Patent GB-1064262-A (GB)
Title: Substituted -a-(3-indolyl)-aliphatic or aryl-substituted aliphatic acids and derivatives
IPC: A61K8/49
Filed: 1964-06-03
Abstract: Novel compounds of formula <FORM:1064262/C2/1> n which R is a hydrogen or halogen atom, or a C1- 5 alkyl, C1- 5 alkoxy, haloalkyl, hydroxy, aryl, aryloxy, aralkyloxy, alkenyloxy, alkynyloxy, cycloalkoxy, cycloalkylalkoxy, nitro, cyano, morpholinyl, amino, substituted amino, aminoalkyl, substituted aminoalkyl, mercapto, C- 5 alkylthio, benzylthio, alkylsulphonamido, dialkylsulphonamido, or C1- 5 alkylsulphonyl radical; R1 is hydroxy, C1- 8 alkoxy, dialkylaminoalkoxy aralkoxy, amino, substituted amino or an -OM radical M being a cation; R2 is a hydrogen atom or C1- 8 hydrocarbon radical; R3 is a hydrogen atom or a C1- 5 alkyl, aralkyl or alkenyl radical; Y is an oxygen, sulphur or nitrogen atom, said nitrogen atom having a hydrogen atom or a C1- 8 hydrocarbon radical attached to it; and A is an aryl, substituted aryl, heteroaryl or substituted heteroaryl radical; are prepared by reacting an N1-alkali metal salt a compound of formula <FORM:1064262/C2/2> in which R1 is a C1- 8 alkyl or C7- 8\t aralkyl radical, with a compound of formula A-Y-CO-Cl in which A and Y are as defined above except that Y is not -NH-, or for compounds wherein Y is -NH-, with an isocyanate of formula A-N=C=O at - 30 DEG  to 150 DEG  C. in an inert organic solvent, followed, if desired, by (1) conversion of the ester to the acid by heating with a dilute solution of a strong alkali, (2) treatment of the acid with a mild dehydrating agent to form the anhydride, and then reaction of the anhydride with ammonia or an amine to produce the amide, (3) conversion of the acid to a salt which is then reacted with an acid chloride to form a mixed anhydride which is treated with ammonia or an amine to produce an amide, (4) reaction of the acid with an alcohol in the presence of an acidic catalyst to form an ester, (5) reaction of the acid with a mild dehydrating agent to form the anhydride, or conversion of the acid to a salt which is reacted with an acid chloride to form a mixed anhydride, the anhydride then being reacted with an alcohol in the presence of a non-hydroxylic base, or with an alkoxide, to produce an ester.  The acids, esters or amides may also be prepared by acylation of the corresponding N-1 unsubstituted acid, ester or amide with an acid halide of formula A-CO-Y-X where Y is as defined above except that Y is not an -NH-radical, and X is a halogen atom, in an anhydrous organic solvent.  The benzyl esters may be converted to the free acid by hydrogenolysis, and tertiary alkyl esters such as the t-butyl ester may be converted to the free acid by heating above 210 DEG  C. or by heating at 25-110 DEG  C. in the presence of a catalytic amount of an acid.  The synthesis of various compounds having a 5-substituent which has a nitrogen atom attached to the benzene ring of the indole nucleus is generally based on the 5-nitro compound, the 5-nitro group being transformed by various methods. Compounds having a 5-hydroxy substituent may be prepared from the corresponding 5-alkoxy or 5-benzyloxy compounds. Salts of the acids are prepared by treating the free acid with a base.  Benzyl a  - (2 - methyl - 5 - methoxy - 3 - indolyl)-acetate is prepared by treating the corresponding methyl ester with benzyl alcohol.ALSO:Synthetic plastics or resins, e.g. a polystyrene, polyethylene, or polypropylene, or a polyacrylic, polyamide or polyester resin contain ultra-violet absorbers of formula <FORM:1064262/C3/1> in which R is hydrogen, halogen, C1- 5 alkyl, C1- 5 alkoxy, haloalkyl, hydroxy, aryl, aryloxy, aralkyloxy, alkenyloxy, alkynyloxy, cycloalkoxy, cycloalkylalkoxy, nitro, cyano, morpholinyl, amino, substituted amino, aminoalkyl, substituted aminoalkyl, mercapto, C1- 5 alkylthio, benzylthio, alkyl- or dialkyl-sulphonamido or C1- 5 alkylsulphonyl; R1 is hydroxy, C1- 8 alkoxy, dialkylaminoalkoxy, aralkoxy, amino, substituted amino or an-OM radical, M being a cation; R2 is hydrogen or a C1- 8 hydrocarbon radical; R3 is hydrogen, or C1- 5 alkyl, aralkyl or alkenyl; Y is an oxygen, sulphur or nitrogen atom, said nitrogen atom having a hydrogen atom or a C1- 8 hydrocarbon radical attached to it; and A is an aryl, substituted aryl, heteroaryl or substituted heteroaryl radical.ALSO:Novel compounds of formula <FORM:1064262/A5-A6/1> in which R is a hydrogen or halogen atom, or a C1-5 alkyl, C1-5 alkoxy, haloalkyl, hydroxy, aryl, aryloxy, aralkyloxy, alkenyloxy, alkynyloxy, cycloalkoxy, cycloalkylalkoxy, nitro, cyano, amino, substituted amino, morpholinyl, aminoalkyl, substituted aminoalkyl, mercapto, C1-5 alkylthio, benylthio, alkylsulphonamido, dialkylsulphonamido, or C1-5 alkylsulhponyl radical; R1 is hydroxy, C1-8 alkoxy, dialkylaminoalkoxy, aralkoxy, amino, substituted amino, or an -OM radical, M being a cation; R2 is a hydrogen atom or C1-8 hydrocarbon radical, R3 is a hydrogen atom or a C1-5 alkyl, aralkyl or alkenyl radical; Y is an oxygen, sulphur or nitrogen atom, said nitrogen atom having a hydrogen atom or a C1-8 hydrocarbon radical attached to it; and A is an aryl, substituted aryl heteroaryl or substituted heteroaryl radical; comprise the active constituent of therapeutic compositions having analgesic, anti-inflammatory and antipyretic activity which may be administered orally, and, since they absorb ultra-violet light are used as sunscreening materials in salves and ointments.