Carbazole-containing sulfonamides and sulfamides: Discovery of cryptochrome modulators as antidiabetic agents

Paul S Humphries; Ross Bersot; John Kincaid; Eric Mabery; Kerryn McCluskie; Timothy Park; Travis Renner; Erin Riegler; Tod Steinfeld; Eric D Turtle; Zhi-Liang Wei; Erik Willis

doi:10.1016/j.bmcl.2015.12.102

Carbazole-containing sulfonamides and sulfamides: Discovery of cryptochrome modulators as antidiabetic agents

Bioorg Med Chem Lett. 2016 Feb 1;26(3):757-760. doi: 10.1016/j.bmcl.2015.12.102. Epub 2015 Dec 30.

Authors

Affiliations

¹ Reset Therapeutics, 260 Littlefield Avenue, Suite 200, South San Francisco, CA 94080, USA. Electronic address: paul@resettherapeutics.com.
² Reset Therapeutics, 260 Littlefield Avenue, Suite 200, South San Francisco, CA 94080, USA.
³ Synterys Inc., 29540 Kohoutek Way, Union City, CA 94587, USA.

PMID: 26778255
DOI: 10.1016/j.bmcl.2015.12.102

Abstract

A series of novel carbazole-containing sulfonamides and sulfamides were synthesized. A structure-activity relationship study of these compounds led to the identification of potent cryptochrome modulators. Based on the results of efficacy studies in diet-induced obese (DIO) mice, and the desired pharmacokinetic parameters, compound 41 was selected for further profiling.

Keywords: Carbazole; Circadian; Cryptochrome; Diabetes; SAR.

MeSH terms

Animals
Blood Glucose / analysis
Carbazoles / chemistry*
Cell Line, Tumor
Cryptochromes / chemistry*
Cryptochromes / genetics
Cryptochromes / metabolism
Diabetes Mellitus, Experimental / drug therapy
Diabetes Mellitus, Experimental / pathology
Diet, High-Fat
Gene Expression Regulation / drug effects
Genes, Reporter
Humans
Hypoglycemic Agents / chemistry*
Hypoglycemic Agents / pharmacology
Hypoglycemic Agents / therapeutic use
Mice
Mice, Inbred C57BL
Mice, Obese
Structure-Activity Relationship
Sulfonamides / chemistry*
Sulfonamides / pharmacology
Sulfonamides / therapeutic use

Substances

Blood Glucose
Carbazoles
Cryptochromes
Hypoglycemic Agents
Sulfonamides
carbazole