JP2008534613A5 - - Google Patents
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- Publication number
- JP2008534613A5 JP2008534613A5 JP2008504447A JP2008504447A JP2008534613A5 JP 2008534613 A5 JP2008534613 A5 JP 2008534613A5 JP 2008504447 A JP2008504447 A JP 2008504447A JP 2008504447 A JP2008504447 A JP 2008504447A JP 2008534613 A5 JP2008534613 A5 JP 2008534613A5
- Authority
- JP
- Japan
- Prior art keywords
- compound
- alkyl
- pharmaceutical composition
- opioid receptor
- hydroxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- 150000001875 compounds Chemical class 0.000 claims description 362
- -1 hydroxy, aminocarbonyl Chemical group 0.000 claims description 121
- 102000003840 Opioid Receptors Human genes 0.000 claims description 62
- 108090000137 Opioid Receptors Proteins 0.000 claims description 62
- 239000003814 drug Substances 0.000 claims description 51
- 239000002253 acid Substances 0.000 claims description 35
- 230000000694 effects Effects 0.000 claims description 31
- 101100244562 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) oprD gene Proteins 0.000 claims description 27
- 108700023159 delta Opioid Receptors Proteins 0.000 claims description 27
- 102000048124 delta Opioid Receptors Human genes 0.000 claims description 27
- 230000000202 analgesic effect Effects 0.000 claims description 14
- 206010021639 Incontinence Diseases 0.000 claims description 13
- 229940005483 opioid analgesics Drugs 0.000 claims description 13
- 239000000556 agonist Substances 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims 147
- 239000008194 pharmaceutical composition Substances 0.000 claims 94
- 150000003839 salts Chemical class 0.000 claims 71
- 125000003118 aryl group Chemical group 0.000 claims 52
- 208000004296 neuralgia Diseases 0.000 claims 48
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 39
- 125000001072 heteroaryl group Chemical group 0.000 claims 37
- 150000001204 N-oxides Chemical class 0.000 claims 34
- 229940002612 prodrug Drugs 0.000 claims 34
- 239000000651 prodrug Substances 0.000 claims 34
- 239000012453 solvate Substances 0.000 claims 34
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 31
- 125000005843 halogen group Chemical group 0.000 claims 27
- DEXMFYZAHXMZNM-UHFFFAOYSA-N Narceine Chemical compound OC(=O)C1=C(OC)C(OC)=CC=C1C(=O)CC1=C(CCN(C)C)C=C(OCO2)C2=C1OC DEXMFYZAHXMZNM-UHFFFAOYSA-N 0.000 claims 24
- 230000001773 anti-convulsant effect Effects 0.000 claims 24
- 230000001430 anti-depressive effect Effects 0.000 claims 24
- 239000001961 anticonvulsive agent Substances 0.000 claims 24
- 239000000935 antidepressant agent Substances 0.000 claims 24
- 229940005513 antidepressants Drugs 0.000 claims 24
- 229960003965 antiepileptics Drugs 0.000 claims 24
- 210000003169 central nervous system Anatomy 0.000 claims 24
- 239000000203 mixture Substances 0.000 claims 24
- 208000021722 neuropathic pain Diseases 0.000 claims 24
