JP5514556B2 - スピロ環式シクロヘキサン誘導体 - Google Patents
スピロ環式シクロヘキサン誘導体 Download PDFInfo
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- JP5514556B2 JP5514556B2 JP2009550672A JP2009550672A JP5514556B2 JP 5514556 B2 JP5514556 B2 JP 5514556B2 JP 2009550672 A JP2009550672 A JP 2009550672A JP 2009550672 A JP2009550672 A JP 2009550672A JP 5514556 B2 JP5514556 B2 JP 5514556B2
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- Prior art keywords
- unsubstituted
- mono
- acid
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- alkyl
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- 125000000113 cyclohexyl group Chemical class [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 title abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 21
- 208000002193 Pain Diseases 0.000 claims abstract description 16
- 230000008569 process Effects 0.000 claims abstract description 11
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 5
- 208000035475 disorder Diseases 0.000 claims abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 65
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 60
- 150000001875 compounds Chemical class 0.000 claims description 56
- 125000001072 heteroaryl group Chemical group 0.000 claims description 56
- 125000003118 aryl group Chemical group 0.000 claims description 51
- 229920006395 saturated elastomer Polymers 0.000 claims description 51
- 150000001934 cyclohexanes Chemical class 0.000 claims description 47
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 40
- 125000000217 alkyl group Chemical group 0.000 claims description 38
- 229910052731 fluorine Inorganic materials 0.000 claims description 34
- 229910052801 chlorine Inorganic materials 0.000 claims description 31
- 229910004013 NO 2 Inorganic materials 0.000 claims description 29
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 28
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 26
- 239000002253 acid Substances 0.000 claims description 25
- 229910052794 bromium Inorganic materials 0.000 claims description 25
- 229910052740 iodine Inorganic materials 0.000 claims description 25
- 239000000203 mixture Substances 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 23
- -1 CF 3 Chemical group 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 10
- 239000013543 active substance Substances 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 10
- 150000007513 acids Chemical class 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- 125000001544 thienyl group Chemical group 0.000 claims description 9
- NKOQRTYLFHGXEJ-UHFFFAOYSA-N 1'-phenyl-1'-pyrrolidin-1-ylspiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,4'-cyclohexane] Chemical compound C1CCCN1C1(C=2C=CC=CC=2)CCC2(C3=C(C4=CC=CC=C4N3)CCO2)CC1 NKOQRTYLFHGXEJ-UHFFFAOYSA-N 0.000 claims description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 8
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 8
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 claims description 8
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 8
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 8
- 208000011117 substance-related disease Diseases 0.000 claims description 8
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 7
- 229940005483 opioid analgesics Drugs 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 7
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 6
- 150000001768 cations Chemical class 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 6
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 5
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 5
- 235000011054 acetic acid Nutrition 0.000 claims description 5
- 235000019253 formic acid Nutrition 0.000 claims description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 claims description 4
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 claims description 4
