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US 4,391,827 AGranted
3-(2-Hydroxy-4-(substituted)phenyl)-cycloalkanone and cycloalkanol analgesic agents and intermediates therefor
AssigneePfizer Inc.
InventorsCharles A. Harbert, Michael R. Johnson, Lawrence S. Melvin, Jr.
Life of this patent
Estimating the term…
Abstract
Cycloalkanones, cycloalkanols and unsaturated analogs thereof, each of which has at the 3-position a 2-hydroxy-4-substituted phenyl group wherein the 4-position substituent is alkyl which can have an oxygen atom as part of the chain, or aralkyl which can have an oxygen atom as part of the alkyl chain, their use for pharmacological and medicinal purposes, intermediates therefor and processes for their preparation.
Claims36
A compound selected from the group consisting of those having the formula ##STR42## wherein R is selected from the group consisting of saturated and unsaturated cycloalkyl moieties selected from the group consisting of ##STR43## wherein A when taken alone is hydrogen;
- B when taken alone is selected from the group consisting of hydroxy, hydroxymethyl and alkanoyloxy having from one to five carbon atoms;
- A and B when taken together are selected from the group consisting of oxo and alkylenedioxy having from two to four carbon atoms
- R.sub.1 is selected from the group consisting of hydrogen, alkanoyl having from one to five carbon atoms, P(O)(OH).sub.2 and mono- and disodium and potassium salts thereof, --CO(CH.sub.2).sub.2 COOH and the sodium and potassium salts thereof, and --CO(CH.sub.2).sub.p NR.sub.5 R.sub.6 wherein p is an integer from 1 to 4, each of R.sub.5 and R.sub.6 when taken together with the nitrogen to which they are attached form a 5- or 6-membered heterocyclic ring (piperidino, pyrrolo, pyrrolidino, morpholino and N-alkylpiperazino having from one to four carbon atoms in the alkyl group);
- R.sub.2 is selected from the group consisting of hydrogen, alkyl having from one to six carbon atoms, alkenyl having from three to six carbon atoms and phenylalkyl having from one to two carbon atoms in the alkyl moiety;
- R.sub.3 is hydrogen;
- R.sub.4 is selected from the group consisting of hydrogen and alkyl having from one to six carbon atoms;
- Z is selected from the group consisting of
- (a) alkylene having from four to eleven carbon atoms;
- and
- (b) --(alk.sub.1).sub.m --O--(alk.sub.2).sub.n -- wherein each of (alk.sub.1) and (alk.sub.2) is alkylene having from one to eleven carbon atoms;
- each of m and n is 0 or 1;
- with the provisos that the summation of carbon atoms in (alk.sub.1) plus (alk.sub.2) is not less than four or greater than eleven;
- and at least one of m and n is 1;
- W is selected from the group consisting of hydrogen, pyridyl and ##STR44## wherein W.sub.1 is selected from the group consisting of hydrogen, fluoro and chloro;
- with the provisos that when W is hydrogen, B is other than hydroxy, Z is alkylene having from seven to eleven carbon atoms or --(alk.sub.1).sub.m --O--(alk.sub.2).sub.n -- wherein each of (alk.sub.1) and (alk.sub.2) is alkylene having from one to eleven carbon atoms with the further proviso that the summation of carbon atoms in (alk.sub.1) plus (alk.sub.2) is not less than seven or greater than eleven carbon atoms;
- and when W is ##STR45## or pyridyl, Z is alkylene having from four to seven carbon atoms or --(alk.sub.1).sub.m --O--(alk.sub.2).sub.n -- wherein each of (alk.sub.1) and (alk.sub.2) is alkylene having from one to seven carbon atoms with the further proviso that the summation of carbon atoms in (alk.sub.1) plus (alk.sub.2) is not less than four or greater than seven carbon atoms;
- and the pharmaceutically acceptable acid addition salts of those compounds wherein R.sub.1 is --CO(CH.sub.2).sub.p NR.sub.5 R.sub.6 and/or W is pyridyl.
