190269-75-1Relevant academic research and scientific papers
COMBINATION THERAPY FOR THE TREATMENT OF URINARY FREQUENCY, URINARY URGENCY AND URINARY INCONTINENCE
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, (2010/11/29)
This invention concerns compositions for the treatment of urinary frequency, urinary urgency and urinary incontinence comprising a selected antagonist of the NK-1 receptor or a pharmaceutically acceptable salt thereof and an anti-muscarinic agent or a pha
Cyclopentane-based human NK1 antagonists. Part 2: Development of potent, orally active, water-soluble derivatives
Meurer, Laura C.,Finke, Paul E.,Owens, Karen A.,Tsou, Nancy N.,Ball, Richard G.,Mills, Sander G.,MacCoss, Malcolm,Sadowski, Sharon,Cascieri, Margaret A.,Tsao, Kwei-Lan,Chicchi, Gary G.,Egger, Linda A.,Luell, Silvi,Metzger, Joseph M.,MacIntyre, D. Euan,Rupniak, Nadia M.J.,Williams, Angela R.,Hargreaves, Richard J.
, p. 4504 - 4511 (2007/10/03)
The synthesis and optimization of a cyclopentane-based hNK1 antagonist scaffold 3, having four chiral centers, will be discussed in the context of its enhanced water solubility properties relative to the marketed anti-emetic hNK1 antagonist EMEND (Aprepitant). Sub-nanomolar hNK1 binding was achieved and oral activity comparable to Aprepitant in two in vivo models will be described.
Stereoselective preparation of a cyclopentane-based NK1 receptor antagonist bearing an unsymmetrically substituted sec-sec ether
Kuethe, Jeffrey T.,Marcoux, Jean-Francois,Wong, Audrey,Wu, Jimmy,Hillier, Michael C.,Dormer, Peter G.,Davies, Ian W.,Hughes, David L.
, p. 7378 - 7390 (2007/10/03)
A highly efficient synthesis of the potent and selective NK-1 receptor antagonist 1 is described. The key transformation involved the etherification reaction between cyclopentanol 12 and chiral imidate 30 which was catalyzed by HBF4 to initially give ether 14 as a 17:1 mixture of diastereomers and in 75% combined yield. The diastereoselectivity was upgraded to 109:1 by crystallization of the triethylamine solvate 44 which was isolated in 54% yield from 12. Mechanistic studies confirmed that the etherification reaction proceeds through an unprecedented SN2 reaction pathway under typical S N1 reaction conditions.
Lactam tachykinin receptor antagonists
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Page/Page column 9, (2010/02/15)
The present invention is directed to certain lactam compounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations compri
Asymmetric synthesis of 1,2,3-trisubstituted cyclopentanes and cyclohexanes as key components of substance P antagonists
Kuethe, Jeffrey T.,Wong, Audrey,Wu, Jimmy,Davies, Ian W.,Dormer, Peter G.,Welch, Christopher J.,Hillier, Michael C.,Hughes, David L.,Reider, Paul J.
, p. 5993 - 6000 (2007/10/03)
An efficient asymmetric synthesis of 1,2,3-trisubstituted cyclopentanes and cyclohexanes is described. Three methods were developed for the preparation of the 2,3-disubstituted cyclopentenones and cyclohexenones, which are key achiral building blocks. These intermediates are reduced catalytically with (R)-2-methyloxazaborolidine in high yield (82-98%) and excellent ee (89-96%). Directed reduction of the chiral allylic alcohols using Red-Al gives exclusively the 1,2-anti stereochemistry (>99:1). Epimerization of the ester center followed by saponification/crystallization affords the desired hydroxyacids in good yield (65-70%) and in high enantiomeric excess (>99%).
