Abstract
A new class of 3-fluoroallyl amine-based SSAO/VAP-1 inhibitors is reported. These compounds have excellent selectivity over diamine oxidase, MAO-A and MAO-B. Synthesis and SAR studies leading to compound 28 (PXS-4159A) are reported. The pharmacokinetic profile of 28 in the rat, together with activity in a murine model of lung inflammation are also disclosed.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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Allyl Compounds / chemical synthesis*
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Allyl Compounds / pharmacokinetics
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Allyl Compounds / pharmacology
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Amine Oxidase (Copper-Containing) / antagonists & inhibitors*
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Amine Oxidase (Copper-Containing) / metabolism
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Amines / chemical synthesis*
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Amines / pharmacokinetics
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Amines / pharmacology
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Animals
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Anti-Inflammatory Agents / chemical synthesis*
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Anti-Inflammatory Agents / pharmacokinetics
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Anti-Inflammatory Agents / pharmacology
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Drug Discovery
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Halogenation
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Humans
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / metabolism
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Mice
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Models, Molecular
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Monoamine Oxidase Inhibitors / chemical synthesis*
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Monoamine Oxidase Inhibitors / pharmacokinetics
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Monoamine Oxidase Inhibitors / pharmacology
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Pneumonia / drug therapy*
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Pneumonia / enzymology
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Rats
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Structure-Activity Relationship
Substances
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Allyl Compounds
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Amines
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Anti-Inflammatory Agents
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Isoenzymes
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Monoamine Oxidase Inhibitors
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Amine Oxidase (Copper-Containing)