Discovery of Thiophene[3,2-d]pyrimidine Derivatives as Potent HIV-1 NNRTIs Targeting the Tolerant Region I of NNIBP was written by Kang, Dongwei;Ding, Xiao;Wu, Gaochan;Huo, Zhipeng;Zhou, Zhongxia;Zhao, Tong;Feng, Da;Wang, Zhao;Tian, Ye;Daelemans, Dirk;De Clercq, Erik;Pannecouque, Christophe;Zhan, Peng;Liu, Xinyong. And the article was included in ACS Medicinal Chemistry Letters in 2017.Application of 777-44-6 This article mentions the following:
The authors’ previous studies led the authors to conclude that thiophene[3,2-d]pyrimidine is a promising scaffold for diarylpyrimidine (DAPY)-type anti-HIV agents with potent activity against resistance-associated human immunodeficiency virus (HIV) variants. In the present study, the authors designed and synthesized a series of thiophenepyrimidine derivatives with various substituents in the right wing region of the structure with the aim of developing new interactions with the tolerant region I of the binding pocket of the HIV-1 non-nucleoside reverse transcriptase (NNRTI), and the authors evaluated their activity against a panel of mutant HIV-1 strains. All the derivatives exhibited moderate to excellent potency against wild-type (WT) HIV-1 in MT-4 cells. Among them, sulfonamide compounds 9b (N-(4-((4-(4-cyano-2,6-dimethylphenoxy)thieno[3,2-d]pyrimidin-2-yl)amino)cyclohexyl)-4-fluorobenzenesulfonamide) and 9d (4-cyano-N-(4-((4-(4-cyano-2,6-dimethylphenoxy)thieno[3,2-d]pyrimidin-2-yl)amino)cyclohexyl)benzenesulfonamide) were single-figure-nanomolar inhibitors with EC50 values of 9.2 and 7.1 nM, resp. Indeed, 9a (N-(4-(N-(4-((4-(4-cyano-2,6-dimethylphenoxy)thieno[3,2-d]pyrimidin-2-yl)amino)cyclohexyl)sulfamoyl)phenyl)acetamide) and 9d were effective against the whole viral panel except RES056. Notably, both compounds showed potent antiviral activity against K103N (EC50 = 0.032 and 0.070 μM) and E138K (EC50 = 0.035 and 0.045 μM, resp.). Furthermore, 9a and 9d exhibited high affinity for WT HIV-1 RT (IC50 = 1.041 and 1.138 μM, resp.) and acted as classical NNRT inhibitors (NNRTIs). These results are expected to be helpful in the design of thiophenepyrimidine-based NNRTIs with more potent activity against HIV strains with RT mutations. In the experiment, the researchers used many compounds, for example, 3-(Trifluoromethyl)benzene-1-sulfonyl chloride (cas: 777-44-6Application of 777-44-6).
3-(Trifluoromethyl)benzene-1-sulfonyl chloride (cas: 777-44-6) belongs to organic chlorides. Chlorination modifies the physical properties of hydrocarbons in several ways. These compounds are typically denser than water due to the higher atomic weight of chlorine versus hydrogen. Aliphatic organochlorides are often alkylating agents as chlorine can act as a leaving group, which can result in cellular damage.Application of 777-44-6
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics