[EN] BICYCLIC HETEROARYL SUBSTITUTED COMPOUNDS<br/>[FR] COMPOSÉS BICYCLIQUES SUBSTITUÉS PAR HÉTÉROARYLE
申请人:BRISTOL MYERS SQUIBB CO
公开号:WO2018013774A1
公开(公告)日:2018-01-18
Disclosed are compounds of Formula (I) to (VIII): (I) (II) (III) (IV) (V) (VI) (VII) (VIII); or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or prodrug thereof, wherein R3 is a bicyclic heteroaryl group substituted with zero to 3 R3a; and R1, R2, R3a, R4, and n are defined herein. Also disclosed are methods of using such compounds as PAR4 inhibitors, and pharmaceutical compositions comprising such compounds. These compounds are useful in inhibiting or preventing platelet aggregation, and are useful for the treatment of a thromboembolic disorder or the primary prophylaxis of a thromboembolic disorder.
公开了公式(I)至(VIII)的化合物:(I) (II) (III) (IV) (V) (VI) (VII) (VIII);或其立体异构体、互变异构体、药物可接受的盐、溶剂化物或前药,其中R3是与0至3个R3a取代的双环杂芳基团;且R1、R2、R3a、R4和n在此定义。还公开了使用这些化合物作为PAR4抑制剂的方法,以及包含这些化合物的药物组合物。这些化合物用于抑制或预防血小板聚集,用于治疗血栓栓塞障碍或作为血栓栓塞障碍的初级预防。
(Chlorosulfonyl)benzenesulfonyl Fluorides—Versatile Building Blocks for Combinatorial Chemistry: Design, Synthesis and Evaluation of a Covalent Inhibitor Library
作者:Kateryna A. Tolmachova、Yurii S. Moroz、Angelika Konovets、Maxim O. Platonov、Oleksandr V. Vasylchenko、Petro Borysko、Sergey Zozulya、Anastasia Gryniukova、Andrey V. Bogolubsky、Sergey Pipko、Pavel K. Mykhailiuk、Volodymyr S. Brovarets、Oleksandr O. Grygorenko
DOI:10.1021/acscombsci.8b00130
日期:2018.11.12
Multigram synthesis of (chlorosulfonyl)benzenesulfonyl fluorides is described. Selective modification of these building blocks at the sulfonyl chloride function under parallelsynthesis conditions is achieved. It is shown that the reaction scope includes the use of (hetero)aromatic and electron-poor aliphatic amines (e.g., amino nitriles). Utility of the method is demonstrated by preparation of the
Parallel Optimization of Potency and Pharmacokinetics Leading to the Discovery of a Pyrrole Carboxamide ERK5 Kinase Domain Inhibitor
作者:Duncan C. Miller、Tristan Reuillon、Lauren Molyneux、Timothy Blackburn、Simon J. Cook、Noel Edwards、Jane A. Endicott、Bernard T. Golding、Roger J. Griffin、Ian Hardcastle、Suzannah J. Harnor、Amy Heptinstall、Pamela Lochhead、Mathew P. Martin、Nick C. Martin、Stephanie Myers、David R. Newell、Richard A. Noble、Nicole Phillips、Laurent Rigoreau、Huw Thomas、Julie A. Tucker、Lan-Zhen Wang、Michael J. Waring、Ai-Ching Wong、Stephen R. Wedge、Martin E. M. Noble、Celine Cano
DOI:10.1021/acs.jmedchem.1c01756
日期:2022.5.12
The nonclassical extracellular signal-related kinase 5 (ERK5) mitogen-activated protein kinase pathway has been implicated in increased cellular proliferation, migration, survival, and angiogenesis; hence, ERK5 inhibition may be an attractive approach for cancer treatment. However, the development of selective ERK5 inhibitors has been challenging. Previously, we described the development of a pyrrole
The invention relates to FSH receptor antagonist according to general formula (I) or a pharmaceutically acceptable salt thereof and to a pharmaceutical composition containing the same. The compounds can be used for the treatment and prevention of endometriosis, for the treatment and prevention of pre-menopausal and peri-menopausal hormone-dependent breast cancer, for contraception, and for the treatment of uterine fibroids and other menstrual-related disorders.