JP2008534613A5 - - Google Patents
Download PDFInfo
- 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
Links
- 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
- 125000001544 thienyl group Chemical group 0.000 claims 1
- 0 *CCCCCC1N=NC(c(cc2)ccc2C2=CC3(CCNCC3)Oc3ccccc23)=NC1 Chemical compound *CCCCCC1N=NC(c(cc2)ccc2C2=CC3(CCNCC3)Oc3ccccc23)=NC1 0.000 description 84
- KSPBEXAAHKCDGM-UHFFFAOYSA-N CCN(C)C(c1ccc(C)cn1)=O Chemical compound CCN(C)C(c1ccc(C)cn1)=O KSPBEXAAHKCDGM-UHFFFAOYSA-N 0.000 description 5
- 102000001490 Opioid Peptides Human genes 0.000 description 5
- 108010093625 Opioid Peptides Proteins 0.000 description 5
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical class 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 5
- 239000003399 opiate peptide Substances 0.000 description 5
- 208000002193 Pain Diseases 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- CQUBDZFYWVPEEG-XKZIYDEJSA-N CCN(CC)C(c(nc1)ccc1/C1=C/CCNCCCCc2c1cccc2)=O Chemical compound CCN(CC)C(c(nc1)ccc1/C1=C/CCNCCCCc2c1cccc2)=O CQUBDZFYWVPEEG-XKZIYDEJSA-N 0.000 description 3
- 230000002530 ischemic preconditioning effect Effects 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- QDYRRFBUVMYCII-UHFFFAOYSA-N CCN(C)C(c1ccc(C)c(O)c1)=O Chemical compound CCN(C)C(c1ccc(C)c(O)c1)=O QDYRRFBUVMYCII-UHFFFAOYSA-N 0.000 description 2
- BNKXWFYUUULVNE-UYOCIXKTSA-N CCN(CC)C(c(cc1)ccc1/C1=C/CCNCCCOc(cc2)c1cc2S(C)(=O)=O)=O Chemical compound CCN(CC)C(c(cc1)ccc1/C1=C/CCNCCCOc(cc2)c1cc2S(C)(=O)=O)=O BNKXWFYUUULVNE-UYOCIXKTSA-N 0.000 description 2
- KMDPIBCWZVMUQL-UHFFFAOYSA-N CCN(CC)C(c(cc1)ccc1C1=CC2(CCNCCC2)Oc(cc2)c1cc2O)=O Chemical compound CCN(CC)C(c(cc1)ccc1C1=CC2(CCNCCC2)Oc(cc2)c1cc2O)=O KMDPIBCWZVMUQL-UHFFFAOYSA-N 0.000 description 2
- PMBNRTXGVLHATL-UHFFFAOYSA-N CCN(CC)C(c(nc1)ccc1C(c1c2)=CC3(CCNCC3)Cc1ccc2O)=O Chemical compound CCN(CC)C(c(nc1)ccc1C(c1c2)=CC3(CCNCC3)Cc1ccc2O)=O PMBNRTXGVLHATL-UHFFFAOYSA-N 0.000 description 2
