Discovery and optimization of N-acyl and N-aroylpyrazolines as B-Raf kinase inhibitors

被引：41

作者：

Blackburn, Christopher ^{[1
]}

Duffey, Matthew O. ^{[1
]}

Gould, Alexandra E. ^{[1
]}

Kulkarni, Bheemashankar ^{[1
]}

Liu, Jane X. ^{[1
]}

Menon, Saurabh ^{[1
]}

Nagayoshi, Masayuki ^{[1
]}

Vos, Tricia J. ^{[1
]}

Williams, Juliet ^{[1
]}

机构：

[1] Millennium Pharmaceut Inc, Cambridge, MA 01239 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 16期

关键词：

B-Raf inhibitor; Pyrazoline; Parallel synthesis; CANCER; BRAF;

D O I：

10.1016/j.bmcl.2010.06.110

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A high throughput screen identified N-aroylpyrazoline 1 as a selective inhibitor of the V600E mutant of B-Raf kinase. Parallel synthesis of acyl, aroyl, and sulfonyl derivatives led to the identification of several potent inhibitors in both enzymatic and cellular (pERK) assays such as compound 42. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：4795 / 4799

页数：5

共 9 条

[1] Synthesis, analgesic, and antiparkinsonian profiles of some pyridine, pyrazoline, and thiopyrimidine derivatives
Abdel-Latif, Nehad A.
Sabry, Nermien M.
Mohamed, Ashraf M.
Abdulla, Mohamed M.
[J]. MONATSHEFTE FUR CHEMIE, 2007, 138 (07): : 715 - 724
[2] Mutations of the BRAF gene in human cancer
Davies, H
Bignell, GR
Cox, C
Stephens, P
Edkins, S
Clegg, S
Teague, J
Woffendin, H
Garnett, MJ
Bottomley, W
Davis, N
Dicks, N
Ewing, R
Floyd, Y
Gray, K
Hall, S
Hawes, R
Hughes, J
Kosmidou, V
Menzies, A
Mould, C
Parker, A
Stevens, C
Watt, S
Hooper, S
Wilson, R
Jayatilake, H
Gusterson, BA
Cooper, C
Shipley, J
Hargrave, D
Pritchard-Jones, K
Maitland, N
Chenevix-Trench, G
Riggins, GJ
Bigner, DD
Palmieri, G
Cossu, A
Flanagan, A
Nicholson, A
Ho, JWC
Leung, SY
Yuen, ST
Weber, BL
Siegler, HF
Darrow, TL
Paterson, H
Marais, R
Marshall, CJ
Wooster, R
[J]. NATURE, 2002, 417 (6892) : 949 - 954
[3] FLAHERTY K, 2009, J CLIN ONCOL, V27, P15
[4] Hingorani SR, 2003, CANCER RES, V63, P5198
[5] Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885
King, Alastair J.
Patrick, Denis R.
Batorsky, Roberta S.
Ho, Maureen L.
Do, Hieu T.
Zhang, Shu Yun
Kumar, Rakesh
Rusnak, David W.
Takle, Andrew K.
Wilson, David M.
Hugger, Erin
Wang, Lifu
Karreth, Florian
Lougheed, Julie C.
Lee, Jae
Chau, David
Stout, Thomas J.
May, Earl W.
Rominger, Cynthia M.
Schaber, Michael D.
Luo, Lusong
Lakdawala, Ami S.
Adams, Jerry L.
Contractor, Rooja G.
Smalley, Keiran S. M.
Herlyn, Meenhard
Morrissey, Michael M.
Tuveson, David A.
Huang, Pearl S.
[J]. CANCER RESEARCH, 2006, 66 (23) : 11100 - 11105
[6] Synthesis, biological properties, and molecular modeling investigations of novel 3,4-diarylpyrazolines as potent and selective CB1 cannabinoid receptor antagonists
Lange, JHM
Coolen, HKAC
van Stuivenberg, HH
Dijksman, JAR
Herremans, AHJ
Ronken, E
Keizer, HG
Tipker, K
McCreary, AC
Veerman, W
Wals, HC
Stork, B
Verveer, PC
den Hartog, AP
de Jong, NMJ
Adolfs, TJP
Hoogendoorn, J
Kruse, CG
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (03) : 627 - 643
[7] Li NX, 2007, CURR OPIN INVEST DR, V8, P452
[8] Design and discovery of small molecules targeting Raf-1 kinase
Lowinger, TB
Riedl, B
Dumas, J
Smith, RA
[J]. CURRENT PHARMACEUTICAL DESIGN, 2002, 8 (25) : 2269 - 2278
[9] Mitogen-activated protein kinase pathways
Robinson, MJ
Cobb, MH
[J]. CURRENT OPINION IN CELL BIOLOGY, 1997, 9 (02) : 180 - 186

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