GB1058427A - Novel benzdiaz[1,4]epine derivatives and the manufacture thereof - Google Patents

Abstract

Compounds of the general formula <FORM:1058427/C2/1> (wherein S stands for substitution, which comprises up to two of the substituents halo, trifluoromethyl, nitro, lower alkyl and amino, A stands for a lower alkylene group, R1 stands for a lower alkyl, lower alkoxy or phenyl group or the group B defined hereinafter, R2 stands for a pyridyl group or a phenyl group which may carry one of the substituents listed for S, R3 stands for a lower alkyl, lower alkanoyloxy or hydroxy group, R4 stands for a lower alkyl group or the group -A-CO-B, B stands for an amino group which may be mono- or disubstituted by lower alkyl, lower alkenyl or phenyl groups, the broken lines denote bonds to optional substituents, the curved arrow denotes that a double bond may be present in the 4,5-position in the absence of an R4 substituent and the term "lower " denotes groups containing not more than seven carbon atoms), N4-oxides of the 4,5-dehydro compounds which do not have an oxygen-containing value of R3 present in the 3-position and acid addition and quaternary salts of the compounds and oxides, are prepared by reacting a compound of the formula <FORM:1058427/C2/2> (wherein R30 stands for a lower alkyl group) or an N4-oxide of a 4,5-dehydro compound or a 1-sodio derivative of either with a compound of the formula R1-CO-A-X (wherein X stands for a chlorine, bromine or iodine atom) and then, if required, modifying the product of the formula <FORM:1058427/C2/3> by one or more of the steps (a) removing any N4-oxide substituent therein by reduction with hydrogen in the presence of Raney nickel or with a phosphorus trihalide; (b) reducing any double bond in the 4,5-position thereof with hydrogen in the presence of a platinum oxide catalyst; (c) appropriately alkylating the product if R4 is absent; (d) quaternizing and subsequently reducing the product if it contains a double bond in the 4,5-position, a borohydride being used for the reduction; (e) reducing any nitro substituent therein to amino and then replacing the latter by halo if desired; (f) replacing any amino substituent therein by halo; (g) introducing an alkanoyloxy group and at the same time removing an N4-oxide substituent from the product when it is a 3-unsubstituted 4-oxide and, if desired, saponifying the resulting 3-alkanoyloxy compound; (h) converting the product into an acid addition or quaternary salt. The compounds of the invention are anticonvulsants and may be administered enterally or parenterally in the form of pharmaceutical preparations which contain them, with or without other (unspecified) active ingredients, in association with a carrier.