- ASHLKFBPPTWZLW-UHFFFAOYSA-N CCN(CC)C(c1cc(O)c(C2c(cc(cc3)F)c3OC3(CCNCC3)C2)cc1)=O Chemical compound CCN(CC)C(c1cc(O)c(C2c(cc(cc3)F)c3OC3(CCNCC3)C2)cc1)=O ASHLKFBPPTWZLW-UHFFFAOYSA-N 0.000 description 2
- LBFLVRFHGHYBNC-UHFFFAOYSA-N CCN(CC)C(c1cc(O)c(C2c3ccccc3CC3(CCNCC3)C2)cc1)=O Chemical compound CCN(CC)C(c1cc(O)c(C2c3ccccc3CC3(CCNCC3)C2)cc1)=O LBFLVRFHGHYBNC-UHFFFAOYSA-N 0.000 description 2
- RUYNPLNPNCOCTL-UHFFFAOYSA-N CCN(CC)C(c1cc(O)c(C2c3ccccc3OC3(CCNCC3)C2)cc1)=O Chemical compound CCN(CC)C(c1cc(O)c(C2c3ccccc3OC3(CCNCC3)C2)cc1)=O RUYNPLNPNCOCTL-UHFFFAOYSA-N 0.000 description 2
- MHEXXGICKXSMNP-UHFFFAOYSA-N CCN(CC)C(c1ccc(C2c3cc(O)ccc3CC3(CCNCC3)C2)cn1)=O Chemical compound CCN(CC)C(c1ccc(C2c3cc(O)ccc3CC3(CCNCC3)C2)cn1)=O MHEXXGICKXSMNP-UHFFFAOYSA-N 0.000 description 2
- WNBUCEYKMNELRV-UHFFFAOYSA-N CCN(CC)C(c1ccc(C2c3ccccc3CC3(CCNCC3)C2)cn1)=O Chemical compound CCN(CC)C(c1ccc(C2c3ccccc3CC3(CCNCC3)C2)cn1)=O WNBUCEYKMNELRV-UHFFFAOYSA-N 0.000 description 2
- AQOZBOAKAGTCSS-UHFFFAOYSA-N CS(NCCCCC[n]1nnc(-c(cc2)ccc2C2=CC3(CCNCC3)Oc3ccccc23)n1)(=O)=O Chemical compound CS(NCCCCC[n]1nnc(-c(cc2)ccc2C2=CC3(CCNCC3)Oc3ccccc23)n1)(=O)=O AQOZBOAKAGTCSS-UHFFFAOYSA-N 0.000 description 2
- 208000000094 Chronic Pain Diseases 0.000 description 2
- 206010021518 Impaired gastric emptying Diseases 0.000 description 2
- 206010054048 Postoperative ileus Diseases 0.000 description 2
- 238000012084 abdominal surgery Methods 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000000841 delta opiate receptor agonist Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 229960005181 morphine Drugs 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- ZHUJMSMQIPIPTF-IBURTVSXSA-N (2r)-2-[[(2s)-2-[[2-[[(2r)-2-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoic acid Chemical compound C([C@@H](C(=O)N[C@H](CC(C)C)C(O)=O)NC(=O)CNC(=O)[C@@H](C)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 ZHUJMSMQIPIPTF-IBURTVSXSA-N 0.000 description 1
- KQWVAUSXZDRQPZ-UMTXDNHDSA-N 4-[(R)-[(2S,5R)-2,5-dimethyl-4-prop-2-enyl-1-piperazinyl]-(3-methoxyphenyl)methyl]-N,N-diethylbenzamide Chemical compound C1=CC(C(=O)N(CC)CC)=CC=C1[C@H](C=1C=C(OC)C=CC=1)N1[C@@H](C)CN(CC=C)[C@H](C)C1 KQWVAUSXZDRQPZ-UMTXDNHDSA-N 0.000 description 1
- DDSCNRYOJYAXOK-DUELTEGESA-N 4-[[(2r,5s)-4-[(r)-[4-(diethylcarbamoyl)phenyl]-(3-hydroxyphenyl)methyl]-2,5-dimethylpiperazin-1-yl]methyl]benzoic acid Chemical compound C1=CC(C(=O)N(CC)CC)=CC=C1[C@H](C=1C=C(O)C=CC=1)N1[C@@H](C)CN(CC=2C=CC(=CC=2)C(O)=O)[C@H](C)C1 DDSCNRYOJYAXOK-DUELTEGESA-N 0.000 description 1
- KKJUPNGICOCCDW-UHFFFAOYSA-N 7-N,N-Dimethylamino-1,2,3,4,5-pentathiocyclooctane Chemical compound CN(C)C1CSSSSSC1 KKJUPNGICOCCDW-UHFFFAOYSA-N 0.000 description 1
- KCKAADCFEJSBIS-UHFFFAOYSA-N C/C=S(\C)/NCCCCC[n]1nnc(-c(cc2)ccc2C2=CC3(CCNCC3)Oc3ccccc23)n1 Chemical compound C/C=S(\C)/NCCCCC[n]1nnc(-c(cc2)ccc2C2=CC3(CCNCC3)Oc3ccccc23)n1 KCKAADCFEJSBIS-UHFFFAOYSA-N 0.000 description 1
- UOPPBDMTBQWZNM-UHFFFAOYSA-N CC(C)(C)c1ccc(C(N(C)C)=O)nc1 Chemical compound CC(C)(C)c1ccc(C(N(C)C)=O)nc1 UOPPBDMTBQWZNM-UHFFFAOYSA-N 0.000 description 1
- RCKWGTUATMCVMD-UHFFFAOYSA-N CC(C)c(cc1)cnc1C(N(C)C)=O Chemical compound CC(C)c(cc1)cnc1C(N(C)C)=O RCKWGTUATMCVMD-UHFFFAOYSA-N 0.000 description 1
- RNRAGHXCVORIEU-UHFFFAOYSA-N CC(C)c(ccc(C(NC)=O)c1)c1O Chemical compound CC(C)c(ccc(C(NC)=O)c1)c1O RNRAGHXCVORIEU-UHFFFAOYSA-N 0.000 description 1
- CIOPQQYVQPJQDC-UHFFFAOYSA-N CC(C)c1ccc(C(N(C)C(C)C)=O)nc1 Chemical compound CC(C)c1ccc(C(N(C)C(C)C)=O)nc1 CIOPQQYVQPJQDC-UHFFFAOYSA-N 0.000 description 1
- QVHWPGNORXGZSU-UHFFFAOYSA-O CC(NCCCCCN1N=C(c(cc2)ccc2C2=CC3(CCNCC3)Oc3ccccc23)[NH2+]N1)=O Chemical compound CC(NCCCCCN1N=C(c(cc2)ccc2C2=CC3(CCNCC3)Oc3ccccc23)[NH2+]N1)=O QVHWPGNORXGZSU-UHFFFAOYSA-O 0.000 description 1
- POPFPNQMBBWLIS-UHFFFAOYSA-N CC(NCCCCC[n]1nnc(-c(cc2)ccc2C2=CC3(CCNCC3)OC3C=CC=CC23)n1)=O Chemical compound CC(NCCCCC[n]1nnc(-c(cc2)ccc2C2=CC3(CCNCC3)OC3C=CC=CC23)n1)=O POPFPNQMBBWLIS-UHFFFAOYSA-N 0.000 description 1
- TUWVNSICLKIRGA-UHFFFAOYSA-N CC(NCCCCC[n]1nnc(-c(cc2)ccc2C2=CC3(CCNCC3)Oc3c2cccc3)n1)=O Chemical compound CC(NCCCCC[n]1nnc(-c(cc2)ccc2C2=CC3(CCNCC3)Oc3c2cccc3)n1)=O TUWVNSICLKIRGA-UHFFFAOYSA-N 0.000 description 1
