170568-17-9Relevant academic research and scientific papers
Method of treating gout with certain indole compounds
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, (2008/06/13)
This invention relates to a method of treating gout with certain indole compounds and other aromatic compounds.
NON-PEPTIDE TACHYKININ RECEPTOR ANTAGONISTS
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, (2008/06/13)
This invention provides a novel series of non-peptidyl compounds which are useful in the treatment or prevention of a physiological disorder associated with an excess of tachykinins. This invention also provides methods for the treatment of such physiolog
2-Acylaminopropanamines as growth hormone secretagogues
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, (2008/06/13)
This invention provides a series of substituted propanamines which are useful in treating a physiological condition which may be modulated by an increase in growth hormone. This invention also provides methods for the treatment of such physiological condi
3-Aryl-1,2-diacetamidopropane derivatives as novel and potent NK-1 receptor antagonists
Hipskind, Philip A.,Howbert, J. Jeffry,Bruns, Robert F.,Cho, Steven S. Y.,Crowell, Thomas A.,Foreman, Mark M.,Gehlert, Donald R.,Iyengar, Smriti,Johnson, Kirk W.,Krushinski, Joseph H.,Li, Dominic L.,Lobb, Karen L.,Mason, Norman R.,Muehl, Brian S.,Nixon, James A.,Phebus, Lee A.,Regoli, Domenico,Simmons, Rosa M.,Threlkeld, Penny G.,Waters, Diane C.,Gitter, Bruce D.
, p. 736 - 748 (2007/10/03)
Early structure-activity studies on racemic tryptophan ester and amide NK- 1 antagonists 5-7 led to the discovery that the potency of the series could be markedly increased by moving the carbonyl function in these molecules to an off-chain position as in the 3-aryl-1,2-diacetamidopropane 9. Further medicinal chemistry incorporating this change resulted in the discovery of a novel series of highly potent aryl amino acid derived NK-1 antagonists of the R stereoisomeric series (IC50's = 100 pM to >5 μM). Compounds in this series were shown to be competitive antagonists using an in vitro NK-1 smooth muscle assay, and this data correlated well with observed human NK-1 binding affinities. Two of these agents, (R)-25 and (R)-32, blocked intrathecal NK-1 agonist-driven [Ac-[Arg6, Sar9, Met(O2)11]-substance P 6-11 (Ac-Sar9)] nociceptive behavior in mice. Both compounds potently blocked the neurogenic dural inflammation following trigeminal ganglion stimulation in the guinea pig after intravenous administration. Further, upon oral administration in this model, (R)-32 was observed to be very potent (ID50 = 91 ng/kg) and have a long duration of action (>8 h at 1 μg/kg). Compound (R)-32, designated LY303870, is currently under clinical development as an NK-1 antagonist with a long duration of action.
