CA2238815A1 - Composition for treating pain - Google Patents
Composition for treating pain Download PDFInfo
- Publication number
- CA2238815A1 CA2238815A1 CA002238815A CA2238815A CA2238815A1 CA 2238815 A1 CA2238815 A1 CA 2238815A1 CA 002238815 A CA002238815 A CA 002238815A CA 2238815 A CA2238815 A CA 2238815A CA 2238815 A1 CA2238815 A1 CA 2238815A1
- Authority
- CA
- Canada
- Prior art keywords
- carbon atoms
- alkyl
- alkoxy
- substituted
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 73
- 208000002193 Pain Diseases 0.000 title claims abstract description 26
- 230000036407 pain Effects 0.000 title claims abstract description 25
- 150000001875 compounds Chemical class 0.000 claims abstract description 137
- 238000000034 method Methods 0.000 claims abstract description 35
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims abstract description 28
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims abstract description 27
- 229960005489 paracetamol Drugs 0.000 claims abstract description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 637
- 125000000217 alkyl group Chemical group 0.000 claims description 267
- 125000003545 alkoxy group Chemical group 0.000 claims description 215
- 229910052739 hydrogen Inorganic materials 0.000 claims description 206
- 239000001257 hydrogen Substances 0.000 claims description 203
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 194
- 125000000304 alkynyl group Chemical group 0.000 claims description 152
- 150000002431 hydrogen Chemical group 0.000 claims description 135
- 125000003342 alkenyl group Chemical group 0.000 claims description 129
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 87
- 229910052757 nitrogen Inorganic materials 0.000 claims description 66
- 125000003118 aryl group Chemical group 0.000 claims description 61
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 53
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 52
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 51
- 230000000202 analgesic effect Effects 0.000 claims description 41
- 125000004122 cyclic group Chemical group 0.000 claims description 38
- 229910052736 halogen Inorganic materials 0.000 claims description 38
- 150000002367 halogens Chemical group 0.000 claims description 38
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 36
- 150000003839 salts Chemical class 0.000 claims description 35
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 33
- 230000002195 synergetic effect Effects 0.000 claims description 32
- 229910052760 oxygen Inorganic materials 0.000 claims description 31
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 30
- 239000001301 oxygen Substances 0.000 claims description 30
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 29
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 28
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 28
- -1 keoprofen Chemical compound 0.000 claims description 28
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 27
- 125000005842 heteroatom Chemical group 0.000 claims description 24
- 229910052794 bromium Inorganic materials 0.000 claims description 22
- 239000000460 chlorine Substances 0.000 claims description 22
- 239000012453 solvate Substances 0.000 claims description 22
- 229910052801 chlorine Inorganic materials 0.000 claims description 21
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 18
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 18
- 239000005864 Sulphur Chemical group 0.000 claims description 18
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 18
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 17
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 17
- 150000002430 hydrocarbons Chemical class 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 12
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 12
