2. Academic Validation
  3. The insulin secretory action of novel polycyclic guanidines: discovery through open innovation phenotypic screening, and exploration of structure-activity relationships

The insulin secretory action of novel polycyclic guanidines: discovery through open innovation phenotypic screening, and exploration of structure-activity relationships

  • Bioorg Med Chem Lett. 2014 Feb 15;24(4):1031-6. doi: 10.1016/j.bmcl.2014.01.021.
Michael B Shaghafi 1,  David G Barrett 2,  Francis S Willard 2,  Larry E Overman 3
Affiliations

Affiliations

  • 1 Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, CA 92697-2025, United States.
  • 2 Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, United States.
  • 3 Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, CA 92697-2025, United States. Electronic address: leoverma@uci.edu.
PMID: 24484900 DOI: 10.1016/j.bmcl.2014.01.021
Abstract

We report the discovery of the glucose-dependent Insulin secretogogue activity of a novel class of polycyclic guanidines through phenotypic screening as part of the Lilly Open Innovation Drug Discovery platform. Three compounds from the University of California, Irvine, 1-3, having the 3-arylhexahydropyrrolo[1,2-c]pyrimidin-1-amine scaffold acted as Insulin secretagogues under high, but not low, glucose conditions. Exploration of the structure-activity relationship around the scaffold demonstrated the key role of the guanidine moiety, as well as the importance of two lipophilic regions, and led to the identification of 9h, which stimulated Insulin secretion in isolated rat pancreatic islets in a glucose-dependent manner.

Keywords

Diabetes; Guanidine; Insulin secretogogue.

Figures
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z