IE47187B1 - 3-(2-hydroxy-4-(substituted)phenyl)cycloalkanone and cycloalkanol analgesic agents - Google Patents
3-(2-hydroxy-4-(substituted)phenyl)cycloalkanone and cycloalkanol analgesic agentsInfo
- Publication number
- IE47187B1 IE47187B1 IE1841/78A IE184178A IE47187B1 IE 47187 B1 IE47187 B1 IE 47187B1 IE 1841/78 A IE1841/78 A IE 1841/78A IE 184178 A IE184178 A IE 184178A IE 47187 B1 IE47187 B1 IE 47187B1
- Authority
- IE
- Ireland
- Prior art keywords
- arh
- hydrogen
- ether
- benzyloxy
- dimethylheptyl
- Prior art date
Links
- 239000000730 antalgic agent Substances 0.000 title abstract description 11
- -1 2-hydroxy-4-substituted phenyl group Chemical group 0.000 claims abstract description 78
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 26
- 239000001961 anticonvulsive agent Substances 0.000 claims abstract description 6
- 239000000932 sedative agent Substances 0.000 claims abstract description 6
- 239000002249 anxiolytic agent Substances 0.000 claims abstract description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 217
- 150000001875 compounds Chemical class 0.000 claims description 197
- 238000000034 method Methods 0.000 claims description 108
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 78
- 239000001257 hydrogen Substances 0.000 claims description 77
- 229910052739 hydrogen Inorganic materials 0.000 claims description 77
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 70
- 238000006243 chemical reaction Methods 0.000 claims description 68
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 63
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 claims description 58
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 55
- 125000004432 carbon atom Chemical group C* 0.000 claims description 50
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 36
- 125000002947 alkylene group Chemical group 0.000 claims description 20
- 125000004043 oxo group Chemical group O=* 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 18
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 17
- 150000002431 hydrogen Chemical class 0.000 claims description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 229920006395 saturated elastomer Polymers 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 11
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 230000000202 analgesic effect Effects 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- MQWCXKGKQLNYQG-UHFFFAOYSA-N 4-methylcyclohexan-1-ol Chemical compound CC1CCC(O)CC1 MQWCXKGKQLNYQG-UHFFFAOYSA-N 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 5
- QCRFMSUKWRQZEM-UHFFFAOYSA-N cycloheptanol Chemical compound OC1CCCCCC1 QCRFMSUKWRQZEM-UHFFFAOYSA-N 0.000 claims description 5
- 159000000001 potassium salts Chemical class 0.000 claims description 5
- 125000004423 acyloxy group Chemical group 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000001589 carboacyl group Chemical group 0.000 claims description 4
- CGZZMOTZOONQIA-UHFFFAOYSA-N cycloheptanone Chemical compound O=C1CCCCCC1 CGZZMOTZOONQIA-UHFFFAOYSA-N 0.000 claims description 4
- 239000003204 tranquilizing agent Substances 0.000 claims description 4
- 230000002936 tranquilizing effect Effects 0.000 claims description 4
- 101100490437 Mus musculus Acvrl1 gene Proteins 0.000 claims description 3
- 230000029936 alkylation Effects 0.000 claims description 3
- 238000005804 alkylation reaction Methods 0.000 claims description 3
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 3
- 230000001773 anti-convulsant effect Effects 0.000 claims description 3
- 229960003965 antiepileptics Drugs 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 230000001624 sedative effect Effects 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- 229910052721 tungsten Inorganic materials 0.000 claims description 3
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims description 2
- 230000000049 anti-anxiety effect Effects 0.000 claims description 2
- PQANGXXSEABURG-UHFFFAOYSA-N cyclohex-2-en-1-ol Chemical compound OC1CCCC=C1 PQANGXXSEABURG-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 claims description 2
- 229940125725 tranquilizer Drugs 0.000 claims description 2
- WXVNSHRGPVHBPD-UHFFFAOYSA-N 4-methylcycloheptan-1-one Chemical compound CC1CCCC(=O)CC1 WXVNSHRGPVHBPD-UHFFFAOYSA-N 0.000 claims 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims 1
- 230000002152 alkylating effect Effects 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- OKTJSMMVPCPJKN-YPZZEJLDSA-N carbon-10 atom Chemical group [10C] OKTJSMMVPCPJKN-YPZZEJLDSA-N 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 abstract description 14
- 229940035676 analgesics Drugs 0.000 abstract description 5
- 125000001424 substituent group Chemical group 0.000 abstract description 5
- 239000002934 diuretic Substances 0.000 abstract description 4
- 229940125681 anticonvulsant agent Drugs 0.000 abstract description 3
- 229940125714 antidiarrheal agent Drugs 0.000 abstract description 3
- 239000003793 antidiarrheal agent Substances 0.000 abstract description 3
- 229940030606 diuretics Drugs 0.000 abstract description 3
- 229940125723 sedative agent Drugs 0.000 abstract description 3
- 125000003710 aryl alkyl group Chemical group 0.000 abstract description 2
- 125000004430 oxygen atom Chemical group O* 0.000 abstract 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 220
- 239000003921 oil Substances 0.000 description 154
- 235000019198 oils Nutrition 0.000 description 154
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 148
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 137
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 98
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 94
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 92
- 239000000243 solution Substances 0.000 description 91
- 239000000203 mixture Substances 0.000 description 79
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 69
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 67
- 238000004458 analytical method Methods 0.000 description 66
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 65
- 239000011541 reaction mixture Substances 0.000 description 65
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 58
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 57
- 239000000741 silica gel Substances 0.000 description 57
- 229910002027 silica gel Inorganic materials 0.000 description 57
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 54
- 239000000047 product Substances 0.000 description 53
- 230000000875 corresponding effect Effects 0.000 description 49
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 49
- 235000019341 magnesium sulphate Nutrition 0.000 description 49
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 47
- 229920002554 vinyl polymer Polymers 0.000 description 47
- 238000002360 preparation method Methods 0.000 description 45
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 35
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 34
- 239000003814 drug Substances 0.000 description 32
- 239000012259 ether extract Substances 0.000 description 32
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 32
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 31
- 229940079593 drug Drugs 0.000 description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- 238000004440 column chromatography Methods 0.000 description 29
- IPZJQDSFZGZEOY-UHFFFAOYSA-N dimethylmethylene Chemical compound C[C]C IPZJQDSFZGZEOY-UHFFFAOYSA-N 0.000 description 29
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
- DLLJVQNYBYOKGS-UHFFFAOYSA-N ethoxyethane;pentane Chemical compound CCCCC.CCOCC DLLJVQNYBYOKGS-UHFFFAOYSA-N 0.000 description 28
- 238000012360 testing method Methods 0.000 description 28
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 26
- 239000000376 reactant Substances 0.000 description 23
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- 238000010992 reflux Methods 0.000 description 19
- 238000011282 treatment Methods 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 239000000284 extract Substances 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 239000000706 filtrate Substances 0.000 description 17
- 239000012442 inert solvent Substances 0.000 description 17
