Glucokinase activators and methods of using same

A compound of the structure

• where Q is
• or a pharmaceutically acceptable salt thereof, and all stereoisomers thereof, including enantiomers and diastereomers thereof;
• wherein R4 and R5 are the same or different and are independently selected from the group consisting of H, alkyl, halogen, CN, —C(O)NR7R8, —CO2R9, and -L-M-Qa;
• L is independently selected from O, S, SO2, or is absent;
• M is independently selected from C1-4 alkyl optionally substituted with OH or C2-5 alkylene, or M is absent;
• Qa is independently selected from the group consisting of halogen, —OR9b, —CO2H, —CO2R9c, —C(O)NR7R8, CN, N-linked amide (—NR7C(O)R8), N-linked sulfonamide) (—NR9SO2R10), N-linked carbamate (—NR8CO2R10), O-linked carbamate (—OCONR7R8), and N-linked urea (—NR9C(O)NR7R8);
• R6 is H, OH, C1-6 alkyl, halogen, CN, —C(O)NH2 or carboxyl, or R6 is absent;
• R7 and R8 (regardless of which group each is a part of) are the same or different and are independently selected from the group consisting of H, alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, or R7 and R8 are cyclized together to form a 3- to 7-membered heterocycle;
• R9 and R9c (regardless of which group each is a part of) are independently selected from the group consisting of H, alkyl, aryl, and arylalkyl;
• R10 (regardless of which group it is a part of) is independently selected from the group consisting of alkyl, aryl, heteroaryl, aralkyl, and heteroarylalkyl;
• R2 and R3 are the same or different, and are independently selected from Y—Z—;
• each —Z—is independently selected from a direct bond, or a linker atom selected from the group consisting of —O—, —N(R9)—, —S—, —S(O)—, —S(O)2—, —C(O)—, and a group of the formula —(CH2)p—C(R11)2—(CH2)q—;
• each Y is independently selected from the group consisting of aryl-Z1—, heteroaryl-Z1, and heterocyclyl-Z1—, where the aryl, heteroaryl or heterocyclyl is connected to Z1 through a ring nitrogen or carbon;
• or Y is independently selected from the group consisting of C3-7cycloalkyl-Z1—, C1-6alkyl-Z1—, C2-6-alkenyl-Z1—, C2-6-alkynyl-Z1—, —Z1—CH(CH3-aFa)2, and —Z1—(CH2)0-4CH3-aFa;
• wherein each Y is independently optionally substituted by up to 3 R12 groups;
• each R12 is independently selected from the group consisting of halogen, —CH3-aFa, CN, NO2, NH2, C1-6alkyl, OC1-6alkyl, —COOH, OH, aryloxy, heteroaryloxy, heterocyclyloxy, —S—R10, —S(O)—R10, —SO2R9, —SO2NR7R8, —NR7R8—CO2R9, —C(O)N7R8, N-linked amide (—NR7C(O)R8), N-linked sulfonamide)(—NR9SO2R10, N-linked carbamate)(—NR8CO2R10, O-linked carbamate (—OCONR7R8), N-linked urea (—NR9C(O)NR7R8), —(CH2)p—PO(OR7)(OR8), —(CH2)p—PO(OR7)R8, —(CH2)p—O—PO(OR7)R8, —(CH2)pO—PO—(R7)R8, —(CH2)p—P(O)R7R8, aryl, heteroaryl, and heterocyclyl;
• wherein each phenyl, naphthyl, heteroaryl, or heterocyclyl ring in Y or R12 is optionally substituted by a member selected from the group consisting of halogen, ═O, ═S, C1-6alkyl, —CH3-aFa, CN, NO2, NH2, —COOH, OH, C1-6alkyl, —OC1-6alkyl, —C(O)OC1-6alkyl, —NR7aR8a, —C(O)NR7aR8a, N-linked amide (—NR7aCOR8a), N-linked sulfonamide (—NR9aSO2R10a), N-linked carbamate (—NR8aCOOR10a), N-linked urea (—NR9aCONR7aR8a), sulfonamide (—SO2NR7aR8a), —(CH2)p—PO(OR7a)(OR8a), —(CH2)p—PO(OR7a)R8a, —(CH2)p—O—PO(OR7a)R8a, —(CH2)pO—PO—(R7a)R8a, or —(CH2)p—P(O)R7aR8a;
• each —Z1—is independently selected from a direct bond, or a linker atom selected from —O—, —N(R9)—, —S—, —S(O)—, —S(O)2—, —C(O)—or a group of the formula —(CH2)p—C(R11)2—(CH2)q—;
• R11 is independently selected from the group consisting of hydrogen, C1-6alkyl, haloC1-6alkyl, and C2-4alkyl-O—C1-4alkyl;
• each a is an integer independently selected from 1, 2, 3;
• p is an integer independently selected from 0, 1 or 2;
• q is an integer independently selected from 0, 1 or 2;
• and p+q <4;
• R7a and R8a are the same or different and are independently selected from the group consisting of H, alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl or R7a and R8a cyclized together to form a 3- to 7-membered heterocyclo;
• R9a and R9b are independently selected from the group consisting of H, alkyl, aryl, heterocyclyl, aralkyl, and heteroarylalkyl;
• and
• R10a is independently selected from the group consisting of alkyl, aryl, heteroaryl, aralkyl and heteroarylalkyl.