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 claims description 12
- 125000001624 naphthyl group Chemical group 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- 229910052717 sulfur Chemical group 0.000 claims description 12
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 11
- 239000011593 sulfur Chemical group 0.000 claims description 11
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 10
- 229960004126 codeine Drugs 0.000 claims description 10
- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- 125000001153 fluoro group Chemical group F* 0.000 claims description 10
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 9
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 9
- 239000000730 antalgic agent Substances 0.000 claims description 9
- 229960001680 ibuprofen Drugs 0.000 claims description 9
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
- 125000003277 amino group Chemical group 0.000 claims description 8
- 229940035676 analgesics Drugs 0.000 claims description 8
- 238000001727 in vivo Methods 0.000 claims description 8
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims description 8
- USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 0.000 claims description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 7
- 101100240516 Caenorhabditis elegans nhr-10 gene Proteins 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- JAQUASYNZVUNQP-USXIJHARSA-N Levorphanol Chemical compound C1C2=CC=C(O)C=C2[C@]23CCN(C)[C@H]1[C@@H]2CCCC3 JAQUASYNZVUNQP-USXIJHARSA-N 0.000 claims description 7
- BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 claims description 7
- UQCNKQCJZOAFTQ-ISWURRPUSA-N Oxymorphone Chemical compound O([C@H]1C(CC[C@]23O)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O UQCNKQCJZOAFTQ-ISWURRPUSA-N 0.000 claims description 7
- RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 claims description 7
- 229960001736 buprenorphine Drugs 0.000 claims description 7
- 150000001721 carbon Chemical group 0.000 claims description 7
- 229960004193 dextropropoxyphene Drugs 0.000 claims description 7
- XLMALTXPSGQGBX-GCJKJVERSA-N dextropropoxyphene Chemical compound C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 XLMALTXPSGQGBX-GCJKJVERSA-N 0.000 claims description 7
- WVLOADHCBXTIJK-YNHQPCIGSA-N hydromorphone Chemical compound O([C@H]1C(CC[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O WVLOADHCBXTIJK-YNHQPCIGSA-N 0.000 claims description 7
- 229960001410 hydromorphone Drugs 0.000 claims description 7
- 229960003406 levorphanol Drugs 0.000 claims description 7
- 229960001797 methadone Drugs 0.000 claims description 7
- 229960002085 oxycodone Drugs 0.000 claims description 7
- VOKSWYLNZZRQPF-GDIGMMSISA-N pentazocine Chemical compound C1C2=CC=C(O)C=C2[C@@]2(C)[C@@H](C)[C@@H]1N(CC=C(C)C)CC2 VOKSWYLNZZRQPF-GDIGMMSISA-N 0.000 claims description 7
- 229960005301 pentazocine Drugs 0.000 claims description 7
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- 229930195734 saturated hydrocarbon Natural products 0.000 claims description 7
- 238000011282 treatment Methods 0.000 claims description 7
- 229930195735 unsaturated hydrocarbon Natural products 0.000 claims description 7
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 6
- 150000005071 1,2,4-oxadiazoles Chemical class 0.000 claims description 6
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 6
- 101100294115 Caenorhabditis elegans nhr-4 gene Proteins 0.000 claims description 6
- 239000004215 Carbon black (E152) Substances 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
- 101100295741 Gallus gallus COR4 gene Proteins 0.000 claims description 6
- XYYVYLMBEZUESM-UHFFFAOYSA-N dihydrocodeine Natural products C1C(N(CCC234)C)C2C=CC(=O)C3OC2=C4C1=CC=C2OC XYYVYLMBEZUESM-UHFFFAOYSA-N 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 6
