Phosphono derivatives of amino acids as metalloproteinase...

C - Chemistry – Metallurgy – 07 – F

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C07F 9/38 (2006.01) A61K 31/66 (2006.01) C07F 9/40 (2006.01) C07F 9/547 (2006.01) C07F 9/6533 (2006.01)

Patent

CA 2105309

2105309 9314096 PCTABS00024 Compounds of formula (I) are described wherein R represents a -P(O)(X1R6)X2R7 group, where X1 and X2, which may be the same of different, is each an oxygen or a sulphur atom, and R6 and R7, which may be the same or different each represents a hydrogen atom or an optionally substituted alkyl, aryl, or aralkyl group; R1 represents a hydrogen atom or an optionally substituted alkyl, alkenyl, aryl, aralkyl, heteroaralkyl or heteroarylthioalkyl group; R2 represents an optionally substituted alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, aralkoxy, or aralkylthio group, or an amino (-NH2), substituted amino, carboxyl (-CO2H) or esterified carboxyl group; R3 represents a hydrogen atom or an alkyl group; R4 represents a hydrogen atom or an alkyl group; R5 represents a group -[Alk]nR8 where Alk is an alkyl or alkenyl group optionally interrupted by one or more -O- or -S- atoms or -N(R9)- groups [where R9 is a hydrogen atom or a C1-6alkyl group], n is zero or an integer 1, and R8 is an optionally substituted cycloalkyl or cycloalkenyl group; X represents an amino (-NH2), or substituted amino, hydroxyl or substituted hydroxyl group; and the salts, solvates and hydrates thereof. The compounds are metalloproteinase inhibitors and in particular have a selective gelatinase action, and may be of use in the treatment of cancer to control the development of tumour metastasises.

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