| abstract |
Propanoic acid derivatives of formula (I) that inhibit the binding of integrin a4b1 to its receptors, for example VCAM-1 (vascular cell adhesion molecule-1) and fibronectin; compounds that inhibit this binding; pharmaceutically active compositions comprising such compounds; and the use of such compounds either as above, or in formulations for the control or prevention of diseases states in which a4b1 is involved are disclosed, wherein: circle Q represents a 2-pyridinone or 2-pyrimidone group; q is an integer of zero to six; M is selected from the group consisting of-C (R9)(R10)- and -(CH2)u-, wherein u is an integer of from 0 to 3; J is selected from the group consisting of -O-, -S- and -NR12-; T is selected from the group consisting of -C(O)- and -(CH2)b- wherein b is an integer of from 0 to 3; L is selected from the group consisting of -O-, -NR13-, -S-, and - (CH2)v wherein v is an integer of 0 or 1; X is selected from the group consisting of -CO2B, -PO3H2, -SO3H, -SO2NH2, -SO2NHCOR14, -OPO3H2, - C(O)NHC(O)R15, -C(O)NHSO2R16, tetrazolyl, oxazolyl and hydroxyl; and, B, R1, R4 R6 R8, R9, R10, R11, R12, R13, R14, R15 and R16 at each occurrence are independently selected from the group consisting of hydrogen, halogen, hydroxyl, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF3, nitro, amino, cyano, carboxy,-N (C1-C3 alkyl)-C(O)(C1-C3alkyl), -NHC(O)NH(C1-C3 alkyl), -NHC(O)N(C1-C3 alkyl)C(O)NH (C1-C3 alkyl), -C1-C3alkylamino, alkenylamino, alkynylamino, di(C1-C3 alkyl)amino, - C(O)O-(C1-C3 alkyl), -C(O)NH-(C1-C3 alkyl), -CH=NOH, -PO3H2, -OPO3H2, -C(O)N(C1-C3 alkyl)2, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO2-(C1-C3 alkyl), -SO3-(C1-C3alkyl), sulfonamido, aryloxyalkyl, carboxyl, carbamate and -C(O)NH(benzyl); wherein B, R1, R4 R6 R8, R9, R10, R11, R12, R13, R14, R15 and R16 are unsubstituted or substituted with at least one electron donating or electron withdrawing group; wherein when L is -NR13-, R4 and R13 taken together may form a ring; and wherein R6 and R8 taken together may form a ring; and wherein R9 and R10 taken together may form a ring. |