ß-LACTAMIC RGD CYCLOPEPTIDES CONTAINING GAMMA (?) TURNS

摘要

The invention relates to a compound having formula I: cyclo[Arg-Gly-Asp-(beta-Lactam)] (I), containing at least one ? turn, wherein (beta-Lactam)- is a fragment of 3-amino-1-(2-carbonylmethyl)-azetidinone having formula II (II) in which R<SUP>1</SUP>, R<SUP>2</SUP>, R<SUP>3</SUP>, R<SUP>4</SUP>, R<SUP>5</SUP> and R<SUP>6</SUP> are selected independently from the group formed by: hydrogen, substituted or non-substituted alkyl, substituted or non-substituted cycloalkyl, substituted or non-substituted alkenyl, substituted or non-substituted aryl, substituted or non-substituted arylalkyl, substituted or non-substituted heterocyclyl, substituted or non-substituted heterocyclylalkyl, -COR<SUB>7</SUB>, -C(O)OR<SUB>7</SUB>, -C(O)NR<SUB>7</SUB>R<SUB>8</SUB> -C=NR<SUB>7</SUB>, -CN, -OR<SUB>7</SUB>, -OC(O)R<SUB>7</SUB>, -S(O)<SUB>t</SUB>-R<SUB>7</SUB>, -NR<SUB>7</SUB>R<SUB>8</SUB>, -NR<SUB>7</SUB>C(O)R<SUB>9</SUB>, -NO<SUB>2</SUB>, -N=CR<SUB>7</SUB>R<SUB>8</SUB> or halogen, whereby two of same can be joined to form a cyclic substituent; or the enantiomers, diastereoisomers or a pharmaceutically-acceptable salt thereof. The inventive compounds selectively inhibit certain integrins and can be used in the treatment of diseases such as cancer, metastasis of solid cancerous tumours, thrombosis, restenosis subsequent to percutaneous transluminal coronary angioplasty (PTCA), rheumatoid arthritis or osteoporosis. In addition, said compounds can be used in diagnostic and analysis systems.