Discovery of 3-Substituted 1H-Indole-2-carboxylic Acid Derivatives as a Novel Class of CysLT1 Selective Antagonists

Huayan Chen; Hui Yang; Zhilong Wang; Xin Xie; Fajun Nan

doi:10.1021/acsmedchemlett.5b00482

Discovery of 3-Substituted 1H-Indole-2-carboxylic Acid Derivatives as a Novel Class of CysLT1 Selective Antagonists

ACS Med Chem Lett. 2016 Jan 22;7(3):335-9. doi: 10.1021/acsmedchemlett.5b00482. eCollection 2016 Mar 10.

Authors

Huayan Chen¹, Hui Yang², Zhilong Wang², Xin Xie², Fajun Nan¹

Affiliations

¹ State Key Laboratory of Drug Research, the National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
² CAS Key Laboratory of Receptor Research, the National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.

Abstract

The indole derivative, 3-((E)-3-((3-((E)-2-(7-chloroquinolin-2yl)vinyl)phenyl)amino)-3-oxoprop-1-en-1-yl)-7-methoxy-1H-indole-2-carboxylic acid (17k), was identified as a novel and highly potent and selective CysLT1 antagonist with IC50 values of 0.0059 ± 0.0011 and 15 ± 4 μM for CysLT1 and CysLT2, respectively.

Keywords: CysLT1; CysLT2; Cysteinyl leukotrienes; asthma; selective antagonists.