- ALUNJDZLXQIJPO-UHFFFAOYSA-N 1'-(azetidin-1-yl)-6-fluoro-1'-phenylspiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,4'-cyclohexane] Chemical compound C12=CC(F)=CC=C2NC2=C1CCOC2(CC1)CCC1(C=1C=CC=CC=1)N1CCC1 ALUNJDZLXQIJPO-UHFFFAOYSA-N 0.000 claims description 4
- OEWXCXVBBXJSIX-UHFFFAOYSA-N 1'-benzyl-6-fluorospiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1CC2(C3=C(C4=CC(F)=CC=C4N3)CCO2)CCC1(N)CC1=CC=CC=C1 OEWXCXVBBXJSIX-UHFFFAOYSA-N 0.000 claims description 4
- VTBQKIVRFSODAM-UHFFFAOYSA-N 1'-butyl-6-fluoro-1'-pyrrolidin-1-ylspiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,4'-cyclohexane] Chemical compound C1CC2(C3=C(C4=CC(F)=CC=C4N3)CCO2)CCC1(CCCC)N1CCCC1 VTBQKIVRFSODAM-UHFFFAOYSA-N 0.000 claims description 4
- VIKBNMWOLLIQPG-UHFFFAOYSA-N 2-methyldecanedioic acid Chemical compound OC(=O)C(C)CCCCCCCC(O)=O VIKBNMWOLLIQPG-UHFFFAOYSA-N 0.000 claims description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 4
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 claims description 4
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 claims description 4
- CEHSUFYIKKLVCO-UHFFFAOYSA-N 6-fluoro-1'-phenyl-1'-pyrrolidin-1-ylspiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,4'-cyclohexane] Chemical compound C12=CC(F)=CC=C2NC2=C1CCOC2(CC1)CCC1(C=1C=CC=CC=1)N1CCCC1 CEHSUFYIKKLVCO-UHFFFAOYSA-N 0.000 claims description 4
- 208000007848 Alcoholism Diseases 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 208000000094 Chronic Pain Diseases 0.000 claims description 4
- 206010013654 Drug abuse Diseases 0.000 claims description 4
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 4
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 4
- OKJIRPAQVSHGFK-UHFFFAOYSA-N N-acetylglycine Chemical compound CC(=O)NCC(O)=O OKJIRPAQVSHGFK-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 claims description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 4
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 claims description 4
- AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Natural products OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 claims description 4
- 235000003704 aspartic acid Nutrition 0.000 claims description 4
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 4
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 206010013663 drug dependence Diseases 0.000 claims description 4
- 239000001530 fumaric acid Substances 0.000 claims description 4
- 235000011087 fumaric acid Nutrition 0.000 claims description 4
- 239000004220 glutamic acid Substances 0.000 claims description 4
- 235000013922 glutamic acid Nutrition 0.000 claims description 4
- FYAQQULBLMNGAH-UHFFFAOYSA-N hexane-1-sulfonic acid Chemical compound CCCCCCS(O)(=O)=O FYAQQULBLMNGAH-UHFFFAOYSA-N 0.000 claims description 4
- 239000004310 lactic acid Substances 0.000 claims description 4
- 235000014655 lactic acid Nutrition 0.000 claims description 4
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- 229960002510 mandelic acid Drugs 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 208000004296 neuralgia Diseases 0.000 claims description 4
- 208000021722 neuropathic pain Diseases 0.000 claims description 4
- 239000011664 nicotinic acid Substances 0.000 claims description 4
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- 235000001968 nicotinic acid Nutrition 0.000 claims description 4
- 235000006408 oxalic acid Nutrition 0.000 claims description 4
- 150000003254 radicals Chemical class 0.000 claims description 4
- 230000001105 regulatory effect Effects 0.000 claims description 4
- 239000011975 tartaric acid Substances 0.000 claims description 4
- 235000002906 tartaric acid Nutrition 0.000 claims description 4
- 229960002663 thioctic acid Drugs 0.000 claims description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 4
- GHLNZJNTCTXKGD-UHFFFAOYSA-N 1'-(azetidin-1-yl)-1'-(3-fluorophenyl)spiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,4'-cyclohexane] Chemical compound FC1=CC=CC(C2(CCC3(CC2)C2=C(C4=CC=CC=C4N2)CCO3)N2CCC2)=C1 GHLNZJNTCTXKGD-UHFFFAOYSA-N 0.000 claims description 3
- NAOLWIGVYRIGTP-UHFFFAOYSA-N 1,3,5-trihydroxyanthracene-9,10-dione Chemical compound C1=CC(O)=C2C(=O)C3=CC(O)=CC(O)=C3C(=O)C2=C1 NAOLWIGVYRIGTP-UHFFFAOYSA-N 0.000 claims description 3
- FFFIRKXTFQCCKJ-UHFFFAOYSA-N 2,4,6-trimethylbenzoic acid Chemical compound CC1=CC(C)=C(C(O)=O)C(C)=C1 FFFIRKXTFQCCKJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- AJHPGXZOIAYYDW-UHFFFAOYSA-N 3-(2-cyanophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)CC1=CC=CC=C1C#N AJHPGXZOIAYYDW-UHFFFAOYSA-N 0.000 claims description 3
- ALYNCZNDIQEVRV-PZFLKRBQSA-N 4-amino-3,5-ditritiobenzoic acid Chemical compound [3H]c1cc(cc([3H])c1N)C(O)=O ALYNCZNDIQEVRV-PZFLKRBQSA-N 0.000 claims description 3
- 208000019901 Anxiety disease Diseases 0.000 claims description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 3
- 206010012735 Diarrhoea Diseases 0.000 claims description 3
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- 239000000654 additive Substances 0.000 claims description 3
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 claims description 3
- 230000001598 anti-natriuretic effect Effects 0.000 claims description 3
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- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
- 239000003193 general anesthetic agent Substances 0.000 claims description 3
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 3
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- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 claims description 3
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- YGWYFBNPSRSUSZ-UHFFFAOYSA-N 1'-(azetidin-1-yl)-6-fluoro-1'-thiophen-2-ylspiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,4'-cyclohexane];2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C12=CC(F)=CC=C2NC2=C1CCOC2(CC1)CCC1(C=1SC=CC=1)N1CCC1 YGWYFBNPSRSUSZ-UHFFFAOYSA-N 0.000 claims 1
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- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims 1
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- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 abstract description 13
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- 102000004169 proteins and genes Human genes 0.000 description 1
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- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
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- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
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- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
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- HZXJVDYQRYYYOR-UHFFFAOYSA-K scandium(iii) trifluoromethanesulfonate Chemical compound [Sc+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F HZXJVDYQRYYYOR-UHFFFAOYSA-K 0.000 description 1
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- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- YSQAUCXWFPBRQG-UHFFFAOYSA-N trimethylsilyl 2,2,2-trifluoroethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)CC(F)(F)F YSQAUCXWFPBRQG-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
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- A61K31/407—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 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
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Landscapes
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- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (3)
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| DE102007009319.7 | 2007-02-22 | ||
| DE102007009319A DE102007009319A1 (de) | 2007-02-22 | 2007-02-22 | Spirocyclische Cyclohexan-Derivate |
| PCT/EP2008/001271 WO2008101660A1 (de) | 2007-02-22 | 2008-02-19 | Spirocyclische cyclohexan-derivate |
