# US 5,192,791 A · Fused ring heterocycles and pharmaceutical compositions containing same > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,192,791 A - Document ID: US5192791A - Status: Granted - Kind: A - Application number: 07/551,457 - Filed: 1990-08-14 - Granted: 1993-03-09 - Earliest claimed: 1988-09-26 - Assignees: Biofor, Ltd. - Inventors: Sung J. Lee - Web page: https://patentgrep.com/patent/US5192791A ## CPC - C07D 207/27: with substituted hydrocarbon radicals directly attached to the ring nitrogen atom - C07D 211/76: attached in position 2 or 6 - C07F 7/0812: {comprising a heterocyclic ring} - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22) ## Abstract A novel class of pyrrolidin-2-one and piperidin-2-one compounds in which the nitrogen atom is bonded to an oxyphenyl radical having tertiary-alkyl and tri-methylsilyl substituents. The compounds possess anti-inflammatory, immunomodulatory, analgesic and anti-pyretic activity and they may be combined with excipients to provide formulations which are useful in treating arthritis and conditions associated with that disease. ## Claims ### Claim 1 A compound of the formula: ##STR13## wherein: R is a member selected from the group consisting of hydrogen, alkyl, alkanoyl and aroyl; R.sup.2 and R.sup.4 are joined to form an unsaturated hydrocarbylene chain having four carbon atoms between their points of attachment to the heterocyclic ring; R.sup.5 and R.sup.6 are the same or different and represent a member selected from the group consisting of hydrogen and lower alkyl; and X.sup.3 and X.sup.4 are the same or different and represent a member selected from the group consisting of tertiary-alkyl and trimethylsilyl; and the non-toxic pharmacologically acceptable salts thereof. ### Claim 2 (depends on 1) The compound according to claim 1 wherein X.sup.3 and X.sup.4 represent tert-butyl. ### Claim 3 (depends on 1) The compound according to claim 1 wherein the unsaturated hydrocarbylene chain is 1,3-butadienylene. ### Claim 4 (depends on 1) A compound according to claim 1 of the formula: ##STR14## wherein: R.sup.2 and R.sup.4 are joined to form an unsaturated hydrocarbylene chain having four carbon atoms between their points of attachment to the heterocyclic ring; R.sup.5 and R.sup.6 are the same or different and represent a member selected from the group consisting of hydrogen and lower alkyl; R.sup.9 is selected from the group consisting of hydrogen, lower alkyl, alkanoyl and aroyl; and X.sup.3 and X.sup.4 are the same or different tertiary-lower alkyl moieties; and the non-toxic pharmacologically acceptable salts thereof. ### Claim 5 (depends on 4) The compound according to claim 4 wherein X.sup.3 and X.sup.4 represent tert-butyl. ### Claim 6 (depends on 4) The compound according to claim 4 wherein R.sup.5 and R.sup.6 represent hydrogen. ### Claim 7 (depends on 5) The compound according to claim 5 wherein R.sup.9 is hydrogen. ### Claim 8 N-(3,5-Di-tert-butyl-4-hydroxyphenyl)isoindolinone. ### Claim 9 A pharmaceutical composition comprising as the active ingredient a compound of the formula: ##STR15## wherein: R is a member selected from the group consisting of hydrogen, alkyl, alkanoyl and aroyl; R.sup.2 and R.sup.4 are joined to form an unsaturated hydrocarbylene chain having four carbon atoms between their points of attachment to the heterocyclic ring; R.sup.5 and R.sup.6 are the same or different and represent a member selected from the group consisting of hydrogen and lower alkyl; and X.sup.3 and X.sup.4 are the same or different and represent a member selected from the group consisting of tertiary-alkyl and trimethylsilyl; or a non-toxic pharmacologically acceptable salt thereof; in combination with a pharmaceutically acceptable carrier. ### Claim 10 (depends on 9) The pharmaceutical composition according to claim 9 wherein the active ingredient is a compound in which X.sup.3 and X.sup.4 are tert-butyl. ### Claim 11 (depends on 9) A pharmaceutical composition according to claim 9 in which the active ingredient is a compound of the formula: ##STR16## wherein: R.sup.2 and R.sup.4 are joined to form an unsaturated hydrocarbylene chain having four carbon atoms between their points of attachment to the heterocyclic ring; R.sup.5 and R.sup.6 are the same or different and represent a member selected from the group consisting of hydrogen and lower alkyl; R.sup.9 is selected from the group consisting of hydrogen, lower alkyl, alkanoyl and aroyl; and X.sup.3 and X.sup.4 are the same or different tertiary-lower alkyl moieties; or a non-toxic pharmacologically acceptable salt thereof; in combination with a pharmaceutically acceptable carrier. ### Claim 12 (depends on 11) The pharmaceutical composition according to claim 11 wherein the active ingredient is a compound in which X.sup.3 and X.sup.4 are tert-butyl. ### Claim 13 (depends on 12) The pharmaceutical composition according to claim 12 wherein the active ingredient is a compound in which R.sup.2 and R.sup.4 are joined to form a 1,3-butadienylene chain. ### Claim 14 (depends on 11) The pharmaceutical composition according to claim 11 wherein the active ingredient is N-(3,5-di-tert-butyl-4-hydroxyphenyl)isoindolinone. ### Claim 15 A method for treating inflammation in a mammal which comprises administering a safe and effective amount of an active ingredient of the formula: ##STR17## wherein: R is a member selected from the group consisting of hydrogen, alkyl, alkanoyl and aroyl; R.sup.2 and R.sup.4 are joined to form an unsaturated hydrocarbylene chain having four carbon atoms between their points of attachment to the heterocyclic ring; R.sup.5 -R.sup.6 are the same or different and represent a member selected from the group consisting of hydrogen and lower alkyl; and X.sup.3 and X.sup.4 are the same or different and represent a member selected from the group consisting of tertiary-alkyl and trimethylsilyl; or a non-toxic pharmacologically acceptable salt thereof. ### Claim 16 (depends on 15) The method according to claim 15 wherein the active ingredient is administered orally. ### Claim 17 (depends on 15) The method according to claim 15 wherein R.sup.2 and R.sup.4 are joined to form a 1,3-butadienylene chain. ### Claim 18 (depends on 15) The method according to claim 15 wherein X.sup.3 and X.sup.4 represent tert-butyl. ### Claim 19 (depends on 15) The method according to claim 15 wherein the active ingredient is a compound of the formula: ##STR18## wherein: R.sup.2 and R.sup.4 are joined to form an unsaturated hydrocarbylene chain having four carbon atoms between their points of attachment to the heterocyclic ring; R.sup.5 and R.sup.6 are the same or different and represent a member selected from the group consisting of hydrogen and lower alkyl; R.sup.9 is selected from the group consisting of hydrogen, lower alkyl, alkanoyl and aroyl; and X.sup.3 and X.sup.4 are the same or different tertiary-lower alkyl moieties; or a non-toxic pharmacologically acceptable salt thereof. ### Claim 20 (depends on 19) The method according to claim 19 wherein the active ingredient is N-(3,5-di-tert-butyl-4-hydroxyphenyl)isoindolinone.