Potent quinoxaline-based inhibitors of PDGF receptor tyrosine kinase activity. Part 2: The synthesis and biological activities of RPR127963 an orally bioavailable inhibitor

被引：182

作者：

He, W ^{[1
]}

Myers, MR ^{[1
]}

Hanney, B ^{[1
]}

Spada, AP ^{[1
]}

Bilder, G ^{[1
]}

Galzcinski, H ^{[1
]}

Amin, D ^{[1
]}

Needle, S ^{[1
]}

Page, K ^{[1
]}

Jayyosi, Z ^{[1
]}

Perrone, MH ^{[1
]}

机构：

[1] Aventis Pharmaceut, Bridgewater, NJ 08807 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 18期

关键词：

D O I：

10.1016/S0960-894X(03)00655-3

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

RPR127963 demonstrates an excellent pharmacokinetic profile in several species and was found to be efficacious in the prevention of restenosis in a Yucatan mini-pig model upon oral administration of 1-5 mg/kg. The in vitro selectivity profile and SAR of the highly optimized PDGF-R tyrosine kinase inhibitor are highlighted. (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：3097 / 3100

页数：4

共 11 条

[1]

BASSETT P, 1999, DRUGS FUTURE, V24, P515

[2] Restenosis following angioplasty in the swine coronary artery is inhibited by an orally active PDGF-receptor tyrosine kinase inhibitor, RPR101511A [J].

Bilder, G ;

Wentz, T ;

Leadley, R ;

Amin, D ;

Byan, L ;

O'Conner, B ;

Needle, S ;

Galczenski, H ;

Bostwick, J ;

Kasiewski, C ;

Myers, M ;

Spada, A ;

Merkel, L ;

Ly, C ;

Persons, P ;

Page, K ;

Perrone, M ;

Dunwiddie, C .

CIRCULATION, 1999, 99 (25) :3292-3299

[3]

Buchdunger E, 2000, J PHARMACOL EXP THER, V295, P139

[4] Clinical management of gastrointestinal stromal tumors: Before and after STI-571 [J].

DeMatteo, RP ;

Heinrich, MC ;

El-Rifai, WM ;

Demetri, G .

HUMAN PATHOLOGY, 2002, 33 (05) :466-477

[5]

HE W, 2000, 219 ACS NAT M SAN FR

[6] Signal transduction via platelet-derived growth factor receptors [J].

Heldin, CH ;

Östman, A ;

Rönnstrand, L .

BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 1998, 1378 (01) :F79-F113

[7] Mechanism of action and in vivo role of platelet-derived growth factor [J].

Heldin, CH ;

Westermark, B .

PHYSIOLOGICAL REVIEWS, 1999, 79 (04) :1283-1316

[8]

MYERS ME, BIOORG MED CHEM LETT

[9]

MYERS MR, 2001, SCI FIN CHEM SPONS C

[10]

Pearlman W.M., 1969, Org. Syn., V49, P75

← 1 2 →