Pyridin-2yl-amino-1, 2, 4-thiadiazole derivatives as glucokinase activators for the treatment of diabetes mellitus

摘要

Provided are compounds of Formula (I): wherein R2, R3, R13, L and D2 are as defined in the specification, which are useful in the treatment and/or prevention of diseases or disorders mediated by deficient levels of glucokinase activity or which can be treated by activating glucokinase including, but not limited to, diabetes mellitus, impaired glucose tolerance, IFG (impaired fasting glucose) and IFG (impaired fasting glycemia), as well as other diseases and disorders such as those discussed herein.;

主权项

1. A compound of general Formula I or a salt thereof, wherein: R13 is a polyhydroxy-(2-6C) alkyl, methoxy(polyhydroxy-(3-6C)alkyl) or polyhydroxy-(5-6C)cycloalkyl; L is O or S; D2 is N or CH; R2 is Ar1, hetAr1, hetAr2, or hetAr3; Ar1 is phenyl or naphthyl, each of which is optionally substituted with one or more groups independently selected from (1-6C)alkyl, F, Br, CF3, OH, CN, SO2Me, C(═O)NH(1-3C alkyl)N(alkyl)2 and C(═O)NH(1-3C alkyl)hetCycl; hetAr1 is a 5-6 membered heteroaryl group having 1-3 ring nitrogen atoms and optionally substituted with one or more groups independently selected from (1-6C alkyl), Cl, CF3 and (1-6C alkyl)OH; hetAr2 is a partially unsaturated 5,6 or 6,6 bicyclic heteroaryl ring system having 1-2 ring nitrogen atoms and optionally having a ring oxygen atom; hetAr3 is a 9-10 membered bicyclic heteroaryl ring having 1-3 ring nitrogen atoms; R3 is Cl, Br, CF3, aryl, hetAra, SR6 or OR6; hetAra is a 6-membered heteroaryl having 1-2 ring nitrogen atoms; R6 is Ar2, hetAr4, (1-6C alkyl), -(1-6C alkyl)OH, polyhydroxy(1-6C alkyl), —CH(R9)—Ar3, —CH(R10)-hetAr5, hetAr6, (5-6C)cycloalkyl substituted with 1 to 4 OH, (1-3 C alkoxy)(1-6C alkyl), or cyclopropyl(1-6C alkyl); Ar2 is phenyl optionally substituted with one or more groups independently selected from (1-6C)alkyl, F, Br, Cl, CF3, CN, OH, O-(1-6C alkyl), C(═O)OH, C(═O)O(1-6C alkyl), C(═O)NH(1-3C alkyl)N(1-3Calkyl)2 and C(═O)NH(1-3C alkyl)hetCyc2; hetAr4 is a 5-6 membered heteroaryl ring having 1-3 nitrogen atoms and optionally substituted with one or more groups independently selected from (1-6C)alkyl, F, Br, Cl, CF3, CN, OH, O-(1-6C alkyl), C(═O)OH, C(═O)O(1-6C alkyl), C(═O)NH(1-3C alkyl)N(1-3Calkyl)2 and C(═O)NH(1-3C alkyl)hetCyc2; Ar3 is phenyl optionally substituted with one or more groups independently selected from F, Cl, Br, and (1-6C)alkyl; hetAr5 is a 5-6-membered heteroaryl having 1-2 ring nitrogen atoms; hetAr6 is a 9-10 membered bicyclic heteroaromatic ring having 2-3 heteroatoms independently selected from N, S and O (provided the ring does not contain an O—O bond) which is optionally substituted with one or more groups independently selected from (1-6C)alkyl, F, Br, Cl, CF3, CN, OH, —O-(1-6C alkyl), C(═O)OH, C(═O)O(1-6C alkyl) and C(═O)NH(1-3C alkyl)N(1-3Calkyl)2; R9 and R10 are independently hydrogen, (1-6C)alkyl, (1-6C)alkylOH, or CF3; and hetCyc1 and hetCyc2 are independently a 5-7 membered heterocyclic ring having 1-2 ring heteroatoms independently selected from N and O.