JP5921555B2 - 新規メチルシクロヘキサン誘導体およびその使用 - Google Patents
新規メチルシクロヘキサン誘導体およびその使用 Download PDFInfo
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- JP5921555B2 JP5921555B2 JP2013531485A JP2013531485A JP5921555B2 JP 5921555 B2 JP5921555 B2 JP 5921555B2 JP 2013531485 A JP2013531485 A JP 2013531485A JP 2013531485 A JP2013531485 A JP 2013531485A JP 5921555 B2 JP5921555 B2 JP 5921555B2
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- Prior art keywords
- pain
- pyridin
- compound
- acid
- pyrrolidine
- Prior art date
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- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical class CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 title claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 122
- 208000002193 Pain Diseases 0.000 claims description 31
- 230000036407 pain Effects 0.000 claims description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 8
- 208000004296 neuralgia Diseases 0.000 claims description 7
- 208000021722 neuropathic pain Diseases 0.000 claims description 7
- 150000004677 hydrates Chemical class 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 208000004998 Abdominal Pain Diseases 0.000 claims description 2
- 208000006820 Arthralgia Diseases 0.000 claims description 2
- 206010058019 Cancer Pain Diseases 0.000 claims description 2
- 208000000094 Chronic Pain Diseases 0.000 claims description 2
- 208000002881 Colic Diseases 0.000 claims description 2
- 208000007914 Labor Pain Diseases 0.000 claims description 2
- 208000035945 Labour pain Diseases 0.000 claims description 2
- 208000000112 Myalgia Diseases 0.000 claims description 2
- 208000004550 Postoperative Pain Diseases 0.000 claims description 2
- 208000005298 acute pain Diseases 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 231100000869 headache Toxicity 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 208000027866 inflammatory disease Diseases 0.000 claims description 2
- 208000013465 muscle pain Diseases 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 206010019233 Headaches Diseases 0.000 claims 1
- 230000003239 periodontal effect Effects 0.000 claims 1
- 239000007858 starting material Substances 0.000 description 59
- 230000015572 biosynthetic process Effects 0.000 description 56
- 238000003786 synthesis reaction Methods 0.000 description 56
- 238000005160 1H NMR spectroscopy Methods 0.000 description 55
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 32
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 17
- 239000002253 acid Substances 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- 239000000203 mixture Substances 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 12
- 241000700159 Rattus Species 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- NYCVCXMSZNOGDH-UHFFFAOYSA-N pyrrolidine-1-carboxylic acid Chemical compound OC(=O)N1CCCC1 NYCVCXMSZNOGDH-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- WOXFMYVTSLAQMO-UHFFFAOYSA-N 2-Pyridinemethanamine Chemical compound NCC1=CC=CC=N1 WOXFMYVTSLAQMO-UHFFFAOYSA-N 0.000 description 5
- 208000004454 Hyperalgesia Diseases 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- -1 alkaline earth metal salts Chemical class 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- CGWZAMNESSHDLI-UHFFFAOYSA-N (4-hydroxycyclohexyl)methyl pyrrolidine-1-carboxylate Chemical compound C1CC(O)CCC1COC(=O)N1CCCC1 CGWZAMNESSHDLI-UHFFFAOYSA-N 0.000 description 3