- 229940124597 therapeutic agent Drugs 0.000 claims 24
- USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 0.000 claims 21
- XYYVYLMBEZUESM-UHFFFAOYSA-N dihydrocodeine Natural products C1C(N(CCC234)C)C2C=CC(=O)C3OC2=C4C1=CC=C2OC XYYVYLMBEZUESM-UHFFFAOYSA-N 0.000 claims 21
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 claims 21
- 229960001797 methadone Drugs 0.000 claims 21
- 239000000126 substance Substances 0.000 claims 19
- 125000003545 alkoxy group Chemical group 0.000 claims 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 17
- 125000004432 carbon atom Chemical group C* 0.000 claims 15
- YQYVFVRQLZMJKJ-JBBXEZCESA-N (+)-cyclazocine Chemical compound C([C@@]1(C)C2=CC(O)=CC=C2C[C@@H]2[C@@H]1C)CN2CC1CC1 YQYVFVRQLZMJKJ-JBBXEZCESA-N 0.000 claims 12
- UVITTYOJFDLOGI-UHFFFAOYSA-N (1,2,5-trimethyl-4-phenylpiperidin-4-yl) propanoate Chemical compound C=1C=CC=CC=1C1(OC(=O)CC)CC(C)N(C)CC1C UVITTYOJFDLOGI-UHFFFAOYSA-N 0.000 claims 12
- WRRSFOZOETZUPG-FFHNEAJVSA-N (4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol;hydrate Chemical compound O.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC WRRSFOZOETZUPG-FFHNEAJVSA-N 0.000 claims 12
- TVYLLZQTGLZFBW-ZBFHGGJFSA-N (R,R)-tramadol Chemical compound COC1=CC=CC([C@]2(O)[C@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-ZBFHGGJFSA-N 0.000 claims 12
- ANQHWGYYOWWJRU-UHFFFAOYSA-N 2,2-dimethylpropanethial Chemical compound CC(C)(C)C=S ANQHWGYYOWWJRU-UHFFFAOYSA-N 0.000 claims 12
- IYNWSQDZXMGGGI-NUEKZKHPSA-N 3-hydroxymorphinan Chemical compound C1CCC[C@H]2[C@H]3CC4=CC=C(O)C=C4[C@]21CCN3 IYNWSQDZXMGGGI-NUEKZKHPSA-N 0.000 claims 12
- 229940127291 Calcium channel antagonist Drugs 0.000 claims 12
- IJVCSMSMFSCRME-KBQPJGBKSA-N Dihydromorphine Chemical compound O([C@H]1[C@H](CC[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O IJVCSMSMFSCRME-KBQPJGBKSA-N 0.000 claims 12
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 claims 12
- ALFGKMXHOUSVAD-UHFFFAOYSA-N Ketobemidone Chemical compound C=1C=CC(O)=CC=1C1(C(=O)CC)CCN(C)CC1 ALFGKMXHOUSVAD-UHFFFAOYSA-N 0.000 claims 12
- JAQUASYNZVUNQP-USXIJHARSA-N Levorphanol Chemical compound C1C2=CC=C(O)C=C2[C@]23CCN(C)[C@H]1[C@@H]2CCCC3 JAQUASYNZVUNQP-USXIJHARSA-N 0.000 claims 12
- XADCESSVHJOZHK-UHFFFAOYSA-N Meperidine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 XADCESSVHJOZHK-UHFFFAOYSA-N 0.000 claims 12
- 229940123685 Monoamine oxidase inhibitor Drugs 0.000 claims 12
- IDBPHNDTYPBSNI-UHFFFAOYSA-N N-(1-(2-(4-Ethyl-5-oxo-2-tetrazolin-1-yl)ethyl)-4-(methoxymethyl)-4-piperidyl)propionanilide Chemical compound C1CN(CCN2C(N(CC)N=N2)=O)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 IDBPHNDTYPBSNI-UHFFFAOYSA-N 0.000 claims 12
- ONBWJWYUHXVEJS-ZTYRTETDSA-N Normorphine Chemical compound C([C@@H](NCC1)[C@@H]2C=C[C@@H]3O)C4=CC=C(O)C5=C4[C@@]21[C@H]3O5 ONBWJWYUHXVEJS-ZTYRTETDSA-N 0.000 claims 12
- 239000008896 Opium Substances 0.000 claims 12
- BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 claims 12
- UQCNKQCJZOAFTQ-ISWURRPUSA-N Oxymorphone Chemical compound O([C@H]1C(CC[C@]23O)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O UQCNKQCJZOAFTQ-ISWURRPUSA-N 0.000 claims 12
- 229940123445 Tricyclic antidepressant Drugs 0.000 claims 12
- 208000000921 Urge Urinary Incontinence Diseases 0.000 claims 12
- 229960001391 alfentanil Drugs 0.000 claims 12
- 239000003242 anti bacterial agent Substances 0.000 claims 12
- 230000001078 anti-cholinergic effect Effects 0.000 claims 12
- 230000000843 anti-fungal effect Effects 0.000 claims 12
- 229940035678 anti-parkinson drug Drugs 0.000 claims 12
- 230000000840 anti-viral effect Effects 0.000 claims 12
- 229940121375 antifungal agent Drugs 0.000 claims 12
- RDJGWRFTDZZXSM-RNWLQCGYSA-N benzylmorphine Chemical compound O([C@@H]1[C@]23CCN([C@H](C4)[C@@H]3C=C[C@@H]1O)C)C1=C2C4=CC=C1OCC1=CC=CC=C1 RDJGWRFTDZZXSM-RNWLQCGYSA-N 0.000 claims 12
- 229940125388 beta agonist Drugs 0.000 claims 12
- 230000008499 blood brain barrier function Effects 0.000 claims 12
- 210000001218 blood-brain barrier Anatomy 0.000 claims 12
- 229960001736 buprenorphine Drugs 0.000 claims 12
- RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 claims 12
- IFKLAQQSCNILHL-QHAWAJNXSA-N butorphanol Chemical compound N1([C@@H]2CC3=CC=C(C=C3[C@@]3([C@]2(CCCC3)O)CC1)O)CC1CCC1 IFKLAQQSCNILHL-QHAWAJNXSA-N 0.000 claims 12
- 229960001113 butorphanol Drugs 0.000 claims 12
- 239000000480 calcium channel blocker Substances 0.000 claims 12
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 12
- 229960004126 codeine Drugs 0.000 claims 12
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Natural products C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 claims 12
- 229950002213 cyclazocine Drugs 0.000 claims 12
- LNNWVNGFPYWNQE-GMIGKAJZSA-N desomorphine Chemical compound C1C2=CC=C(O)C3=C2[C@]24CCN(C)[C@H]1[C@@H]2CCC[C@@H]4O3 LNNWVNGFPYWNQE-GMIGKAJZSA-N 0.000 claims 12
- 229950003851 desomorphine Drugs 0.000 claims 12
- WDEFBBTXULIOBB-WBVHZDCISA-N dextilidine Chemical compound C=1C=CC=CC=1[C@@]1(C(=O)OCC)CCC=C[C@H]1N(C)C WDEFBBTXULIOBB-WBVHZDCISA-N 0.000 claims 12
- 229960004193 dextropropoxyphene Drugs 0.000 claims 12
- XLMALTXPSGQGBX-GCJKJVERSA-N dextropropoxyphene Chemical compound C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 XLMALTXPSGQGBX-GCJKJVERSA-N 0.000 claims 12
- 229960003461 dezocine Drugs 0.000 claims 12
- VTMVHDZWSFQSQP-VBNZEHGJSA-N dezocine Chemical compound C1CCCC[C@H]2CC3=CC=C(O)C=C3[C@]1(C)[C@H]2N VTMVHDZWSFQSQP-VBNZEHGJSA-N 0.000 claims 12
- 229960002069 diamorphine Drugs 0.000 claims 12
- 229960000920 dihydrocodeine Drugs 0.000 claims 12
- RBOXVHNMENFORY-DNJOTXNNSA-N dihydrocodeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC RBOXVHNMENFORY-DNJOTXNNSA-N 0.000 claims 12
- RHUWRJWFHUKVED-UHFFFAOYSA-N dimenoxadol Chemical compound C=1C=CC=CC=1C(C(=O)OCCN(C)C)(OCC)C1=CC=CC=C1 RHUWRJWFHUKVED-UHFFFAOYSA-N 0.000 claims 12
- 229950011187 dimenoxadol Drugs 0.000 claims 12
- QIRAYNIFEOXSPW-UHFFFAOYSA-N dimepheptanol Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(O)CC)C1=CC=CC=C1 QIRAYNIFEOXSPW-UHFFFAOYSA-N 0.000 claims 12
- SVDHSZFEQYXRDC-UHFFFAOYSA-N dipipanone Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)CC)CC(C)N1CCCCC1 SVDHSZFEQYXRDC-UHFFFAOYSA-N 0.000 claims 12
- 229960002500 dipipanone Drugs 0.000 claims 12
- 239000003937 drug carrier Substances 0.000 claims 12
- ZOWQTJXNFTWSCS-IAQYHMDHSA-N eptazocine Chemical compound C1N(C)CC[C@@]2(C)C3=CC(O)=CC=C3C[C@@H]1C2 ZOWQTJXNFTWSCS-IAQYHMDHSA-N 0.000 claims 12
- 229950010920 eptazocine Drugs 0.000 claims 12
- 229960002428 fentanyl Drugs 0.000 claims 12
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 claims 12
- 125000000623 heterocyclic group Chemical group 0.000 claims 12
- WVLOADHCBXTIJK-YNHQPCIGSA-N hydromorphone Chemical compound O([C@H]1C(CC[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O WVLOADHCBXTIJK-YNHQPCIGSA-N 0.000 claims 12
- 229960001410 hydromorphone Drugs 0.000 claims 12
- IFKPLJWIEQBPGG-UHFFFAOYSA-N isomethadone Chemical compound C=1C=CC=CC=1C(C(C)CN(C)C)(C(=O)CC)C1=CC=CC=C1 IFKPLJWIEQBPGG-UHFFFAOYSA-N 0.000 claims 12
- 229950009272 isomethadone Drugs 0.000 claims 12
- 229960003029 ketobemidone Drugs 0.000 claims 12
- RCYBMSQOSGJZLO-BGWNEDDSSA-N levophenacylmorphan Chemical compound C([C@]12CCCC[C@H]1[C@H]1CC3=CC=C(C=C32)O)CN1CC(=O)C1=CC=CC=C1 RCYBMSQOSGJZLO-BGWNEDDSSA-N 0.000 claims 12
- 229950007939 levophenacylmorphan Drugs 0.000 claims 12
- 229960003406 levorphanol Drugs 0.000 claims 12
- 229950010274 lofentanil Drugs 0.000 claims 12
- IMYHGORQCPYVBZ-NLFFAJNJSA-N lofentanil Chemical compound CCC(=O)N([C@@]1([C@@H](CN(CCC=2C=CC=CC=2)CC1)C)C(=O)OC)C1=CC=CC=C1 IMYHGORQCPYVBZ-NLFFAJNJSA-N 0.000 claims 12
- RDOIQAHITMMDAJ-UHFFFAOYSA-N loperamide Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)N(C)C)CCN(CC1)CCC1(O)C1=CC=C(Cl)C=C1 RDOIQAHITMMDAJ-UHFFFAOYSA-N 0.000 claims 12
- 229960001571 loperamide Drugs 0.000 claims 12
- 229960000365 meptazinol Drugs 0.000 claims 12
- JLICHNCFTLFZJN-HNNXBMFYSA-N meptazinol Chemical compound C=1C=CC(O)=CC=1[C@@]1(CC)CCCCN(C)C1 JLICHNCFTLFZJN-HNNXBMFYSA-N 0.000 claims 12
- 229950009131 metazocine Drugs 0.000 claims 12
- YGSVZRIZCHZUHB-COLVAYQJSA-N metazocine Chemical compound C1C2=CC=C(O)C=C2[C@]2(C)CCN(C)[C@@]1([H])[C@@H]2C YGSVZRIZCHZUHB-COLVAYQJSA-N 0.000 claims 12
- 239000002899 monoamine oxidase inhibitor Substances 0.000 claims 12
- 229960000805 nalbuphine Drugs 0.000 claims 12
- NETZHAKZCGBWSS-CEDHKZHLSA-N nalbuphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]1(O)CC[C@@H]3O)CN2CC1CCC1 NETZHAKZCGBWSS-CEDHKZHLSA-N 0.000 claims 12
- 239000004084 narcotic analgesic agent Substances 0.000 claims 12
- 229960004300 nicomorphine Drugs 0.000 claims 12
- HNDXBGYRMHRUFN-CIVUWBIHSA-N nicomorphine Chemical compound O([C@H]1C=C[C@H]2[C@H]3CC=4C5=C(C(=CC=4)OC(=O)C=4C=NC=CC=4)O[C@@H]1[C@]52CCN3C)C(=O)C1=CC=CN=C1 HNDXBGYRMHRUFN-CIVUWBIHSA-N 0.000 claims 12
- 229950011519 norlevorphanol Drugs 0.000 claims 12
- 229960004013 normethadone Drugs 0.000 claims 12
- WCJFBSYALHQBSK-UHFFFAOYSA-N normethadone Chemical compound C=1C=CC=CC=1C(CCN(C)C)(C(=O)CC)C1=CC=CC=C1 WCJFBSYALHQBSK-UHFFFAOYSA-N 0.000 claims 12
- 229950006134 normorphine Drugs 0.000 claims 12
- 229960001027 opium Drugs 0.000 claims 12
- 229960002085 oxycodone Drugs 0.000 claims 12
- 229960005118 oxymorphone Drugs 0.000 claims 12
- 229940124707 pain therapeutics Drugs 0.000 claims 12
- VOKSWYLNZZRQPF-GDIGMMSISA-N pentazocine Chemical compound C1C2=CC=C(O)C=C2[C@@]2(C)[C@@H](C)[C@@H]1N(CC=C(C)C)CC2 VOKSWYLNZZRQPF-GDIGMMSISA-N 0.000 claims 12
- 229960005301 pentazocine Drugs 0.000 claims 12
- 229960000482 pethidine Drugs 0.000 claims 12
- LOXCOAXRHYDLOW-UHFFFAOYSA-N phenadoxone Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)CC)CC(C)N1CCOCC1 LOXCOAXRHYDLOW-UHFFFAOYSA-N 0.000 claims 12
- 229950004540 phenadoxone Drugs 0.000 claims 12
- 229960004315 phenoperidine Drugs 0.000 claims 12
- IPOPQVVNCFQFRK-UHFFFAOYSA-N phenoperidine Chemical compound C1CC(C(=O)OCC)(C=2C=CC=CC=2)CCN1CCC(O)C1=CC=CC=C1 IPOPQVVNCFQFRK-UHFFFAOYSA-N 0.000 claims 12
- XJKQCILVUHXVIQ-UHFFFAOYSA-N properidine Chemical compound C=1C=CC=CC=1C1(C(=O)OC(C)C)CCN(C)CC1 XJKQCILVUHXVIQ-UHFFFAOYSA-N 0.000 claims 12
- 229950004345 properidine Drugs 0.000 claims 12
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 claims 12
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 claims 12
- GGCSSNBKKAUURC-UHFFFAOYSA-N sufentanil Chemical group C1CN(CCC=2SC=CC=2)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 GGCSSNBKKAUURC-UHFFFAOYSA-N 0.000 claims 12
- 229960004739 sufentanil Drugs 0.000 claims 12
- 229960001402 tilidine Drugs 0.000 claims 12
- 229960004380 tramadol Drugs 0.000 claims 12
- TVYLLZQTGLZFBW-GOEBONIOSA-N tramadol Natural products COC1=CC=CC([C@@]2(O)[C@@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-GOEBONIOSA-N 0.000 claims 12
- 239000003029 tricyclic antidepressant agent Substances 0.000 claims 12
- 206010046494 urge incontinence Diseases 0.000 claims 12
- 230000003444 anaesthetic effect Effects 0.000 claims 11
- 230000003110 anti-inflammatory effect Effects 0.000 claims 11
- 230000003115 biocidal effect Effects 0.000 claims 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 11
- 229910052799 carbon Inorganic materials 0.000 claims 10
- 125000004438 haloalkoxy group Chemical group 0.000 claims 10
- 150000004677 hydrates Chemical class 0.000 claims 9
- LLPOLZWFYMWNKH-CMKMFDCUSA-N hydrocodone Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC LLPOLZWFYMWNKH-CMKMFDCUSA-N 0.000 claims 9
- 229960000240 hydrocodone Drugs 0.000 claims 9
- WTJBNMUWRKPFRS-UHFFFAOYSA-N hydroxypethidine Chemical compound C=1C=CC(O)=CC=1C1(C(=O)OCC)CCN(C)CC1 WTJBNMUWRKPFRS-UHFFFAOYSA-N 0.000 claims 9
