Des-A-ring benzothiadiazines: inhibitors of HCV genotype 1 NS5B RNA-dependent RNA polymerase |
| |
Authors: | Donner Pamela L Xie Qinghua Pratt John K Maring Clarence J Kati Warren Jiang Wen Liu Yaya Koev Gennadiy Masse Sherie Montgomery Debra Molla Akhter Kempf Dale J |
| |
Affiliation: | Antiviral Research, Global Pharmaceutical Research, and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. Pamela.l.donner@abbott.com |
| |
Abstract: | In our program to discover non-nucleoside, small molecule inhibitors of genotype 1 HCV polymerase, we investigated a series of promising analogs based on a benzothiadiazine screening hit that contains an ABCD ring system. After demonstrating that a methylsulfonylamino D-ring substituent increased the enzyme potency into the low nanomolar range, we explored a minimum core required for activity by truncating to a three-ring system. Described herein are the syntheses and structure-activity relationship of a set of inhibitors lacking the A-ring of an ABCD ring system. We observed that small aromatic rings and alkenyl groups appended to the 5-position of the B-ring were optimal, resulting in inhibitors with low nanomolar potencies. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|