GB1392254A - Tricyclic quinazolinone derivatives - Google Patents

Abstract

1392254 Tricyclic quinazolinone derivatives SANDOZ Ltd 11 July 1972 [15 July 1971] 32342/72 Heading C2C Novel compounds of the Formula I wherein either R 1 and R 2 are the same or different and each is hydrogen, fluorine, chlorine, or C 1-3 alkyl; or R 1 and R 2 each is hydroxy; or R I and R 2 each is C 1-2 alkoxy; or one of R 1 and R 2 is bromine, hydroxy or C 1-2 alkoxy and the other is hydrogen; n is 1, 2 or 3 and either R is C 1-5 alkyl or is a radical III or IV in which m is 1 or 2 and either Y and Y 1 are the same or different and each is hydrogen, fluorine, chlorine or C 1-3 alkyl; or Y and Y 1 each is hydroxy; or Y and Y 1 each is C 1-2 alkoxy; or one of Y and Y 1 is bromine, hydroxy or C 1-2 alkoxy and the other is hydrogen, with the proviso that (I) no more than two of R 1 , R 2 , Y and Y 1 is hydroxy; (II) R 1 and R 2 each is other than hydroxy when Y or Y 1 is C 1-2 alkoxy; (III) Y and Y 1 each is other than hydroxy when R 1 or R 2 is C 1-2 alkoxy; (IV) when R is a C 1-5 alkyl or a radical III in which m is 1 and Y and Y 1 each is hydrogen, then at least one of R 1 and R 2 is other than hydrogen, fluorine or chlorine and R 1 and R 2 may not both be a C 1-2 alkoxy, may be prepared by (a) reacting a compound V with a compound VI wherein W is oxygen or sulphur and R 4 is C 1-4 alkyl or benzyl; (b) for compounds Ia wherein R<SP>1</SP>, R<SP>1</SP> 1 and R<SP>1</SP> 2 are the same as R, Rl and R 2 except none is or contains a hydroxy group, by reacting a compound VII with a cyclizing agent and treating the resulting product with an acid-binding agent; (c) dealkylating a compound I in which at least one of R, R 1 and R 2 is or contains a C 1-2 alkoxy group to produce the corresponding compound I in which at least one of R, R 1 and R 2 is or contains a hydroxyl group. Intermediates of the Formula VII may be prepared by reacting an N-(R substituted) anthranilic acid with ammonium thiocyanate to produce an appropriately substituted 2-thio- 1,2,3,4 - tetrahydroquinazolin - 4 - one, which is reacted with methyl iodide to yield the corresponding 2 - methyl mercapto - 1,4 - dihydroquinazolin-4-one which is reacted with a C 2-4 alkanolamine to yield the required intermediate VII. Isatoic anhydride may be N-substituted using a compound RC1. Pharmaceutical compositions of the compound I show bronchodilatory activity when administered orally, parenterally or by inhalation with the usual excipients.