Identification of 4-(2-furanyl)pyrimidin-2-amines as Janus kinase 2 inhibitors

Yazhou Wang; Wei Huang; Minhang Xin; Pan Chen; Li Gui; Xinge Zhao; Feng Tang; Jia Wang; Fei Liu

doi:10.1016/j.bmc.2016.10.011

Identification of 4-(2-furanyl)pyrimidin-2-amines as Janus kinase 2 inhibitors

Yazhou Wang
, Wei Huang
, Minhang Xin
, Pan Chen
, Li Gui
, Xinge Zhao
, Feng Tang
, Jia Wang
, Fei Liu

Health Science Center

Central China Normal University
Jiangsu Simcere Pharmaceutical Co. Ltd

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

Janus kinases inhibitor is considered to have therapeutic potential for the treatment of oncology and immune-inflammatory diseases. Two series of 4-(2-benzofuranyl)pyrimidin-2-amine and 4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl)pyrimidin-2-amine derivatives have been designed and synthesized. Primary SAR studies resulted in the discovery of a novel class of 4,5,6,7-tetrahydrofuro[3,2-c]pyridine based JAK2 inhibitors with higher potency (IC₅₀of 0.7 nM) and selectivity (>30 fold) to JAK3 kinase than tofacitinib.

Original language	English
Pages (from-to)	75-83
Number of pages	9
Journal	Bioorganic and Medicinal Chemistry
Volume	25
Issue number	1
DOIs	https://doi.org/10.1016/j.bmc.2016.10.011
State	Published - 2017

Keywords

4,5,6,7-Tetrahydro-furo[3,2-c]pyridine
4-(2-Furanyl)pyrimidin-2-amine
JAK2 inhibitor
Kinase selectivity

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10.1016/j.bmc.2016.10.011

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title = "Identification of 4-(2-furanyl)pyrimidin-2-amines as Janus kinase 2 inhibitors",

abstract = "Janus kinases inhibitor is considered to have therapeutic potential for the treatment of oncology and immune-inflammatory diseases. Two series of 4-(2-benzofuranyl)pyrimidin-2-amine and 4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl)pyrimidin-2-amine derivatives have been designed and synthesized. Primary SAR studies resulted in the discovery of a novel class of 4,5,6,7-tetrahydrofuro[3,2-c]pyridine based JAK2 inhibitors with higher potency (IC50of 0.7 nM) and selectivity (>30 fold) to JAK3 kinase than tofacitinib.",

keywords = "4,5,6,7-Tetrahydro-furo[3,2-c]pyridine, 4-(2-Furanyl)pyrimidin-2-amine, JAK2 inhibitor, Kinase selectivity",

author = "Yazhou Wang and Wei Huang and Minhang Xin and Pan Chen and Li Gui and Xinge Zhao and Feng Tang and Jia Wang and Fei Liu",

note = "Publisher Copyright: {\textcopyright} 2016 Elsevier Ltd",

year = "2017",

doi = "10.1016/j.bmc.2016.10.011",

language = "英语",

volume = "25",

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journal = "Bioorganic and Medicinal Chemistry",

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TY - JOUR

T1 - Identification of 4-(2-furanyl)pyrimidin-2-amines as Janus kinase 2 inhibitors

AU - Wang, Yazhou

AU - Huang, Wei

AU - Xin, Minhang

AU - Chen, Pan

AU - Gui, Li

AU - Zhao, Xinge

AU - Tang, Feng

AU - Wang, Jia

AU - Liu, Fei

PY - 2017

Y1 - 2017

N2 - Janus kinases inhibitor is considered to have therapeutic potential for the treatment of oncology and immune-inflammatory diseases. Two series of 4-(2-benzofuranyl)pyrimidin-2-amine and 4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl)pyrimidin-2-amine derivatives have been designed and synthesized. Primary SAR studies resulted in the discovery of a novel class of 4,5,6,7-tetrahydrofuro[3,2-c]pyridine based JAK2 inhibitors with higher potency (IC50of 0.7 nM) and selectivity (>30 fold) to JAK3 kinase than tofacitinib.

AB - Janus kinases inhibitor is considered to have therapeutic potential for the treatment of oncology and immune-inflammatory diseases. Two series of 4-(2-benzofuranyl)pyrimidin-2-amine and 4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl)pyrimidin-2-amine derivatives have been designed and synthesized. Primary SAR studies resulted in the discovery of a novel class of 4,5,6,7-tetrahydrofuro[3,2-c]pyridine based JAK2 inhibitors with higher potency (IC50of 0.7 nM) and selectivity (>30 fold) to JAK3 kinase than tofacitinib.

KW - 4,5,6,7-Tetrahydro-furo[3,2-c]pyridine

KW - 4-(2-Furanyl)pyrimidin-2-amine

KW - JAK2 inhibitor

KW - Kinase selectivity

UR - https://www.scopus.com/pages/publications/85006285073

U2 - 10.1016/j.bmc.2016.10.011

DO - 10.1016/j.bmc.2016.10.011

M3 - 文章

C2 - 27771180

AN - SCOPUS:85006285073

SN - 0968-0896

VL - 25

SP - 75

EP - 83

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 1

ER -

Identification of 4-(2-furanyl)pyrimidin-2-amines as Janus kinase 2 inhibitors

Abstract

Keywords

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