Inhibitors and substrates of thrombin

Abstract

This invention provides peptides of the formula ##STR1## wherein X is H, CH.sub.3 or an N-protecting group; Y is (1) C.sub.3 -C.sub.9 alkyl optionally substituted by C.sub.1 -C.sub.4 alkoxy, (2) C.sub.5 -C.sub.10 aryl optionally substituted by C.sub.1 -C.sub.4 alkoxy, (3) C.sub.5 -C.sub.10 alkylaryl optionally substituted by C.sub.1 -C.sub.4 alkoxy, (4) (CH.sub.2).sub.n --Q or ##STR2## wherein Q is H, amino, amidino, imidizole, guanidino or isothioureido and n is 1-5; Z is COR.sub.1, ##STR3## wherein: R.sub.1 is H, OH, CH.sub.2 Cl, CH.sub.2 --CH.sub.2 --CO-pip, CF.sub.2 --CF.sub.2 --CO-pip, CH.sub.2 --CH(CH.sub.3)--CO-pip, CF.sub.2 --CF(CF.sub.3)--CO-pip, CH.sub.2 --CH.sub.2 --CO-Pro-NHEt, CF.sub.2 --CF.sub.2 --CO-Pro-NHEt or a chromophoric group, R.sub.2 and R.sub.3 may be the same or different and are selected from the group consisting of OH, OR.sub.6 and NR.sub.6 R.sub.7, wherein R.sub.6 and R.sub.7 may be the same or different and are selected from the group consisting of C.sub.1-10 alkyl, phenyl or C.sub.6 -C.sub.10 arylalkyl, or, R.sub.2 and R.sub.3 taken together represent the residue of a diol, R.sub.4 and R.sub.5 are the same or different and are selected from: (1) R.sub.2 and R.sub.3, wherein R.sub.2 and R.sub.3 may be the same or different and are selected from the group consisting of OH, OR.sub.6 and NR.sub.6 R.sub.7, wherein R.sub.6 and R.sub.7 may be the same or different and are selected from the group consisting of C.sub.1-10 alkyl, phenyl or C.sub.6 -C.sub.10 arylalkyl, or, R.sub.2 and R.sub.3 taken together represent the residue of a diol, (2) Gly-pip, (3) Ala-pip or (4) Gly-Pro-NHEt; Aa.sub.1 is Dpa, Nal or Dba; and Aa.sub.2 is ##STR4## or C.sub.1 -C.sub.3 alkyl-substituted derivatives of it, wherein R.sub.8 is CH.sub.2, CH.sub.2 --CH.sub.2, S--CH.sub.2, S--C(CH.sub.3).sub.2 or CH.sub.2 --CH.sub.2 --CH.sub.2.

Dependencies are inferred from the claim text.