Synthesis and structure-activity relationships of novel histamine H 1 antagonists: Indolylpiperidinyl benzoic acid derivatives
A series of indolylpiperidinyl derivatives were prepared and evaluated for their activity as histamine H1 antagonists. Structure-activity relationship studies were directed toward improving in vivo activity and pharmacokinetic profile of our first lead (1). Substitution of fluorine in position 6 on the indolyl ring led to higher in vivo activity in the inhibition of histamine-induced cutaneous vascular permeability assay but lower selectivity toward 5HT2 receptor. Extensive optimization was carried out within this series and a number of histamine H1 antagonists showing potency and long duration of action in vivo and low brain penetration or cardiotoxic potential were identified. Within this novel series, indolylpiperidines 15, 20, 48, 51 and 52 exhibited a long half-life in rat and have been selected for further preclinical evaluation.
This invention provides methods of treating a physiological disorder associated with an excess of tachykinins in a mammal which comprises administering to a mammal in need of said treatment a compound selected from a series of substituted morpholines. Thi
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(2008/06/13)
Bisindoles as tachykinin receptor antagonists
This invention provides a series of substituted bisindole propanamides which are useful as tachykinin receptor antagonists and as serotonin agonists. This invention also provides methods for the treatment of related disorders as well as pharmaceutical for
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(2008/06/13)
5-HT1F agonists for the treatment of migraine
This invention provides novel 5-HT1F agonists which are useful for the treatment of migraine and associated disorders.
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(2008/06/13)
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