Synthesis and evaluation of alkoxy-phenylamides and alkoxy-phenylimidazoles as potent sphingosine-1-phosphate receptor subtype-1 agonists
Discovery of two potent and selective sphingosine-1-phosphate receptor agonist chemotypes, alkoxy-phenylamide and alkoxy-phenylimidazole, with potent in vivo oral activity in mouse. In the design of potent and selective sphingosine-1-phosphate receptor agonists, we were able to identify two series o...
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Published in: | Bioorganic & medicinal chemistry letters 2009-01, Vol.19 (2), p.369-372 |
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Main Authors: | , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Discovery of two potent and selective sphingosine-1-phosphate receptor agonist chemotypes, alkoxy-phenylamide and alkoxy-phenylimidazole, with potent in vivo oral activity in mouse.
In the design of potent and selective sphingosine-1-phosphate receptor agonists, we were able to identify two series of molecules based on phenylamide and phenylimidazole analogs of FTY-720. Several designed molecules in these scaffolds have demonstrated selectivity for S1P receptor subtype 1 versus 3 and excellent in vivo activity in mouse. Two molecules PPI-4621 (
4b) and PPI-4691 (
10a), demonstrated dose responsive lymphopenia, when administered orally. |
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ISSN: | 0960-894X 1464-3405 |
DOI: | 10.1016/j.bmcl.2008.11.072 |