Format

Send to

Choose Destination
J Med Chem. 2014 Mar 27;57(6):2807-12. doi: 10.1021/jm401356t. Epub 2014 Feb 24.

Design, synthesis, crystallographic studies, and preliminary biological appraisal of new substituted triazolo[4,3-b]pyridazin-8-amine derivatives as tankyrase inhibitors.

Author information

1
Dipartimento di Chimica e Tecnologia del Farmaco, Università degli Studi di Perugia , Via del Liceo 1, 06123 Perugia, Italy.

Abstract

Searching for selective tankyrases (TNKSs) inhibitors, a new small series of 6,8-disubstituted triazolo[4,3-b]piridazines has been synthesized and characterized biologically. Structure-based optimization of the starting hit compound NNL (3) prompted us to the discovery of 4-(2-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-ylamino)ethyl)phenol (12), a low nanomolar selective TNKSs inhibitor working as NAD isostere as ascertained by crystallographic analysis. Preliminary biological data candidate this new class of derivatives as a powerful pharmacological tools in the unraveling of TNKS implications in physiopathological conditions.

PMID:
24527792
PMCID:
PMC4406096
DOI:
10.1021/jm401356t
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Chemical Society Icon for PubMed Central
Loading ...
Support Center