Design and Optimization of an Acyclic Amine Series of TRPV4 Antagonists by Electronic Modulation of Hydrogen Bond Interactions was written by Patterson, Jaclyn R.;Terrell, Lamont R.;Donatelli, Carla A.;Holt, Dennis A.;Jolivette, Larry J.;Rivero, Ralph A.;Roethke, Theresa J.;Shu, Arthur;Stoy, Patrick;Ye, Guosen;Youngman, Mark;Lawhorn, Brian G.. And the article was included in Journal of Medicinal Chemistry in 2020.Formula: C7H3Cl2F3O2S This article mentions the following:
Investigation of TRPV4 as a potential target for the treatment of pulmonary edema associated with heart failure generated a novel series of acyclic amine inhibitors displaying exceptional potency and PK properties. The series arose through a scaffold hopping approach, which relied on use of an internal H-bond to replace a saturated heterocyclic ring. Optimization of the lead through investigation of both aryl regions revealed approaches to increase potency through substituents believed to enhance sep. intramol. and intermol. H-bond interactions. A proposed internal H-bond between the amine and neighboring benzenesulfonamide was stabilized by electronically modulating the benzenesulfonamide. In the aryl ether moiety, substituents para to the nitrile demonstrated an electronic effect on TRPV4 recognition. Finally, the acyclic amines inactivated CYP3A4 and this liability was addressed by modifications that sterically preclude formation of a putative metabolic intermediate complex to deliver advanced TRPV4 antagonists as leads for discovery of novel medicines. In the experiment, the researchers used many compounds, for example, 4-Chloro-2-(trifluoromethyl)benzene-1-sulfonyl chloride (cas: 54090-42-5Formula: C7H3Cl2F3O2S).
4-Chloro-2-(trifluoromethyl)benzene-1-sulfonyl chloride (cas: 54090-42-5) belongs to organic chlorides. An organic chloride is an organic compound containing at least one covalently bonded atom of chlorine. Their wide structural variety and divergent chemical properties lead to a broad range of names and applications.While alkyl bromides and iodides are more reactive, alkyl chlorides tend to be less expensive and more readily available. Alkyl chlorides readily undergo attack by nucleophiles.Formula: C7H3Cl2F3O2S
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics