IL176457A - Cyclohexane Spiro History Compressed with Ortho-Compressed Tricyclic System, Process for Preparation and Pharmaceuticals Containing Them - Google Patents
Cyclohexane Spiro History Compressed with Ortho-Compressed Tricyclic System, Process for Preparation and Pharmaceuticals Containing ThemInfo
- Publication number
- IL176457A IL176457A IL176457A IL17645706A IL176457A IL 176457 A IL176457 A IL 176457A IL 176457 A IL176457 A IL 176457A IL 17645706 A IL17645706 A IL 17645706A IL 176457 A IL176457 A IL 176457A
- Authority
- IL
- Israel
- Prior art keywords
- singly
- unsubstituted
- alkyl
- multiply substituted
- acid
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 31
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 19
- 230000008569 process Effects 0.000 title claims description 23
- 238000002360 preparation method Methods 0.000 title claims description 10
- 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 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 51
- 208000002193 Pain Diseases 0.000 claims abstract description 19
- 230000036407 pain Effects 0.000 claims abstract description 12
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 71
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 55
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 50
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 49
- 125000001072 heteroaryl group Chemical group 0.000 claims description 48
- 229920006395 saturated elastomer Polymers 0.000 claims description 45
- 239000000203 mixture Substances 0.000 claims description 43
- -1 cyclohexane compound Chemical class 0.000 claims description 35
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 29
- 125000003118 aryl group Chemical group 0.000 claims description 28
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 28
- 238000006243 chemical reaction Methods 0.000 claims description 27
- 239000002253 acid Substances 0.000 claims description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 21
- 125000003107 substituted aryl group Chemical group 0.000 claims description 20
- 229910052794 bromium Inorganic materials 0.000 claims description 16
- 229910052740 iodine Inorganic materials 0.000 claims description 15
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 13
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 8
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 5
- 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 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 208000000094 Chronic Pain Diseases 0.000 claims description 4
- 206010012335 Dependence Diseases 0.000 claims description 4
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 4
- 239000012752 auxiliary agent Substances 0.000 claims description 4
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 4
- 208000004296 neuralgia Diseases 0.000 claims description 4
- 208000021722 neuropathic pain Diseases 0.000 claims description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 3
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 claims description 3
- 208000005298 acute pain Diseases 0.000 claims description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 239000012948 isocyanate Substances 0.000 claims description 3
- 150000002513 isocyanates Chemical class 0.000 claims description 3
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 3
- 239000007800 oxidant agent Substances 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 2
- GWZCLMWEJWPFFA-UHFFFAOYSA-N 2-thiophen-3-ylacetonitrile Chemical compound N#CCC=1C=CSC=1 GWZCLMWEJWPFFA-UHFFFAOYSA-N 0.000 claims description 2
- 206010013654 Drug abuse Diseases 0.000 claims description 2
- 208000026251 Opioid-Related disease Diseases 0.000 claims description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 2
- 150000008064 anhydrides Chemical class 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 2
- 125000002560 nitrile group Chemical group 0.000 claims description 2
- 201000000988 opioid abuse Diseases 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims 2
- 229940098779 methanesulfonic acid Drugs 0.000 claims 2
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 claims 2
- CQVKMVQRSNNAGO-UHFFFAOYSA-N 2-[4-formyl-3-methyl-n-(2-methylsulfonyloxyethyl)anilino]ethyl methanesulfonate Chemical compound CC1=CC(N(CCOS(C)(=O)=O)CCOS(C)(=O)=O)=CC=C1C=O CQVKMVQRSNNAGO-UHFFFAOYSA-N 0.000 claims 1
- 125000002843 carboxylic acid group Chemical group 0.000 claims 1
- 230000000911 decarboxylating effect Effects 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 claims 1
- 230000007062 hydrolysis Effects 0.000 claims 1
- 238000006460 hydrolysis reaction Methods 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- 230000001590 oxidative effect Effects 0.000 claims 1
- 108010020615 nociceptin receptor Proteins 0.000 abstract description 11
- 102000048266 Nociceptin Human genes 0.000 abstract description 9
