Abstract
Systematic SAR studies on the HTS hit pyridine-2-carboxylic acid thiazol-2-ylamide (PACT) analogues revealed that the scaffold of PCAT is indispensable for the inhibition of type I MetAP. For effective inhibition of the enzyme, the most suitable position to modify is the 3-position of the pyridine ring of PCAT, and the best substituents are those containing O or N atoms connected directly with the pyridine ring. These findings provide useful information for the design and discovery of more potent inhibitors of type I MetAPs.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amides / chemistry*
-
Amides / pharmacology
-
Aminopeptidases / antagonists & inhibitors*
-
Anti-Bacterial Agents / chemical synthesis*
-
Anti-Bacterial Agents / pharmacology
-
Antifungal Agents / chemical synthesis
-
Antifungal Agents / pharmacology
-
Bacterial Proteins / antagonists & inhibitors
-
Escherichia coli / enzymology
-
Humans
-
Inhibitory Concentration 50
-
Methionyl Aminopeptidases
-
Pyridines / chemical synthesis
-
Pyridines / pharmacology
-
Salmonella typhimurium / enzymology
-
Structure-Activity Relationship
-
Thiazoles / chemistry*
-
Thiazoles / pharmacology
-
Thioamides / chemical synthesis*
-
Thioamides / pharmacology
Substances
-
Amides
-
Anti-Bacterial Agents
-
Antifungal Agents
-
Bacterial Proteins
-
Pyridines
-
Thiazoles
-
Thioamides
-
pyridine-2-carboxylic acid thiazol-2-ylamide
-
Aminopeptidases
-
Methionyl Aminopeptidases