AU2003220894B8 - Kappa-opioid receptor agonist comprising 2-phenylbenzothiazoline derivative - Google Patents
Kappa-opioid receptor agonist comprising 2-phenylbenzothiazoline derivative Download PDFInfo
- Publication number
- AU2003220894B8 AU2003220894B8 AU2003220894A AU2003220894A AU2003220894B8 AU 2003220894 B8 AU2003220894 B8 AU 2003220894B8 AU 2003220894 A AU2003220894 A AU 2003220894A AU 2003220894 A AU2003220894 A AU 2003220894A AU 2003220894 B8 AU2003220894 B8 AU 2003220894B8
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- Australia
- Prior art keywords
- acetyl
- compound
- chloro
- propoxy
- alkoxy
- Prior art date
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- XBHOUXSGHYZCNH-UHFFFAOYSA-N 2-phenyl-1,3-benzothiazole Chemical class C1=CC=CC=C1C1=NC2=CC=CC=C2S1 XBHOUXSGHYZCNH-UHFFFAOYSA-N 0.000 title description 10
- 239000002632 kappa opiate receptor agonist Substances 0.000 title 1
- 229940126470 kappa opioid receptor agonist Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 359
- 125000003545 alkoxy group Chemical group 0.000 claims description 65
- 150000002148 esters Chemical class 0.000 claims description 60
- 125000000217 alkyl group Chemical group 0.000 claims description 57
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 48
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 38
- 150000003839 salts Chemical class 0.000 claims description 29
- 229910052736 halogen Inorganic materials 0.000 claims description 25
- 150000002367 halogens Chemical class 0.000 claims description 25
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 21
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 19
- 125000002252 acyl group Chemical group 0.000 claims description 19
- 125000003118 aryl group Chemical group 0.000 claims description 18
- WOHLSTOWRAOMSG-UHFFFAOYSA-N 2,3-dihydro-1,3-benzothiazole Chemical compound C1=CC=C2SCNC2=C1 WOHLSTOWRAOMSG-UHFFFAOYSA-N 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 125000002947 alkylene group Chemical group 0.000 claims description 13
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 11
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 217
- 239000000243 solution Substances 0.000 description 108
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 89
- -1 isobutyryl valeryl Chemical group 0.000 description 72
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 69
- 239000000203 mixture Substances 0.000 description 52
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 238000000034 method Methods 0.000 description 41
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
- 239000011541 reaction mixture Substances 0.000 description 36
- 238000001816 cooling Methods 0.000 description 35
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 28
- 102000003840 Opioid Receptors Human genes 0.000 description 25
- 108090000137 Opioid Receptors Proteins 0.000 description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 239000003814 drug Substances 0.000 description 23
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
- 238000002360 preparation method Methods 0.000 description 22
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000000872 buffer Substances 0.000 description 18
- 239000013078 crystal Substances 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- QVVAWONRFLJUBP-UHFFFAOYSA-N 1,3-benzothiazol-3-ium;chloride Chemical compound Cl.C1=CC=C2SC=NC2=C1 QVVAWONRFLJUBP-UHFFFAOYSA-N 0.000 description 17
- 229940121954 Opioid receptor agonist Drugs 0.000 description 17
- 229940079593 drug Drugs 0.000 description 17
- 239000003402 opiate agonist Substances 0.000 description 17
- 238000010898 silica gel chromatography Methods 0.000 description 16
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 15
- 229910052757 nitrogen Inorganic materials 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- PUMTTZYYKPFOTK-UHFFFAOYSA-N 1-[6-chloro-2-(2-hydroxy-5-methoxyphenyl)-2h-1,3-benzothiazol-3-yl]ethanone Chemical compound COC1=CC=C(O)C(C2N(C3=CC=C(Cl)C=C3S2)C(C)=O)=C1 PUMTTZYYKPFOTK-UHFFFAOYSA-N 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 238000011534 incubation Methods 0.000 description 13
