Patent GB-1185934-A (GB)
Title: Derivatives of 1,3(2H,4H)-Dioxoisoquinoline and preparation thereof
IPC: C07D217/26
Filed: 1967-11-24
Abstract: 1,185,934. Derivatives of 1,3-(2H,4H)-dioxoisoquinoline. CHAS. PFIZER & CO. Inc. 24 Nov., 1967 [28 June, 1967; 11 Oct., 1967], No. 53700/67. Heading C2C. The invention comprises novel derivatives of 1,3-(2H,4H)-dioxoisoquinoline of the Formulµ I and II wherein R 1  is H; C 1-6  alkyl; C 2-6  alkenyl; cycloalkyl containing up to 6 C atoms; -OCH 3 ; -OH; benzyloxy; propargyl; 2-furyl; 2-tetrahydrofuryl ; furfuryl; tetrahydrofurfuryl; phenyl with up to one substitutent selected from F, Cl, Br, C 1-2  alkoxy, C 1-3  alkyl, -CF 3 , -NO 2 , -NH 2 , CH 3 SO 2 - CF 3 SO 2 -, (CH 3 ) 2 NSO 2 -, CH 3 CONH-, and -OH; or benzyl with up to one nuclear substituent selected from F, Cl, Br, C 1-2  alkoxy, C 1-3  alkyl, -CF 3 , -NO 2 , -NH 2 , CH 3 SO 2 - CF 3 SO 2 -, (CH 3 ) 2 NSO 2 -, CHgCONH-, and -OH; R 2  is primary or secondary C 1-6  alkyl; primary or secondary C 2-6  alkenyl; primary or secondary C 3-6  alkynyl; or alkoxyethyl containing up to 4 C atoms; R 3  is H, C 1-6  alkyl; C 2-6  alkenyl; C 3-5  alkynyl; cycloalkyl containing up to 6 C atoms; carbalkoxyalkyl containing up to 5 C atoms; polyfluoroalkyl containing up to 3 C atoms; acyl containing up to 4 C atoms; benzoyl; tetrahydrofurfuryl; adamentyl; pyridyl; phenyl containing up to 2 substituents each selected from F, Cl, Br, C 1-2  alkoxy, -C 1-3  alkyl, CH 3 CO; CF 3 -, -NO 2 , -N-H 2 , CH 3 SO 2 -, CF 3 SO 2 -, (CH 3 ) 2 NSO 2 -, CH 3 CONH-, and OH; naphthyl with up to 1 substituent selected from the above group; or aralkyl containing up to 8C atoms with up to 1 nuclear substituent selected from the above group; or R 2  and R 3 , taken together with the N atom form a pyrrolidine, piperidine, hexamethyleneimine, morpholine, piperazine, N-methylpiperazine or N- phenyl piperazine ring; provided that R 2  is always H when R 3  is tertiary alkyl, tertiary alkenyl, tertiary alkynyl, nitro-substituted phenyl, nitre-substituted aralkyl or acyl; and X 1  and X 2  are each H; F; CP; Br; C 1-2  alkoxy; C 1-3  alkyl; CH 3 CO-; CF 3 -; NO 2 ; NH  2 ; CH 3 SO 2 ; CF 3 SO 2 ; (CH 3 ) 2 NSO 2 ; OH or CH 3 CONH-; and compounds of the Formulµ V and VI wherein R 5  is C 1-6  alkyl. The carboxamides of the Formulµ I and II, wherein R 2  and R 3  are both hydrogen are prepared by reacting inorganic cyanates with the appropriate 1,3(2H, 4H) - dioxoisoquinolines or 5,6,7,8 - tetrahydro- 1,3(2H,4H) - dioxoisoquinolines, which are obtained by treating the corresponding homophthalic acid or tetrahydrohomophthalic acid respectively with an amine of the formula R 1 NH 2 . Compounds of Formulµ I and II wherein R 2 . is H and R 5  is other than H are made by reacting the appropriate 1,3(2H,4H). dioxoisoquinolines or tetrahydroderivatives thereof with an isocyanate of the formula R 3 NCO, or by the aminolysis of the corresponding compounds of Formulµ V and VI with an amine of the formula R 3 NH 2 , or by heating the corresponding compounds of Formulµ I and II wherein R 2  is H and R 3  is substituted or unsubstituted phenyl with a primary amine of the formula R 3 NH 2 . The last two mentioned methods are also suitable for the preparation of compounds of Formulµ I and II wherein neither R 2  nor R 3  is hydrogen, substituting secondary amines of the formula R 2 (R 3 )NH for the amines of formula R 3 NH 2 . Compounds of Formulµ V and VI are obtained by treating the corresponding compounds of Formulµ I and II,  wherein R 2  is H and R 3  is substituted or unsubstituted phenyl with an excess of an alkanol containing up to 6 C atoms, for at least one hour at a temperature of from 50‹ C. to reflux temperature. Pharmaceutical compositions, having anti- . inflammatory activity and suitable for oral or parenteral administration, contain the above novel carboxamides of Formulµ I and II as the active ingredient and a pharmaceutical carrier.