Novel pyridopyrimidine derivatives as inhibitors of stable toxin a (STa) induced cGMP synthesis

Eric A Tanifum; Alexander Y Kots; Byung-Kwon Choi; Ferid Murad; Scott R Gilbertson

doi:10.1016/j.bmcl.2009.04.024

Novel pyridopyrimidine derivatives as inhibitors of stable toxin a (STa) induced cGMP synthesis

Bioorg Med Chem Lett. 2009 Jun 1;19(11):3067-71. doi: 10.1016/j.bmcl.2009.04.024. Epub 2009 Apr 12.

Authors

Eric A Tanifum¹, Alexander Y Kots, Byung-Kwon Choi, Ferid Murad, Scott R Gilbertson

Affiliation

¹ Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77555-0650, USA.

PMID: 19409779
DOI: 10.1016/j.bmcl.2009.04.024

Abstract

A series of pyridopyrimidine derivatives were synthesized and evaluated for their ability to inhibit cyclic nucleotide synthesis in the presence of stable toxin a of Escherichia coli. The structure activity relationships around the basic core structure were examined and examples with better activity and potentially better pharmacological properties are presented.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bacterial Toxins / metabolism*
Cell Line, Tumor
Cyclic GMP / biosynthesis*
Enterotoxins / metabolism*
Escherichia coli / metabolism
Escherichia coli Proteins
Guanylate Cyclase / antagonists & inhibitors
Guanylate Cyclase / metabolism
Humans
Pyrimidines / chemical synthesis
Pyrimidines / chemistry*
Pyrimidines / pharmacology
Receptors, Enterotoxin
Receptors, Guanylate Cyclase-Coupled
Receptors, Peptide / antagonists & inhibitors
Receptors, Peptide / metabolism
Structure-Activity Relationship

Substances

Bacterial Toxins
Enterotoxins
Escherichia coli Proteins
Pyrimidines
Receptors, Peptide
heat stable toxin (E coli)
Guanylate Cyclase
Receptors, Enterotoxin
Receptors, Guanylate Cyclase-Coupled
Cyclic GMP