HEXAHYDROAZEPINES

摘要

1285025 Hexahydroazepine derivatives JOHN WYETH & BRO Ltd 12 Aug 1969 [16 Aug 1968 4 Sept 1968 28 Jan 1969] 39201/68 42060/68 and 4694/69 Heading C2C Novel compounds of Formula I: and the acid addition and quaternary ammonium salts thereof, in which R1 is a hydrogen atom, a lower alkyl radical, a benzyl radical or a lower alkanoyl radical, R2 is a lower alkyl radical, R3 is a hydrogen atom, a lower alkyl, lower alkenyl, lower alkynyl, cyclopropylmethyl, lower alkanoyl, lower alkoxycarbonyl, formyl, phenacyl or phenethyl group both of which may be substituted in the benzene ring or a #- benzoylethyl radical which may be substituted in the benzene ring, n is 3 or 4, m is 0 or 1 with the proviso that n+m is always equal to 4, R is a hydrogen atom or a lower alkyl radical when m is 0, or a hydrogen atom only when m is 1, and the term "lower" means that the radical contains up to 6, preferably up to 4 carbon atoms, are generally prepared by (a) cyclizing a compound of Formula II: in which X is -CH 2 .NH 2 when Y is -(CH 2 ) 4 . - Hal, -(CH 2 ) 4 .OH or -(CH 2 ) 3 .COOAlk, or X is -CN when Y is -(CH 2 ) 3 .COOALK, or X is -COOAlk when Y is -(CH 2 ) 4 .NH 2 or -(CH 2 ) 3 .CN; Hal is a halogen atom and Alk is a lower alkyl radical, and, if necessary, reducing and/or alkylating or acylating the product or (b) reducing a compound of the Formula III: wherein X-Y is -N = CR-, R and R3 being as defined above and Y1 is -CH 2 -, or X-Y is and Y1 is C=O, Z is R2 or COR4, R2 being as defined above and R4 being hydrogen or lower alkyl, p is 2 or 3 and m is 0 or 1 and m+p is 3. Other methods are also disclosed. Starting materials and intermediates are prepared according to the following reaction schemes: Pharmaceutical compositions having analgesic activity and, in some eases, the ability to antagonise narcotic analgesics, comprise a compound of Formula I together with a pharmaceutical carrier. The compositions may be administered orally or parenterally.