Patent GB-1453885-A (GB)
Title: Cyctopenla-j,k-phenanthren-4-yl alkanoic acids and their derivatives
IPC: C07C229/40
Filed: 1974-04-29
Abstract: 1453885 Cyclopenta[j, k]pheranthren-4-ylalkanoic acids and derivatives MERCK & CO Inc 29 April 1974 [4 May 1973] 18578/74 Heading C2C Novel compounds I in which each of R 1  and R 2  is hydrogen or alkyl; R 3  is hydrogen, alkyl, halogen, halogenated alkyl, phenyl, alkylthio, phenylthio, alkenyl, alkoxyphenyl or benzyl; R 4 , R 5  and R 6  are each hydrogen, halogen, alkyl, acyloxy, alkoxy, benzyloxy, halogenated benzyloxy, (C 1-5  alkyl)-benzyloxy, acylamino, alkylamino, dialkylamino, dialkylaminoalkyl, sulfamoyl, alkylthio, mercapto, hydroxy, hydroxyalkyl, alkenyl, alkenyloxy, alkylsulfinyl, alkylsulfonyl, dialkylsulfamoyl, carboxyl, carbalkoxy, carbamido, cyano, halogenated alkyl, cycloalkyl, phenyl, benzyl, benzylthio, phenoxy or cycloalkoxy, or R 5  is joined to R 6  to form a methylenedioxy radical and R 4  is hydrogen or R 5  is joined to R 4  to form a butadienylene radical and R 6  is hydrogen; R 7  is hydrogen, halogen, methyl, alkylthio, alkenylsulfinyl or alkylsulfonyl; R 8  is hydrogen, halogen, hydroxy, alkoxy, haloalkyl, phenyl, alkanoylamino or alkanoyl; and M is hydroxy, C 1-5  alkoxy, C 2-5  alkenyloxy, phenoxy, substituted C 1-5  alkoxy, amino, alkylamino, dialkylamino, N-morpholino, hydroxyalkylamino, polyhydroxyalkylamino, dialkylaminoalkylamino, aminoalkylamino, #- D - glucopyranuronyloxy, benzylamino, phenethylamino, (benzyloxycarbonylmethyl)amino, carboxymethylamino, 1 - piperidinyl, 1 - pyrrolidinyl, 1 - piperazinyl, 4 - methyl - 1 - piperazinyl, 4 - phenyl - 1 - piperazinyl, 4 - (2 - hydroxyethyl) - 1 - piperazinyl, 2 - hydroxyethylamino, 2 - ethoxyethylamino, di - (#- ethoxyethyl)amino, anilino, p - ethoxyanilino, p - chloroanilino, p - fluoroanilino, p - trifluoromethylanilino, cyclohexylamino, D- glucosamino, tetra - O - acetyl - D - glucosamino, D - galactosylamino, D - mannosylamino, D - mannosamino, or the group OMe, in which Me is a cation, or are anhydrides of the acids are prepared by cyclizing a compound II and if desired hydrolysing an ester to the free acid and forming an ester, amide or anhydride derivative from the free acid by known methods. Compounds II (M=OCH 3 , R 1 =H and R 1  = H or Me) are prepared by condensing a corresponding 7-iodo-3-indenyl-aliphatic acid with an R 7 , R 8  substituted 2-iodobenzaldehyde. The 2-iodobenzaldehydes are prepared by diazotization of an anthranilic acid and reaction with KI to produce the corresponding 2-iodobenzoic acid which is reduced to the aldehyde. Substituted anthranilic acids are prepared by reduction of 2-nitrobenzoic acids. 4-Methylthio- 2-nitrobenzoic acid is prepared reacting the corresponding 4-chloro compound with MeSH. The 7 - iodo - 3 - indenyl - acetic and α -(7- iodo-3-indenyl)propionic acids are prepared by reacting a 4-iodo-indanone with an α-bromoacetate or propionate followed by dehydration. 4-Iodo-indanones are prepared by nitration using KNO 2  or NaNO 2  at the 4-position of an indanone, reduction to the amino group and diazotization followed by treatment with KI. Compounds I have anti-inflammatory, analgesic and anti-pyretic activity and form with a carrier a pharmaceutical composition which may be administered orally, parenterally, rectally or topically.