- ODXHLALYJPVMFX-MKKAVFGOSA-N CC/C=C\C(\C(NC)=O)=C/CC Chemical compound CC/C=C\C(\C(NC)=O)=C/CC ODXHLALYJPVMFX-MKKAVFGOSA-N 0.000 description 1
- XXAZQNVVGYYMKK-UHFFFAOYSA-N CC1(C2N=NN(CCCCN)CC2=C)C=CC(C2=CC3(CCNCC3)Oc3ccccc23)=CC1 Chemical compound CC1(C2N=NN(CCCCN)CC2=C)C=CC(C2=CC3(CCNCC3)Oc3ccccc23)=CC1 XXAZQNVVGYYMKK-UHFFFAOYSA-N 0.000 description 1
- JZBNOTYANAOUDW-UHFFFAOYSA-N CCC(C)c(cc1)ccc1C(N(C)C)=O Chemical compound CCC(C)c(cc1)ccc1C(N(C)C)=O JZBNOTYANAOUDW-UHFFFAOYSA-N 0.000 description 1
- NJPTURHUXQBKMA-UHFFFAOYSA-N CCCC(C(CCN)CC(c(ccc(CN(CC)CC)c1)c1N=O)c1c2)Oc1ccc2F Chemical compound CCCC(C(CCN)CC(c(ccc(CN(CC)CC)c1)c1N=O)c1c2)Oc1ccc2F NJPTURHUXQBKMA-UHFFFAOYSA-N 0.000 description 1
- IRPHEFOVXQSPOP-UHFFFAOYSA-N CCCOCC(c1ccc2OCC=C(c(cc3)ccc3C(N(CC)CC)=O)c2c1)=O Chemical compound CCCOCC(c1ccc2OCC=C(c(cc3)ccc3C(N(CC)CC)=O)c2c1)=O IRPHEFOVXQSPOP-UHFFFAOYSA-N 0.000 description 1
- OYZKUOHWLXCJFR-XSONURMYSA-N CCN(C)C(/C(/C=C\C(C)=C)=C/C)=O Chemical compound CCN(C)C(/C(/C=C\C(C)=C)=C/C)=O OYZKUOHWLXCJFR-XSONURMYSA-N 0.000 description 1
- AOHMUEZHBJPIGT-UHFFFAOYSA-N CCN(C)C(c(nc1)ccc1I)=O Chemical compound CCN(C)C(c(nc1)ccc1I)=O AOHMUEZHBJPIGT-UHFFFAOYSA-N 0.000 description 1
- NGYXEWOVOMASSX-UHFFFAOYSA-N CCN(C)C(c1cc(N=O)c(C)cc1)=O Chemical compound CCN(C)C(c1cc(N=O)c(C)cc1)=O NGYXEWOVOMASSX-UHFFFAOYSA-N 0.000 description 1
- XKRIEDJHQAVVIV-LXSLZTFBSA-N CCN(CC)C(C(/C=C\C(\C(c1ccccc1C1)=CC11CCNCCC1)=C/N)=C)=O Chemical compound CCN(CC)C(C(/C=C\C(\C(c1ccccc1C1)=CC11CCNCCC1)=C/N)=C)=O XKRIEDJHQAVVIV-LXSLZTFBSA-N 0.000 description 1
- VZIWSCWIMWVAIR-UHFFFAOYSA-N CCN(CC)C(C(C=C1)=C=CCC=C1C1=CC2(CNCC2)Oc2c1cccc2)=O Chemical compound CCN(CC)C(C(C=C1)=C=CCC=C1C1=CC2(CNCC2)Oc2c1cccc2)=O VZIWSCWIMWVAIR-UHFFFAOYSA-N 0.000 description 1
- NXEQPPHAUCTRKF-UHFFFAOYSA-N CCN(CC)C(C)c(nc1)ccc1C1=CC2(CCNCCC2)Oc2ccc(C)cc12 Chemical compound CCN(CC)C(C)c(nc1)ccc1C1=CC2(CCNCCC2)Oc2ccc(C)cc12 NXEQPPHAUCTRKF-UHFFFAOYSA-N 0.000 description 1
