Substituted 6,11-ethano-6,11-dihydrobenzo[B]quinolizinium salts and compositions and methods of use thereof

A pharmaceutical composition which comprises a compound of the formula:

• ##STR235## wherein:
• R.sup.1 is hydrogen, or from one to four, the same or different, substituents in any of the 1-,2-, 3- or 4- positions selected from the group consisting of lower-alkoxy, lower-alkyl, halogen, hydroxy, OC(O)alkyl-CH=CH-alkyl, OC(O)alkyl, OC(O)-lower-alkenyl-C(O)Oalkyl, alkoxy, OC(O)alkylC(O)Oalkyl, hydroxymethyl, nitro, amino and lower-alkylsulfonylamino or R.sup.1 is a fused benzene ring;
• R.sup.2 is hydrogen, lower-alkyl, cyano or lower-alkoxycarbonyl;
• R.sup.3 and R.sup.4 are independently hydrogen, or lower-alkyl;
• or R.sup.3 and R.sup.4 together form a cycloalkyl ring, or a lower alkylidene group;
• R.sup.5 and R.sup.6 are independently a 5-membered heterocyclic ring system or said 5-membered heterocyclic ring system substituted on any available carbon atom thereof by hydroxy, lower-alkyl, oxo, nitro, halogen, or lower-alkoxy;
• or on any available nitrogen atom thereof by loweralkyl, phenyl-lower-alkyl trilower-alkylsilyl, lower-alkylphenylsulfonyl, or trilower-alkylsilyl-lower-alkoxy-lower-alkyl;
• or R.sup.3 and R.sup.5, and/or R.sup.4 and R.sup.6 taken together with the cabon atoms to which they are attached form a bicyclic ring system of the formula A:
• ##STR236## wherein A is a 5-membered heterocyclic ring system and n is one (or said A ring substituted on any available carbon atom thereof by lower-alkoxy, or lower-alkyl);
• R.sup.7 is hydrogen, or from one to four, the same or different, substituents in any of the 7-, 8-,9-, or 10- positions selected from the group consisting of lower-alkyl, lower-alkanoyloxy, halogen, nitro, hydroxy, lower-alkoxy, methylenedioxy, polyfluorolower-alkyl, OCO(CH.sub.2).sub.m C(O)Oalkyl, OC(O)alkyl, C(O)Oalkyl, CO.sub.2.sup.-, carboxy, sulfo, SO.sub.3.sup.-, PO.sub.3 H;
• PO.sub.3.sup.- cyano, polychlorolower-alkyl, OC(O)alkyl-CH=CH-alkyl, OC(O)-lower-alkenyl-C(O)Oalkyl, alkoxy, OC(O)alkylC(O)Oalkyl, halomethyl, hydroxymethyl, amino and lower-alkylsulfonylamino wherein m is an integer from one to four and/or R.sup.7 is a fused pyrazole ring;
• X.sup.- is an anion;
• and p is zero when R.sup.7 is a negatively charged radical and p is one when R.sup.7 is other than a negatively charged radical;
• or a pharmaceutically acceptable acid-addition salt of basic members thereof;
• or a solvate thereof;
• or a stereoisomer thereof;
• together with a pharmaceutically acceptable carrier, adjuvant, diluent or vehicle, with the proviso that at least one of R.sup.5 and R.sup.6 when taken individually must be a substituted or unsubstituted 5-membered heterocyclic ring system and R.sup.5 and R.sup.6 cannot be furanyl.

A method for the treatment or prevention of neurotoxic injuries which comprises administering to a patient in need of such treatment an effective amount of a compound of the formula:

• ##STR237## wherein:
• R.sup.1 is hydrogen, or from one to four, the same or different, substituents in any of the 1-,2-, 3- or 4- positions selected from the group consisting of lower-alkoxy, lower-alkyl, halogen, hydroxy, OC(O)alkyl-CH=CH-alkyl, OC(O)alkyl, OC(O)-lower-alkenyl-C(O)Oalkyl, alkoxy, OC(O)alkylC(O)Oalkyl, hydroxymethyl, nitro, amino and lower-alkylsulfonylamino or R.sup.1 is a fused benzene ring;
• R.sup.2 is hydrogen, lower-alkyl, cyano or lower-alkoxycarbonyl;
• R.sup.3 and R.sup.4 are independently hydrogen, or lower-alkyl;
• or R.sup.3 and R.sup.4 together form a cycloalkyl ring, or a lower alkylidene group;
• R.sup.5 and R.sup.6 are independently a 5- membered heterocyclic ring system or said 5-membered heterocyclic ring system substituted on any available carbon atom thereof by hydroxy, lower-alkyl, oxo, nitro, halogen, or lower-alkoxy;
• or on any available nitrogen atom thereof by lower-alkyl, phenyl-lower-alkyl, trilower-alkylsilyl, lower-alkylphenylsulfonyl, or trilower-alkylsilyl-lower-alkoxy-lower-alkyl;
• or R.sup.3 and R.sup.5, and/or R.sup.4 and R.sup.6 taken together with the carbon atoms to which they are attached form a bicyclic ring system of the formula A:
• ##STR238## wherein A is a 5-membered heterocyclic ring system and n is one (or said A ring substituted on any available carbon atom thereof by lower-alkoxy, or lower-alkyl);
• R.sup.7 is hydrogen, or from one to four, the same or different, substituents in any of the 7-, 8-,9-, or 10-positions selected from the group consisting of lower-alkyl, lower-alkanoyloxy, halogen, nitro, hydroxy, lower-alkoxy, methylenedioxy, polyfluorolower-alkyl, OCO(CH.sub.2).sub.m C(O)Oalkyl, OC(O)alkyl, C(O)Oalkyl, CO.sub.2.sup.-, carboxy, sulfo, SO.sub.3.sup.-, PO.sub.3 H;
• PO.sub.3.sup.- cyano, polychlorolower-alkyl, OC(O)alkyl-CH=CH-alkyl, OC(O)-lower-alkenyl-C(O)Oalkyl, alkoxy, OC(O)alkylC(O)Oalkyl, halomethyl, hydroxymethyl, amino and lower-alkylsulfonylamino wherein m is an integer from one to four and/or R.sup.7 is a fused pyrazole ring;
• X.sup.- is an anion;
• and p is zero when R.sup.7 is a negatively charged radical and p is one when R.sup.7 is other than a negatively charged radical;
• or a pharmaceutically acceptable acid-addition salt of basic members thereof;
• or a solvate thereof;
• or a stereoisomer thereof;
• together with a pharmaceutically acceptable carrier, adjuvant, diluent or vehicle, with the proviso that at least one of R.sup.5 and R.sup.6 when taken individually must be a substituted or unsubstituted 5-membered heterocyclic ring system and R.sup.5 and R.sup.6 cannot be furanyl.