Discovery and optimization of pyrazole amides as antagonists of CCR1.

Basic Information

ID: ALA4371017

Journal: Bioorg Med Chem Lett

Title: Discovery and optimization of pyrazole amides as antagonists of CCR1.

Authors: Harcken C, Sarko C, Mao C, Lord J, Raudenbush B, Razavi H, Liu P, Swinamer A, Disalvo D, Lee T, Lin S, Kukulka A, Grbic H, Patel M, Patel M, Fletcher K, Joseph D, White D, Amodeo L, Berg K, Brown M, Thomson DS.

Abstract: A HTS screen for CCR1 antagonists afforded a novel sub-micromolar hit 5 containing a pyrazole core. In this report the design, optimization, and SAR of novel CCR1 antagonists based on a pyrazole core motif is presented. Optimization led to the advanced candidate compounds (S)-16q and (S)-16r with 250-fold improved CCR1 potency, excellent off-target selectivity and attractive drug-like properties.

CiteXplore: 30455146

DOI: 10.1016/j.bmcl.2018.11.015

Patent ID: ┄