Serendipitous discovery of 2-((phenylsulfonyl)methyl)-thieno[3,2-d]pyrimidine derivatives as novel HIV-1 replication inhibitors

Junwon Kim; Jeongjin Kwon; Doohyun Lee; Suyeon Jo; Dong-Sik Park; Jihyun Choi; Eunjung Park; Jong Yeon Hwang; Yoonae Ko; Inhee Choi; Moon Kyeong Ju; JiYe Ahn; Junghwan Kim; Sung-Jun Han; Tae-Hee Kim; Jonathan Cechetto; Jiyoun Nam; Sujin Ahn; Peter Sommer; Michel Liuzzi; Jinhwa Lee

doi:10.1016/j.bmcl.2014.10.007

Serendipitous discovery of 2-((phenylsulfonyl)methyl)-thieno[3,2-d]pyrimidine derivatives as novel HIV-1 replication inhibitors

Bioorg Med Chem Lett. 2014 Dec 1;24(23):5473-7. doi: 10.1016/j.bmcl.2014.10.007. Epub 2014 Oct 23.

Authors

Junwon Kim¹, Jeongjin Kwon¹, Doohyun Lee¹, Suyeon Jo¹, Dong-Sik Park¹, Jihyun Choi¹, Eunjung Park¹, Jong Yeon Hwang¹, Yoonae Ko¹, Inhee Choi¹, Moon Kyeong Ju¹, JiYe Ahn¹, Junghwan Kim¹, Sung-Jun Han¹, Tae-Hee Kim¹, Jonathan Cechetto¹, Jiyoun Nam¹, Sujin Ahn¹, Peter Sommer¹, Michel Liuzzi¹, Jinhwa Lee¹

Affiliation

¹ Institut Pasteur Korea, 16, Daewangpangyo-ro 712 beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, Republic of Korea.

PMID: 25455487
DOI: 10.1016/j.bmcl.2014.10.007

Abstract

We identified a novel class of 2-((phenylsulfonyl)methyl)-thieno[3,2-d]pyrimidine compounds as potent HIV-1 replication inhibitors serendipitously during the process of evaluation of triazolothienopyrimidine (TTPM) compounds. Herein, we report synthesis and biological evaluation of 2-((phenylsulfonyl)methyl)-thieno[3,2-d]pyrimidine compounds using a cell-based full replication assay to identify thienopyrimidines 6 and 30, which could be further utilized as viable lead compounds.

Keywords: Cell-based assay; HIV-1; Inhibitor; Structure–activity relationship; Thienopyrimidine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Drug Discovery
HIV-1 / drug effects*
Humans
Pyrimidines / chemistry*
Structure-Activity Relationship

Substances

Pyrimidines
pyrimidine