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- 125000006239 protecting group Chemical group 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- 241001465754 Metazoa Species 0.000 description 15
- 241000699670 Mus sp. Species 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- 150000002148 esters Chemical group 0.000 description 15
- 235000011167 hydrochloric acid Nutrition 0.000 description 15
- 229960000443 hydrochloric acid Drugs 0.000 description 15
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 14
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 14
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 125000001743 benzylic group Chemical group 0.000 description 14
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 14
- 238000006722 reduction reaction Methods 0.000 description 14
- 230000009467 reduction Effects 0.000 description 13
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 12
- 238000010828 elution Methods 0.000 description 12
- 235000019256 formaldehyde Nutrition 0.000 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 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 12
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 12
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 11
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- 239000012279 sodium borohydride Substances 0.000 description 11
- 229910000033 sodium borohydride Inorganic materials 0.000 description 11
- JZLCKKPJQXZUDI-UHFFFAOYSA-N 2-methyl-2-(3-phenylmethoxyphenyl)propanal Chemical compound O=CC(C)(C)C1=CC=CC(OCC=2C=CC=CC=2)=C1 JZLCKKPJQXZUDI-UHFFFAOYSA-N 0.000 description 10
- 239000005909 Kieselgur Substances 0.000 description 10
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- 125000004356 hydroxy functional group Chemical group O* 0.000 description 10
- 150000002576 ketones Chemical class 0.000 description 10
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- 238000002425 crystallisation Methods 0.000 description 9
- 230000008025 crystallization Effects 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
- 238000007239 Wittig reaction Methods 0.000 description 5
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- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
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- 125000002243 cyclohexanonyl group Chemical class *C1(*)C(=O)C(*)(*)C(*)(*)C(*)(*)C1(*)* 0.000 description 5
- 238000006264 debenzylation reaction Methods 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
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- LGRLWUINFJPLSH-UHFFFAOYSA-N methanide Chemical compound [CH3-] LGRLWUINFJPLSH-UHFFFAOYSA-N 0.000 description 5
- 230000003040 nociceptive effect Effects 0.000 description 5
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- KRIOVPPHQSLHCZ-UHFFFAOYSA-N propiophenone Chemical compound CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 description 1
- OSFBJERFMQCEQY-UHFFFAOYSA-N propylidene Chemical compound [CH]CC OSFBJERFMQCEQY-UHFFFAOYSA-N 0.000 description 1
- 125000004309 pyranyl group Chemical class O1C(C=CC=C1)* 0.000 description 1
- BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 1
- 230000036647 reaction Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- XXOFMPZKIYNSTG-UHFFFAOYSA-N sodium;2-phenylethanolate Chemical compound [Na+].[O-]CCC1=CC=CC=C1 XXOFMPZKIYNSTG-UHFFFAOYSA-N 0.000 description 1
- SYXYWTXQFUUWLP-UHFFFAOYSA-N sodium;butan-1-olate Chemical compound [Na+].CCCC[O-] SYXYWTXQFUUWLP-UHFFFAOYSA-N 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical group CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/72—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 spiro-condensed with carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/001—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by modification in a side chain
- C07C37/002—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by modification in a side chain by transformation of a functional group, e.g. oxo, carboxyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/01—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis
- C07C37/055—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/01—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis
