BICYCLO (2.2.2) OCTANE DERIVATIVES CHOLECYSTOKININ AND/OR GASTRIN ANTAGONISTS

摘要

Compounds of formula (I) wherein R<1> and R<2> are independently H, methyl, halo, carboxy, esterified carboxy, amidated carboxy, carboxymethyl, esterified carboxymethyl or amidated carboxymethyl; R<3> and R<4> (or each R<3> and R<4> group, when m or n is 2 or more) are independently selected from halo, amino, nitro, cyano, sulphamoyl, sulphonyl, trifluoromethyl, C1 to C3 alkyl, C1 to C3 alkoxy, hydroxy, C1 to C3 hydroxyalkyl, C1 to C3 alkylcarboxyamino, carboxy, esterified carboxy and amidated carboxy; R<5> and R<6> are independently selected from H and the groups recited above for R<3>; m is from 0 to 4, provided that m is not more than 2 unless R<3> is exclusively halo; n is from 0 to 4, provided that n is not more than 2 unless R<4> is exclusively halo; R<7>, R<9> and R<10> are independently H or C1 to C3 alkyl; R<8> is H or C1 to C15 hydrocarbyl, in which one or more hydrogen atoms of the hydrocarbyl group may be replaced by a halogen atom, and up to two of the carbon atoms may be replaced by a nitrogen, oxygen or sulphur atom, provided that R<8> does not contain a -O-O-group; U is aryl, substituted aryl, heterocyclic, substituted heterocyclic or cycloalkyl, and Z is a group of formula (II) or (III) (wherein R is H or C1 to C3 alkyl; X is -CO2H or tetrazolyl; Y is H, -CO2H, tetrazolyl, -CH2OH, -CO2Me or -CONH2, and a is from 0 to 2); and pharmaceutically acceptable salts thereof have a high affinity for CCK and/or gastrin receptors.