Discovery and SAR of novel [1,6]naphthyridines as potent inhibitors of Spleen Tyrosine Kinase (SYK)

被引：46

作者：

Cywin, CL

Zhao, BP

McNeil, DW

Hrapchak, M

Prokopowicz, AS

Goldberg, DR

Morwick, TM

Gao, A

Jakes, S

Kashem, M

Magolda, RL

Soll, RM

Player, MR

Bobko, MA

Rinker, J

DesJarlais, RL

Winters, MP

机构：

[1] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06801 USA

[2] 3 Dimens Pharmaceut Inc, Exton, PA 19341 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 08期

关键词：

D O I：

10.1016/S0960-894X(03)00163-X

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The discovery of novel 5,7-disubstituted[1,6]naphthyridines as potent inhibitors of Spleen Tyrosine Kinase (SYK) is discussed. The SAR reveals the necessity for a 7-aryl group with preference towards para substitution and that this in combination with 5-aminoalkylamino substituents further improved the potency of the compounds. The initial SAR as well as a survey of the other positions is discussed in detail. (C) 2003 Elsevier Science Ltd. All rights reserved.

引用

页码：1415 / 1418

页数：4

共 8 条

[1] AMES DE, J CHEM SOC P1, P705
[2] Brun EM, 2000, SYNTHESIS-STUTTGART, P273
[3] OLIVER JM, 1994, J BIOL CHEM, V269, P29697
[4] RIVERA VM, 1995, MOL CELL BIOL, V15, P1582
[5] Protein tyrosine kinase Syk in mast cell signaling
Siraganian, RP
Zhang, J
Suzuki, K
Sada, K
[J]. MOLECULAR IMMUNOLOGY, 2002, 38 (16-18) : 1229 - 1233
[6] TAYLOR JA, 1995, MOL CELL BIOL, V15, P4149
[7] Tyrosine kinase SYK: essential functions for immunoreceptor signalling
Turner, M
Schweighoffer, E
Colucci, F
Di Santo, JP
Tybulewicz, VL
[J]. IMMUNOLOGY TODAY, 2000, 21 (03): : 148 - 154
[8] Zhang C, 1996, CHINESE CHEM LETT, V7, P1

← 1 →