Patent ID: 6441004
Filing Date: 2002-08-27
Classification: A61K,A61P

Abstract:
A method for antagonising an MCP-1 mediated effect in a warm-blooded animal in need thereof comprising administering to said animal an antagonising-effective amount of a compound of the formula (I): whereinR1 is independently selected from trifluoromethyl, C1-4alkyl, halo, hydroxy, C1-4alkoxy, C1-4alkanoyl, C1-4alkanoyloxy, amino, cyano, C1-4alkylamino, di(C1-4alkyl)amino, C1-4alkanoylamino, nitro, carbamoyl, C1-4alkoxycarbonyl, thiol, C1-4alkylsulphanyl, C1-4alkylsulphinyl, C1-4alkylsulphonyl, sulphonamido, carbamoyl C1-4alkyl, Nâ€”(C1-4alkyl)carbamoylC1-4alkyl, Nâ€”(C1-4alkyl)2carbamoyl-C1-4alkyl, hydroxy C1-4alkyl, C1-4alkoxy C1-4alkyl, morpholino, pyrrolidinyl, carboxy C1-4alkylamino, R3 and â€”OR3, where R3 is optionally substituted aryl or an optionally substituted 5- or 6-membered heteroaryl ring; p is 0-4 and R1 can have the same or different values when p is 2-4 with the proviso that no more than one R1 can be chosen from the group amino, C1-4alkylamino, di(C1-4alkyl)amino, morpholino and pyrrolidinyl; T is of the formula â€”(CHR4)mâ€”, where R4 is independently selected from hydrogen or C1-4alkyl and m=1-3 and R4 can have different values when m is 2 or 3; X is CO2R4, SO3H, cyano, â€”SO2NHR4, â€”SO2NHAr, or â€”CONHR5 wherein: R4 is as defined above; Ar is an optionally substituted phenyl or optionally substituted 5 or 6 membered heteroaryl ring; and R5 is H, cyano, C1-4alkyl, OH, â€”SO2â€”C1-4alkyl, â€”SO2CF3, or â€”SO2-phenyl, or R5 is â€”(CHR4)râ€”COOH where r is 1-3 and each R4 can take a different value, as defined above, when r is 2-3; A is selected from phenyl, naphthyl, furyl, pyridyl and thienyl; R2 is independently selected from trifluoromethyl, C1-4alkyl, halo, hydroxy, CF3Oâ€”, C1-4alkoxy, C1-4alkanoyl, C1-4alkanoyloxy, amino, cyano, C1-4alkylamino, (C1-4alkyl)2amino, C1-4alkanoylamino, nitro, carboxy, carbamoyl, C1-4alkoxycarbonyl, thiol, C1-4alkylsulphanyl, C1-4alkylsulphinyl, C1-4alkylsulphonyl, sulphonamido, carbamoylC1-4alkyl, Nâ€”(C1-4alkyl)carbamoylC1-4alkyl, Nâ€”(C1-4alkyl)2carbamoyl-C1-4alkyl, hydroxyC1-4alkyl, C1-4alkoxyC1-4alkyl or two R2 values together may form a divalent radical of the formula â€”O(CH2)1-4Oâ€” attached to adjacent carbon atoms on ring A; q is 0-4 and R2 can have the same or different values when q is 2-4; Z is hydrogen, fluoro, chloro, bromo, iodo, methyl, trifluoromethyl, hydroxymethyl, carboxyC3-6cycloalkyl or; Z is â€”(CHR4)râ€”NR6R7, where r is 0-2, R6 and R7 are independently selected from H and C1-4alkyl, or R6 and R7 together with the nitrogen to which they are attached form a 5 or 6 membered non-aromatic ring optionally containing one further heteroatom selected from O, N or S; or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof.