142001-92-1Relevant academic research and scientific papers
4-Amino-2-(aryl)-butylbenzamides and their conformationally constrained analogues. Potent antagonists of the human neurokinin-2 (NK2) receptor
MacKenzie, A. Roderick,Marchington, Allan P.,Middleton, Donald S.,Newman, Sandra D.,Selway, Christopher N.,Terrett, Nicholas K.
, p. 2211 - 2215 (2007/10/03)
A library, evaluating a range of piperazines, piperidines and acyclic amines, as replacements for the 4-hydroxy-4-phenylpiperidine moiety in lead (1b) was prepared. These efforts identified the 4-((N)-benzimidazolone)piperidine analogue (2a) which was further optimised using classical single-compound synthesis to yield the 3-((N)-morpholino)azetidine (2j). Conformationally constrained analogues of (2j), generally offered no potency advantage in this particular series.
Spiro-substituted piperidines as neurokinin receptor antagonists. I. Design and synthesis of (±)-N-[2-(3,4-Dichlorophenyl)-4- (spiro[isobenzofuran-1(3H),4'-piperidin]-1'-yl)butyl]-N-methylbenzamide, YM- 35375, as a new lead compound for novel neurokinin receptor antagonists
Kubota, Hirokazu,Fujii, Masahiro,Ikeda, Ken,Takeuchi, Makoto,Shibanuma, Tadao,Isomura, Yasuo
, p. 351 - 354 (2007/10/03)
Analysis of the structural requirements of compound 1 (SR48968), a potent NK2 receptor antagonist, revealed that the 4-phenyl group of the piperidine is essential for binding with the NK2 receptor and occupies an equatorial position. Energy calculation of a variety of substituted 4-phenyl piperidines revealed that spiro[isobenzofuran-1(3H), 4'-piperidine] possesses a conformationally restricted equatorial phenyl group. Our compound 12 (YM- 35375) possessing this spiro-substituted piperidine bound to the NK2 receptor with an IC50 value of 84nM and to the NK1 receptor with an IC50 value of 710nM. It showed more potent inhibitory activity (ID50 41μg/kg (i.v.)) against [β-Ala8]-NKA(4-10)-induced bronchoconstriction in guinea pigs than (±)-SR48968 (ID50 68μg/kg (i.v.)). YM-35375 may be a new lead compound for novel NK2 receptor antagonists or NK1-NK2 dual antagonists.
PIPERIDINE DERIVATIVES, PROCESS FOR OBTAINING THEM AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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, (2008/06/13)
Piperidine derivatives, process for obtaining them and pharmaceutical compositions containing them, of formula STR1 used as neurokinin receptor antagonists, which are, in particular, useful for the treatment of all substance P-and neurokinin-dependent pathologies.
Aryl substituted heterocycles
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, (2008/06/13)
The present invention concerns the novel use of aryl substituted heterocycles of formula I, set out below, which antagonize the pharmacological actions of one of ent endogenous neuropeptide tachykinins an the neurokinin 2 (NK2) receptor making them useful whenever such antagonism is desired, such as in the treatment of asthma and related conditions. The invention also provides pharmaceutical compositions containing the aryl substituted heterocycles for use in such treatment. Certain novel aryl substituted heterocycles of formula I and novel intermediates for their manufacture are also provided. STR1
Therapeutic heterocycles which antagonize neurokinin receptors
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, (2008/06/13)
Compounds of formula I STR1 wherein G, J, L, M, m and D have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of neurokinin A and useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.
N-ALKYLENEPIPERIDINO COMPOUNDS, THEIR ENANTIOMERS AND PHARMACEUTICAL COMPOSITIONS
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, (2008/06/13)
The invention relates to N-alkylenepiperidino compounds of formula STR1 as well as their enantiomers, and pharmaceutical compositions containing them that are useful as antagonists of neurokinin receptors in the treatment of substance P-and/or neurokinin-independent pathologies.
