9-Hydroxyoctahydrobenzo[c]quinolines and their pharmaceutical compositions and method of use

A process for producing analgesia in a mammal which comprises administering to the mammal an analgesic producing quantity of a compound selected from the group consisting of those having the formula ##STR74## and the pharmaceutically acceptable acid addition salts thereof, wherein

• R.sub.1 is selected from the group consisting of hydrogen, benzoyl, alkanoyl having from one to five carbon atoms and --CO--(Ch.sub.2).sub.p --NR.sub.2 R.sub.3 wherein p is 0 or an integer from 1 to 4;
• each of R.sub.2 and R.sub.3 when taken individually is selected from the group consisting of hydrogen and alkyl having from one to four carbon atoms;
• R.sub.2 and R.sub.3 when taken together with the nitrogen to which they are attached form a 5- or 6-membered heterocyclic ring selected from the group consisting of piperidino, pyrrolo, pyrrolidino, morpholino and N-alkylpiperazino having from one to four carbon atoms in the alkyl group;
• R.sub.4 is selected from the group consisting of hydrogen, alkyl having from 1 to 6 carbon atoms and --(CH.sub.2).sub.z --C.sub.6 H.sub.5 wherein z is an integer from 1 to 4;
• R.sub.5 is selected from the group consisting of hydrogen, methyl and ethyl;
• R.sub.6 is selected from the group consisting of hydrogen, --(CH.sub.2).sub.y --carbalkoxy having from one to four carbon atoms in the alkoxy group and wherein y is 0 or an integer from 1 to 4, carbobenzyloxy, formyl, alkanoyl having from two to five carbon atoms, alkyl having from one to six carbon atoms and --(CH.sub.2).sub.x --C.sub.6 H.sub.5 wherein x is an integer from 1 to 4;
• and CO(CH.sub.2).sub.x-1 --C.sub.6 H.sub.5 ;
• Z is selected from the group consisting of
• (a) alkylene having from one to nine carbon atoms;
• (b) --(alk.sub.1).sub.m --X--(alk.sub.2).sub.n --wherein each of (alk.sub.1) and (alk.sub.2) is alkylene having from one to nine carbon atoms, with the proviso that the summation of carbon atoms in (alk.sub.1) plus (alk.sub.2) is not greater than nine;
• each of m and n is 0 or 1;
• X is selected from the group consisting of O, S, SO and SO.sub.2 ;
• and
• W is selected from the group consisting of hydrogen, methyl, pyridyl, piperidyl, ##STR75## wherein W.sub.1 is selected from the group consisting of hydrogen, fluoro and chloro;
• and ##STR76## wherein W.sub.2 is selected from the group consisting of hydrogen and ##STR77## a is an integer from 1 to 5 and b is 0 or an integer from 1 to 5;
• with the proviso that the sum of a and b is not greater than 5;
• and
• R' is selected from the group consisting of hydroxy, alkanoyloxy having 1 to 5 carbon atoms, hydroxymethyl, oxo, alkylene dioxy having from 2 to 4 carbon atoms and methylene.

A pharmaceutical composition in unit dosage form suitable for use as an analgesic, comprising a pharmaceutical carrier and, as active ingredient, from 0.01 to 50 mg. of a compound selected from the group consisting of those having the formula ##STR78## and the pharmaceutically-acceptable acid addition salts thereof, wherein R.sub.1 is selected from the group consisting of hydrogen, benzoyl, alkanoyl having from one to five carbon atoms and --CO--(CH.sub.2).sub.p --NR.sub.2 R.sub.3 wherein p is 0 or an integer from 1 to 4;

• each of R.sub.2 and R.sub.3 when taken individually is selected from the group consisting of hydrogen and alkyl having from one to four carbon atoms;
• R.sub.2 and R.sub.3 when taken together with the nitrogen to which they are attached form a 5- or 6-membered heterocyclic ring selected from the group consisting of piperidino, pyrrolo, pyrrolidino, morpholino and N-alkylpiperazino having from one to four carbon atoms in the alkyl group;
• R.sub.4 is selected from the group consisting of hydrogen, alkyl having from 1 to 6 carbon atoms and --(CH.sub.2).sub.z --C.sub.6 H.sub.5 wherein z is an integer from 1 to 4;
• R.sub.5 is selected from the group consisting of hydrogen, methyl and ethyl;
• R.sub.6 is selected from the group consisting of hydrogen, --(CH.sub.2).sub.y --carbalkoxy having from one to four carbon atoms in the alkoxy group and wherein y is 0 or an integer from 1 to 4, carbobenzyloxy, formyl, alkanoyl having from two to five carbon atoms, alkyl having from one to six carbon atoms and --(CH.sub.2).sub.x --C.sub.6 H.sub.5 wherein x is an integer from 1 to 4;
• and CO(CH.sub.2).sub.x-1 C.sub.6 H.sub.5 ;
• Z is selected from the group consisting of
• (a) alkylene having from one to nine carbon atoms;
• (b) --(alk.sub.1).sub.m --X--(alk.sub.2).sub.n --wherein each of (alk.sub.1) and (alk.sub.2 ) is alkylene having from one to nine carbon atoms, with the proviso that the summation of carbon atoms, in (alk.sub.1) plus (alk.sub.2) is not greater than nine;
• each of m and n is 0 or 1;
• X is selected from the group consisting of O, S, SO, and SO.sub.2 ;
• and
• W is selected from the group consisting of hydrogen, methyl, pyridyl, piperidyl, ##STR79## wherein W.sub.1 is selected from the group consisting of hydrogen, fluoro and chloro;
• and ##STR80## wherein W.sub.2 is selected from the group consisting of hydrogen and ##STR81## a is an integer from 1 to 5 and b is 0 or an integer from 1 to 5;
• with the proviso that the sum of a and b is not greater than 5;
• and R' is selected from the group consisting of hydroxy, alkanoyloxy having from 1 to 5 carbon atoms, hydroxymethyl, oxo, alkylene dioxy having from 2 to 4 carbon atoms and methylene.