Hetrocyclic compounds that are inhibitors of the enzyme DPP-IV

A compound of formula II

• 63
• A is C2-C6 alkylene;
• C2-C10 alkenylene;
• C3-C7 cycloalkylene;
• C3-C7 cycloheteroalkylene;
• arylene;
• heteroarylene;
• C1-C2 alkylene-arylene;
• arylene-C1-C2 alkylene;
• or C1-C2 alkylene-arylene-C1-C2 alkylene, wherein each alkylene, alkenylene, cycloalkylene, cycloheteroalkylene, arylene, or heteroarylene is optionally substituted with one or more R3 independently;
• R1 is aryl optionally substituted with one or more R2 independently, or heteroaryl optionally substituted with one or more R2 independently;
• R2 is H;
• C1-C7 alkyl;
• C2-C7 alkenyl;
• C2-C7 alkynyl;
• C3-C7 cycloalkyl;
• C3-C7 cycloheteroalkyl;
• —NHCOR3;
• —NHSO2R3;
• —SR3;
• —SOR3;
• —SO2R3;
• —OCOR3;
• —CO2R4;
• —CON(R4)2;
• —CSN(R4)2;
• —NHCON(R4)2;
• —NHCSN(R4)2;
• —NHCONNH2;
• —SO2N(R4)2;
• —OR4;
• cyano;
• —CF3;
• nitro;
• or halogen, wherein each alkyl, alkenyl, alkynyl, cycloalkyl and cycloheteroalkyl is optionally substituted with one or more R3 independently;
• R3 is C1-C10 alkyl;
• C2-C10 alkenyl;
• C2-C10 alkynyl;
• C3-C7 cycloalkyl;
• aryl;
• heteroaryl;
• OR10;
• N(R10)2;
• or SR10, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heteroaryl is optionally substituted with one or more R10 independently;
• R4 is H;
• C1-C10 alkyl;
• C2-C10 alkenyl;
• C2-C10 alkynyl;
• C3-C7 cycloalkyl;
• C3-C7 cycloheteroalkyl;
• aryl;
• aryl-C1-C5 alkylene;
• heteroaryl;
• heteroaryl-C1-C5 alkylene, —CF3 or —CHF2, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, aryl-C1-C5 alkylene, heteroaryl, and heteroaryl-C1-C5 alkylene is optionally substituted with one or more R10 independently;
• R5 is H;
• C1-C10 alkyl;
• C2-C10 alkenyl;
• C2-C10 alkynyl;
• C3-C7 cycloalkyl;
• C3-C7 cycloheteroalkyl;
• aryl;
• heteroaryl;
• —OR7;
• aryl-C1-C5 alkylene;
• heteroaryl-C1-C5 alkylene;
• —C1-C5-alkyl-C(═O)-aryl;
• —C1-C5-alkyl-C(═O)-heteroaryl;
• or —[(CH2)0-O]p—C1-C5 alkyl, wherein o and p are 1-3 independently, and wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, heteroaryl, aryl-C1-C5 alkylene, —C1-C5-alkyl-C(═O)-aryl, —C1-C5-alkyl-C(═O)-heteroaryl and heteroaryl-C1-C5 alkylene is optionally substituted with one or more R7 independently;
• R6 is H;
• C1-C10 alkyl;
• C2-C10 alkenyl;
• C2-C10 alkynyl;
• C3-C7 cycloalkyl;
• C3-C7 cycloheteroalkyl;
• aryl;
• heteroaryl;
• aryl-C1-C5 alkylene;
• heteroaryl-C1-C5 alkylene;
• or C3-C7 cycloheteroalkyl-C1-C5 alkylene, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, C3-C7 cycloheteroalkyl-C1-C5 alkylene, aryl, heteroaryl, aryl-C1-C5 alkylene, and heteroaryl-C1-C5 alkylene is optionally substituted with one or more R10 independently;
• R7 is H;
• ═O;
• C1-C10 alkyl;
• C2-C10 alkenyl;
• C2-C10 alkynyl;
• C3-C7 cycloalkyl;
• C3-C7 cycloheteroalkyl;
• aryl;
• heteroaryl;
• OR10;
• N(R10)2;
• SR10;
• cyano;
• hydroxy;
• halogen;
• —CF3;
• —CCl3;
• —OCF3;
• or —OCH3 wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, and heteroaryl is optionally substituted with one or more R10 independently;
• R8 is H;
• C1-C10 alkyl;
• C2-C10 alkenyl;
• C2-C10 alkynyl;
• C3-C7 cycloalkyl;
• C3-C7 cycloheteroalkyl;
• aryl;
• heteroaryl;
• OR10;
• N(R10)2;
• or SR10, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, and heteroaryl is optionally substituted with one or more R10 independently;
• R9 is H;
• C1-C10 alkyl optionally substituted with one or more R8 independently;
• or halogen;
• R10 is H;
• —CF3;
• —CCl3;
• —OCF3;
• —OCH3;
• cyano;
• halogen;
• —OH, —COCH3;
• —CONH2;
• —CONHCH3;
• —CON(CH3)2;
• —NO2;
• —SO2NH2;
• or —SO2N(CH3)2;
• if two R4 or two R10 are attached to the same nitrogen they may be connected to form a 3- to 7-membered ring;
• R11 is H or C1-C6 alkyl optionally substituted with one or more R3 independently;
• R12 is H;
• C1-C6 alkyl optionally substituted with one or more R3 independently;
• or
• If A is C3-C7 cycloalkylene or C3-C7 cycloheteroalkylene R12 may be a valence bond between the nitrogen to which R12 is attached and one of the atoms in the cycloalkylene or cycloheteroalkylene;
• or a salt thereof with a pharmaceutically acceptable acid or base.