Synthesis and biological evaluation of novel 7-substituted 3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amines as potent Bruton's tyrosine kinase (BTK) inhibitors

Minhang Xin; Xinge Zhao; Wei Huang; Qiu Jin; Gang Wu; Yazhou Wang; Feng Tang; Hua Xiang

doi:10.1016/j.bmc.2015.08.039

Synthesis and biological evaluation of novel 7-substituted 3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amines as potent Bruton's tyrosine kinase (BTK) inhibitors

Minhang Xin
, Xinge Zhao
, Wei Huang
, Qiu Jin
, Gang Wu
, Yazhou Wang
, Feng Tang
, Hua Xiang

Health Science Center

Jiangsu Simcere Pharmaceutical Co. Ltd
Central China Normal University
China Pharmaceutical University

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

12 Scopus citations

Abstract

A series of novel 7-substituted 3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amines as potent BTK inhibitors were designed, synthesized and evaluated. These thieno[3,2-c]pyridin-4-amine derivatives displayed variant inhibitory activities against BTK in vitro. Among these, 7-pyrazol-4-yl substituted 3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amine subseries showed high BTK inhibition and several compounds displayed superior BTK inhibitory activity. Comprehensive SAR was disclosed and compound 13b showed excellent potency (IC₅₀ = 11.8 nM), outstanding hydrophilicity (A log P = 3.53), and relatively good kinase selectivity, being a promising lead for further evaluation.

Original language	English
Article number	12543
Pages (from-to)	6250-6257
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	23
Issue number	19
DOIs	https://doi.org/10.1016/j.bmc.2015.08.039
State	Published - 1 Oct 2015

Keywords

BTK inhibitors
Inhibitory activity
Kinase selectivity
Thieno[3,2-c]pyrid-4-amine

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10.1016/j.bmc.2015.08.039

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title = "Synthesis and biological evaluation of novel 7-substituted 3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amines as potent Bruton's tyrosine kinase (BTK) inhibitors",

abstract = "A series of novel 7-substituted 3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amines as potent BTK inhibitors were designed, synthesized and evaluated. These thieno[3,2-c]pyridin-4-amine derivatives displayed variant inhibitory activities against BTK in vitro. Among these, 7-pyrazol-4-yl substituted 3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amine subseries showed high BTK inhibition and several compounds displayed superior BTK inhibitory activity. Comprehensive SAR was disclosed and compound 13b showed excellent potency (IC50 = 11.8 nM), outstanding hydrophilicity (A log P = 3.53), and relatively good kinase selectivity, being a promising lead for further evaluation.",

keywords = "BTK inhibitors, Inhibitory activity, Kinase selectivity, Thieno[3,2-c]pyrid-4-amine",

author = "Minhang Xin and Xinge Zhao and Wei Huang and Qiu Jin and Gang Wu and Yazhou Wang and Feng Tang and Hua Xiang",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Ltd.",

year = "2015",

month = oct,

day = "1",

doi = "10.1016/j.bmc.2015.08.039",

language = "英语",

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T1 - Synthesis and biological evaluation of novel 7-substituted 3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amines as potent Bruton's tyrosine kinase (BTK) inhibitors

AU - Xin, Minhang

AU - Zhao, Xinge

AU - Huang, Wei

AU - Jin, Qiu

AU - Wu, Gang

AU - Wang, Yazhou

AU - Tang, Feng

AU - Xiang, Hua

PY - 2015/10/1

Y1 - 2015/10/1

N2 - A series of novel 7-substituted 3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amines as potent BTK inhibitors were designed, synthesized and evaluated. These thieno[3,2-c]pyridin-4-amine derivatives displayed variant inhibitory activities against BTK in vitro. Among these, 7-pyrazol-4-yl substituted 3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amine subseries showed high BTK inhibition and several compounds displayed superior BTK inhibitory activity. Comprehensive SAR was disclosed and compound 13b showed excellent potency (IC50 = 11.8 nM), outstanding hydrophilicity (A log P = 3.53), and relatively good kinase selectivity, being a promising lead for further evaluation.

AB - A series of novel 7-substituted 3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amines as potent BTK inhibitors were designed, synthesized and evaluated. These thieno[3,2-c]pyridin-4-amine derivatives displayed variant inhibitory activities against BTK in vitro. Among these, 7-pyrazol-4-yl substituted 3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amine subseries showed high BTK inhibition and several compounds displayed superior BTK inhibitory activity. Comprehensive SAR was disclosed and compound 13b showed excellent potency (IC50 = 11.8 nM), outstanding hydrophilicity (A log P = 3.53), and relatively good kinase selectivity, being a promising lead for further evaluation.

KW - BTK inhibitors

KW - Inhibitory activity

KW - Kinase selectivity

KW - Thieno[3,2-c]pyrid-4-amine

UR - https://www.scopus.com/pages/publications/84941939936

U2 - 10.1016/j.bmc.2015.08.039

DO - 10.1016/j.bmc.2015.08.039

M3 - 文章

C2 - 26344595

AN - SCOPUS:84941939936

SN - 0968-0896

VL - 23

SP - 6250

EP - 6257

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 19

M1 - 12543

ER -

Synthesis and biological evaluation of novel 7-substituted 3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amines as potent Bruton's tyrosine kinase (BTK) inhibitors

Abstract

Keywords

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