- 239000003960 organic solvent Substances 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 230000027455 binding Effects 0.000 description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 description 12
- 208000002193 Pain Diseases 0.000 description 11
- 125000004104 aryloxy group Chemical group 0.000 description 11
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 11
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 150000001412 amines Chemical class 0.000 description 10
- 230000000202 analgesic effect Effects 0.000 description 10
- 125000000623 heterocyclic group Chemical group 0.000 description 10
- 125000006239 protecting group Chemical group 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 9
- 230000003502 anti-nociceptive effect Effects 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 125000003282 alkyl amino group Chemical group 0.000 description 8
- 125000001769 aryl amino group Chemical group 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 239000013641 positive control Substances 0.000 description 8
- QGWNDRXFNXRZMB-UUOKFMHZSA-K GDP(3-) Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O QGWNDRXFNXRZMB-UUOKFMHZSA-K 0.000 description 7
- 239000013543 active substance Substances 0.000 description 7
- 235000015165 citric acid Nutrition 0.000 description 7
- QGWNDRXFNXRZMB-UHFFFAOYSA-N guanidine diphosphate Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O QGWNDRXFNXRZMB-UHFFFAOYSA-N 0.000 description 7
- 239000012452 mother liquor Substances 0.000 description 7
- 230000000144 pharmacologic effect Effects 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 125000003396 thiol group Chemical class [H]S* 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- 239000000556 agonist Substances 0.000 description 6
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 6
- 125000005129 aryl carbonyl group Chemical group 0.000 description 6
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- KHVVCKGCWWQHHX-UHFFFAOYSA-N 1-[6-chloro-2-[2-(3-chloropropoxy)-5-methoxyphenyl]-2h-1,3-benzothiazol-3-yl]ethanone Chemical compound COC1=CC=C(OCCCCl)C(C2N(C3=CC=C(Cl)C=C3S2)C(C)=O)=C1 KHVVCKGCWWQHHX-UHFFFAOYSA-N 0.000 description 5
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 150000001350 alkyl halides Chemical class 0.000 description 5
- 239000000730 antalgic agent Substances 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 229940044601 receptor agonist Drugs 0.000 description 5
- 239000000018 receptor agonist Substances 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
- 125000004434 sulfur atom Chemical group 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- KTQBGMMWEAVGEQ-RYUDHWBXSA-N (2s,4s)-3-acetyl-5,5-dimethyl-2-phenyl-1,3-thiazolidine-4-carboxylic acid Chemical compound S1C(C)(C)[C@H](C(O)=O)N(C(=O)C)[C@@H]1C1=CC=CC=C1 KTQBGMMWEAVGEQ-RYUDHWBXSA-N 0.000 description 4
- FZHSPPYCNDYIKD-UHFFFAOYSA-N 5-methoxysalicylaldehyde Chemical compound COC1=CC=C(O)C(C=O)=C1 FZHSPPYCNDYIKD-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- 208000003251 Pruritus Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- GFOWYEIMOUPRRY-ZLBDCPSSSA-N [2-(3-acetyl-6-chloro-2h-1,3-benzothiazol-2-yl)-4-methoxyphenyl] (2s,4s)-3-acetyl-5,5-dimethyl-2-phenyl-1,3-thiazolidine-4-carboxylate Chemical compound C1([C@H]2N([C@H](C(S2)(C)C)C(=O)OC2=CC=C(C=C2C2N(C3=CC=C(Cl)C=C3S2)C(C)=O)OC)C(C)=O)=CC=CC=C1 GFOWYEIMOUPRRY-ZLBDCPSSSA-N 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 229940035676 analgesics Drugs 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 4
- 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 4
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 125000004430 oxygen atom Chemical group O* 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 125000003386 piperidinyl group Chemical group 0.000 description 4
- 229910021642 ultra pure water Inorganic materials 0.000 description 4
- 239000012498 ultrapure water Substances 0.000 description 4
- ROSJMNJJOXFJGH-UHFFFAOYSA-N 1-[2-(2-hydroxy-5-methoxyphenyl)-2h-1,3-benzothiazol-3-yl]ethanone Chemical compound COC1=CC=C(O)C(C2N(C3=CC=CC=C3S2)C(C)=O)=C1 ROSJMNJJOXFJGH-UHFFFAOYSA-N 0.000 description 3
- VRVRGVPWCUEOGV-UHFFFAOYSA-N 2-aminothiophenol Chemical class NC1=CC=CC=C1S VRVRGVPWCUEOGV-UHFFFAOYSA-N 0.000 description 3
- YKJUYTXCRIKRND-UHFFFAOYSA-N 2-phenyl-2,3-dihydro-1,3-benzothiazole Chemical compound S1C2=CC=CC=C2NC1C1=CC=CC=C1 YKJUYTXCRIKRND-UHFFFAOYSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 150000001266 acyl halides Chemical class 0.000 description 3
- 230000001139 anti-pruritic effect Effects 0.000 description 3
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
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- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 3
- 230000003533 narcotic effect Effects 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
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- 125000004585 polycyclic heterocycle group Chemical group 0.000 description 3
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 3
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- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
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- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- NYATUQLQYZIJCY-WDEREUQCSA-N (2r,4r)-3-acetyl-2-phenyl-1,3-thiazolidine-4-carboxylic acid Chemical compound CC(=O)N1[C@H](C(O)=O)CS[C@@H]1C1=CC=CC=C1 NYATUQLQYZIJCY-WDEREUQCSA-N 0.000 description 2
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
- LXRJYRHCFXSKAQ-UHFFFAOYSA-N 1-[2-(2-hydroxy-5-methoxyphenyl)-5-(trifluoromethyl)-2h-1,3-benzothiazol-3-yl]ethanone Chemical compound COC1=CC=C(O)C(C2N(C3=CC(=CC=C3S2)C(F)(F)F)C(C)=O)=C1 LXRJYRHCFXSKAQ-UHFFFAOYSA-N 0.000 description 2
- SOUPXBYYLVRNSD-UHFFFAOYSA-N 1-[2-[2-(2-bromoethoxy)-5-methoxyphenyl]-6-chloro-2h-1,3-benzothiazol-3-yl]ethanone Chemical compound COC1=CC=C(OCCBr)C(C2N(C3=CC=C(Cl)C=C3S2)C(C)=O)=C1 SOUPXBYYLVRNSD-UHFFFAOYSA-N 0.000 description 2
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/428—Thiazoles condensed with carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
- C07D277/66—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2 with aromatic rings or ring systems directly attached in position 2
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2009201233A AU2009201233B2 (en) | 2002-03-29 | 2009-03-30 | Kappa-opioid receptor agonist comprising 2-phenylbenzothiazoline derivative |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2002-097500 | 2002-03-29 | ||
| JP2002097500 | 2002-03-29 | ||
| PCT/JP2003/003928 WO2003082840A1 (en) | 2002-03-29 | 2003-03-28 | κ-OPIOID RECEPTOR AGONIST COMPRISING 2-PHENYLBENZOTHIAZOLINE DERIVATIVE |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2009201233A Division AU2009201233B2 (en) | 2002-03-29 | 2009-03-30 | Kappa-opioid receptor agonist comprising 2-phenylbenzothiazoline derivative |
Publications (3)
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|---|---|
| AU2003220894A1 AU2003220894A1 (en) | 2003-10-13 |
| AU2003220894B2 AU2003220894B2 (en) | 2009-02-05 |
| AU2003220894B8 true AU2003220894B8 (en) | 2009-02-19 |
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| AU2003220894A Ceased AU2003220894B8 (en) | 2002-03-29 | 2003-03-28 | Kappa-opioid receptor agonist comprising 2-phenylbenzothiazoline derivative |
| AU2009201233A Ceased AU2009201233B2 (en) | 2002-03-29 | 2009-03-30 | Kappa-opioid receptor agonist comprising 2-phenylbenzothiazoline derivative |
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| AU2009201233A Ceased AU2009201233B2 (en) | 2002-03-29 | 2009-03-30 | Kappa-opioid receptor agonist comprising 2-phenylbenzothiazoline derivative |
Country Status (10)
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| EP1642590A4 (en) * | 2003-07-04 | 2009-05-13 | Santen Pharmaceutical Co Ltd | MEANS TO INHIBIT THE DEGRADATION OF THE PAIN LIMIT |
| US7642274B2 (en) | 2004-07-02 | 2010-01-05 | Santen Pharmaceutical Co., Ltd. | Inhibitor of pain threshold decrease |
| EP1849465A4 (en) * | 2005-02-18 | 2008-12-24 | Takeda Pharmaceutical | AGENT FOR CONTROLLING THE FUNCTION OF THE GPR34 RECEPTOR |
| US9303027B2 (en) | 2010-07-19 | 2016-04-05 | Dr. Reddy's Laboratories Ltd. | Kappa opioid receptor agonists |
| CN104271552B (zh) | 2012-03-05 | 2017-08-08 | 雷迪博士实验室有限公司 | 作为kappa阿片样物质受体(kor)激动剂的取代的杂环乙酰胺 |
| JP6275517B2 (ja) | 2013-03-22 | 2018-02-07 | あゆみ製薬株式会社 | Ｉｌ−２産生抑制 |
| WO2015093567A1 (ja) | 2013-12-18 | 2015-06-25 | 国立大学法人京都大学 | 疼痛に関する化合物及び医薬組成物 |