- IIWLNIXFZVVHNP-UHFFFAOYSA-N CCN(CC)C(C1(C)NC=C(C2c3cc(O)ccc3CC3(CCNCC3)C2)C=C1)=O Chemical compound CCN(CC)C(C1(C)NC=C(C2c3cc(O)ccc3CC3(CCNCC3)C2)C=C1)=O IIWLNIXFZVVHNP-UHFFFAOYSA-N 0.000 description 1
- LSJQTFCMCKGRRV-UHFFFAOYSA-N CCN(CC)C(C1C=CC(C(c2c3)=CC4(CCNCCC4)Oc2ccc3S(CC)(=O)=O)=CC1)=O Chemical compound CCN(CC)C(C1C=CC(C(c2c3)=CC4(CCNCCC4)Oc2ccc3S(CC)(=O)=O)=CC1)=O LSJQTFCMCKGRRV-UHFFFAOYSA-N 0.000 description 1
- JIVGLKZIQYWQKU-UHFFFAOYSA-N CCN(CC)C(c(cc1)cc(O)c1C(c1c2)=CC3(CCNCC3)Cc1ccc2F)=O Chemical compound CCN(CC)C(c(cc1)cc(O)c1C(c1c2)=CC3(CCNCC3)Cc1ccc2F)=O JIVGLKZIQYWQKU-UHFFFAOYSA-N 0.000 description 1
- MZAVBABAQLMNSC-UHFFFAOYSA-N CCN(CC)C(c(cc1)cc(O)c1C(c1c2)=CC3(CCNCC3)Oc1ccc2F)=O Chemical compound CCN(CC)C(c(cc1)cc(O)c1C(c1c2)=CC3(CCNCC3)Oc1ccc2F)=O MZAVBABAQLMNSC-UHFFFAOYSA-N 0.000 description 1
- QQPOKIWCIVANSL-UHFFFAOYSA-N CCN(CC)C(c(cc1)cc(O)c1C1=CC2(CCNCCC2)Oc2ccccc12)=O Chemical compound CCN(CC)C(c(cc1)cc(O)c1C1=CC2(CCNCCC2)Oc2ccccc12)=O QQPOKIWCIVANSL-UHFFFAOYSA-N 0.000 description 1
- ROTBWAVZCLGOFG-UHFFFAOYSA-N CCN(CC)C(c(cc1)cc(O)c1C1=CC2(CNCC2)Oc2c1cccc2)=O Chemical compound CCN(CC)C(c(cc1)cc(O)c1C1=CC2(CNCC2)Oc2c1cccc2)=O ROTBWAVZCLGOFG-UHFFFAOYSA-N 0.000 description 1
- JNALGVALUCQACQ-KSEXSDGBSA-N CCN(CC)C(c(cc1)ccc1/C(/c(c(F)ccc1)c1OCC1)=C/CCCCC1=C)=O Chemical compound CCN(CC)C(c(cc1)ccc1/C(/c(c(F)ccc1)c1OCC1)=C/CCCCC1=C)=O JNALGVALUCQACQ-KSEXSDGBSA-N 0.000 description 1
- IRHCKHONRPUCFW-YXSASFKJSA-N CCN(CC)C(c(cc1)ccc1/C(/c1c2)=C/CCNCCCOc1ccc2O)=O Chemical compound CCN(CC)C(c(cc1)ccc1/C(/c1c2)=C/CCNCCCOc1ccc2O)=O IRHCKHONRPUCFW-YXSASFKJSA-N 0.000 description 1
- PSJJJVVLDHRDIB-ZBKNUEDVSA-N CCN(CC)C(c(cc1)ccc1/C1=C/CCNCCCOc2c1c(O)ccc2)=O Chemical compound CCN(CC)C(c(cc1)ccc1/C1=C/CCNCCCOc2c1c(O)ccc2)=O PSJJJVVLDHRDIB-ZBKNUEDVSA-N 0.000 description 1
- GRCREHFUVCOYQZ-GXHLCREISA-N CCN(CC)C(c(cc1)ccc1/C1=C/CCNCCOc2c1c(OC(F)F)ccc2)=O Chemical compound CCN(CC)C(c(cc1)ccc1/C1=C/CCNCCOc2c1c(OC(F)F)ccc2)=O GRCREHFUVCOYQZ-GXHLCREISA-N 0.000 description 1
