Carbazole-containing amides and ureas: Discovery of cryptochrome modulators as antihyperglycemic agents

  • Bioorg Med Chem Lett. 2018 Feb 1;28(3):293-297. doi: 10.1016/j.bmcl.2017.12.051.
Paul S Humphries  1 ,  Ross Bersot  2 ,  John Kincaid  3 ,  Eric Mabery  2 ,  Kerryn McCluskie  2 ,  Timothy Park  2 ,  Travis Renner  2 ,  Erin Riegler  2 ,  Tod Steinfeld  2 ,  Eric D Turtle  2 ,  Zhi-Liang Wei  3 ,  Erik Willis  2
Affiliations
  • 1. Reset Therapeutics, 260 Littlefield Avenue, Suite 200, South San Francisco, CA 94080, USA. Electronic address: [email protected].
  • 2. Reset Therapeutics, 260 Littlefield Avenue, Suite 200, South San Francisco, CA 94080, USA.
  • 3. Synterys, 29540 Kohoutek Way, Union City, CA 94587, USA.
PMID: 29292223 DOI: 10.1016/j.bmcl.2017.12.051
Abstract

A series of novel carbazole-containing amides and ureas were synthesized. A structure-activity relationship study of these compounds led to the identification of potent Cryptochrome modulators. Based on the desired pharmacokinetic/pharmacodynamic parameters and the results of efficacy studies in db/db mice, compound 50 was selected for further profiling.

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