INHIBITORS AND SUBSTRATES OF THROMBIN

摘要

Peptides which act as inhibitors or substrates of thrombin are derived from the formula D-Phe-Pro-Arg or its analogues, wherein Phe is substituted by (FORMULA) wherein Ar1 and Ar2 are the same or different and are selected from the group consisting of phenyl, thienyl, pyridyl, naphthyl, thionaphthyl, indolyl and saturated groups corresponding to these, optionally substituted by up to three groups selected from C1-C3 alkyl and C1-C3 alkoxy, L1 and L2 are the same or different and are selected from the group consisting of CH2, CH2-CH2, O-CH2, S-CH2, Ar-L taken together optionally means H, diphenyl-methyl, fluorenyl or saturated groups corresponding to these, but one of the Ar-L cannot be H when the other Ar-L means H or benzyl, and Arg may be substituted by an amino acid of the formula (FORMULA)wherein (FORMULA)where Q = H, amino, amidino, imidazole, guanidino or isothioureido and n = 1-5, preferably 3-5, or C3-C9 alkyl and C5-C10 aryl or alkylaryl optionally substituted by up to three groups selected from hydroxy and C1-C4 alkoxy; (FORMULA) where (FORMULA)or a chromophoric group e.g. pNA, MCA, R2 and R3 are the same or different and are selected from the group consisting of OH, OR6 and NR6R7, or R2 and R3 taken together represent the residue of a diol; where R6 and R7, which are the same or different, are C1-C10 alkyl, phenyl or C6-C10 arylalkyl, R4 and R5 are the same or different and are selected from R2, R3, Gly-pip, Ala-pip or Gly-Pro-NHEt.