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Discovery of IDO1 inhibitors containing a decahydroquinoline, decahydro-1,6-naphthyridine, or octahydro-1H-pyrrolo[3,2-c]pyridine scaffold.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2021 Oct 01; Vol. 49, pp. 128314. Date of Electronic Publication: 2021 Aug 13. - Publication Year :
- 2021
-
Abstract
- A series of IDO1 inhibitors containing a decahydroquinoline, decahydro-1,6-naphthyridine, or octahydro-1H-pyrrolo[3,2-c]pyridine scaffold were identified with good cellular and human whole blood activity against IDO1. These inhibitors contain multiple chiral centers and all diastereomers were separated. The absolute stereochemistry of each isomers were not determined. Compounds 15 and 27 stood out as leads due to their good cellular as well as human whole blood IDO1 inhibition activity, low unbound clearance, and reasonable mean residence time in rat cassette PK studies.<br /> (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Catalytic Domain
Enzyme Inhibitors chemical synthesis
Enzyme Inhibitors metabolism
Enzyme Inhibitors pharmacokinetics
HeLa Cells
Humans
Indoleamine-Pyrrole 2,3,-Dioxygenase chemistry
Indoleamine-Pyrrole 2,3,-Dioxygenase metabolism
Molecular Docking Simulation
Naphthyridines chemical synthesis
Naphthyridines metabolism
Naphthyridines pharmacokinetics
Pyrroles chemical synthesis
Pyrroles metabolism
Pyrroles pharmacokinetics
Quinolines chemical synthesis
Quinolines metabolism
Quinolines pharmacokinetics
Rats
Stereoisomerism
Structure-Activity Relationship
Enzyme Inhibitors pharmacology
Indoleamine-Pyrrole 2,3,-Dioxygenase antagonists & inhibitors
Naphthyridines pharmacology
Pyrroles pharmacology
Quinolines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 49
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 34391891
- Full Text :
- https://doi.org/10.1016/j.bmcl.2021.128314