- 229930195733 hydrocarbon Natural products 0.000 claims description 6
- LLPOLZWFYMWNKH-CMKMFDCUSA-N hydrocodone Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC LLPOLZWFYMWNKH-CMKMFDCUSA-N 0.000 claims description 6
- 229960000240 hydrocodone Drugs 0.000 claims description 6
- 229960005181 morphine Drugs 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 125000005309 thioalkoxy group Chemical group 0.000 claims description 6
- LLPOLZWFYMWNKH-UHFFFAOYSA-N trans-dihydrocodeinone Natural products C1C(N(CCC234)C)C2CCC(=O)C3OC2=C4C1=CC=C2OC LLPOLZWFYMWNKH-UHFFFAOYSA-N 0.000 claims description 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
- FRZNJFWQVYAVCE-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)phenyl]urea Chemical compound C1=CC(C)=CC=C1N1C(NC(=O)NC=2C=CC(OCCN3CCOCC3)=CC=2)=CC(C(C)(C)C)=N1 FRZNJFWQVYAVCE-UHFFFAOYSA-N 0.000 claims description 5
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- UZHSEJADLWPNLE-GRGSLBFTSA-N naloxone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 0.000 claims description 5
- 229960004127 naloxone Drugs 0.000 claims description 5
- DQCKKXVULJGBQN-XFWGSAIBSA-N naltrexone Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=O)O)CC1)O)CC1CC1 DQCKKXVULJGBQN-XFWGSAIBSA-N 0.000 claims description 5
- 229960003086 naltrexone Drugs 0.000 claims description 5
- 229960002009 naproxen Drugs 0.000 claims description 5
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims description 5
- RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 claims description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 4
- SBDNJUWAMKYJOX-UHFFFAOYSA-N Meclofenamic Acid Chemical compound CC1=CC=C(Cl)C(NC=2C(=CC=CC=2)C(O)=O)=C1Cl SBDNJUWAMKYJOX-UHFFFAOYSA-N 0.000 claims description 4
- XADCESSVHJOZHK-UHFFFAOYSA-N Meperidine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 XADCESSVHJOZHK-UHFFFAOYSA-N 0.000 claims description 4
- IFKLAQQSCNILHL-QHAWAJNXSA-N butorphanol Chemical compound N1([C@@H]2CC3=CC=C(C=C3[C@@]3([C@]2(CCCC3)O)CC1)O)CC1CCC1 IFKLAQQSCNILHL-QHAWAJNXSA-N 0.000 claims description 4
- 229960001113 butorphanol Drugs 0.000 claims description 4
- 229960001259 diclofenac Drugs 0.000 claims description 4
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 claims description 4
- 229960001419 fenoprofen Drugs 0.000 claims description 4
- 229960002390 flurbiprofen Drugs 0.000 claims description 4
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 claims description 4
- 229960000905 indomethacin Drugs 0.000 claims description 4
- 229940013798 meclofenamate Drugs 0.000 claims description 4
- 229960005118 oxymorphone Drugs 0.000 claims description 4
- 229960000482 pethidine Drugs 0.000 claims description 4
- 229960002702 piroxicam Drugs 0.000 claims description 4
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 claims description 4
- 229960000894 sulindac Drugs 0.000 claims description 4
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 claims description 4
- 229960001017 tolmetin Drugs 0.000 claims description 4
- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 claims description 4
- IJVCSMSMFSCRME-UHFFFAOYSA-N 3-methyl-2,4,4a,5,6,7,7a,13-octahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7,9-diol Chemical compound C12CCC(O)C3OC4=C5C32CCN(C)C1CC5=CC=C4O IJVCSMSMFSCRME-UHFFFAOYSA-N 0.000 claims description 3
- 229960001349 alphaprodine Drugs 0.000 claims description 3
- UVAZQQHAVMNMHE-XJKSGUPXSA-N alphaprodine Chemical compound C=1C=CC=CC=1[C@@]1(OC(=O)CC)CCN(C)C[C@@H]1C UVAZQQHAVMNMHE-XJKSGUPXSA-N 0.000 claims description 3
- 229960002428 fentanyl Drugs 0.000 claims description 3
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 24
- WCVITKASZUHCJT-UHFFFAOYSA-N 3-(1-azabicyclo[2.2.1]heptan-3-yl)-3-oxopropanenitrile Chemical compound C1CC2C(C(CC#N)=O)CN1C2 WCVITKASZUHCJT-UHFFFAOYSA-N 0.000 claims 7
- 239000002253 acid Substances 0.000 claims 7
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 6
- SWZCFCQHJDPDGI-UHFFFAOYSA-N 1-azabicyclo[2.2.1]heptan-3-yl(cyclopropyl)methanone Chemical compound C1N(C2)CCC2C1C(=O)C1CC1 SWZCFCQHJDPDGI-UHFFFAOYSA-N 0.000 claims 6
- KECPMSIFTAVDOH-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl(cyclopropyl)methanone Chemical compound C1N(CC2)CCC2C1C(=O)C1CC1 KECPMSIFTAVDOH-UHFFFAOYSA-N 0.000 claims 6
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 6
- JPPJGUGNQMPEAX-UHFFFAOYSA-N n-methoxy-1-azabicyclo[2.2.1]heptane-3-carboxamide Chemical compound C1CC2C(C(=O)NOC)CN1C2 JPPJGUGNQMPEAX-UHFFFAOYSA-N 0.000 claims 6
- GNNVBIVIGBDZRV-UHFFFAOYSA-N n-methoxy-1-azabicyclo[2.2.2]octane-3-carboxamide Chemical compound C1CC2C(C(=O)NOC)CN1CC2 GNNVBIVIGBDZRV-UHFFFAOYSA-N 0.000 claims 6
- IQWCBYSUUOFOMF-UHFFFAOYSA-N n-methoxy-1-azabicyclo[2.2.2]octane-3-carboximidoyl cyanide Chemical compound C1CC2C(C(C#N)=NOC)CN1CC2 IQWCBYSUUOFOMF-UHFFFAOYSA-N 0.000 claims 6
- NHMGDKNLFKFFJN-UHFFFAOYSA-N n-methoxy-1-azabicyclo[3.2.1]octane-5-carboxamide Chemical compound C1N2CCC1(C(=O)NOC)CCC2 NHMGDKNLFKFFJN-UHFFFAOYSA-N 0.000 claims 6
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 3
- 101100134922 Gallus gallus COR5 gene Proteins 0.000 claims 3
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims 3
- BIPUHAHGLJKIPK-UHFFFAOYSA-N dicyclopropylmethanone Chemical compound C1CC1C(=O)C1CC1 BIPUHAHGLJKIPK-UHFFFAOYSA-N 0.000 claims 2
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 claims 2
- 229960000805 nalbuphine Drugs 0.000 claims 2
- NETZHAKZCGBWSS-CEDHKZHLSA-N nalbuphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]1(O)CC[C@@H]3O)CN2CC1CCC1 NETZHAKZCGBWSS-CEDHKZHLSA-N 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000003551 muscarinic effect Effects 0.000 abstract description 42
- 229940005483 opioid analgesics Drugs 0.000 abstract description 5
- 241000700159 Rattus Species 0.000 description 13
- 241000282414 Homo sapiens Species 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 210000002683 foot Anatomy 0.000 description 6
- 238000009472 formulation Methods 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 4
- 229960001138 acetylsalicylic acid Drugs 0.000 description 4
- 230000006399 behavior Effects 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 210000000548 hind-foot Anatomy 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 125000006413 ring segment Chemical group 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 3
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 208000004454 Hyperalgesia Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 3
- 125000002619 bicyclic group Chemical group 0.000 description 3
- 230000001713 cholinergic effect Effects 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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- A—HUMAN NECESSITIES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US829995P | 1995-12-07 | 1995-12-07 | |
| US60/008,299 | 1995-12-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2238815A1 true CA2238815A1 (en) | 1997-06-12 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002238815A Abandoned CA2238815A1 (en) | 1995-12-07 | 1996-12-05 | Composition for treating pain |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP0871445A4 (cs) |
| JP (1) | JP2000501709A (cs) |
| KR (1) | KR19990071976A (cs) |
| CN (1) | CN1208349A (cs) |
| AU (1) | AU705031B2 (cs) |
| CA (1) | CA2238815A1 (cs) |
| CZ (1) | CZ174698A3 (cs) |
| EA (1) | EA199800533A1 (cs) |
| IL (1) | IL124419A0 (cs) |
| NO (1) | NO982562L (cs) |
| NZ (1) | NZ324988A (cs) |
| PL (1) | PL327137A1 (cs) |
