Synthesis and profiling of a diverse collection of azetidine-based scaffolds for the development of CNS-focused lead-like libraries.

J Org Chem
Authors
Keywords
Abstract

The synthesis and diversification of a densely functionalized azetidine ring system to gain access to a wide variety of fused, bridged, and spirocyclic ring systems is described. The in vitro physicochemical and pharmacokinetic properties of representative library members are measured in order to evaluate the use of these scaffolds for the generation of lead-like molecules to be used in targeting the central nervous system. The solid-phase synthesis of a 1976-membered library of spirocyclic azetidines is also described.

Year of Publication
2012
Journal
J Org Chem
Volume
77
Issue
17
Pages
7187-211
Date Published
2012 Sep 07
ISSN
1520-6904
URL
DOI
10.1021/jo300974j
PubMed ID
22853001
PubMed Central ID
PMC3454511
Links
Grant list
UL1DE019585 / DE / NIDCR NIH HHS / United States
RL1HG004671 / HG / NHGRI NIH HHS / United States
RL1CA133834 / CA / NCI NIH HHS / United States
UL1 DE019585 / DE / NIDCR NIH HHS / United States
RL1GM084437 / GM / NIGMS NIH HHS / United States
P50 GM069721 / GM / NIGMS NIH HHS / United States
RL1 GM084437 / GM / NIGMS NIH HHS / United States
RL1 HG004671 / HG / NHGRI NIH HHS / United States
RL1 CA133834 / CA / NCI NIH HHS / United States