- 229950008496 hydroxypethidine Drugs 0.000 claims 9
- ZBAFFZBKCMWUHM-UHFFFAOYSA-N propiram Chemical compound C=1C=CC=NC=1N(C(=O)CC)C(C)CN1CCCCC1 ZBAFFZBKCMWUHM-UHFFFAOYSA-N 0.000 claims 9
- 229950003779 propiram Drugs 0.000 claims 9
- LLPOLZWFYMWNKH-UHFFFAOYSA-N trans-dihydrocodeinone Natural products C1C(N(CCC234)C)C2CCC(=O)C3OC2=C4C1=CC=C2OC LLPOLZWFYMWNKH-UHFFFAOYSA-N 0.000 claims 9
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 7
- 150000007513 acids Chemical class 0.000 claims 6
- 125000003831 tetrazolyl group Chemical group 0.000 claims 6
- 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 claims 5
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 5
- 125000002947 alkylene group Chemical group 0.000 claims 4
- GPZLDQAEBHTMPG-UHFFFAOYSA-N clonitazene Chemical compound N=1C2=CC([N+]([O-])=O)=CC=C2N(CCN(CC)CC)C=1CC1=CC=C(Cl)C=C1 GPZLDQAEBHTMPG-UHFFFAOYSA-N 0.000 claims 4
- 229950001604 clonitazene Drugs 0.000 claims 4
- 125000003282 alkyl amino group Chemical group 0.000 claims 3
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims 3
- 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims 2
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 2
- 125000005842 heteroatom Chemical group 0.000 claims 2
- 125000004076 pyridyl group Chemical group 0.000 claims 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 1
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- 229940035674 anesthetics Drugs 0.000 claims 1
- 229940121363 anti-inflammatory agent Drugs 0.000 claims 1
- 239000002260 anti-inflammatory agent Substances 0.000 claims 1
- 229940088710 antibiotic agent Drugs 0.000 claims 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
- 239000011737 fluorine Substances 0.000 claims 1
- 239000003193 general anesthetic agent Substances 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 150000003536 tetrazoles Chemical class 0.000 claims 1
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| US8828996B2 (en) | 2011-03-14 | 2014-09-09 | Vertex Pharmaceuticals Incorporated | Morpholine-spirocyclic piperidine amides as modulators of ion channels |
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| CN107602515A (zh) * | 2017-10-13 | 2018-01-19 | 南开大学 | 一类5a5b6c三环螺环内酯衍生物及其制备方法和用途 |
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- 2006-03-31 NZ NZ562144A patent/NZ562144A/en not_active IP Right Cessation
- 2006-03-31 MX MX2007011962A patent/MX2007011962A/es active IP Right Grant
- 2006-03-31 JP JP2008504447A patent/JP5118788B2/ja not_active Expired - Fee Related
- 2006-03-31 AU AU2006230517A patent/AU2006230517B2/en not_active Ceased
-
2007
- 2007-10-07 IL IL186342A patent/IL186342A0/en unknown
-
2009
- 2009-08-17 US US12/542,302 patent/US8022060B2/en not_active Expired - Fee Related
-
2011
- 2011-04-29 US US13/097,940 patent/US20110218186A1/en not_active Abandoned
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