The discovery and optimisation of pyrido[2,3-d]pyrimidine-2,4-diamines as potent and selective inhibitors of mTOR kinase

被引：76

作者：

Malagu, Karine ^{[2
]}

Duggan, Heather ^{[2
]}

Menear, Keith ^{[2
]}

Hummersone, Marc ^{[2
]}

Gomez, Sylvie ^{[2
]}

Bailey, Christine ^{[2
]}

Edwards, Peter ^{[2
]}

Drzewiecki, Jan ^{[2
]}

Leroux, Frederic ^{[2
]}

Quesada, Mar Jimenez ^{[2
]}

Hermann, Gesine ^{[2
]}

Maine, Stephanie ^{[2
]}

Molyneaux, Carrie-Anne ^{[2
]}

Le Gall, Armelle ^{[2
]}

Pullen, James ^{[2
]}

Hickson, Ian ^{[2
]}

Smith, Lisa ^{[2
]}

Maguire, Sharon ^{[2
]}

Martin, Niall ^{[2
]}

Smith, Graeme ^{[1
,2
]}

Pass, Martin ^{[1
]}

机构：

[1] AstraZeneca, Macclesfield SK10 4TG, Cheshire, England

[2] KuDOS Pharmaceut Ltd, Cambridge 3B4 0WG, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 20期

关键词：

Antitumour; mTOR; Serine/threonine kinase; SIGNALING FUNCTIONS; MAMMALIAN PROTEIN; RAPAMYCIN; TARGET; WORTMANNIN; LY294002; PATHWAY; S6K1;

D O I：

10.1016/j.bmcl.2009.08.038

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We describe a novel series of potent inhibitors of the kinase activity of mTOR. The compounds display good selectivity relative to other PI3K-related kinase family members and, in cellular assays, inhibit both mTORC1 and mTORC2 complexes and exhibit good antiproliferative activity. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：5950 / 5953

页数：4

共 50 条

[1] 7-Phenyl-pyrido[2,3-d]pyrimidine-2,4-diamines: Novel and highly selective protein tyrosine phosphatase 1B inhibitors
Cheung, Adrian Wai-Hing
Banner, Bruce
Bose, Jolly
Kim, Kyungjin
Li, Shiming
Marcopulos, Nicholas
Orzechowski, Lucja
Sergi, Joseph A.
Thakkar, Kshitij C.
Wang, Bing-Bing
Yun, Weiya
Zwingelstein, Catherine
Berthel, Steven
Olivier, Andree R.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (24) : 7518 - 7522
[2] IMPROVED SYNTHESIS OF METHYL-SUBSTITUTED AND PHENYL-SUBSTITUTED PYRIDO-[2,3-D]PYRIMIDINE-2,4-DIAMINES
TROSCHUTZ, R
DENNSTEDT, T
ARCHIV DER PHARMAZIE, 1994, 327 (04) : 221 - 224
[3] SYNTHESES OF 5-ARYL-5,8-DIHYDROPYRIDO[2,3-D]PYRIMIDINE-2,4-DIAMINES
TROSCHUTZ, R
ARCHIV DER PHARMAZIE, 1984, 317 (08) : 709 - 713
[4] REGIOSELECTIVE SYNTHESIS OF PYRROLO[2,3-D]-PYRIMIDINE-2,4-DIONES AND "PYRIDO[2,3-D]-PYRIMIDINE-2,4-DIONES
TAMURA, Y
SAKAGUCHI, T
KAWASAKI, T
KITA, Y
HETEROCYCLES, 1975, 3 (02) : 183 - 186
[5] N4-Aryl-6-substitutedphenylmethyl-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines as receptor tyrosine kinase inhibitors
Gangjee, Aleem
Kurup, Sonali
Ihnat, Michael A.
Thorpe, Jessica E.
Disch, Bryan
BIOORGANIC & MEDICINAL CHEMISTRY, 2012, 20 (02) : 910 - 914
[6] SYNTHESIS OF PYRIDO[2,3-D]PYRIMIDINE-2,4-DIONES
WAWZONEK, S
JOURNAL OF ORGANIC CHEMISTRY, 1976, 41 (19): : 3149 - 3151
[7] Syntheses and evaluation of pyrido[2,3-d]pyrimidine-2,4-diones as PDE 4 inhibitors
Nam, G
Yoon, CM
Kim, E
Rhee, CK
Kim, JH
Shin, JH
Kim, SH
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (05) : 611 - 614
[8] MEDI 373-N4-(3-bromophenyl)-7-(substitutedbenzyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines as novel potent multiple receptor tyrosine kinase inhibitors
Gangjee, Aleem
Zaware, Nilesh
Yang, Jie
Ihnat, Michael A.
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2008, 236
[9] Synthesis and Herbicidal Activity of Pyrido[2,3-d]pyrimidine-2,4-dione-Benzoxazinone Hybrids as Protoporphyrinogen Oxidase Inhibitors
Wang, Da-Wei
Li, Qian
Wen, Kai
Ismail, Ismail
Liu, Dan-Dan
Niu, Cong-Wei
Wen, Xin
Yang, Guang-Fu
Xi, Zhen
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2017, 65 (26) : 5278 - 5286
[10] Synthesis and biological evaluation of pyrido[2,3-d]pyrimidine-2,4-dione derivatives as eEF-2K inhibitors
Edupuganti, Ramakrishna
Wang, Qiantao
Tavares, Clint D. J.
Chitjian, Catrina A.
Bachman, James L.
Ren, Pengyu
Anslyn, Eric V.
Dalby, Kevin N.
BIOORGANIC & MEDICINAL CHEMISTRY, 2014, 22 (17) : 4910 - 4916

← 1 2 3 4 5 →