Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ester doai
Reexamination Certificate
2005-02-22
2005-02-22
Criares, Theodore J. (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Ester doai
C514S529000, C514S548000, C514S551000, C514S552000, C514S517000, C514S533000, C514S310000, C514S973000
Reexamination Certificate
active
06858649
ABSTRACT:
The selective potentiation and/or inhibition of the 5-HT2Aand/or 5-HT1Aresponse to serotonin (5-HT) is achieved using analogs of oleamide. Selective potentiation and/or inhibition of the 5-HT2Aand/or 5-HT1Aleads to a modulation of serotonergic signal transduction of cells having various receptor subtypes. A subset of analogs is identified that inhibits rather than potentiates the 5-HT2A, but not the 5-HT1A, receptor response. These analogs enable the selective modulation of serotonin receptor subtypes and even have opposing effects on the different subtypes. An analysis of the activity of the oleamide analogs discloses that the structural features required for activity are highly selective. In particular, the presence, position, and stereochemistry of the 9-cis double bond is required and even subtle structural variations reduce or eliminate activity. Secondary or tertiary amides may replace the primary amide but follow a well-defined relationship requiring small amide substituents suggesting that the carboxamide serves as a hydrogen bond acceptor but not donor. Alternative modifications at the carboxamide as well as modifications of the methyl terminus or the hydrocarbon region spanning the carboxamide and double bond typically eliminate activity.
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Criares Theodore J.
Lewis Donald G.
The Scripps Research Institute
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