Abstract
In this manuscript we wish to report the discovery of MK-7246 (4), a potent and selective CRTH2 (DP2) antagonist. SAR studies leading to MK-7246 along with two synthetic sequences enabling the preparation of this novel class of CRTH2 antagonist are reported. Finally, the pharmacokinetic and metabolic profile of MK-7246 is disclosed.
Copyright © 2010 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Carbolines / chemistry*
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Carbolines / pharmacokinetics
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Carbolines / therapeutic use
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Humans
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Lung Diseases / drug therapy*
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Macaca mulatta
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Microsomes, Liver / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptors, Immunologic / antagonists & inhibitors*
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Receptors, Immunologic / metabolism
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Receptors, Prostaglandin / antagonists & inhibitors*
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Receptors, Prostaglandin / metabolism
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Structure-Activity Relationship
Substances
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((7R)-7-(((4-fluorophenyl)sulfonyl)(methyl)amino)-6,7,8,9-tetrahydropyrido(1,2-a)indol-10-yl)acetic acid
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Carbolines
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Receptors, Immunologic
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Receptors, Prostaglandin
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prostaglandin D2 receptor