR6.