Carbocyclic[g]indole inhibitors of human nonpancreatic s-PLA2

J Scott Sawyer; Douglas W Beight; Edward C R Smith; David W Snyder; Marcia K Chastain; Richard L Tielking; Lawrence W Hartley; Donald G Carlson

doi:10.1021/jm0401309

Carbocyclic[g]indole inhibitors of human nonpancreatic s-PLA2

J Med Chem. 2005 Feb 10;48(3):893-6. doi: 10.1021/jm0401309.

Authors

J Scott Sawyer¹, Douglas W Beight, Edward C R Smith, David W Snyder, Marcia K Chastain, Richard L Tielking, Lawrence W Hartley, Donald G Carlson

Affiliation

¹ Discovery Chemistry Research and Technology, The Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. [email protected]

PMID: 15689175
DOI: 10.1021/jm0401309

Abstract

A vinyl azide cyclization method was used to synthesize three different carbocyclic[g]indole scaffolds as inhibitors of human nonpancreatic secretory phospholipase A2. Each scaffold demonstrated potent enzyme activity in a chromogenic assay system, with select examples also demonstrating potent activity in a secondary DOC/PC assay. Compound 11, representative of the cyclopent[g]indole series, gave an IC50 of 10 nM for the inhibition of hnps-PLA2 in the chromogenic assay.

MeSH terms

Acetates / chemical synthesis*
Acetates / chemistry
Cyclopentanes / chemical synthesis*
Cyclopentanes / chemistry
Humans
Indoles / chemical synthesis*
Indoles / chemistry
Phospholipases A / antagonists & inhibitors*
Phospholipases A / chemistry
Phospholipases A2
Structure-Activity Relationship

Substances

2-((3-(2-amino-1,2-dioxoethyl)-2-methyl-1-benzyl-1,6,7,8-tetrahydrocyclopent(g)indol-4-yl)oxy)acetic acid
Acetates
Cyclopentanes
Indoles
Phospholipases A
Phospholipases A2