- JPHPSFADHXONRW-UHFFFAOYSA-N (4-oxocyclohexyl)methyl pyrrolidine-1-carboxylate Chemical compound C1CCCN1C(=O)OCC1CCC(=O)CC1 JPHPSFADHXONRW-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 208000035154 Hyperesthesia Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 150000003840 hydrochlorides Chemical class 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- MRFPCUSUVCKCOR-UHFFFAOYSA-N (4-aminocyclohexyl)methyl pyrrolidine-1-carboxylate Chemical compound C1CC(N)CCC1COC(=O)N1CCCC1 MRFPCUSUVCKCOR-UHFFFAOYSA-N 0.000 description 2
- SEHDQTAFJJSRNL-UHFFFAOYSA-N (4-hydroxyiminocyclohexyl)methyl pyrrolidine-1-carboxylate Chemical compound C1CC(=NO)CCC1COC(=O)N1CCCC1 SEHDQTAFJJSRNL-UHFFFAOYSA-N 0.000 description 2
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
- MVQVNTPHUGQQHK-UHFFFAOYSA-N 3-pyridinemethanol Chemical compound OCC1=CC=CN=C1 MVQVNTPHUGQQHK-UHFFFAOYSA-N 0.000 description 2
- AODBGHUVYYWBRL-UHFFFAOYSA-N 4-(aminomethyl)cyclohexan-1-ol Chemical compound NCC1CCC(O)CC1 AODBGHUVYYWBRL-UHFFFAOYSA-N 0.000 description 2
- VGRZISGVNOKTQU-UHFFFAOYSA-N 4-(hydroxymethyl)cyclohexan-1-ol Chemical compound OCC1CCC(O)CC1 VGRZISGVNOKTQU-UHFFFAOYSA-N 0.000 description 2
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
- LTPVSOCPYWDIFU-UHFFFAOYSA-N 4-methoxyphenylethylamine Chemical compound COC1=CC=C(CCN)C=C1 LTPVSOCPYWDIFU-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 206010065390 Inflammatory pain Diseases 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 208000001294 Nociceptive Pain Diseases 0.000 description 2
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
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- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
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- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 150000001728 carbonyl compounds Chemical class 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
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- NAHHNSMHYCLMON-UHFFFAOYSA-N 2-pyridin-3-ylethanamine Chemical compound NCCC1=CC=CN=C1 NAHHNSMHYCLMON-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/06—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
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- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/40—Acylated substituent nitrogen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
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Description
Arはフェニル、ピリジンおよびピリジン−N−オキシドからなる群から選択されるが、これらはそれぞれ水素原子、直鎖または分岐C1〜C6アルキル、ハロゲン、直鎖または分岐C1〜C6アルコキシおよびトリフルオロメチルからなる群から選択される1以上の同一または異なる置換基によって置換されており;
XはO、(C=O)O、NR1(C=O)O、NH、(C=O)NHまたはO(C=O)NHであり;R1はHまたはCH3であり;
YはCH2、OまたはN−R2であり;R2はHまたはCH3であり;
AはOまたはNHであり;
BはCHまたはNであり;
mは0〜2の整数であり、nは0または1である。)
Claims (5)
- 下記式I:
Arはフェニル、ピリジンおよびピリジン−N−オキシドからなる群から選択されるが、これらはそれぞれ水素原子、直鎖または分岐C1〜C6アルキル、ハロゲン、直鎖または分岐C1〜C6アルコキシおよびトリフルオロメチルからなる群から選択される1以上の同一または異なる置換基によって置換されており;
XはO、(C=O)O、NR1(C=O)O、NH、(C=O)NHまたはO(C=O)NHであり;R1はHまたはCH3であり;
YはCH2、OまたはN−R2であり;R2はHまたはCH3であり;
AはOまたはNHであり;
BはCHまたはNであり;
mは0〜2の整数であり、nは0または1である。)
で表されるメチルシクロヘキサン誘導体、薬学的に許容されるその塩、溶媒和物、水和物およびこれらの組み合わせからなる群から選択される化合物。 - 化合物が以下の構造のいずれかを有する、請求項1に記載の化合物。
- 痛みの予防または治療のための医薬組成物であって、
治療上有効量の請求項1に記載のメチルシクロヘキサン誘導体と
