Discovery, synthesis and biological characterization of a series of N-(1-(1,1-dioxidotetrahydrothiophen-3-yl)-3-methyl-1H-pyrazol-5-yl)acetamide ethers as novel GIRK1/2 potassium channel activators | Zendy

Swagat Sharma | Zendy; Lauren Lesiak | Zendy; Christopher D. Aretz | Zendy; Yu Du | Zendy; Sushil Kumar | Zendy; Nagsen Gautam | Zendy; Yazen Alnouti | Zendy; Nikilesh V. Dhuria | Zendy; Yashpal S. Chhonker | Zendy; C. David Weaver | Zendy; Corey R. Hopkins | Zendy

Open Access

Discovery, synthesis and biological characterization of a series of N-(1-(1,1-dioxidotetrahydrothiophen-3-yl)-3-methyl-1H-pyrazol-5-yl)acetamide ethers as novel GIRK1/2 potassium channel activators

Author(s) -

Swagat Sharma,

Lauren Lesiak,

Christopher D. Aretz,

Yu Du,

Sushil Kumar,

Nagsen Gautam,

Yazen Alnouti,

Nikilesh V. Dhuria,

Yashpal S. Chhonker,

C. David Weaver,

Corey R. Hopkins

Publication year - 2021

Publication title -

rsc medicinal chemistry

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.754

H-Index - 55

ISSN - 2632-8682

DOI - 10.1039/d1md00129a

Subject(s) - acetamide , sulfone , ether , potency , chemistry , activator (genetics) , in vitro , biological activity , combinatorial chemistry , stereochemistry , organic chemistry , biochemistry , receptor

The present study describes the discovery and characterization of a series of N -(1-(1,1-dioxidotetrahydrothiophen-3-yl)-3-methyl-1 H -pyrazol-5-yl)acetamide ethers as G protein-gated inwardly-rectifying potassium (GIRK) channel activators. From our previous lead optimization efforts, we have identified a new ether-based scaffold and paired this with a novel sulfone-based head group to identify a potent and selective GIRK1/2 activator. In addition, we evaluated the compounds in tier 1 DMPK assays and have identified compounds that display nanomolar potency as GIRK1/2 activators with improved metabolic stability over the prototypical urea-based compounds.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research