- PULGYDLMFSFVBL-SMFNREODSA-N nociceptin Chemical compound C([C@@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O)[C@@H](C)O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 PULGYDLMFSFVBL-SMFNREODSA-N 0.000 abstract description 9
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 208000019901 Anxiety disease Diseases 0.000 abstract description 2
- 230000036506 anxiety Effects 0.000 abstract description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 83
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 42
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- 150000001934 cyclohexanes Chemical class 0.000 description 34
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 239000007787 solid Substances 0.000 description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 239000012074 organic phase Substances 0.000 description 19
- 150000003254 radicals Chemical class 0.000 description 17
- 239000000243 solution Substances 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- 235000015165 citric acid Nutrition 0.000 description 14
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 108090000622 Nociceptin Proteins 0.000 description 10
- 239000004480 active ingredient Substances 0.000 description 10
- 238000010438 heat treatment Methods 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 150000001768 cations Chemical class 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 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 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 229940093499 ethyl acetate Drugs 0.000 description 7
- 235000019439 ethyl acetate Nutrition 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- 150000001450 anions Chemical class 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 230000009191 jumping Effects 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- MBBOMCVGYCRMEA-UHFFFAOYSA-N tryptophol Chemical compound C1=CC=C2C(CCO)=CNC2=C1 MBBOMCVGYCRMEA-UHFFFAOYSA-N 0.000 description 6
- 241000282412 Homo Species 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 102000003840 Opioid Receptors Human genes 0.000 description 5
- 108090000137 Opioid Receptors Proteins 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 229940005483 opioid analgesics Drugs 0.000 description 5
- 239000000825 pharmaceutical preparation Substances 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- KBWHYRUAHXHHFO-UHFFFAOYSA-N 3-(bromomethyl)thiophene Chemical compound BrCC=1C=CSC=1 KBWHYRUAHXHHFO-UHFFFAOYSA-N 0.000 description 4
- QENGPZGAWFQWCZ-UHFFFAOYSA-N 3-Methylthiophene Chemical compound CC=1C=CSC=1 QENGPZGAWFQWCZ-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 235000011054 acetic acid Nutrition 0.000 description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 4
- 125000002877 alkyl aryl group Chemical group 0.000 description 4
- 230000003444 anaesthetic effect Effects 0.000 description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
- 230000003502 anti-nociceptive effect Effects 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 229940093476 ethylene glycol Drugs 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 229960005181 morphine Drugs 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- MXTYSYXDDDVPBQ-UHFFFAOYSA-N 2-(5-fluoro-1h-indol-3-yl)ethanol Chemical compound C1=C(F)C=C2C(CCO)=CNC2=C1 MXTYSYXDDDVPBQ-UHFFFAOYSA-N 0.000 description 3
- VWWRJDSMXNKMTJ-UHFFFAOYSA-N 4-oxo-1-thiophen-3-ylcyclohexane-1-carbonitrile Chemical compound C1CC(=O)CCC1(C#N)C1=CSC=C1 VWWRJDSMXNKMTJ-UHFFFAOYSA-N 0.000 description 3
- 239000004342 Benzoyl peroxide Substances 0.000 description 3
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 3
- 101001122476 Homo sapiens Mu-type opioid receptor Proteins 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 3
- 102100028647 Mu-type opioid receptor Human genes 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 125000003342 alkenyl group Chemical group 0.000 description 3
- 125000006193 alkinyl group Chemical group 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
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- 229960004132 diethyl ether Drugs 0.000 description 3
- 238000006073 displacement reaction Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000002285 radioactive effect Effects 0.000 description 3
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 3
- 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 description 2
- 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 description 2
- VIKBNMWOLLIQPG-UHFFFAOYSA-N 2-methyldecanedioic acid Chemical compound OC(=O)C(C)CCCCCCCC(O)=O VIKBNMWOLLIQPG-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- LUTOSMMOQSDXDA-UHFFFAOYSA-N 4-(dimethylamino)-4-pyridin-2-ylcyclohexan-1-one Chemical compound C=1C=CC=NC=1C1(N(C)C)CCC(=O)CC1 LUTOSMMOQSDXDA-UHFFFAOYSA-N 0.000 description 2