| WO (1) | WO1997020561A1 (cs) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU6966998A (en) * | 1997-04-11 | 1998-11-11 | Eli Lilly And Company | Composition for treating pain |
| AU5123200A (en) | 1999-06-04 | 2000-12-28 | Eli Lilly And Company | 7-oxo-2-azabicyclo(2.2.1)heptanes as selective muscarinic receptor antagonist |
| JP6539274B2 (ja) | 2013-08-12 | 2019-07-03 | ファーマシューティカル マニュファクチュアリング リサーチ サービシズ，インコーポレーテッド | 押出成形された即放性乱用抑止性丸剤 |
| WO2015095391A1 (en) | 2013-12-17 | 2015-06-25 | Pharmaceutical Manufacturing Research Services, Inc. | Extruded extended release abuse deterrent pill |
| US9492444B2 (en) | 2013-12-17 | 2016-11-15 | Pharmaceutical Manufacturing Research Services, Inc. | Extruded extended release abuse deterrent pill |
| AU2015290098B2 (en) | 2014-07-17 | 2018-11-01 | Pharmaceutical Manufacturing Research Services, Inc. | Immediate release abuse deterrent liquid fill dosage form |
| WO2016064873A1 (en) | 2014-10-20 | 2016-04-28 | Pharmaceutical Manufacturing Research Services, Inc. | Extended release abuse deterrent liquid fill dosage form |
| WO2020206410A1 (en) * | 2019-04-04 | 2020-10-08 | University Of Maryland, Baltimore | Methods of using muscarinic antagonists in the treatment of depression |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2998450A (en) * | 1958-05-19 | 1961-08-29 | Warner Lambert Pharmaceutical | Process of preparing nu-acetyl-p-amino phenol |
| GB8717446D0 (en) * | 1987-07-23 | 1987-08-26 | Merck Sharp & Dohme | Chemical compounds |
| NZ225999A (en) * | 1987-09-10 | 1992-04-28 | Merck Sharp & Dohme | Azacyclic- or azabicyclic-substituted thiadiazole derivatives and pharmaceutical compositions |
| US5260293A (en) * | 1988-01-30 | 1993-11-09 | Merck Sharp & Dohme Limited | Pyrazines, pyrimidines and pyridazines useful in the treatment of senile dementia |
| IL89351A0 (en) * | 1988-03-14 | 1989-09-10 | Lundbeck & Co As H | 4,5,6,7-tetrahydroisothiazolo(4,5-c)pyridines,process for their preparation and pharmaceutical compositions containing them |
| US5418240A (en) * | 1990-08-21 | 1995-05-23 | Novo Nordisk A/S | Heterocyclic compounds and their preparation and use |
| US5478577A (en) * | 1993-11-23 | 1995-12-26 | Euroceltique, S.A. | Method of treating pain by administering 24 hour oral opioid formulations exhibiting rapid rate of initial rise of plasma drug level |
| CA2185805A1 (en) * | 1994-03-18 | 1995-09-28 | Georg Frank | Low dosage ketoprofen |
-
1996
- 1996-12-05 CZ CZ981746A patent/CZ174698A3/cs unknown
- 1996-12-05 WO PCT/US1996/019309 patent/WO1997020561A1/en not_active Application Discontinuation
- 1996-12-05 JP JP9521397A patent/JP2000501709A/ja active Pending
- 1996-12-05 NZ NZ324988A patent/NZ324988A/xx unknown
- 1996-12-05 CN CN96199837A patent/CN1208349A/zh active Pending
- 1996-12-05 IL IL12441996A patent/IL124419A0/xx unknown
- 1996-12-05 KR KR1019980704267A patent/KR19990071976A/ko not_active Withdrawn
- 1996-12-05 CA CA002238815A patent/CA2238815A1/en not_active Abandoned
- 1996-12-05 EA EA199800533A patent/EA199800533A1/ru unknown
- 1996-12-05 AU AU12791/97A patent/AU705031B2/en not_active Ceased
- 1996-12-05 PL PL96327137A patent/PL327137A1/xx unknown
- 1996-12-05 EP EP96943584A patent/EP0871445A4/en not_active Withdrawn
-
1998
- 1998-06-04 NO NO982562A patent/NO982562L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP0871445A1 (en) | 1998-10-21 |
| NO982562D0 (no) | 1998-06-04 |
| AU705031B2 (en) | 1999-05-13 |
| NZ324988A (en) | 1999-08-30 |
| AU1279197A (en) | 1997-06-27 |
| CN1208349A (zh) | 1999-02-17 |
| EA199800533A1 (ru) | 1999-02-25 |
| CZ174698A3 (cs) | 1998-10-14 |
| EP0871445A4 (en) | 2001-01-10 |
| KR19990071976A (ko) | 1999-09-27 |
| PL327137A1 (en) | 1998-11-23 |
| WO1997020561A1 (en) | 1997-06-12 |
| JP2000501709A (ja) | 2000-02-15 |
| NO982562L (no) | 1998-07-10 |
| IL124419A0 (en) | 1998-12-06 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |