Patent ES-366842-A1 (ES)
Title: Pyrrole lower alkanoic acids and derivatives
IPC: C07D207/337
Filed: 1969-05-06
Abstract: Novel compounds I in which X is O, S or NY Y is H or an alkyl, cycloalkyl, aralkyl, aryl or heteroaryl radical which may be substituted or an acyl radical Z is H or alkyl Ar and Ar1 are aryl or heteroaryl radicals and R is an aliphatie acid radical of 2-6 C or a functional derivative thereof, the said radical being attached to the heterocyclic ring by a C of the aliphatic chain are prepared by cyclization of an appropriate substituted butane precursor, e.g. a compound wherein A, B, D and G are selected in any order from Ar, Ar1, R1 and H R1 being the same as R or a radical convertible thereto, with an appropriate cyclizing agent which introduces the hetero atom simultaneously. Compounds I may be converted into other compounds I by conventional methods. Aldehydic groups may be introduced into appropriate heterocyclic compounds and the aldehydic group then converted into the desired group R in known manner. Intermediates isolated are 3,4-dibenzoylbutyric acid (prepared from 1-(41-morpholino)styrene and 3-benzoyl-3-bromo-propionic acid) ethyl 3,6-dioxo-4,6-diphenyl-hexanoate (prepared from 1 - (41 - morpholino)styrene and ethyl 4- bromo - 4 - phenyl - acetoacetate) ethyl 4,7- dioxo-5,6-diphenylheptanoate (prepared from 2- (11-pyrrolidino)styrene and ethyl 5-bromo-4- oxo-5-phenyl-valerate) methyl 4,7-dioxo-6,7-diphenyl-heptanoate (prepared from methyl 5- bromo-4-oxo-valerate and the morpholino enamine of deoxybenzoin) ethyl 4,5-diphenyl-3- formyl-5-oxo-valerate (prepared from ethyl 3- bromo-4-oxo-butyrate and the morpholino enamine of deoxybenzoin) diethyl [alpha]#-di-(p-fluoro- or chlorobenzoyl)ethyl-malonate (prepared from 1,2 - di - (p - fluoro- or chlorobenzoyl)ethylene and diethyl malonate) and the corresponding acids (prepared by hydrolysis) 3,4-di-(p fluoro-or chlorobenzoyl)butyricacid (prepared by heating the [alpha]#-di-(p-fluoro- or chlorobenzoyl)ethyl-malonic acid) 2,5 - diphenyl -fur - 3 - yl - malonic acid diethyl ester (prepared by cyclization of diethyl [alpha]#-di-benzoylethyl-malonate with phosphoric oxide) ethyl 2-(p-chlorobenzoyl)- 3-benzoylpropionate (prepared from ethyl p-chlorobenzoylacetate and phenacyl bromide in the presence of sodium) 2-(p-chlorophenyl)-3-ethoxycarbonyl-5-phenylfuran (prepared by cyclization of the previous intermediate) ethyl 3-(pchlorobenzoyl) - 2 - benzoylpropionate and 5 - (pchlorophenyl) - 3 - ethoxy - carbonyl - 2 - phenylfuran (prepared similarly to the preceding intermediates) ethyl 3,6 - dioxo - 4,6 - diphenylhexanoate (prepared from 1-(41-morpholino)- styrene and ethyl 4 - bromo - 4 - phenylacetoacetate) ethyl 4,7 - dioxo - 5,6 - diphenylheptanoate (prepared from 2-(11-pyrrolidino)- styrene and ethyl 5-bromo-4-oxo-5-phenylvalerate) 3 - benzoyl - 5 - oxo - 4 - phenylvaleric acid (prepared from 2-(11-pyrrolidino)styrene and #-benzoyl-#-bromopropionic acid) and its ethyl ester 1,2-dibenzoyl-1-methyl-ethylene (prepared from mesaconyl dichloride and benzene) diethyl [alpha]# - dibenzoylpropylmalonate (prepared from 1,2-dibenzoyl- 1 -methylethylene and diethyl malonate), and the corresponding acid and 3,4-dibenzoylvaleric acid (prepared by heating [alpha]#-dibenzoylpropylmalonic acid). Pharmaceutical compositions comprise a compound I together with a suitable carrier and/or diluent, and have anti-inflammatory activity.