2. Academic Validation
  3. Discovery of triazolopyrimidine-based PDE8B inhibitors: exceptionally ligand-efficient and lipophilic ligand-efficient compounds for the treatment of diabetes

Discovery of triazolopyrimidine-based PDE8B inhibitors: exceptionally ligand-efficient and lipophilic ligand-efficient compounds for the treatment of diabetes

  • Bioorg Med Chem Lett. 2012 Sep 1;22(17):5721-6. doi: 10.1016/j.bmcl.2012.06.079.
Michael P DeNinno 1,  Stephen W Wright,  John B Etienne,  Thanh V Olson,  Benjamin N Rocke,  Jeffrey W Corbett,  Daniel W Kung,  Kenneth J DiRico,  Kim M Andrews,  Michele L Millham,  Janice C Parker,  William Esler,  Maria van Volkenburg,  David D Boyer,  Karen L Houseknecht,  Shawn D Doran
Affiliations

Affiliation

  • 1 Pfizer Global Research & Development-Groton Laboratories, Groton, CT 06340, USA. mike_deninno@sd.vrtx.com
PMID: 22858141 DOI: 10.1016/j.bmcl.2012.06.079
Abstract

PDE8B is a cAMP-specific isoform of the broader class of phosphodiesterases (PDEs). As no selective PDE8B inhibitors had been reported, a high throughput screen was run with the goal of identifying selective tools for exploring the potential therapeutic utility of PDE8B inhibition. Of the numerous hits, one was particularly attractive since it was amenable to rapid deconstruction leading to inhibitors with very high ligand efficiency (LE) and lipophilic ligand efficiency (LLE). These triazolopyrimidines were optimized for potency, selectivity and ADME properties ultimately leading to compound 42. This compound was highly potent and selective with good bioavailability and advanced into pre-clinical development.

Figures
Products
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