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| JP2010519265A JP2010519265A (ja) | 2010-06-03 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| DE102006033114A1 (de) * | 2006-07-18 | 2008-01-24 | Grünenthal GmbH | Spirocyclische Azaindol-Derivate |
| ES2523580T3 (es) | 2008-01-11 | 2014-11-27 | Albany Molecular Research, Inc. | Piridoindoles substituidos con (1-Azinona) |
| JP5599774B2 (ja) | 2008-03-27 | 2014-10-01 | グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング | ヒドロキシメチルシクロヘキシルアミン類 |
| CL2009000731A1 (es) | 2008-03-27 | 2009-05-15 | Gruenenthal Gmbh | Compuestos derivados de ciclohexano espirociclicos sustituidos, composicion farmaceutica que contiene a dicho compuesto y su uso como moduladores del receptor de opioides µ y el receptor orl-1 para tratar el dolor, ansiedad, depresion, epilepsia, alzheimer, abuso de alcohol, hipertension, anorexia, obesidad y diarrea. |
| US8357705B2 (en) | 2008-03-27 | 2013-01-22 | Gruenenthal Gmbh | Substituted cyclohexyldiamines |
| PL2257526T3 (pl) | 2008-03-27 | 2012-05-31 | Gruenenthal Gmbh | Pochodne spiro (5.5) undekanu |
| ES2694103T3 (es) | 2008-03-27 | 2018-12-18 | Grünenthal GmbH | Derivados de 4-aminociclohexano sustituidos |
| US8618299B2 (en) | 2009-07-01 | 2013-12-31 | Albany Molecular Research, Inc. | Azinone-substituted azapolycycle MCH-1 antagonists, methods of making, and use thereof |
| WO2011003007A1 (en) | 2009-07-01 | 2011-01-06 | Albany Molecular Research, Inc. | Azabicycloalkane-indole and azabicycloalkane-pyrrolo-pyridine mch-1 antagonists, methods of making, and use thereof |
| JP2012532144A (ja) | 2009-07-01 | 2012-12-13 | アルバニー モレキュラー リサーチ， インコーポレイテッド | アジノン置換アゼピノ［ｂ］インドールおよびピリド−ピロロ−アゼピンｍｃｈ−１拮抗薬、ならびにその作製方法および使用 |
| US9073925B2 (en) | 2009-07-01 | 2015-07-07 | Albany Molecular Research, Inc. | Azinone-substituted azabicycloalkane-indole and azabicycloalkane-pyrrolo-pyridine MCH-1 antagonists, methods of making, and use thereof |
| HUE033692T2 (en) | 2010-12-08 | 2017-12-28 | Gruenenthal Gmbh | A method for the synthesis of substituted aminocyclohexanone derivatives |
| US8993765B2 (en) | 2010-12-21 | 2015-03-31 | Albany Molecular Research, Inc. | Tetrahydro-azacarboline MCH-1 antagonists, methods of making, and uses thereof |
| US8697700B2 (en) | 2010-12-21 | 2014-04-15 | Albany Molecular Research, Inc. | Piperazinone-substituted tetrahydro-carboline MCH-1 antagonists, methods of making, and uses thereof |
| SI2797925T1 (sl) * | 2011-12-12 | 2016-07-29 | Gruenenthal Gmbh | Postopek za pripravo (1r,4r)-6'-fluoro(N,N-dimetil- in N-metil)-4-fenil-4',9'-dihidro-3'H-spiro(cikloheksan-1,1'-pirano-(3,4,b) indol)-4-amina |
| BR112015022509A2 (pt) | 2013-03-15 | 2017-07-18 | Gruenenthal Gmbh | forma cristalina de cis-(e)-4-(3-fluorofenil)-2',3',4',9'-tetra-hidro-n,n-dimetil-2'-(1-oxo-3-fenil-2-propenil)-espiro[ciclohexano-1,1'[1h]-pirido[3,4-b]indol]-4-amina cristalina |
| TW201607923A (zh) | 2014-07-15 | 2016-03-01 | 歌林達有限公司 | 被取代之氮螺環（４．５）癸烷衍生物 |
| CN106660954A (zh) | 2014-07-15 | 2017-05-10 | 格吕伦塔尔有限公司 | 取代氮杂螺(4.5)癸烷衍生物 |
| US10022353B2 (en) * | 2015-01-23 | 2018-07-17 | Grünenthal GmbH | Cebranopadol for treating pain in subjects with impaired hepatic and/or impaired renal function |
| CN107383027A (zh) * | 2017-07-24 | 2017-11-24 | 扬州大学 | 一种四氢螺类化合物的合成方法 |
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| RU2265018C2 (ru) * | 2001-04-18 | 2005-11-27 | Эро-Селтик, С.А. | Производные бензимидазола и фармацевтические композиции на их основе |
| DE10252667A1 (de) | 2002-11-11 | 2004-05-27 | Grünenthal GmbH | Spirocyclische Cyclohexan-Derivate |
| DE10360792A1 (de) * | 2003-12-23 | 2005-07-28 | Grünenthal GmbH | Spirocyclische Cyclohexan-Derivate |
| DE102005016460A1 (de) * | 2005-04-11 | 2006-10-19 | Grünenthal GmbH | Spriocyclische Cyclohexanderivate zur Behandlung von Substanzabhängigkeit |
| DE102006046745A1 (de) | 2006-09-29 | 2008-04-03 | Grünenthal GmbH | Gemischte ORL1/µ-Agonisten zur Behandlung von Schmerz |
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