SAR of 3,4-dihydropyrido[3,2-d]pyrimidone p38 inhibitors

被引：121

作者：

Liu, LP

Stelmach, JE

Natarajan, SR

Chen, MH

Singh, SB

Schwartz, CD

Fitzgerald, CE

O'Keefe, SJ

Zaller, DM

Schmatz, DM

Doherty, JB

机构：

[1] Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA

[2] Merck Res Labs, Dept Inflamat Res, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 22期

关键词：

D O I：

10.1016/j.bmcl.2003.08.059

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Development for a class of potent 3,4-dihydropyrido(3,2-d)pyrimidone inhibitors of p38a MAP kinase is described. Modification of N-1 aryl and C-6 arylsulfide in 3,4-dihydropyrido (3,2-d)pyrimidone analogues for the interaction with the hydrophobic pockets in p38 active site is also discussed. (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：3979 / 3982

页数：4

共 19 条

[11] Role of p38 mitogen-activated protein kinase in rhinovirus-induced cytokine production by bronchial epithelial cells [J].

Griego, SD ;

Weston, CB ;

Adams, JL ;

Tal-Singer, R ;

Dillon, SB .

JOURNAL OF IMMUNOLOGY, 2000, 165 (09) :5211-5220

[12] Acquisition of sensitivity of stress-activated protein kinases to the p38 inhibitor, SB 203580, by alteration of one or more amino acids within the ATP binding pocket [J].

Gum, RJ ;

McLaughlin, MM ;

Kumar, S ;

Wang, ZL ;

Bower, MJ ;

Lee, JC ;

Adams, JL ;

Livi, GP ;

Goldsmith, EJ ;

Young, PR .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (25) :15605-15610

[13] A MAP KINASE TARGETED BY ENDOTOXIN AND HYPEROSMOLARITY IN MAMMALIAN-CELLS [J].

HAN, J ;

LEE, JD ;

BIBBS, L ;

ULEVITCH, RJ .

SCIENCE, 1994, 265 (5173) :808-811

[14] A PROTEIN-KINASE INVOLVED IN THE REGULATION OF INFLAMMATORY CYTOKINE BIOSYNTHESIS [J].

LEE, JC ;

LAYDON, JT ;

MCDONNELL, PC ;

GALLAGHER, TF ;

KUMAR, S ;

GREEN, D ;

MCNULTY, D ;

BLUMENTHAL, MJ ;

HEYS, JR ;

LANDVATTER, SW ;

STRICKLER, JE ;

MCLAUGHLIN, MM ;

SIEMENS, IR ;

FISHER, SM ;

LIVI, GP ;

WHITE, JR ;

ADAMS, JL ;

YOUNG, PR .

NATURE, 1994, 372 (6508) :739-746

[15] 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

[16] p38 MAP kinase inhibitors.: Part 1:: Design and development of a new class of potent and highly selective inhibitors based on 3,4-dihydropyrido[3,2-d]pyrimidone scaffold [J].

Natarajan, SR ;

Wisnoski, DD ;

Singh, SB ;

Stelmach, JE ;

O'Neill, EA ;

Schwartz, CD ;

Thompson, CM ;

Fitzgerald, CE ;

O'Keefe, SJ ;

Kumar, S ;

Hop, CECA ;

Zaller, DM ;

Schmatz, DM ;

Doherty, JB .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (02) :273-276

[17] Design and synthesis of potent, orally bioavailable dihydroquinazolinone inhibitors of p38 MAP kinase [J].

Stelmach, JE ;

Liu, LP ;

Patela, SB ;

Pivnichny, JV ;

Scapin, G ;

Singh, S ;

Hop, CECA ;

Wang, Z ;

Strauss, JR ;

Cameron, PM ;

Nichols, EA ;

O'Keefe, SJ ;

O'Neill, EA ;

Schmatz, DM ;

Schwartz, CD ;

Thompson, CM ;

Zaller, DM ;

Doherty, JB .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (02) :277-280

[18] Structural basis of inhibitor selectivity in MAP kinases [J].

Wang, ZL ;

Canagarajah, BJ ;

Boehm, JC ;

Kassisa, S ;

Cobb, MH ;

Young, PR ;

Abdel-Meguid, S ;

Adams, JL ;

Goldsmith, EJ .

STRUCTURE, 1998, 6 (09) :1117-1128

[19] The structural basis for the specificity of pyridinylimidazole inhibitors of p38 MAP kinase [J].

Wilson, KP ;

McCaffrey, PG ;

Hsiao, K ;

Pazhanisamy, S ;

Galullo, V ;

Bemis, GW ;

Fitzgibbon, MJ ;

Garon, PR ;

Murcko, MA ;

Su, MSS .

CHEMISTRY & BIOLOGY, 1997, 4 (06) :423-431

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