| 摘要 |
1,195,066. Quinazolinones. SANDOZ Ltd. 21 Aug., 1967 [29 Aug., 1966; 4 May, 1967], No. 38358/67. Heading C2C. Novel 2-quinazolinones of the general Formula (I): wherein R is H, F, Cl, or Br; R 1 is C 1 to C 5 alkyl (other than tertiary alkyl having the tertiary C atom directly attached to the quinazolinone N atom), allyl or propargyl; and R 2 is phenyl or substituted phenyl of formula wherein Y is F, Cl, Br, OH, C 1 to C 4 alkyl, C 1 to C 4 alkoxy, or CF 3 ; and Y 1 is H, F, Cl, Br, C 1 to C 4 alkyl, or C 1 to C 4 alkoxy, are prepared by (1) reacting a compound of the general formula wherein R, R 1 and R 2 are as above, at a temperature of 140‹ C. or higher, with an alkyl (C 1 to C 5 ) carbamate in the presence of a Lewis acid; or (2) reacting a quinazolinone corresponding to (I) above but having an alkali metal atom in place of R 1 , with a compound R 1 X, where X is Br, Cl, or Iodine, in an inert organic solvent; or (3) if R 1 is methyl, oxidizing a compound of general Formula (VI): or of general Formula (VII): R 1 , R 2 and X being as above; or (4) if R 1 is C 1 to C 5 alkyl as defined above and one or both of Y and Y 1 are hydroxy, hydrolysing the corresponding compound in which one or both of Y and Y 1 are C 1 to C 4 alkoxy, under acidic conditions. The novel intermediates (VI) are prepared by reacting a quinazoline with CH 3 X, and are reduced to give the novel compounds (VII). 4 - (p - Chlorophenyl) - quinazoline is prepared from quinazoline and p-chlorophenyl-lithium and the 4-p-chlorophenyl-3,4-dihydroquinazoline produced is oxidized. Pharmaceutical compositions having anti-inflammatory activity comprise compounds of Formula (I) together with a physiologically acceptable carrier or diluent, and may be in forms for oral or parenteral administration, including oral prolonged release form. |
