p38 inhibitors: Piperidine- and 4-aminopiperidine-substituted naphthyridinones, quinolinones, and dihydroquinazolinones

被引：36

作者：

Hunt, JA

Kallashi, F

Ruzek, RD

Sinclair, PJ

Ita, I

McCormick, SX

Pivnichny, JV

Hop, CECA

Kumar, S

Wang, Z

O'Keefe, SJ

O'Neill, EA

Porter, G

Thompson, JE

Woods, A

Zaller, DM

Doherty, JB

机构：

[1] Merck & Co Inc, Dept Med Chem, Rahway, NJ 07065 USA

[2] Merck & Co Inc, Dept Drug Metab, Rahway, NJ 07065 USA

[3] Merck & Co Inc, Dept Inflammat & Rheumatol, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 03期

关键词：

D O I：

10.1016/S0960-894X(02)00990-3

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We have synthesized a series of C7-piperidine- and 4-aminopiperidine-substituted naphthyridinones, quinolinones, and dihydroquinazolinones that are highly potent inhibitors of both p38 MAP kinase activity and TNF-alpha release. The 4-aminopenta-methylpiperidine naphthyridinone 5, which was designed to block metabolism at major 'hot spots', combined excellent inhibitory potency with good oral bioavailability in the rat. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：467 / 470

页数：4

共 4 条

[1]

BAO JD, UNPUB

[2] Design and synthesis of potent, selective, and orally bioavailable tetrasubstituted imidazole inhibitors of p38 mitogen-activated protein kinase [J].

Liverton, NJ ;

Butcher, JW ;

Claiborne, CF ;

Claremon, DA ;

Libby, BE ;

Nguyen, KT ;

Pitzenberger, SM ;

Selnick, HG ;

Smith, GR ;

Tebben, A ;

Vacca, JP ;

Varga, SL ;

Agarwal, L ;

Dancheck, K ;

Forsyth, AJ ;

Fletcher, DS ;

Frantz, B ;

Hanlon, WA ;

Harper, CF ;

Hofsess, SJ ;

Kostura, M ;

Lin, J ;

Luell, S ;

O'Neill, EA ;

Orevillo, CJ ;

Pang, M ;

Parsons, J ;

Rolando, A ;

Sahly, Y ;

Visco, DM ;

O'Keefe, SJ .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (12) :2180-2190

[3]

NATARAJAN SR, IN PRESS BIOORG MED

[4]

STELMACH JE, IN PRESS BIOORG MED

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