14 more elements
A pharmaceutical composition in unit dosage form comprising a pharmaceutically acceptable carrier or diluent and an analgesic, tranquilizer, sedative, antiaxiety or anticonvulsant effective amount of a compound selected from the group consisting of those having the formula ##STR48## wherein R is selected from the group consisting of saturated and unsaturated cycloalkyl moieties selected from the group consisting of ##STR49## wherein A when taken alone is hydrogen;
- B when taken alone is selected from the group consisting of hydroxy, hydroxymethyl and alkanoyloxy having from one to five carbon atoms;
- A and B when taken together are selected from the group consisting of oxo and alkylenedioxy having from two to four carbon atoms
- R.sub.1 is selected from the group consisting of hydrogen, alkanoyl having from one to five carbon atoms, P(O)(OH).sub.2 and mono- and disodium and potassium salts thereof, --CO(CH.sub.2).sub.2 COOH and the sodium and potassium salts thereof, and --CO(CH.sub.2).sub.p NR.sub.5 R.sub.6 wherein p is an integer from 1 to 4, each of R.sub.5 and R.sub.6 when taken together with the nitrogen to which they are attached form a 5- or 6-membered heterocyclic ring (piperidino, pyrrolo, pyrrolidino, morpholino and N-alkylpiperazino having from one to four carbon atoms in the alkyl group);
- R.sub.2 is selected from the group consisting of hydrogen, alkyl having from one to six carbon atoms, alkenyl having from three to six carbon atoms and phenylalkyl having from one to two carbon atoms in the alkyl moiety;
- R.sub.3 is hydrogen;
- R.sub.4 is selected from the group consisting of hydrogen and alkyl having from one to six carbon atoms;
- Z is selected from the group consisting of
- (a) alkylene having from four to eleven carbon atoms;
- and
- (b) --(alk.sub.1).sub.m --O--(alk.sub.2).sub.n -- wherein each of (alk.sub.1) and (alk.sub.2) is alkylene having from one to eleven carbon atoms;
- each of m and n is 0 or 1;
- with the provisos that the summation of carbon atoms in (alk.sub.1) plus (alk.sub.2) is not less than four or greater than eleven;
- and at least one of m and n is 1;
- W is selected from the group consisting of hydrogen, pyridyl and ##STR50## wherein W.sub.1 is selected from the group consisting of hydrogen, fluoro and chloro;
- with the provisos that when W is hydrogen, Z is alkylene having from seven to eleven carbon atoms or --(alk.sub.1).sub.m --O--(alk.sub.2).sub.n -- wherein each of (alk.sub.1) and (alk.sub.2) is alkylene having from one to eleven carbon atoms with the further proviso that the summation of carbon atoms in (alk.sub.1) plus (alk.sub.2) is not less than seven or greater than eleven carbon atoms;
- and when W is ##STR51## or pyridyl, Z is alkylene having from four to seven carbon atoms or --(alk.sub.1).sub.m --O--(alk.sub.2).sub.n -- wherein each of (alk.sub.1) and (alk.sub.2) is alkylene having from one to seven carbon atoms with the further proviso that the summation of carbon atoms in (alk.sub.1) plus (alk.sub.2) is not less than four or greater than seven carbon atoms;
- and the pharmaceutically acceptable acid addition salts of those compounds wherein R.sub.1 is --CO(CH.sub.2).sub.p NR.sub.5 R.sub.6 and/or W is pyridyl.
14 more elements
A method 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 ##STR52## wherein R is selected from the group consisting of saturated cycloalkyl moieties selected from the group consisting of ##STR53## wherein A when taken alone is hydrogen;
- B when taken alone is selected from the group consisting of hydroxy, hydroxymethyl and alkanoyloxy having from one to five carbon atoms;
- A and B when taken together are selected from the group consisting of oxo and alkylenedioxy having from two to four carbon atoms;
- R.sub.1 is selected from the group consisting of hydrogen, alkanoyl having from one to five carbon atoms, P(O)(OH).sub.2 and mono- and disodium and potassium salts thereof, --CO(CH.sub.2).sub.2 COOH and the sodium and potassium salts thereof, and --CO(CH.sub.2).sub.p NR.sub.5 R.sub.6 wherein p is an integer from 1 to 4, each of R.sub.5 and R.sub.6 when taken together with the nitrogen to which they are attached form a 5- or 6-membered heterocyclic ring (piperidino, pyrrolo, pyrrolidino, morpholino and N-alkylpiperazino having from one to four carbon atoms in the alkyl group);
- R.sub.2 is selected from the group consisting of hydrogen, alkyl having from one to six carbon atoms, alkenyl having from three to six carbon atoms and phenylalkyl having from one to two carbon atoms in the alkyl moiety;
- R.sub.3 is hydrogen,
- R.sub.4 is selected from the group consisting of hydrogen and alkyl having from one to six carbon atoms;
- Z is selected from the group consisting of
- (a) alkylene having from four to eleven carbon atoms;
- and
- (b) --(alk.sub.1).sub.m --O--(alk.sub.2).sub.n -- wherein each of (alk.sub.1) and (alk.sub.2) is alkylene having from one to eleven carbon atoms;
- each of m and n is 0 or 1;
- with the provisos that the summation of carbon atoms in (alk.sub.1) plus (alk.sub.2) is not less than four or greater than eleven;
- and at least one of m and n is 1;
- W is selected from the group consisting of hydrogen, pyridyl and ##STR54## wherein W.sub.1 is selected from the group consisting of hydrogen, fluoro and chloro;
- with the proviso that when W is hydrogen, Z is alkylene having from seven to eleven carbon atoms or --(alk.sub.1).sub.m --O--(alk.sub.2).sub.n -- wherein each of (alk.sub.1) and (alk.sub.2) is alkylene having from one to eleven carbon atoms with the further proviso that the summation of carbon atoms in (alk.sub.1) plus (alk.sub.2) is not less than seven or greater than eleven carbon atoms;
- and
- when W is ##STR55## or pyridyl, Z is alkylene having from four to seven carbon atoms or --(alk.sub.1)--O--(alk.sub.2)-- wherein each of (alk.sub.1) and (alk.sub.2) is alkylene having from one to seven carbon atoms with the further proviso that the summation of carbon atoms in (alk.sub.1) plus (alk.sub.2) is not less than four or greater than seven carbon atoms;
- and the pharmaceutically acceptable acid addition salts of those compounds wherein R.sub.1 is --CO(CH.sub.2).sub.p NR.sub.5 R.sub.6 and/or W is pyridyl.
15 more elements
Dependencies are inferred from the claim text.