| WO2018230711A1 (ja) | 2017-06-16 | 2018-12-20 | 学校法人同志社 | ｍＴＯＲインヒビターを含む、眼の症状、障害または疾患を治療または予防するための医薬およびその応用 |
| US20200121652A1 (en) | 2017-06-16 | 2020-04-23 | The Doshisha | Compounds having caspase inhibitory activity, pharmaceutical agent containing said compounds and for treating or preventing corneal endothelial symptoms, disorders, or diseases, and application of said pharmaceutical agent |
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| US547513A (en) * | 1895-10-08 | Chell | ||
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| JPS5846079A (ja) | 1981-09-12 | 1983-03-17 | Santen Pharmaceut Co Ltd | ベンゾチアゾリン環を有するエ−テル類 |
| JPS5967276A (ja) | 1982-09-01 | 1984-04-16 | Santen Pharmaceut Co Ltd | ベンゾチアゾリン誘導体 |
| JPS60139679A (ja) | 1983-12-27 | 1985-07-24 | Santen Pharmaceut Co Ltd | ２−アリ−ルベンゾチアゾリン誘導体 |
| JPS6183175A (ja) * | 1984-09-06 | 1986-04-26 | Santen Pharmaceut Co Ltd | ベンゾチアゾリン誘導体およびそれを主成分とする循環器官用薬剤 |
| JPS62221679A (ja) | 1986-03-19 | 1987-09-29 | Santen Pharmaceut Co Ltd | ベンゾチアゾリン誘導体 |
| JPH066581B2 (ja) * | 1986-03-19 | 1994-01-26 | 参天製薬株式会社 | フエノキシアルキルアミン側鎖を有するベンゾチアゾリン誘導体 |
| JPH08231399A (ja) * | 1995-02-23 | 1996-09-10 | Shionogi & Co Ltd | モルヒネ禁断抑制作用剤 |
| US6174891B1 (en) * | 1996-11-25 | 2001-01-16 | Toray Industries, Inc. | Antipruritic agent |
| JP2000344821A (ja) | 1999-06-01 | 2000-12-12 | Toagosei Co Ltd | オレフィン重合用触媒 |
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- 2003-03-28 AU AU2003220894A patent/AU2003220894B8/en not_active Ceased
- 2003-03-28 CN CNB2006101392068A patent/CN100522954C/zh not_active Expired - Fee Related
- 2003-03-28 EP EP03715569A patent/EP1496053B1/en not_active Expired - Lifetime
- 2003-03-28 CN CN038072750A patent/CN1642929B/zh not_active Expired - Fee Related
- 2003-03-28 KR KR1020047015318A patent/KR101035931B1/ko not_active IP Right Cessation
- 2003-03-28 EP EP09000611A patent/EP2042173A3/en not_active Withdrawn
- 2003-03-28 NZ NZ535987A patent/NZ535987A/en not_active IP Right Cessation
- 2003-03-28 CA CA2480560A patent/CA2480560C/en not_active Expired - Fee Related
- 2003-03-28 WO PCT/JP2003/003928 patent/WO2003082840A1/ja active Application Filing
- 2003-03-28 ES ES03715569T patent/ES2390052T3/es not_active Expired - Lifetime
-
2006
- 2006-05-15 US US11/434,028 patent/US7410987B2/en not_active Expired - Fee Related
-
2009
- 2009-02-02 JP JP2009021413A patent/JP5061134B2/ja not_active Expired - Fee Related
- 2009-03-30 AU AU2009201233A patent/AU2009201233B2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| US7410987B2 (en) | 2008-08-12 |
| CN1642929A (zh) | 2005-07-20 |
| JP5061134B2 (ja) | 2012-10-31 |
| WO2003082840A1 (en) | 2003-10-09 |
| US20050113430A1 (en) | 2005-05-26 |
| CN100522954C (zh) | 2009-08-05 |
| EP1496053A1 (en) | 2005-01-12 |
| EP2042173A2 (en) | 2009-04-01 |
| ES2390052T3 (es) | 2012-11-06 |
| CN1911918A (zh) | 2007-02-14 |
| CN1642929B (zh) | 2010-05-12 |
| KR20040095329A (ko) | 2004-11-12 |
| NZ535987A (en) | 2006-08-31 |
| US7112598B2 (en) | 2006-09-26 |
| EP1496053B1 (en) | 2012-06-20 |
| AU2009201233B2 (en) | 2012-07-05 |
| CA2480560C (en) | 2011-02-15 |
| JP2009143940A (ja) | 2009-07-02 |
| AU2003220894B2 (en) | 2009-02-05 |
| EP2042173A3 (en) | 2010-02-24 |
| US20060205796A1 (en) | 2006-09-14 |
| CA2480560A1 (en) | 2003-10-09 |
| AU2009201233A1 (en) | 2009-04-23 |
| AU2003220894A1 (en) | 2003-10-13 |
| KR101035931B1 (ko) | 2011-05-23 |
| EP1496053A4 (en) | 2008-01-16 |
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| Date | Code | Title | Description |
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| TH | Corrigenda |
Free format text: IN VOL 23, NO 5, PAGE(S) 6642 UNDER THE HEADING APPLICATIONS ACCEPTED -NAME INDEX UNDER THE NAME SANTEN PHARMACEUTICAL CO., LTD., APPLICATION NO. 2003220894, UNDER INID (72), CORRECT THE CO-INVENTOR NAME TO READ FUJIMURA, KEN-ICHI |
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| FGA | Letters patent sealed or granted (standard patent) | ||
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Owner name: AYUMI PHARMACEUTICAL CORPORATION Free format text: FORMER OWNER WAS: SANTEN PHARMACEUTICAL CO., LTD. |
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| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |