SUBSTITUTED CYCLOPROPYL COMPOUNDS, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF TREATMENT

摘要

Substituted cyclopropyl piperidinyl compounds and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. The compounds are useful as agonists of the G-protein coupled receptor GPR-119. Pharmaceutical compositions and methods of treatment are also included.;

主权项

1. A compound represented by the formula: or a pharmaceutically acceptable salt thereof, wherein: bonds x and y are in trans orientation in reference to one another; ring A represents a 5- or 6-membered aryl or heteroaryl ring, the heteroaryl ring containing 1-4 heteroatoms, 1-4 of which are nitrogen atoms, and 0-1 of which are oxygen or sulfur atoms; X1 is oxygen or nitrogen; m is an integer selected from 0-3; n is an integer selected from 1-3; where m+n can be no more than 5; R1 is selected from:
halogen;C1-6alkyl;OC1-6alkyl;C(O)C1-6alkyl;C(O)C3-6cycloalkyl;C(O)NHC1-6alkyl;S(O)0-2C1-6alkyl;SO2C3-6cycloalkyl;SO2NRbRc, wherein Rb and Rc are independently selected from H or C1-6alkyl; —C1-2alkylCONRdRe wherein Rd and Re are independently selected from the group consisting of H, C1-6alkyl, C3-6cycloalkyl, haloC1-6alkyl, haloC3-6cycloalkyl, C(O)NH2, C1-6alkoxy, and C3-6cycloalkylC1-6alkoxy; wherein Rd and Re, if individually alkyl, alkoxy or C(O)NH2, can together form a 4-6-membered saturated heterocyclic ring having 1 nitrogen atom which 4-6-membered ring may be optionally substituted with 1-3 substituents independently selected from halogen, hydroxy, oxo; C1-6alkyl, C1-6alkoxy; or CO2C1-6alkyl;—CH2-heteroaryl, wherein the heteroaryl is a 5-6 membered heteroaryl ring containing 1-4 heteroatoms independently selected from nitrogen or oxygen;or a 5-6 membered heteroaryl or saturated heterocyclic ring containing 1-4 heteroatoms, 1-4 of which are nitrogen atoms, and 0-1 of which are oxygen or sulfur atoms,wherein the R1 alkyl, cycloalkyl, heteroaryl or heterocyclic moiety is optionally substituted with 1-3 of halogen; hydroxy; oxo; C1-6alkyl; NH2; and O—C1-6alkyl; each R2 is independently selected from halogen, CN, C1-6alkyl or haloC1-6alkyl; R5 is hydrogen, C1-3 alkyl, C1-3alkoxy, or cyano;
B represents (a) a 6 membered aryl ring or a 5-6 membered heteroaryl ring containing 1-4 heteroatoms, 1-4 of which are nitrogen atoms, and 0-1 of which are oxygen or sulfur atoms, said ring being optionally substituted with 1-3 groups selected from R3, wherein each R3 is independently selected from
halogen;hydroxyl;C1-6alkyl;C(O)OC1-6alkyl;C═O;CN;C1-6alkoxy;C3-6cycloalkyl;C(═O)—(O)n—R′, wherein n is an integer from 0-3 and R′ is C1-6alkyl or H;5-6 membered heteroaryl ring containing 1-4 heteroatoms independently selected from nitrogen or oxygen;C(═O)—Rf, wherein Rf is 5-6 membered heteroaryl ring containing 1-4 heteroatoms independently selected from nitrogen or oxygen;or haloC1-6alkoxy;wherein the R3 alkyl moiety is optionally substituted with 1-3 substituents independently selected from:
halogen, hydroxy, C1-6alkyl, or C1-6alkoxy; or b) CO2R4, wherein R4 is selected from:
C1-6alkyl; orC3-6 cycloalkyl, wherein the alkyl and cycloalkyl are optionally substituted with 1-3 substituents independently selected from:
halogen,C1-6alkyl, orC3-6cycloalkyl.