- C07C37/055—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group
- C07C37/0555—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group being esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
- C07C39/12—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic with no unsaturation outside the aromatic rings
- C07C39/17—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic with no unsaturation outside the aromatic rings containing other rings in addition to the six-membered aromatic rings, e.g. cyclohexylphenol
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
- C07C39/23—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic, containing six-membered aromatic rings and other rings, with unsaturation outside the aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
- C07C39/24—Halogenated derivatives
- C07C39/42—Halogenated derivatives containing six-membered aromatic rings and other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
- C07C403/02—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains containing only carbon and hydrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/26—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/48—Preparation of compounds having groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/48—Preparation of compounds having groups
- C07C41/50—Preparation of compounds having groups by reactions producing groups
- C07C41/56—Preparation of compounds having groups by reactions producing groups by condensation of aldehydes, paraformaldehyde, or ketones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/23—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/30—Compounds having groups
- C07C43/315—Compounds having groups containing oxygen atoms singly bound to carbon atoms not being acetal carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/20—Unsaturated compounds containing keto groups bound to acyclic carbon atoms
- C07C49/255—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing ether groups, groups, groups, or groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
- C07C49/703—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups
- C07C49/747—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
- C07C49/753—Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/95—Esters of quinone carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/117—Esters of phosphoric acids with cycloaliphatic alcohols
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/18—Systems containing only non-condensed rings with a ring being at least seven-membered
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Neurology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US83310277A | 1977-09-13 | 1977-09-13 | |
US92668778A | 1978-07-25 | 1978-07-25 |
Publications (2)
Publication Number | Publication Date |
---|---|
IE781841L IE781841L (en) | 1979-03-13 |
IE47187B1 true IE47187B1 (en) | 1984-01-11 |
Family
ID=27125579
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IE1841/78A IE47187B1 (en) | 1977-09-13 | 1978-09-12 | 3-(2-hydroxy-4-(substituted)phenyl)cycloalkanone and cycloalkanol analgesic agents |
Country Status (27)
Country | Link |
---|---|
JP (1) | JPS5448741A (no) |
AR (1) | AR224618A1 (no) |
AT (1) | AT361455B (no) |
AU (1) | AU513523B2 (no) |
CA (1) | CA1110261A (no) |
CH (1) | CH635812A5 (no) |
DE (1) | DE2839836C2 (no) |
DK (1) | DK400878A (no) |
ES (3) | ES473288A1 (no) |
FI (1) | FI66584C (no) |
FR (1) | FR2402639A1 (no) |
GB (1) | GB2004870B (no) |
GR (1) | GR74134B (no) |
HK (1) | HK13284A (no) |
IE (1) | IE47187B1 (no) |
IL (1) | IL55556A (no) |
IN (1) | IN150334B (no) |
IT (1) | IT1099054B (no) |
KE (1) | KE3352A (no) |
LU (1) | LU80220A1 (no) |
MX (1) | MX5306E (no) |
MY (1) | MY8500094A (no) |
NL (2) | NL7809274A (no) |
NO (2) | NO149426C (no) |
NZ (1) | NZ188391A (no) |
PH (2) | PH15252A (no) |
SE (1) | SE431085B (no) |
Families Citing this family (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IN162851B (no) * | 1980-09-19 | 1988-07-16 | Pfizer | |
