263387-98-0Relevant academic research and scientific papers
Structural Analysis and Optimization of NK1 Receptor Antagonists through Modulation of Atropisomer Interconversion Properties
Albert, Jeffrey S.,Ohnmacht, Cyrus,Bernstein, Peter R.,Rumsey, William L.,Aharony, David,Alelyunas, Yun,Russell, Daniel J.,Potts, William,Sherwood, Scott A.,Shen, Lihong,Dedinas, Robert F.,Palmer, William E.,Russell, Keith
, p. 519 - 529 (2007/10/03)
We have previously described a series of antagonists that showed high potency and selectivity for the NK1 receptor. However, these compounds also had the undesirable property of existing as a mixture of interconverting rotational isomers. Here
Novel n-( 2-phenyl-3-aminopropyl)naphtamides
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Page/Page column 7-8, (2010/02/05)
A compound of the formula wherein R1, R2, R3, R4, R5, R6, X1 and X2 are as defined in the specification useful for the treatment of diseases in which action of the neu
A new approach to the rapid parallel development of four neurokinin antagonists. Part 3. Assembly of neurokinin antagonists
Parker, Jeremy S.,Bowden, Sharon A.,Firkin, Catherine R.,Moseley, Jonathan D.,Murray, Paul M.,Welham, Matthew J.,Wisedale, Richard,Young, Maureen J.,Moss, William O.
, p. 67 - 73 (2013/09/05)
Four neurokinin antagonists were assembled using a rapid parallel development approach. Research Department processes were scaled up if process safety and robustness were not compromised. Using this approach, 1 kg of each compound was rapidly delivered fo
Design, synthesis, and SAR of tachykinin antagonists: Modulation of balance in NK1/NK2 receptor antagonist activity
Albert, Jeffrey S.,Andisik, Donald,Barthlow, Herbert,Bernstein, Peter R.,Bialecki, Russell A.,Dedinas, Robert,Dembofsky, Bruce T.,Hill, Daniel,Kirkland, Karin,Koether, Gerard M.,Kosmider, Benedict J.,Ohnmacht, Cyrus,Palmer, William,Potts, William,Rumsey, William,Shen, Lihong,Shenvi, Ashok,Sherwood, Scott,Aharony, David,Warwick, Paul J.,Russell, Keith
, p. 3972 - 3983 (2007/10/03)
Through optimization of compounds based on the dual NK1/NK2 antagonist ZD6021, it was found that alteration of two key regions could modulate the balance of NK1 and NK2 potency. Substitution of the 2-naphthalene position in analogues of ZD6021 resulted in increased NK1 potency and thus afforded NK1 preferential antagonists. Alterations of the piperidine region could then increase NK2 potency to restore dual NK1/NK2 selectivity. Through these efforts, three novel receptor antagonists from a single chemically related series were identified; two are dual NK1/NK2 antagonists, and the third is an NK1 preferential antagonist. In this paper, the factors affecting the balance of NK1 and NK2 selectivity in this series are discussed and the in vitro and in vivo properties of the novel antagonists are described.
