ALPHA-HYDROXYESTER AND ALPHA-KETOESTER FUNCTIONALIZED THROMBIN INHIBITORS

被引：46

作者：

IWANOWICZ, EJ

LIN, J

ROBERTS, DGM

MICHEL, IM

SEILER, SM

机构：

[1] Bristol-Myers Squibb Pharmaceutical Research Institute Princeton

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1992年 / 2卷 / 12期

关键词：

D O I：

10.1016/S0960-894X(00)80440-0

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

alpha-Hydroxy- and alpha-ketoester functionalized D-Phe-Pro-Lys tripeptides were found to be potent thrombin active site inhibitors. The ketoester derivatives were characterized by slow binding kinetics. The most potent of the series was 9 (BMS 181,412) with an overall inhibition constant K(i)* of 0.00 17 muM.

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收藏

页码：1607 / 1612

页数：6

相关论文

共 19 条

[1] ALPHA-DIKETONE AND ALPHA-KETO ESTER DERIVATIVES OF N-PROTECTED AMINO-ACIDS AND PEPTIDES AS NOVEL INHIBITORS OF CYSTEINE AND SERINE PROTEINASES [J].

ANGELASTRO, MR ;

MEHDI, S ;

BURKHART, JP ;

PEET, NP ;

BEY, P .

JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (01) :11-13

[2]

BAGDY D, 1992, THROMB HAEMOSTASIS, V67, P325

[3]

BAGDY D, 1992, THROMB HAEMOSTASIS, V67, P357

[4] HIGHLY-ACTIVE AND SELECTIVE ANTICOAGULANTS - D-PHE-PRO-ARG-H, A FREE TRIPEPTIDE ALDEHYDE PRONE TO SPONTANEOUS INACTIVATION, AND ITS STABLE N-METHYL DERIVATIVE, D-MEPHE-PRO-ARG-H [J].

BAJUSZ, S ;

SZELL, E ;

BAGDY, D ;

BARABAS, E ;

HORVATH, G ;

DIOSZEGI, M ;

FITTLER, Z ;

SZABO, G ;

JUHASZ, A ;

TOMORI, E ;

SZILAGYI, G .

JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (06) :1729-1735

[5]

BAJUSZ S, 1978, INT J PEPT PROT RES, V12, P217

[6] A NOVEL METHOD FOR THE PREPARATION OF PEPTIDYL ALPHA-KETO ESTERS [J].

BURKHART, JP ;

PEET, NP ;

BEY, P .

TETRAHEDRON LETTERS, 1990, 31 (10) :1385-1388

[7] SUBSTRATE-RELATED PHOSPHONOPEPTIDES, A NEW CLASS OF THROMBIN INHIBITORS [J].

CHENG, L ;

GOODWIN, CA ;

SCULLY, MF ;

KAKKAR, VV ;

CLAESON, G .

TETRAHEDRON LETTERS, 1991, 32 (49) :7333-7336

[8] DESIGN, SYNTHESIS, AND KINETIC EVALUATION OF A UNIQUE CLASS OF ELASTASE INHIBITORS, THE PEPTIDYL ALPHA-KETOBENZOXAZOLES, AND THE X-RAY CRYSTAL-STRUCTURE OF THE COVALENT COMPLEX BETWEEN PORCINE PANCREATIC ELASTASE AND AC-ALA-PRO-VAL-2-BENZOXAZOLE [J].

EDWARDS, PD ;

MEYER, EF ;

VIJAYALAKSHMI, J ;

TUTHILL, PA ;

ANDISIK, DA ;

GOMES, B ;

STRIMPLER, A .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1992, 114 (05) :1854-1863

[9] THROMBIN [J].

FENTON, JW .

ANNALS OF THE NEW YORK ACADEMY OF SCIENCES-SERIES, 1986, 485 :5-15

[10] THROMBIN STRUCTURE AND FUNCTION - WHY THROMBIN IS THE PRIMARY TARGET FOR ANTITHROMBOTICS [J].

FENTON, JW ;

OFOSU, FA ;

MOON, DG ;

MARAGANORE, JM .

BLOOD COAGULATION & FIBRINOLYSIS, 1991, 2 (01) :69-75