BETA-LACTAMIC RGD CYCLOPEPTIDES CONTAINING GAMMA TURNS

摘要

A compound of the formula (I):
€ƒ€ƒ€ƒ€ƒ€ƒ€ƒ€ƒ€ƒ cyclo [Arg-Gly-Asp-(beta-Lactam)]€ƒ€ƒ€ƒ€ƒ€ƒ(I)
containing at least one ³ turn where (beta-Lactam)- is a fragment of 3-amino-1-(2-carbonylmethyl)-azetidin-2-one of the formula (II)
where R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are selected independently from the group formed by hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted aryl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, -COR 7 , -C(0)OR 7 , -CO)NR 7 R 8 -C=NR 7 -CN, -OR 7 , - _ OC(O) 7 , -S(O) t -R 7 , -NR 7 R 8 , -NR 7 C(O)R 9 , -NO 2 , -N=CR 7 R 8 or halogen; where two of them can be bridged to form a cyclic substituent; their enantiomers, diastereomers or their pharmaceutically acceptable salts. These compounds selectively inhibit certain integrins and are useful for the treatment of diseases such as cancer, metastasis of cancerous solid tumors, thrombosis, restenosis following percutaneous transluminal coronary angioplasty (PTCA), rheumatoid arthritis or osteoporosis. They are also useful in systems of diagnostic and analysis.