Phosphono/biaryl substituted dipeptide derviatives

Details Phosphono/biaryl substituted dipeptide derviatives Phosphono/biaryl substituted dipeptide derviatives

C - Chemistry, Metallurgy

07

K

C07K 5/06 (2006.01) C07F 9/38 (2006.01) C07F 9/40 (2006.01) C07F 9/655 (2006.01) C07F 9/6553 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2067592

4-18629/A/CGC 1544 Phosphono/biaryl substituted dipeptide derivatives Abtract of the Disclosure Novel N-phosphonomethyl-biaryl substituted dipeptide derivatives of forrnula I Image wherein R and R' represent independently hydrogen, carbocyclic aryl, 6-tetrahydronaphthyl, 5-indanyl, acyloxymethyl or acyloxymethyl monosubstituted on methyl carbon by C1-C20-alkyl, by C5-C7-cycloalkyl, by aryl or by aryl-lower alkyl; A represents a direct bond, lower alkylene, phenylene or cyclohexylene; m represents I or zero, provided that m represents 1 when A is a direct bond; R1 represents phenyl, phenyl substituted by one to three substituents selected from lower alkyl, hydroxy, lower alkoxy, lower alkanoyloxy, halogen, cyano, trifluoromethyl, lower alkanoylamino or loweralkoxycarbonyl, naphthyl, naphthyl substituted by lower alkyl, lower alkoxy or halogen, thienyl, thienyl substituted by lower alkyl, furanyl, furanyl substituted by lower alkyl, pyridyl, pyridyl substituted by lower alkyl, halogen or cyano, pyrrolyl or N-lower alkylpyrrolyl; R2 represents hydrogen, hydroxy, lower alkyl, aryl-lower alkyl, C5-C7-cycloalkyl-lower alkyl, amino-lower alkyl, hydroxy-lower alkyl, lower alkylthio-lower alkyl, lower aLkoxy-lower alkyl, aryl-lower alkylthio-lower alkyl or aryl-lower alkoxy-lower alkyl; COR3 represents carboxyl or carboxyl derivatized in form of a pharmaceutically acceptable ester or amide; and pharmaceutically acceptable salts thereof are useful as neutral endopeptidase (NEP) inhibitors. Suitable methods for their be manufacture are described.

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