Cyclic anticoagulant peptides

Claim 1

A peptide derivative of the general formula 1: wherein X is an amino terminal residue selected from hydrogen, one or two alkyl groups of from 1 to 6 carbon atoms, one or two acyl groups of from 2 to 10 carbon atoms, carbobenzyloxy, or t-butyloxycarbonyl; A, is a bond or is a peptide containing from 1 to 5 residues of any amino acid; A 2 is Phe, SubPhe, β-(2- and 3-thienyl)alanine. β-(2- and 3-furanyl)alanine, β-(2-, 3-, and 4-pyridyl)-alanine, β-(benzothienyl-2- and 3-yl)alanine, β-(1- and 2-naphthyl)alanine, Tyr, or Trp; A3 is Glu or Asp; A4. is any amino acid; As is IIe, Val, Leu, Nle, or Thr; A 7 ; is any amino acid; A 8 is Glu or Asp; A 10 is a lipophilic amino acid selected from Tyr, Tyr(S0 3 H), Trp, Phe. Leu, Nle, Ile, Val, His, and Pro or is a dipeptide containing at least one of these lipophilic amino acids; A 11 is a bond or is a peptide fragment containing from one to five residues of any amino acid; Y is a carboxy terminal residue selected from OH, (C 1 -C 6 )alkoxy, amino, mono- or di-(C 1 -C 4 )alkyl substituted amino, or benzylamino; R, R , R 1 , and R 1 ' are each selected from a hydrogen or (C 1 -C 4 )alkyl group; B is selected from -S-, -S-S-, or -S-Alk 3 -S-; Alki, Alk 2 , and AIk 3 are each selected from a (C 1 -C 8 )methylene or ethylene group; and wherein "D" and "L" indicate that the stereochemistry of the indicated carbon is that corresponding to D-cysteine and L-cysteine, respectively/and the pharmaceutically acceptable salts thereof.