Discovery of highly potent, selective, orally bioavailable, metabotropic glutamate subtype 5 (mGlu5) receptor antagonists devoid of cytochrome P450 1A2 inhibitory activity

Structure–activity relationship studies focused on bio-isosteric replacements of 2-pyridyl resulted in mGlu5 receptor antagonists with reduced inhibition of cytochrome P450 1A2. This led to highly potent, selective and orally bioavailable 2-imidazolyl tetrazoles such as 10 that are devoid of cytochr...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2004-11, Vol.14 (22), p.5481-5484
Hauptverfasser: Smith, Nicholas D., Poon, Steve F., Huang, Dehua, Green, Mitchell, King, Christopher, Tehrani, Lida, Roppe, Jeffrey R., Chung, Janice, Chapman, Deborah P., Cramer, Merryl, Cosford, Nicholas D.P.
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Sprache:eng
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Zusammenfassung:Structure–activity relationship studies focused on bio-isosteric replacements of 2-pyridyl resulted in mGlu5 receptor antagonists with reduced inhibition of cytochrome P450 1A2. This led to highly potent, selective and orally bioavailable 2-imidazolyl tetrazoles such as 10 that are devoid of cytochrome P450 inhibitory activity. Structure–activity relationship studies focused on bio-isosteric replacements of 2-pyridyl resulted in mGlu5 receptor antagonists with reduced inhibition of cytochrome P450 1A2. This led to highly potent, selective and orally bioavailable 2-imidazolyl tetrazoles such as ( 10) that are devoid of cytochrome P450 inhibitory activity.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2004.09.018