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160969-03-9Relevant articles and documents
Preparation method of silodosin intermediate
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, (2019/04/13)
The invention discloses a preparation method of a silodosin intermediate and relates to the technical field of chemical synthesis of drugs. The preparation method comprises the following steps: subjecting salicyaldehyde and ethylene carbonate to transesterification to obtain 2-(2-hydroxyethoxy)benzaldehyde; then, carrying out a Dakin oxidation reaction to obtain sodium 2-(2-hydroxyethoxy) phenol;then, subjecting sodium 2-(2-hydroxyethoxy) phenol and trifluoroethanol to an etherification reaction to obtain 2-[2-(2,2,2-trifluoroethyoxy)phenoxy]ethyl alcohol; and finally, subjecting 2-[2-(2,2,2-trifluoroethyoxy)phenoxy]ethyl alcohol and methanesulfonyl chloride to an esterfication reaction to obtain the silodosin intermediate 2-[2-(2,2,2-trifluoroethyoxy)phenoxy]ethyl methanesulfonate. The preparation method is novel and short in synthesis route, and a target product can be prepared by only four-step reaction. Both raw materials and reagents used for preparation are cheap, available andenvironment-friendly, all the reaction conditions are mild and controllable, the preparation method is convenient and simple in operation, and the prepared silodosin intermediate is high in purity andyield, suitable for industrial production and wide in prospect and industrial application value.
N-Arylpiperazinyl-N'-propylamino derivatives of heteroaryl amides as functional uroselective α1-adrenoceptor antagonists
Elworthy, Todd R.,Ford, Anthony P. D. W.,Bantle, Gary W.,Morgans Jr., David J.,Ozer, Rachel S.,Palmer, Wylie S.,Repke, David B.,Romero, Magarita,Sandoval, Leticia,Sjogren, Eric B.,Talamás, Francisco X.,Vazquez, Alfredo,Wu, Helen,Arredondo, Nicolas F.,Blue Jr., David R.,DeSousa, Andrea,Gross, Lisa M.,Kava, M. Shannon,Lesnick, John D.,Vimont, Rachel L.,Williams, Timothy J.,Zhu, Quan-Ming,Pfister, Jürg R.,Clarke, David E.
, p. 2674 - 2687 (2007/10/03)
Novel arylpiperazines were identified as α1-adrenoceptor (AR) subtype- selective antagonists by functional in vitro screening. 3-[4-(ortho- Substituted phenyl)piperazin-1:yl]propylamines were derivatized with N,N- dimethyl anthranilamides, nicotinamides, as well as carboxamides of quinoline, 1,8-naphthyridine, pyrazolo[3,4-b]pyridine, isoxazolo[3,4- b]pyridine, imidazo[4,5-b]pyridine, and pyrazolo[1,5-a]pyrimidines. Strips of rabbit bladder neck were employed as a predictive assay for antagonism in the human lower tract. Rings of rat aorta were used as a 'negative screen' for the test antagonists. Binding to α1-ARs was relatively sensitive to size and electronic features of the arylpiperazine portion of the antagonists and permissive to these features on the heteroaryl carboxamide side. These structure-affinity findings were exploited to produce nicotinamides (e.g. 13ii and 25x) and pyrazolo[3,4-b]pyridines (e.g. 37f and 37y) ligands with nanomolar affinity at the α1-AR subtype prevalent in the human lower urinary tract (pA2 values: 8.8, 10.7, 9.3, and 9.9, respectively) and displaying 2-3 orders of magnitude selectivity over the α(1D)-AR.
N-ARYLOXYALKYL TRYPTAMINE ALPHA1-ADRENERGIC RECEPTOR ANTAGONISTS
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, (2008/06/13)
The present invention relates to novel N-aryloxyalkyl tryptamine . alpha. 1-adrenergic receptor antagonists of the formula I: STR1 in which n is 2, 3 or 4; q is 1, 2 or 3; t is 0, 1, 2 or 3; z is 0, 1, 2 or 3; each R 1 and R 2 are independently hydroxy, halogen, cyano, (C 1-8)alkyl, (C 1-8)alkyloxy or trifluoromethyl; and R 2 is hydrogen, (C 1-4)alkyl, fluoro(C 1-4)alkyl, difluoro(C 1-4) alkyl, trifluoro(C 1-4)alkyl, (C 1-4) alkyloxy(C 1-4)alkyl, oxo(C 1-4)alkyl, (C 1-8)cycloalkyl, (C. sub.1-8)cycloalkylmethyl or allyl or phenyl(C 1-4)alkyl or heterocyclo(C 1-8)alkyl (optionally substituted with one to two substituents independently selected from (C 1-4)alkyl, (C 1-4) alkyloxy, trifluoromethyl and halogen); R. sup.3 and R 4 are independently hydrogen, (C 1-4) alkyl, (C 1-8)cycloalkyl, (C 1-8)cycloalkylmethyl or allyl; and R. sup. 5 is hydrogen, (C 1-4)alkyl, (C 1-8)cycloalkyl, (C 1-8) cycloalkylmethyl, allyl, (C 1-4) alkylsulfonyl and aminocarbonyl; with the proviso that when n is 2, t is 0, q is 1, z is 0, 1 or 2, R 5 is hydrogen and R 6 is hydroxy or (C 1-8)alkyloxy then at least one of R 3 and R 4 is not hydrogen; and the pharmaceutically acceptable salts, individual isomers, and mixtures of isomers thereof; their uses as therapeutic agents and the methods of their making.
