NEW RETINOID DERIVATIVES ENDOWED WITH CYTOTOXIC AND/OR ANTIANGIOGENIC PROPERTIES

592330 Disclosed are 3-adamantan-1-yl-4'-((E)-2-carboxy-vinyl)-biphenyl / (E)-3-(3'-adamantan-1-yl-biphenyl-4-yl)-acrylic acid derivatives as represented by the general formula I, wherein R1 is H, O(CO)OR4, NR4R5, CN, alkyl, cycloalkyl or heterocycloalkyl; wherein alkyl, cycloalkyl and heterocycloalkyl are optionally substituted once or more with alkyl, (CH2)nCOR3, O(CO)OR4, OH or NR4R5; n is 0 or 1; R3 is OH, amino, alkyl-amino or benzyloxy; R4 and R5 are independently H, alkyl, or R4 and R5 taken together with the nitrogen atom to which they are attached form a heterocycloalkyl group, or NR4R5 form a nitro group; R2 is absent or is alkylene, hydroxyalkylene, aminocarbonylalkylene, alkenylene, cycloalkylene, heterocycloalkylene, -(OCH2CH2)m-O-, branched or linear polyaminoalkylene, phenyloxy optionally substituted with nitro; m is an integer comprised between 1 and 4; A is CH2-, -CO-, -CH2-(CO)-, -NH(CO)- or -[CO-(CHR6)-NH]w-; R6 is the side chain of a natural amino acid radical; w is 1; their tautomers, their geometrical isomers, their optically active forms, as well as their pharmaceutically acceptable salts, hydrate or solvate thereof; with the proviso that R1-R2-A does not represent alkyl or alkyl-CO. Representative compounds include (S)-2-amino-3-methyl-butyric acid 3-adamantan-1-yl-4'-((E)-2-carboxy-vinyl)-biphenyl-4-yl ester hydrochloride, (E)-3-(3'-adamantan-1-yl-4'-{ 2-[2-(2-carboxymethoxy-ethoxy)-ethoxy]-acetoxy} -biphenyl-4-yl)-acrylic acid, 4-morpholin-4-yl-butyric acid 3-adamantan-1-yl-4'-((E)-2-carboxy-vinyl)-biphenyl-4-yl ester hydrochloride, 4-(4-methyl-piperazin-1-yl)-butyric acid 3-adamantan-1-yl-4'-((E)-2-carboxy-vinyl)-biphenyl-4-yl ester dihydrochloride, 1-amino-cyclopropanecarboxylic acid 3-adamantan-1-yl-4'-((E)-2-carboxy-vinyl)biphenyl-4-yl ester and (E)-3-(3'-adamantan-1-yl-4'-cyanomethoxybiphenyl-4-yl)-acrylic acid. Further disclosed is a pharmaceutical composition comprising a compound of formula I as defined above as active ingredient and at least one pharmaceutically acceptable excipient and/or diluent, for treating arthritic conditions, tumours, metastatic cancer, diabetic retinopathy, psoriasis, chronic inflammatory diseases or atherosclerosis.