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Azabenzthiazole inhibitors of leukotriene A₄ hydrolase.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2012 Dec 15; Vol. 22 (24), pp. 7504-11. Date of Electronic Publication: 2012 Oct 17. - Publication Year :
- 2012
-
Abstract
- Previously, benzthiazole containing LTA(4)H inhibitors were discovered that were potent (1-3), but were associated with the potential for a hERG liability. Utilizing medicinal chemistry first principles (e.g., introducing rigidity, lowering cLogD) a new benzthiazole series was designed, congeners of 1-3, which led to compounds 7a, 7c, 12a-d which exhibited LTA(4)H IC(50)=3-6 nM and hERG Dofetilide Binding IC(50)=8.9-> >10 μM.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Aza Compounds chemical synthesis
Aza Compounds chemistry
Benzothiazoles chemical synthesis
Benzothiazoles chemistry
Dose-Response Relationship, Drug
Drug Design
Enzyme Inhibitors chemical synthesis
Enzyme Inhibitors chemistry
Epoxide Hydrolases metabolism
Ether-A-Go-Go Potassium Channels antagonists & inhibitors
Humans
Mice
Molecular Structure
Structure-Activity Relationship
Aza Compounds pharmacology
Benzothiazoles pharmacology
Enzyme Inhibitors pharmacology
Epoxide Hydrolases antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 22
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 23127888
- Full Text :
- https://doi.org/10.1016/j.bmcl.2012.10.036