Patent ID: 6686350
Filing Date: 2004-02-03
Classification: A61K,C07C,C07D,C07K,G01N

Abstract:
A cell adhesion inhibitor having Formula (I)Aâ€”Bâ€ƒâ€ƒ(I), whereinA comprises a VLA-4 specificity determinant which does not impart significant IIb/IIIa activity and is selected from the group consisting of aliphatic acyl optionally substituted with N-alkyl- or N-arylamido; aroyl; alkyl- or arylsulfonyl; aralkylcarbonyl optionally substituted with aryl; alkoxycarbonyl; aralkyloxycarbonyl; cycloalkylcarbonyl optionally fused with aryl; alkylsulfonyl; aralkylsulfonyl; arylsulfonyl; cycloalkylsulfonyl optionally fused with aryl; aralkoxycarbonyl; aryloxycarbonyl; cycloalkyloxycarbonyl; alkenoyl optionally substituted with aryl; alkenylsulfonyl optionally substituted with aryl; alkynoyl optionally substituted with aryl; alkynylsulfonyl optionally substituted with aryl; cycloalkenylcarbonyl; cycloalkenylsulfonyl; cycloalkylalkanoyl; cylcoalkylalkylsulfonyl; arylaroyl, biarylsulfonyl; alkoxysulfonyl; aralkoxysulfonyl; aryloxysulfonyl; N-arylurea-substituted alkanoyl; N-arylurea-substituted alkylsulfonyl; cycloalkenyl-substituted carbonyl; cycloalkenyl-substituted sulfonyl; alkenoxycarbonyl optionally substituted with aryl; alkenoxysulfonyl optionally substituted with aryl; alkynoxycarbonyl optionally substituted with aryl; alkynoxysulfonyl optionally substituted with aryl; acylamino-substituted alkanoyl; acylamino-substituted alkylsulfonyl; aminocarbonyl-substituted alkanoyl; carbamoyl-substituted alkanoyl; carbamoyl-substituted alkylsulfonyl; heterocyclylalkanoyl; carboxyalkyl-substituted aralkoyl; carboxyalkyl-substituted aralkylsulfonyl; oxocarbocyclyl-fused aroyl; oxocarbocyclyl-fused arylsulfonyl; Nâ€²,Nâ€²-alkyl, arylhydrazinocarbonyl; aryloxy-substituted alkanoyl; alkenyl; alkynyl; cycloalkyl; aryl-fused cycloalkyl; cycloalkenyl; aryl; aryl-substituted alkyl; aryl-substituted alkenyl; aryl-substituted alkynyl; cycloalkyl-substituted alkyl; cycloalkenyl-substituted cylcoalkyl; biaryl; alkoxy; alkenoxy; alkynoxy; aryl-substituted alkoxy; alkylamino; alkenylamino; alkynylamino; aryl-substituted alkylamino; aryl-substituted alkenylamino; aryl-substituted alkynylamino; aryloxy; arylamino; N-alkylurea-substituted alkyl; N-arylurea-substituted alkyl; alkylcarbonylamino-substituted alkyl; heterocyclyl; heterocyclyl-substituted amino; carboxyalky-substituted aralkyl; oxocarbocyclyl-fused aryl; alkylaminocarbonyl; arylaminocarbonyl and aralkylaminocarbonyl optionally substituted with bis(alkylsulfonyl)amino, alkoxycarbonylamino or alkenyl; heterocyclylsulfonyl; heterocyclyloxycarbonyl; mono- or di-alkylaminocarbonyl optionally substituted with aryl; mono- or di-aralkylaminocarbonyl; mono- or di-arylaminocarbonyl; (aryl)(alkyl)aminocarbonyl; mono- or di-cycloalkylaminocarbonyl; heterocyclylaminocarbonyl; (alkyl)(heterocyclyl)aminocarbonyl; (aralkyl)(heterocyclyl)aminocarbonyl; alkylaminosulfonyl; arylaminosulfonyl; alkenyl- or alkynyl-aminocarbonyl optionally substituted with aryl; alkenyl- or alkynyl-aminosulfonyl optionally substituted with aryl; heterocyclylaminosulfonyl; aryl-substituted alkenoxy; aryl-substituted alkynoxy; arylurea-substituted arylalkylcarbonylamino, heteroarylamido-substituted arylalkylcarbonylamino, and arylurea-substituted arylurea; and B is of Formula IIa â€ƒwherein A1 is selected from the group consisting of NR1, O, S, (CR1R2)r, and N[(CR1R2)m(C&boxH;Y)A2R1]; A2 is selected from the group consisting of O, NR2, S, and (CR1R2)r; X is selected from the group consisting of CH2, O, and S; Y is H2 or O; r=0 or 1; n=0, 1, 2, 3, 4, or 5; m=1, 2, 3, or 4; W is selected from the group consisting of CO2H, SO3H, PO4H2, tetrazole, and H; each of R1 and R2, independently, is selected from the group consisting of H, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, aralkyl, heterocycle, and alkyl optionally substituted with cycloalkyl, cycloalkenyl, heterocycle, alkenyl, alkynyl, alkoxyl, hydroxyl, halogen, aralkoxy, thioalkoxy, carboxy, alkoxycarbonyl, or carboxamide; R3 is R1, or alkyl substituted with heteroaryl, aminocarbonyl, amino, guanidine, amido, urea, alkylcarbonyl, or alkoxyaryl; each of R5 and R6, independently, is selected from the group consisting of H, OR1, halogen, alkyl, SR1, NZR12, and NR1R2; Z is CO or (CR1R2)n; and R12 is selected from the group consisting of H, alkyl, cycloalkenyl, aryl, aralkyl, heterocycle; alkyl optionally substituted with cycloalkyl, heterocycle, alkoxyl, hydroxyl, halogen, aralkoxy, thioalkoxy, carboxy, alkoxycarbonyl, carboxamide, and aralkoxy.