Abstract
High throughput screening using Automated Ligand Identification System (ALIS) resulted in the discovery of a new series of S-adenosyl-L-homocysteine hydrolase inhibitors based on non-adenosine analogs. The optimization campaign led to very potent and competitive compound 39 with a Ki value of 1.5 nM. Compound 39 could be a promising lead compound for research to reduce elevated homocysteine levels.
Keywords:
Competitive; Homocysteine; S-Adenosyl-l-homocysteine hydrolase inhibitors.
Copyright © 2014 Elsevier Ltd. All rights reserved.
MeSH terms
-
Adenosine / chemistry
-
Adenosylhomocysteinase / antagonists & inhibitors*
-
Adenosylhomocysteinase / metabolism
-
Amides / chemical synthesis
-
Amides / chemistry
-
Amides / pharmacology*
-
Amines / chemical synthesis
-
Amines / chemistry
-
Amines / pharmacology*
-
Dose-Response Relationship, Drug
-
Drug Discovery*
-
Enzyme Inhibitors / chemical synthesis
-
Enzyme Inhibitors / chemistry*
-
Enzyme Inhibitors / pharmacology*
-
High-Throughput Screening Assays
-
Humans
-
Molecular Structure
-
Monomethylhydrazine / chemical synthesis
-
Monomethylhydrazine / chemistry
-
Monomethylhydrazine / pharmacology*
-
Structure-Activity Relationship
Substances
-
Amides
-
Amines
-
Enzyme Inhibitors
-
Adenosylhomocysteinase
-
Adenosine
-
Monomethylhydrazine