Development of the new potent non-peptide gpIIb/IIIa antagonist NSL-95301 by utilizing combinatorial technique

被引：27

作者：

Harada, T

Katada, J

Tachiki, A

Asari, T

Iijima, K

Uno, I

Ojima, I

Hayashi, Y

机构：

[1] NIPPON STEEL CORP LTD, ADV MAT & TECHNOL RES LABS, LIFE SCI RES CTR, KAWASAKI, KANAGAWA 211, JAPAN

[2] SUNY STONY BROOK, DEPT CHEM, STONY BROOK, NY 11794 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1997年 / 7卷 / 02期

关键词：

D O I：

10.1016/S0960-894X(96)00610-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthetic study of new non-peptide gpIIb/IIIa antagonist, NSL-95301, is presented. The combinatorial technique was engaged in the lead compound discovery process and optimization process to find (+)-NSL-95301. The IC50 value of collagen induced platelet aggregation inhibitory activity is 92 nM. (C) 1997, Elsevier Science Ltd.

引用

收藏

页码：209 / 212

页数：4

相关论文

共 23 条

[1] STRUCTURAL STUDIES OF A FAMILY OF HIGH-AFFINITY LIGANDS FOR GPIIB/IIIA [J].

BACH, AC ;

EYERMANN, CJ ;

GROSS, JD ;

BOWER, MJ ;

HARLOW, RL ;

WEBER, PC ;

DEGRADO, WF .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1994, 116 (08) :3207-3219

[2]

BOGUSKY MJ, 1992, INT J PEPT PROT RES, V39, P63

[3]

CADROY Y, 1990, CARDIOVASCULAR PHARM, P515

[4] PLATELETS AND THROMBOLYTIC THERAPY [J].

COLLER, BS .

NEW ENGLAND JOURNAL OF MEDICINE, 1990, 322 (01) :33-42

[5] UNSTABLE ANGINA WITH FATAL OUTCOME - DYNAMIC CORONARY THROMBOSIS LEADING TO INFARCTION AND OR SUDDEN-DEATH - AUTOPSY EVIDENCE OF RECURRENT MURAL THROMBOSIS WITH PERIPHERAL EMBOLIZATION CULMINATING IN TOTAL VASCULAR OCCLUSION [J].

FALK, E .

CIRCULATION, 1985, 71 (04) :699-708

[6] NOVEL ANTIPLATELET THERAPIES FOR TREATMENT OF PATIENTS WITH ISCHEMIC-HEART-DISEASE - INHIBITORS OF THE PLATELET GLYCOPROTEIN IIB/IIIA INTEGRIN RECEPTOR [J].

FRISHMAN, WH ;

BURNS, B ;

ATAC, B ;

ALTURK, N ;

ALTAJAR, B ;

LERRICK, K .

AMERICAN HEART JOURNAL, 1995, 130 (04) :877-892

[7] Design and synthesis of new antagonist peptides for platelet GPIIb/IIIa receptor as anti-thrombotic agents [J].

Hayashi, Y ;

Sato, Y ;

Katada, J ;

Takiguchi, Y ;

Ojima, I ;

Uno, I .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1996, 6 (12) :1351-1356

[8]

HUMPHRIES MJ, 1990, J CELL SCI, V97, P585

[9] CONFORMATIONS OF ARG-GLY-ASP CONTAINING HETERODETIC CYCLIC-PEPTIDES - SOLUTION AND CRYSTAL STUDIES [J].

KOPPLE, KD ;

BAURES, PW ;

BEAN, JW ;

DAMBROSIO, CA ;

HUGHES, JL ;

PEISHOFF, CE ;

EGGLESTON, DS .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1992, 114 (24) :9615-9623

[10] FROM PEPTIDE TO NONPEPTIDE .2. THE DE-NOVO DESIGN OF POTENT, NON-PEPTIDAL INHIBITORS OF PLATELET-AGGREGATION BASED ON A BENZODIAZEPINEDIONE SCAFFOLD [J].

MCDOWELL, RS ;

BLACKBURN, BK ;

GADEK, TR ;

MCGEE, LR ;

RAWSON, T ;

REYNOLDS, ME ;

ROBARGE, KD ;

SOMERS, TC ;

THORSETT, ED ;

TISCHLER, M ;

WEBB, RR ;

VENUTI, MC .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1994, 116 (12) :5077-5083