薬学的に許容される担体とを含む医薬組成物。 - 痛みが急性痛または慢性痛である、請求項3に記載の医薬組成物。
- 痛みが、癌性疼痛、陣痛、疝痛、神経因性疼痛、術後痛、糖尿病痛、ヘルペス後疼痛、炎症性疾患痛、筋肉痛、関節痛、頭痛および歯周疾患痛からなる群から選択される、請求項3に記載の医薬組成物。
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KR10-2010-0094463 | 2010-09-29 | ||
KR20100094463 | 2010-09-29 | ||
PCT/KR2011/007117 WO2012044046A2 (en) | 2010-09-29 | 2011-09-28 | Novel methylcyclohexane derivatives and uses thereof |
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JP2013538848A JP2013538848A (ja) | 2013-10-17 |
JP5921555B2 true JP5921555B2 (ja) | 2016-05-24 |
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US (1) | US8822463B2 (ja) |
EP (1) | EP2621899B1 (ja) |
JP (1) | JP5921555B2 (ja) |
KR (1) | KR101803955B1 (ja) |
CN (1) | CN103237790B (ja) |
AU (1) | AU2011308174A1 (ja) |
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CA (1) | CA2813189C (ja) |
CL (1) | CL2013000835A1 (ja) |
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JP3153015B2 (ja) * | 1992-09-07 | 2001-04-03 | サントリー株式会社 | 4−(アミノメチル)シクロヘキサンカルボキサミド誘導体 |
GB0030710D0 (en) * | 2000-12-15 | 2001-01-31 | Hoffmann La Roche | Piperazine derivatives |
US6802897B1 (en) * | 2002-05-31 | 2004-10-12 | Marathon Ashland Petroleum Llc | Biodiesel sulfur slurry |
FR2842885B1 (fr) * | 2002-07-24 | 2004-09-10 | Inst Francais Du Petrole | Procede de transport des petroles bruts lourds sous forme de dispersion |
AU2004258751C1 (en) * | 2003-07-28 | 2008-07-17 | Merz Pharma Gmbh & Co. Kgaa | The use of 1-amino-alkylcyclohexane compounds in the treatment of pain hypersensitivity |
US20060063930A1 (en) | 2004-08-20 | 2006-03-23 | Agoston Gregory E | Compositions and methods comprising proteinase activated receptor antagonists |
FR2878937B1 (fr) * | 2004-12-07 | 2007-02-09 | Inst Francais Du Petrole | Methode de traitement d'un hydrocarbure visqueux par inertage in situ des asphaltenes |
BRPI0607517A2 (pt) * | 2005-04-13 | 2009-09-08 | Neuraxon Inc | compostos de indol substituìdo, composição farmacêutica compreendendo o mesmo, método para tratar e uso do mesmo |
TW200938203A (en) * | 2007-12-17 | 2009-09-16 | Intervet Int Bv | Anthelmintic agents and their use |
WO2009089425A1 (en) * | 2008-01-09 | 2009-07-16 | Pgxhealth Llc | Intrathecal treatment of neuropathic pain with a2ar agonists |
US20090298834A1 (en) | 2008-06-02 | 2009-12-03 | Hassan Pajouhesh | 4-(aminomethyl)cyclohexanamine derivatives as calcium channel blockers |
JP4964854B2 (ja) | 2008-10-01 | 2012-07-04 | ハートウェア・インコーポレーテッド | 血栓形成阻止手段を備えたシールレス血液ポンプ |
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MX2013003389A (es) | 2013-06-24 |
KR20120033271A (ko) | 2012-04-06 |
RU2013114767A (ru) | 2014-11-10 |
ES2556460T3 (es) | 2016-01-18 |
JP2013538848A (ja) | 2013-10-17 |
WO2012044046A2 (en) | 2012-04-05 |
CN103237790B (zh) | 2014-12-03 |
US20130217686A1 (en) | 2013-08-22 |
CA2813189C (en) | 2020-04-28 |
KR101803955B1 (ko) | 2017-12-01 |
WO2012044046A3 (en) | 2012-06-07 |
EP2621899A2 (en) | 2013-08-07 |
BR112013005873A2 (pt) | 2016-05-10 |
EP2621899B1 (en) | 2015-10-21 |
ZA201301674B (en) | 2014-05-28 |
AU2011308174A1 (en) | 2013-03-21 |
US8822463B2 (en) | 2014-09-02 |
CL2013000835A1 (es) | 2013-10-18 |
EP2621899A4 (en) | 2014-03-26 |
CA2813189A1 (en) | 2012-04-05 |
CN103237790A (zh) | 2013-08-07 |
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R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |