Abstract
An SAR campaign designed to increase polarity in the 'tail' region of benzothiazole 1 resulted in two series of structurally novel 5-and 6-substituted S1P(1) agonists. Structural optimization for potency ultimately delivered carboxamide (+)-11f, which in addition to possessing improved physicochemical properties relative to starting benzothiazole 1, also displayed good S1P(3) selectivity and acceptable in vivo lymphocyte-depleting activity.
Copyright © 2011. Published by Elsevier Ltd.
MeSH terms
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Animals
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Benzothiazoles / chemistry*
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CHO Cells
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Cell Line, Tumor
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Chemistry, Pharmaceutical / methods
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Chemistry, Physical / methods
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Cricetinae
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Cricetulus
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Drug Design
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Female
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Green Fluorescent Proteins / metabolism
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Humans
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Ketones
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Lymphocytes / cytology
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Lymphocytes / drug effects*
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Models, Chemical
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Rats
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Rats, Inbred Lew
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Receptors, G-Protein-Coupled / metabolism
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Receptors, Lysosphingolipid / agonists*
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Receptors, Lysosphingolipid / chemistry*
Substances
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Benzothiazoles
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Ketones
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Receptors, G-Protein-Coupled
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Receptors, Lysosphingolipid
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Green Fluorescent Proteins