# US 8,541,398 B2 · Hydrogen sulfide derivatives of non-steroidal anti-inflammatory drugs > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,541,398 B2 - Document ID: US8541398B2 - Status: Granted - Kind: B2 - Application number: 12/704,412 - Filed: 2010-02-11 - Published: 2010-08-19 - Granted: 2013-09-24 - Earliest claimed: 2005-05-27 - Assignees: Antibe Therapeutics Inc. - Applicants: John L. Wallace; Giuseppe Cirino; Vincenzo Santagada; Giuseppe Caliendo - Inventors: John L. Wallace; Giuseppe Cirino; Vincenzo Santagada; Giuseppe Caliendo - Web page: https://patentgrep.com/patent/US8541398B2 ## CPC - C07C 219/14: having at least one of the hydroxy groups esterified by a carboxylic acid having the esterifying carboxyl group bound to a carbon atom of a six-membered aromatic ring - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - C07C 327/48: having carbon atoms of thiocarboxamide groups bound to carbon atoms of six-membered aromatic rings - C07D 209/18: Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals - C07D 209/32: Oxygen atoms - C07D 309/30: Oxygen atoms, e.g. delta-lactones - C07D 339/04: having the hetero atoms in positions 1 and 2, e.g. lipoic acid - C07D 409/12: linked by a chain containing hetero atoms as chain links - C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## Abstract The present invention relates to derivatives of non-steroidal anti-inflammatory drugs (NSAIDs) having improved anti-inflammatory properties useful in the treatment of inflammation, pain and fever. More particularly, NSAIDs are derivatized with a hydrogen sulfide (H2S) releasing moiety to produce novel anti-inflammatory compounds having reduced side effects. ## Claims ### Claim 1 A compound of the formula: A—Y—X (Formula I) wherein A is an NSAID radical, Y is selected from the group consisting of —C(O)O—, —C(O)NH—, —C(O)OC(O)—, —C(O)NHCH2C(O)—, or zero, and X is either or a salt thereof; whereby when Y is zero, the compound may be a salt of A and X. ### Claim 2 A compound of the formula: B—C(O)O—X (Formula II) where B—C(O)O— is derived from an NSAID having a free carboxyl group or a carboxy-substituted NSAID, and X is or a salt thereof. ### Claim 3 (depends on 1) The compound according to claim 1, wherein the NSAID is selected from the group consisting of acetylsalicylic acid (ASA), diclofenac, naproxen, indomethacin, flurbiprofen, sulindac, ibuprofen, aceclofenac, acemetacin, benoxaprofen, benzofenac, bromfenac, bucloxic acid, butibufen, carprofen, celecoxib, cicloprofen, cinmetacin, clidenac, clopirac, diflusinal, etodolac, etoricoxib, fenbufen, fenclofenac, fenclorac, fenoprofen, fentiazac, flunoxaprofen, furaprofen, furobufen, furafenac, ibufenac, indoprofen, isoxepac, ketoprofen, ketorolac, loxoprofen, lonazolac, lumiracoxib, metiazinic, mefenamic acid, meclofenamic acid, meloxicam, nabumetone, piromidic acid, salsalate, miroprofen, oxaprozin, oxepinac, paracoxib, phenylbutazone, pirprofen, piroxicam, pirozolac, protizinic acid, rofecoxib, sodium salicylate, suprofen, tiaprofenic acid, tolmetin, valdecoxib, and zomepirac. ### Claim 4 (depends on 2) The compound according to claim 2, wherein the NSAID is selected from the group consisting of acetylsalicylic acid, naproxen, indomethacin, flurbiprofen, ibuprofen, aceclofenac, acemetacin, benoxaprofen, benzofenac, bromfenac, bucloxic acid, butibufen, carprofen, celecoxib, cicloprofen, cinmetacin, clidenac, clopirac, etodolac, etoricoxib, fenbufen, fenclofenac, fenclorac, fenoprofen, fentiazac, flunoxaprofen, furaprofen, furobufen, furafenac, ibufenac, indoprofen, isoxepac, loxoprofen, lonazolac, lumiracoxib, metiazinic, mefenamic