US4285867A (en) * | 1980-09-19 | 1981-08-25 | Pfizer Inc. | Pharmacologically active 4-[2-hydroxy-4-(substituted)phenyl]naphthalen-2(1H)-ones and 2-ols, derivatives thereof and intermediates therefor |
US5650270A (en) * | 1982-02-01 | 1997-07-22 | Northeastern University | Molecular analytical release tags and their use in chemical analysis |
US4709016A (en) * | 1982-02-01 | 1987-11-24 | Northeastern University | Molecular analytical release tags and their use in chemical analysis |
JPS58201737A (ja) * | 1982-05-18 | 1983-11-24 | Mitsui Toatsu Chem Inc | 新規芳香族アルカン誘導体、その製造法およびそれを有効成分とする殺虫、殺ダニ剤 |
GB8330099D0 (en) * | 1983-11-11 | 1983-12-21 | Ici Plc | Cycloalkane derivatives |
IL75480A0 (en) * | 1985-06-11 | 1985-10-31 | Yissum Res Dev Co | Alkoxyphenol derivatives and pharmaceutical compositions containing them |
US4623657A (en) * | 1985-09-05 | 1986-11-18 | Hoechst-Roussel Pharmaceuticals Inc. | Spiro [benzofuran-2(3H),1'-cycloheptane]s and their therapeutic use |
IE70521B1 (en) * | 1989-02-28 | 1996-12-11 | Zeneca Pharma Sa | Heterocycles with inhibitory activity of 5-lipoxygenase |
US6828460B2 (en) | 1999-03-22 | 2004-12-07 | Pfizer Inc. | Resorcinol derivatives |
ES2238993T3 (es) * | 1999-03-22 | 2005-09-16 | Pfizer Inc. | Derivados de resorcinol. |
US7612101B2 (en) | 2006-04-24 | 2009-11-03 | Allergan, Inc. | Abnormal cannabidiols as agents for lowering intraocular pressure |
US7718830B2 (en) | 2006-04-24 | 2010-05-18 | Allergan, Inc. | Abnormal cannabidiols as agents for lowering intraocular pressure |
US7618966B2 (en) | 2006-04-24 | 2009-11-17 | Allergan, Inc. | Abnormal Cannabidiols as agents for lowering intraocular pressure |
WO2007127711A2 (en) * | 2006-04-24 | 2007-11-08 | Allergan, Inc. | Abnormal cannabidiols as agents for lowering intraocular pressure |
CN109369514B (zh) * | 2018-12-10 | 2021-10-26 | 天津科技大学 | 一种六元碳环衍生物的合成方法 |
EP3997098A4 (en) * | 2019-07-12 | 2023-10-11 | Canopy Growth Corporation | CANNABINOIDS DERIVATIVES |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SU487907A1 (ru) * | 1973-09-21 | 1975-10-15 | Полоцкий Химический Комбинат Им. 50-Летия Белор.Сср | Полимерна композици |
-
1978
- 1978-08-28 SE SE7809060A patent/SE431085B/sv unknown
- 1978-09-01 IN IN649/DEL/78A patent/IN150334B/en unknown
- 1978-09-06 CA CA310,713A patent/CA1110261A/en not_active Expired
- 1978-09-11 GR GR57203A patent/GR74134B/el unknown
- 1978-09-12 AT AT658778A patent/AT361455B/de not_active IP Right Cessation
- 1978-09-12 ES ES473288A patent/ES473288A1/es not_active Expired
- 1978-09-12 FI FI782794A patent/FI66584C/fi not_active IP Right Cessation
- 1978-09-12 GB GB7836418A patent/GB2004870B/en not_active Expired
- 1978-09-12 JP JP11217078A patent/JPS5448741A/ja active Granted
- 1978-09-12 IL IL55556A patent/IL55556A/xx unknown
- 1978-09-12 NL NL7809274A patent/NL7809274A/xx not_active Application Discontinuation
- 1978-09-12 LU LU80220A patent/LU80220A1/fr unknown
- 1978-09-12 NZ NZ188391A patent/NZ188391A/en unknown
- 1978-09-12 NO NO783087A patent/NO149426C/no unknown
- 1978-09-12 DK DK400878A patent/DK400878A/da not_active Application Discontinuation
- 1978-09-12 FR FR7826194A patent/FR2402639A1/fr not_active Withdrawn
- 1978-09-12 IE IE1841/78A patent/IE47187B1/en unknown
- 1978-09-12 IT IT27558/78A patent/IT1099054B/it active
- 1978-09-13 AR AR273693A patent/AR224618A1/es active
- 1978-09-13 CH CH955678A patent/CH635812A5/fr not_active IP Right Cessation
- 1978-09-13 AU AU39818/78A patent/AU513523B2/en not_active Expired
- 1978-09-13 DE DE2839836A patent/DE2839836C2/de not_active Expired
- 1978-09-13 MX MX787390U patent/MX5306E/es unknown
- 1978-09-13 PH PH21596A patent/PH15252A/en unknown
-
1979
- 1979-05-02 ES ES480150A patent/ES480150A1/es not_active Expired
- 1979-05-02 ES ES480149A patent/ES8100795A1/es not_active Expired
- 1979-09-03 NO NO792840A patent/NO792840L/no unknown
- 1979-10-09 PH PH23144A patent/PH16597A/en unknown
-
1983
- 1983-09-30 NL NL8303358A patent/NL8303358A/nl not_active Application Discontinuation
- 1983-11-22 KE KE3352A patent/KE3352A/xx unknown
-
1984
- 1984-02-16 HK HK132/84A patent/HK13284A/xx unknown
-
1985
- 1985-12-30 MY MY94/85A patent/MY8500094A/xx unknown
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