Novel C-5 aminomethyl pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases

被引：34

作者：

Mastalerz, Harold

Chang, Ming

Gavai, Ashvinikumar

Johnson, Walter

Langley, David

Lee, Francis Y.

Marathe, Punit

Mathur, Arvind

Oppenheimer, Simone

Tarrant, James

Tokarski, John S.

Vite, Gregory D.

Vyas, Dolatrai M.

Wong, Henry

Wong, Tai W.

Zhang, Hongjian

Zhang, Guifen

机构：

[1] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Oncol Chem, Wallingford, CT 06492 USA

[2] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Discovery Biol, Wallingford, CT 06492 USA

[3] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Metab & Pharmacokinet, Wallingford, CT 06492 USA

[4] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Aided Drug Design & Chem Synth, Wallingford, CT 06492 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 10期

关键词：

pyrrolotriazine; EGFR; HER2; kinase inhibitor;

D O I：

10.1016/j.bmcl.2007.02.050

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel C-5 aminomethyl pyrrolotriazines were prepared and optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. The homopiperazine, 1p, emerged as a key lead and it showed promising oral efficacy in EGFR and dual EGFR/HER2 driven human tumor xenograft models. It is hypothesized that the C-5 homopiperazine side chain binds in the ribose-phosphate portion of the ATP binding pocket. (c) 2007 Elsevier Ltd. All rights reserved.

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收藏

页码：2828 / 2833

页数：6

相关论文

共 19 条

[1] Inhibitors of epidermal growth factor receptor tyrosine kinase: Novel C-5 substituted anilinoquinazolines designed to target the ribose pocket [J].

Ballard, P ;

Bradbury, RH ;

Harris, CS ;

Hennequin, LFA ;

Hickinson, M ;

Johnson, PD ;

Kettle, JG ;

Klinowska, T ;

Leach, AG ;

Morgentin, R ;

Pass, M ;

Ogilvie, DJ ;

Olivier, A ;

Warin, N ;

Williams, EJ .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (06) :1633-1637

[2] 5-Substituted 4-anilinoquinazolines as potent, selective and orally active inhibitors of erbB2 receptor tyrosine kinase [J].

Ballard, P ;

Bradbury, RH ;

Hennequin, LFA ;

Hickinson, DM ;

Johnson, PD ;

Kettle, JG ;

Klinowska, T ;

Morgentin, R ;

Ogilvie, DJ ;

Olivier, A .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (19) :4226-4229

[3] Critical update and emerging trends in epidermal growth factor receptor targeting in cancer [J].

Baselga, J ;

Arteaga, CL .

JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (11) :2445-2459

[4] Combined anti-EGF receptor and anti-HER2 receptor therapy in breast cancer: a promising strategy ready for clinical testing [J].

Baselga, J .

ANNALS OF ONCOLOGY, 2002, 13 (01) :8-9

[5] Development of a hypusine reagent for peptide synthesis [J].

Bergeron, RJ ;

Ludin, C ;

Muller, R ;

Smith, RE ;

Phanstiel, O .

JOURNAL OF ORGANIC CHEMISTRY, 1997, 62 (10) :3285-3290

[6] Comparison of the biochemical and kinetic properties of the type 1 receptor tyrosine kinase intracellular domains - Demonstration of differential sensitivity to kinase inhibitors [J].

Brignola, PS ;

Lackey, K ;

Kadwell, SH ;

Hoffman, C ;

Horne, E ;

Carter, HL ;

Stuart, JD ;

Blackburn, K ;

Moyer, MB ;

Alligood, KJ ;

Knight, WB ;

Wood, ER .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (02) :1576-1585

[7]

FLORENCE KY, 2006, PHYS DESK REFERENCE

[8] 2-NITROBENZENESULFONAMIDES AND 4-NITROBENZENESULFONAMIDES - EXCEPTIONALLY VERSATILE MEANS FOR PREPARATION OF SECONDARY-AMINES AND PROTECTION OF AMINES [J].

FUKUYAMA, T ;

JOW, CK ;

CHEUNG, M .

TETRAHEDRON LETTERS, 1995, 36 (36) :6373-6374

[9]

Griffith W.P., 1990, Aldrichim Acta, V23, P13

[10] Targeting EGFR and HER-2 receptor tyrosine kinases for cancer drug discovery and development [J].

Kamath, Shantaram ;

Buolamwini, John K. .

MEDICINAL RESEARCH REVIEWS, 2006, 26 (05) :569-594