acid, meclofenamic acid, meloxicam, nabumetone, piromidic acid, salsalate, miroprofen, oxaprozin, oxepinac, paracoxib, phenylbutazone, pirprofen, piroxicam, pirozolac, protizinic acid, rofecoxib, sodium salicylate, suprofen, tiaprofenic acid, tolmetin, valdecoxib, and zomepirac. ### Claim 5 (depends on 1) The compound according to claim 1, wherein the NSAID is selected from the group consisting of acetylsalicylic acid, naproxen, indomethacin, flurbiprofen, ibuprofen, aceclofenac, acemetacin, benoxaprofen, benzofenac, bromfenac, bucloxic acid, butibufen, carprofen, cicloprofen, cinmetacin, clidenac, clopirac, fenbufen, fenclofenac, fenclorac, fenoprofen, fentiazac, flunoxaprofen, furaprofen, furobufen, furafenac, ibufenac, indoprofen, isoxepac, loxoprofen, lonazolac, lumiracoxib, metiazinic, mefenamic acid, nabumetone, piromidic acid, salsalate, miroprofen, oxaprozin, oxepinac, phenylbutazone, pirprofen, pirozolac, protizinic acid, suprofen, tiaprofenic acid, and tolmetin. ### Claim 6 (depends on 1) The compound according to claim 1, wherein the NSAID is selected from the group consisting of acetylsalicylic acid, diclofenac, indomethacin, lumiracoxib, naproxen, ibuprofen, ketoprofen and flurbiprofen; Y is —C(O)O—; and X is or a salt thereof. ### Claim 7 (depends on 1) Compound of claim 1 where the compound is or a pharmaceutically acceptable salt thereof. ### Claim 8 (depends on 1) Compound of claim 1 where the compound is or a pharmaceutically acceptable salt thereof. ### Claim 9 (depends on 1) Compound of claim 1 where the compound is or a pharmaceutically acceptable salt thereof. ### Claim 10 (depends on 1) Compound of claim 1 where the compound is or a pharmaceutically acceptable salt thereof. ### Claim 11 (depends on 1) Compound of claim 1 where the compound is or a pharmaceutically acceptable salt thereof. ### Claim 12 (depends on 1) Compound of claim 1 where the compound is or a pharmaceutically acceptable salt thereof. ### Claim 13 (depends on 1) Compound of claim 1 where the compound is or a pharmaceutically acceptable salt thereof. ### Claim 14 (depends on 1) Compound of claim 1 where the compound is or a pharmaceutically acceptable salt thereof. ### Claim 15 (depends on 1) A pharmaceutical composition comprising a compound as claimed in claim 1 and a pharmaceutically acceptable excipient or carrier. ### Claim 16 (depends on 1) The compound according to claim 1, wherein the NSAID is selected from the group consisting of acetylsalicylic acid (ASA), naproxen, indomethacin, flurbiprofen, ibuprofen, aceclofenac, acemetacin, benoxaprofen, benzofenac, bromfenac, bucloxic acid, butibufen, carprofen, celecoxib, cicloprofen, cinmetacin, clidenac, clopirac, etodolac, etoricoxib, fenbufen, fenclofenac, fenclorac, fenoprofen, fentiazac, flunoxaprofen, furaprofen, furobufen, furafenmac, ibufenac, indoprofen, isoxepac, loxoprofen, lonazolac, lumiracoxib, metiazinic, mefenamic acid, meclofenamic acid, meloxicam, nabumetone, piromidic acid, salsalate, miroprofen, oxaprozin, oxepinac, paracoxib, phenylbutazone, pirprofen, piroxicam, pirozolac, protizinic acid, rofecoxib, sodium salicylate, suprofen, tiaprofenic acid, tolmetin, valdecoxib, and zomepirac. ### Claim 17 (depends on 2) The compound according to claim 2, wherein the NSAID is selected from the group consisting of acetylsalicylic acid, diclofenac, indomethacin, lumiracoxib, naproxen, ibuprofen, ketoprofen and flurbiprofen. ### Claim 18 (depends on 2) A pharmaceutical composition comprising a compound as claimed in claim 2 and a pharmaceutically acceptable excipient or carrier.