- ALYNCZNDIQEVRV-PZFLKRBQSA-N 4-amino-3,5-ditritiobenzoic acid Chemical compound [3H]c1cc(cc([3H])c1N)C(O)=O ALYNCZNDIQEVRV-PZFLKRBQSA-N 0.000 description 2
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 2
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 description 2
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—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
- 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
- C07D491/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- 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
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Psychiatry (AREA)
- Physical Education & Sports Medicine (AREA)
- Endocrinology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Reproductive Health (AREA)
- Hematology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Obesity (AREA)
- Child & Adolescent Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Anesthesiology (AREA)
- Dermatology (AREA)
- Gynecology & Obstetrics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10360792A DE10360792A1 (de) | 2003-12-23 | 2003-12-23 | Spirocyclische Cyclohexan-Derivate |
| PCT/EP2004/014539 WO2005066183A1 (de) | 2003-12-23 | 2004-12-21 | Spirocyclische cyclohexan-derivate mit affinität zum orl1-rezeptor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL176457A0 IL176457A0 (en) | 2006-10-05 |
| IL176457A true IL176457A (en) | 2013-11-28 |
Family
ID=34706497
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL176457A IL176457A (en) | 2003-12-23 | 2006-06-21 | Cyclohexane Spiro History Compressed with Ortho-Compressed Tricyclic System, Process for Preparation and Pharmaceuticals Containing Them |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US7332519B2 (enExample) |
| EP (1) | EP1725567B1 (enExample) |
| JP (1) | JP4885733B2 (enExample) |
| KR (1) | KR101152693B1 (enExample) |
| CN (1) | CN1922189B (enExample) |
| AR (1) | AR047163A1 (enExample) |
| AT (1) | ATE390430T1 (enExample) |
| AU (1) | AU2004312147B2 (enExample) |
| BR (1) | BRPI0418052A2 (enExample) |
| CA (1) | CA2550868C (enExample) |
| CY (1) | CY1107975T1 (enExample) |
| DE (2) | DE10360792A1 (enExample) |
| DK (1) | DK1725567T3 (enExample) |
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| US3843681A (en) * | 1971-06-01 | 1974-10-22 | American Home Prod | 1-carboxamido pyrano(thiopyrano)(3,4-6)indole derivatives |
| FR2663935A1 (fr) * | 1990-06-27 | 1992-01-03 | Adir | Nouveaux 1,2,3,4,5,6-hexahydroazepino [4,5-b] indoles et 1,2,3,4-tetrahydrobethacarbolines, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent. |
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| DE10123163A1 (de) * | 2001-05-09 | 2003-01-16 | Gruenenthal Gmbh | Substituierte Cyclohexan-1,4-diaminderivate |
| DE10252667A1 (de) * | 2002-11-11 | 2004-05-27 | Grünenthal GmbH | Spirocyclische Cyclohexan-Derivate |
| DE10360793A1 (de) * | 2003-12-23 | 2005-07-28 | Grünenthal GmbH | Spirocyclische Cyclohexan-Derivate |
-
2003
- 2003-12-23 DE DE10360792A patent/DE10360792A1/de not_active Withdrawn
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2004
- 2004-12-21 RU RU2006126787/04A patent/RU2383544C2/ru not_active IP Right Cessation
- 2004-12-21 PT PT04804136T patent/PT1725567E/pt unknown
- 2004-12-21 NZ NZ548317A patent/NZ548317A/en not_active IP Right Cessation
- 2004-12-21 ES ES04804136T patent/ES2303964T3/es not_active Expired - Lifetime
- 2004-12-21 SI SI200430663T patent/SI1725567T1/sl unknown
- 2004-12-21 EP EP04804136A patent/EP1725567B1/de not_active Expired - Lifetime
- 2004-12-21 JP JP2006546040A patent/JP4885733B2/ja not_active Expired - Fee Related
- 2004-12-21 CN CN2004800420360A patent/CN1922189B/zh not_active Expired - Fee Related
- 2004-12-21 AU AU2004312147A patent/AU2004312147B2/en not_active Ceased
- 2004-12-21 WO PCT/EP2004/014539 patent/WO2005066183A1/de not_active Ceased
- 2004-12-21 HR HR20080272T patent/HRP20080272T3/xx unknown
- 2004-12-21 MX MXPA06007171A patent/MXPA06007171A/es active IP Right Grant
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- 2004-12-21 DE DE502004006697T patent/DE502004006697D1/de not_active Expired - Lifetime
- 2004-12-21 KR KR1020067014815A patent/KR101152693B1/ko not_active Expired - Fee Related
- 2004-12-21 DK DK04804136T patent/DK1725567T3/da active
- 2004-12-21 BR BRPI0418052A patent/BRPI0418052A2/pt not_active Application Discontinuation
- 2004-12-21 PL PL04804136T patent/PL1725567T3/pl unknown
- 2004-12-22 AR ARP040104857A patent/AR047163A1/es not_active Application Discontinuation
- 2004-12-23 US US11/019,372 patent/US7332519B2/en not_active Expired - Fee Related
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2005
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- 2006-06-21 IL IL176457A patent/IL176457A/en not_active IP Right Cessation
- 2006-06-21 EC EC2006006667A patent/ECSP066667A/es unknown
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