Structure-Activity Study of Tripeptide Thrombin Inhibitors Using. alpha.-Alkyl Amino Acids and Other Conformationally Constrained Amino Acid Substitutions

…, GF Smith, DS Gifford-Moore…

Index: Shuman, Robert T.; Rothenberger, Robert B.; Campbell, Charles S.; Smith, Gerald F.; Gifford-Moore, Donetta S.; et al. Journal of Medicinal Chemistry, 1995 , vol. 38, # 22 p. 4446 - 4453

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Citation Number: 60

Abstract

In our continuing effort to design novel thrombin inhibitors, a series of conformationally constrained amino acids (eg a-alkyl, N-alkyl cyclic, etc.) were utilized in a systematic structureactivity study of the P3, P2, and P1 positions of tripeptide arginal thrombin inhibitors. Early examples of this effort include: D-MePhe-Pro-Arg-H (151, Boc-D-Phg-Pro-Arg-H i 18), u-1-Tiq-Pro-Arg-H (23, D-1-Tiq=~-1, 2, 3, 4-tetrahydroisoquinolin-l-ylcarbonyl), and Boc-D- ...