Synthesis and optimization of substituted furo[2,3-d]-pyrimidin-4-amines and 7H-pyrrolo[2,3-d]pyrimidin-4-amines as ACK1 inhibitors

被引：61

作者：

Jiao, XianYun ^{[1
]}

Kopecky, David J. ^{[1
]}

Liu, JinSong ^{[2
]}

Liu, JinQian ^{[1
]}

Jaen, Juan C. ^{[1
]}

Cardozo, Mario G. ^{[2
]}

Sharma, Rajiv ^{[1
]}

Walker, Nigel ^{[2
]}

Wesche, Holger ^{[3
]}

Li, Shyun ^{[3
]}

Farrelly, Ellyn ^{[4
]}

Xiao, Shou-Hua ^{[4
]}

Wang, Zhulun ^{[2
]}

Kayser, Frank ^{[1
]}

机构：

[1] Amgen Inc, Dept Med Chem, 1120 Vet Blvd, San Francisco, CA 94080 USA

[2] Amgen Inc, Dept Mol Struct & Characterizat, San Francisco, CA 94080 USA

[3] Amgen Inc, Dept Oncol, San Francisco, CA 94080 USA

[4] Amgen Inc, Dept Lead Discovery, San Francisco, CA 94080 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 19期

关键词：

ACK1; Cancer; Tyrosine kinase inhibitor; Furo[2,3-d]-pyrimidin-4-amine; 7H-Pyrrolo[2,3-d]pyrimidin-4-amine; CDC42-ASSOCIATED TYROSINE KINASE; PALLADIUM-CATALYZED HETEROANNULATION; INDOLES; STIMULATION; GROWTH; CDC42;

D O I：

10.1016/j.bmcl.2012.08.020

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Two classes of ACK1 inhibitors, 4,5,6-trisubstituted furo[2,3-d]pyrimidin4-amines and 4,5,6-trisubstituted 7H-pyrrolo[2,3-d]pyrimidin-4-amines, were discovered and evaluated as ACK1 inhibitors. Further structural refinement led to the identification of potent and selective dithiolane inhibitor 37. (C) 2012 Published by Elsevier Ltd.

引用

页码：6212 / 6217

页数：6

共 30 条

[1] Cdc42-dependent nuclear translocation of non-receptor tyrosine kinase, ACK
Ahmed, I
Calle, Y
Sayed, MA
Kamal, JM
Rengaswamy, P
Manser, E
Meiners, S
Nur-E-Kamal, A
[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2004, 314 (02) : 571 - 579
[2] PALLADIUM-CATALYZED REDUCTIVE ADDITION OF ARYL IODIDES TO ARYL AND ALKYLETHYNYLSILANES - A STEREO AND REGIOSELECTIVE ROUTE TO FUNCTIONALIZED 2,2-DISUBSTITUTED VINYLSILANES
ARCADI, A
CACCHI, S
MARINELLI, F
[J]. TETRAHEDRON LETTERS, 1986, 27 (52) : 6397 - 6400
[3] Synthesis and functionalization of Indoles through palladium-catalyzed reactions
Cacchi, S
Fabrizi, G
[J]. CHEMICAL REVIEWS, 2005, 105 (07) : 2873 - 2920
[4] Identification, SAR Studies, and X-ray Co-crystallographic Analysis of a Novel Furanopyrimidine Aurora Kinase A Inhibitor
Coumar, Mohane Selvaraj
Tsai, Ming-Tsung
Chu, Chang-Ying
Uang, Biing-Jiun
Lin, Wen-Hsing
Chang, Chun-Yu
Chang, Teng-Yuan
Leou, Jiun-Shyang
Teng, Chi-Huang
Wu, Jian-Sung
Fang, Ming-Yu
Chen, Chun-Hwa
Hsu, John T-A
Wu, Su-Ying
Chao, Yu-Sheng
Hsieh, Hsing-Pang
[J]. CHEMMEDCHEM, 2010, 5 (02) : 255 - 267
[5] Discovery of 4-amino-5,6-biaryl-furo[2,3-d]pyrimidines as inhibitors of Lck:: Development of an expedient and divergent synthetic route and preliminary SAR
DiMauro, Erin F.
Newcomb, John
Nunes, Joseph J.
Bemis, Jean E.
Boucher, Christina
Buchanan, John L.
Buckner, William H.
Cheng, Alan
Faust, Theodore
Hsieh, Faye
Huang, Xin
Lee, Josie H.
Marshall, Teresa L.
Martin, Matthew W.
McGowan, David C.
Schneider, Stephen
Turci, Susan M.
White, Ryan D.
Zhu, Xiaotian
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (08) : 2305 - 2309
[6] Multiple roles for Cdc42 in cell regulation
Erickson, JW
Cerione, RA
[J]. CURRENT OPINION IN CELL BIOLOGY, 2001, 13 (02) : 153 - 157
[7] Farthing C.N., 2008, U.S. Patent, Patent No. [7,358,250, 7358250]
[8] Overexpression of Arabidopsis ACK1 alters leaf morphology and retards growth and development
Han, W
Rhee, HI
Cho, JW
Ku, MSB
Song, PS
Wang, MH
[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 330 (03) : 887 - 890
[9] Statistical and theoretical investigations on the directionality of nonbonded S...O interactions.: Implications for molecular design and protein engineering
Iwaoka, M
Takemoto, S
Tomoda, S
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2002, 124 (35) : 10613 - 10620
[10] Synthesis of 1,2,3-Trisubstituted pyrrolo[3,2-c]quinolines via palladium-catalyzed heteroannulation with internal alkynes
Kang, SK
Park, SS
Kim, SS
Choi, JK
Yum, EK
[J]. TETRAHEDRON LETTERS, 1999, 40 (23) : 4379 - 4382

← 1 2 3 →