Discovery of novel Bruton's tyrosine kinase (BTK) inhibitors bearing a pyrrolo[2,3-d]pyrimidine scaffold

Xinge Zhao; Wei Huang; Yazhou Wang; Minhang Xin; Qiu Jin; Jianfeng Cai; Feng Tang; Yong Zhao; Hua Xiang

doi:10.1016/j.bmc.2014.10.043

Discovery of novel Bruton's tyrosine kinase (BTK) inhibitors bearing a pyrrolo[2,3-d]pyrimidine scaffold

Xinge Zhao
, Wei Huang
, Yazhou Wang
, Minhang Xin
, Qiu Jin
, Jianfeng Cai
, Feng Tang
, Yong Zhao
, Hua Xiang

医学部

科研成果: 期刊稿件 › 文章 › 同行评审

30 引用（Scopus）

摘要

A series of novel reversible BTK inhibitors was designed based on the structure of the recently reported preclinical drug RN486. Knowledge of the binding mode of RN486 led to the design of new inhibitors that utilized pyrrolo[2,3-d]pyrimidine to conformationally restrain key pharmacophoric groups within the molecule. Comprehensive SAR was disclosed and the most promising compound 4x displayed superior activity both in BTK enzyme (IC₅₀ = 4.8 nM) and cellular inhibition (IC₅₀ = 17 nM) assays to that of RN486.

源语言	英语
页（从-至）	891-901
页数	11
期刊	Bioorganic and Medicinal Chemistry
卷	23
期	4
DOI	https://doi.org/10.1016/j.bmc.2014.10.043
出版状态	已出版 - 15 2月 2015

访问文件

10.1016/j.bmc.2014.10.043

其它文件与链接

链接到 Scopus 的出版物

引用此

@article{59edbbe7cb5141faa8b64c0f58537cc3,

title = "Discovery of novel Bruton's tyrosine kinase (BTK) inhibitors bearing a pyrrolo[2,3-d]pyrimidine scaffold",

abstract = "A series of novel reversible BTK inhibitors was designed based on the structure of the recently reported preclinical drug RN486. Knowledge of the binding mode of RN486 led to the design of new inhibitors that utilized pyrrolo[2,3-d]pyrimidine to conformationally restrain key pharmacophoric groups within the molecule. Comprehensive SAR was disclosed and the most promising compound 4x displayed superior activity both in BTK enzyme (IC50 = 4.8 nM) and cellular inhibition (IC50 = 17 nM) assays to that of RN486.",

keywords = "BTK inhibitors, Pyrrolo[23-d]pyrimidine, SAR",

author = "Xinge Zhao and Wei Huang and Yazhou Wang and Minhang Xin and Qiu Jin and Jianfeng Cai and Feng Tang and Yong Zhao and Hua Xiang",

year = "2015",

month = feb,

day = "15",

doi = "10.1016/j.bmc.2014.10.043",

language = "英语",

volume = "23",

pages = "891--901",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Ltd",

number = "4",

}

TY - JOUR

T1 - Discovery of novel Bruton's tyrosine kinase (BTK) inhibitors bearing a pyrrolo[2,3-d]pyrimidine scaffold

AU - Zhao, Xinge

AU - Huang, Wei

AU - Wang, Yazhou

AU - Xin, Minhang

AU - Jin, Qiu

AU - Cai, Jianfeng

AU - Tang, Feng

AU - Zhao, Yong

AU - Xiang, Hua

PY - 2015/2/15

Y1 - 2015/2/15

N2 - A series of novel reversible BTK inhibitors was designed based on the structure of the recently reported preclinical drug RN486. Knowledge of the binding mode of RN486 led to the design of new inhibitors that utilized pyrrolo[2,3-d]pyrimidine to conformationally restrain key pharmacophoric groups within the molecule. Comprehensive SAR was disclosed and the most promising compound 4x displayed superior activity both in BTK enzyme (IC50 = 4.8 nM) and cellular inhibition (IC50 = 17 nM) assays to that of RN486.

AB - A series of novel reversible BTK inhibitors was designed based on the structure of the recently reported preclinical drug RN486. Knowledge of the binding mode of RN486 led to the design of new inhibitors that utilized pyrrolo[2,3-d]pyrimidine to conformationally restrain key pharmacophoric groups within the molecule. Comprehensive SAR was disclosed and the most promising compound 4x displayed superior activity both in BTK enzyme (IC50 = 4.8 nM) and cellular inhibition (IC50 = 17 nM) assays to that of RN486.

KW - BTK inhibitors

KW - Pyrrolo[23-d]pyrimidine

KW - SAR

UR - https://www.scopus.com/pages/publications/84922331712

U2 - 10.1016/j.bmc.2014.10.043

DO - 10.1016/j.bmc.2014.10.043

M3 - 文章

C2 - 25596757

AN - SCOPUS:84922331712

SN - 0968-0896

VL - 23

SP - 891

EP - 901

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 4

ER -

Discovery of novel Bruton's tyrosine kinase (BTK) inhibitors bearing a pyrrolo[2,3-d]pyrimidine scaffold

摘要

访问文件

其它文件与链接

学术指纹

引用此