Synthesis and biological evaluation of α-sulfonamido-N-adamantanecarboxamide derivatives as 11β-HSD1 inhibitors

Young Hoon Kim; Seung Kyu Kang; Gwi Bin Lee; Kyu Myung Lee; Jaladi Ashok Kumar; Ki Young Kim; Sang Dal Rhee; Jeongmin Joo; Myung Ae Bae; Won Koo Lee; Jin Hee Ahn

doi:10.1039/C5MD00096C

Synthesis and biological evaluation of α-sulfonamido-N-adamantanecarboxamide derivatives as 11β-HSD1 inhibitors

Young Hoon Kim,^a Seung Kyu Kang,^b Gwi Bin Lee,^b Kyu Myung Lee,^b Jaladi Ashok Kumar,^b Ki Young Kim,^bc Sang Dal Rhee,^b Jeongmin Joo,^b Myung Ae Bae,^b Won Koo Lee^a and Jin Hee Ahn*^bc

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* Corresponding authors

^a Department of Chemistry, Sogang University, Seoul 121-742, Republic of Korea

^b Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea
E-mail: jhahn@krict.re.kr

^c Department of Medicinal and Pharmaceutical Chemistry, University of Science and Technology, Daejeon, Republic of Korea

Abstract

A series of α-sulfonamido-N-adamantanecarboxamide derivatives as 11β-HSD1 inhibitors was identified. Among them, compound 7j was the most active with an IC₅₀ value of 8 nM in humans 11β-HSD1. Compound 7j exhibited reasonable stability, permeability and safety profiles (CYP and hERG). Compound 7j showed good ex vivo 11 β-HSD1 inhibition with ~80% inhibition after 20 MPK oral dosing.

MedChemComm

Synthesis and biological evaluation of α-sulfonamido-N-adamantanecarboxamide derivatives as 11β-HSD1 inhibitors

Abstract

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Synthesis and biological evaluation of α-sulfonamido-N-adamantanecarboxamide derivatives as 11β-HSD1 inhibitors

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