Abstract
Optimization starting with our lead compound 1 (IC(50)=4.9 nM) led to the identification of pyrrolidinyl phenylurea derivatives. Further modification toward improvement of the bioavailability provided (R)-1-(1-((6-fluoronaphthalen-2-yl)methyl)pyrrolidin-3-yl)-3-(2-(2-hydroxyethoxy)phenyl)urea 32 (IC(50)=1.7 nM), a potent and orally active CCR3 antagonist.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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Administration, Oral
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Animals
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Biological Availability
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Half-Life
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Macaca fascicularis
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Phenylurea Compounds / chemical synthesis
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Phenylurea Compounds / chemistry*
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Phenylurea Compounds / pharmacokinetics
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Pyrrolidines / chemical synthesis
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Pyrrolidines / chemistry*
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Pyrrolidines / pharmacokinetics
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Receptors, CCR3 / antagonists & inhibitors*
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Receptors, CCR3 / metabolism
Substances
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1-(1-((6-fluoronaphthalen-2-yl)methyl)pyrrolidin-3-yl)-3-(2-(2-hydroxyethoxy)phenyl)urea
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Phenylurea Compounds
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Pyrrolidines
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Receptors, CCR3
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pyrrolidine