Patent GB-1271082-A (GB)
Title: Furan, pyrrole and thiophene derivatives
Inventor: CAVALLA JOHN FREDERICK
IPC: C07D207/333
Filed: 1968-05-07
Abstract: 1,271,082. Furyl-, pyrryl- and thienylaliphatic carboxylic acids. JOHN WYETH & BRO. Ltd. 6 May, 1969 [7 May, 1968], No. 21615/68. Heading C2C. 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 Ar<SP>1</SP> 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, Ar<SP>1</SP>, R<SP>1</SP> and H; R<SP>1</SP> 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-(4<SP>1</SP>-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- (1<SP>1</SP>-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 α#-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 α#-di-(p-fluoro- or chlorobenzoyl)ethyl-malonic acid); 2,5 - diphenyl -fur - 3 - yl - malonic acid diethyl ester (prepared by cyclization of diethyl α#-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-(4<SP>1</SP>-morpholino)- styrene and ethyl 4 - bromo - 4 - phenylacetoacetate); ethyl 4,7 - dioxo - 5,6 - diphenylheptanoate (prepared from 2-(1<SP>1</SP>-pyrrolidino)- styrene and ethyl 5-bromo-4-oxo-5-phenylvalerate); 3 - benzoyl - 5 - oxo - 4 - phenylvaleric acid (prepared from 2-(1<SP>1</SP>-pyrrolidino)styrene and #-benzoyl-#-bromopropionic acid) and its ethyl ester; 1,2-dibenzoyl-1-methyl-ethylene (prepared from mesaconyl dichloride and benzene); diethyl α# - dibenzoylpropylmalonate (prepared from 1,2-dibenzoyl- 1 -methylethylene and diethyl malonate), and the corresponding acid; and 3,4-dibenzoylvaleric acid (prepared by heating α#-dibenzoylpropylmalonic acid). Pharmaceutical compositions comprise a compound I together with a suitable carrier and/or diluent, and have anti-inflammatory activity.