Structure-based design of imidazo[1,2-a] pyrazine derivatives as selective inhibitors of Aurora-A kinase in cells

被引：28

作者：

Bouloc, Nathalie ^{[1
]}

Large, Jonathan M. ^{[1
]}

Kosmopoulou, Magda ^{[2
]}

Sun, Chongbo ^{[1
]}

Faisal, Amir ^{[1
]}

Matteucci, Mizio ^{[1
]}

Reynisson, Johannes ^{[1
]}

Brown, Nathan ^{[1
]}

Atrash, Butrus ^{[1
]}

Blagg, Julian ^{[1
]}

McDonald, Edward ^{[1
]}

Linardopoulos, Spiros ^{[1
,3
]}

Bayliss, Richard ^{[2
]}

Bavetsias, Vassilios ^{[1
]}

机构：

[1] Inst Canc Res, Canc Res UK Canc Therapeut Unit, Sutton SM2 5NG, Surrey, England

[2] Inst Canc Res, Chester Beatty Labs, Sect Struct Biol, London SW3 6JB, England

[3] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England

来源：

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

关键词：

Aurora-A; Selectivity; Kinases; SMALL-MOLECULE INHIBITOR; CRYSTAL-STRUCTURE; DISCOVERY; POTENT; IDENTIFICATION; MLN8054; OVEREXPRESSION; EXPRESSION; CARCINOMA;

D O I：

10.1016/j.bmcl.2010.08.091

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Co-crystallisation of the imidazo[ 1,2-a] pyrazine derivative 15 (3-chloro-N-(4-morpholinophenyl)-6-( pyridin-3-yl)imidazo[1,2-a]pyrazin-8-amine) with Aurora-A provided an insight into the interactions of this class of compound with Aurora kinases. This led to the design and synthesis of potent Aurora-A inhibitors demonstrating up to 70-fold selectivity in cell-based Aurora kinase pharmacodynamic biomarker assays. (c) 2010 Elsevier Ltd. All rights reserved.

引用

页码：5988 / 5993

页数：6

共 37 条

[1]

[Anonymous], 2008, Comprehensive Heterocyclic Chemistry III

[2] High expression of Aurora-B/Aurora and Ipl1-like midbody-associated protein (AIM-1) in astrocytomas [J].

Araki, K ;

Nozaki, K ;

Ueba, T ;

Tatsuka, M ;

Hashimoto, N .

JOURNAL OF NEURO-ONCOLOGY, 2004, 67 (1-2) :53-64

[3]

BAVETSIAS V, 2007, Patent No. 2007072017

[4] Imidazo[4,5-b]pyridine Derivatives As Inhibitors of Aurora Kinases: Lead Optimization Studies toward the Identification of an Orally Bioavailable Preclinical Development Candidates [J].

Bavetsias, Vassilios ;

Large, Jonathan M. ;

Sun, Chongbo ;

Bouloc, Nathalie ;

Kosmopoulou, Magda ;

Matteucci, Mizio ;

Wilsher, Nicola E. ;

Martins, Vanessa ;

Reynisson, Johannes ;

Atrash, Butrus ;

Faisal, Amir ;

Urban, Frederique ;

Valenti, Melanie ;

Brandon, Alexis de Haven ;

Box, Gary ;

Raynaud, Florence I. ;

Workman, Paul ;

Eccles, Suzanne A. ;

Bayliss, Richard ;

Blagg, Julian ;

Linardopoulos, Spiros ;

McDonald, Edward .

JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (14) :5213-5228

[5] A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers [J].

Bischoff, JR ;

Anderson, L ;

Zhu, YF ;

Mossie, K ;

Ng, L ;

Souza, B ;

Schryver, B ;

Flanagan, P ;

Clairvoyant, F ;

Ginther, C ;

Chan, CSM ;

Novotny, M ;

Slamon, DJ ;

Plowman, GD .

EMBO JOURNAL, 1998, 17 (11) :3052-3065

[6] SYNTHESIS AND ANTIBRONCHOSPASTIC ACTIVITY OF 8-ALKOXY AND 8-(ALKYLAMINO)IMIDAZO[1,2-A]PYRAZINES [J].

BONNET, PA ;

MICHEL, A ;

LAURENT, F ;

SABLAYROLLES, C ;

RECHENCQ, E ;

MANI, JC ;

BOUCARD, M ;

CHAPAT, JP .

JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (18) :3353-3358

[7] PdCl2-catalyzed reduction of organic halides by triethylsilane [J].

Boukherroub, R ;

Chatgilialoglu, C ;

Manuel, G .

ORGANOMETALLICS, 1996, 15 (05) :1508-1510

[8] HETEROCYCLES .167. TELE-SUBSTITUTION AND OTHER TRANSFORMATIONS OF IMIDAZO[1,2-A]-AND S-TRIAZOLO[4,3-A]PYRAZINES [J].

BRADAC, J ;

FUREK, Z ;

JANEZIC, D ;

MOLAN, S ;

SMERKOLJ, I ;

STANOVNIK, B ;

TISLER, M ;

VERCEK, B .

JOURNAL OF ORGANIC CHEMISTRY, 1977, 42 (26) :4197-4201

[9] The cellular geography of aurora kinases [J].

Carmena, M ;

Earnshaw, WC .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2003, 4 (11) :842-854

[10] PHA-739358, a potent inhibitor of Aurora kinases with a selective target inhibition profile relevant to cancer [J].

Carpinelli, Patrizia ;

Ceruti, Roberta ;

Giorgini, Maria Laura ;

Cappella, Paolo ;

Gianellini, Laura ;

Croci, Valter ;

Degrassi, Anna ;

Texido, Gernma ;

Rocchetti, Maurizio ;

Vianello, Paola ;

Rusconi, Luisa ;

Storici, Paola ;

Zugnoni, Paola ;

Arrigoni, Claudio ;

Soncini, Chiara ;

Alli, Cristina ;

Patton, Veronica ;

Marsiglio, Aurelio ;

Ballinari, Dario ;

Pesenti, Enrico ;

Fancelli, Daniele ;

Moll, Jurgen .

MOLECULAR CANCER THERAPEUTICS, 2007, 6 (12) :3158-3168

← 1 2 3 4 →