- PISVSMTUURWWKG-UHFFFAOYSA-N CCN(CC)C(c(cc1)ccc1C(C1(C)C2)=CC3(CCNCCC3)OC1=CC=C2S(C)(=O)=O)=O Chemical compound CCN(CC)C(c(cc1)ccc1C(C1(C)C2)=CC3(CCNCCC3)OC1=CC=C2S(C)(=O)=O)=O PISVSMTUURWWKG-UHFFFAOYSA-N 0.000 description 1
- VVDDZVOEEZNVKE-UHFFFAOYSA-N CCN(CC)C(c(cc1)ccc1C(c1c2)=CC3(CNCC3)Oc1ccc2O)=O Chemical compound CCN(CC)C(c(cc1)ccc1C(c1c2)=CC3(CNCC3)Oc1ccc2O)=O VVDDZVOEEZNVKE-UHFFFAOYSA-N 0.000 description 1
- HIVYEJTUZBMWFO-UHFFFAOYSA-N CCN(CC)C(c(cc1)ccc1C1=CC2(CC(C)NCC2)Oc2ccccc12)=O Chemical compound CCN(CC)C(c(cc1)ccc1C1=CC2(CC(C)NCC2)Oc2ccccc12)=O HIVYEJTUZBMWFO-UHFFFAOYSA-N 0.000 description 1
- WUYXJNVNSNCOPQ-UHFFFAOYSA-N CCN(CC)C(c(cc1)ccc1C1=CC2(CCNCC2)Cc(cc2)c1cc2O)=O Chemical compound CCN(CC)C(c(cc1)ccc1C1=CC2(CCNCC2)Cc(cc2)c1cc2O)=O WUYXJNVNSNCOPQ-UHFFFAOYSA-N 0.000 description 1
- ZYSLYSAQKGEGDQ-UHFFFAOYSA-N CCN(CC)C(c(cc1)ccc1C1=CC2(CCNCC2)Cc2cccc(O)c12)=O Chemical compound CCN(CC)C(c(cc1)ccc1C1=CC2(CCNCC2)Cc2cccc(O)c12)=O ZYSLYSAQKGEGDQ-UHFFFAOYSA-N 0.000 description 1
- JLXQTVALARFFLW-UHFFFAOYSA-N CCN(CC)C(c(cc1)ccc1C1=CC2(CCNCC2)Oc2cccc(N3CCCC3)c12)=O Chemical compound CCN(CC)C(c(cc1)ccc1C1=CC2(CCNCC2)Oc2cccc(N3CCCC3)c12)=O JLXQTVALARFFLW-UHFFFAOYSA-N 0.000 description 1
- QBLPUOOMBNMDOZ-UHFFFAOYSA-N CCN(CC)C(c(cc1)ccc1C1=CC2(CCNCCC2)Oc2cccc(O)c12)=O Chemical compound CCN(CC)C(c(cc1)ccc1C1=CC2(CCNCCC2)Oc2cccc(O)c12)=O QBLPUOOMBNMDOZ-UHFFFAOYSA-N 0.000 description 1
- PZKCLPWZGDGEBF-UHFFFAOYSA-N CCN(CC)C(c(cc1)ccc1C1=CC2(CNCC2)Oc2cccc(O)c12)=O Chemical compound CCN(CC)C(c(cc1)ccc1C1=CC2(CNCC2)Oc2cccc(O)c12)=O PZKCLPWZGDGEBF-UHFFFAOYSA-N 0.000 description 1
- NBFWMDKRULORNP-GUNHTJMXSA-N CCN(CC)C(c(nc1)ccc1/C1=C/CC/N=C\COc2c1c(OC(F)F)ccc2)=O Chemical compound CCN(CC)C(c(nc1)ccc1/C1=C/CC/N=C\COc2c1c(OC(F)F)ccc2)=O NBFWMDKRULORNP-GUNHTJMXSA-N 0.000 description 1
- BJXTYLNQIHMYHK-UHFFFAOYSA-N CCN(CC)C(c(nc1)ccc1C(c1c2)=CC3(CCNCCC3)Oc1ccc2F)=O Chemical compound CCN(CC)C(c(nc1)ccc1C(c1c2)=CC3(CCNCCC3)Oc1ccc2F)=O BJXTYLNQIHMYHK-UHFFFAOYSA-N 0.000 description 1
- VZMRWCDQCYFJGL-UHFFFAOYSA-N CCN(CC)C(c(nc1)ccc1C1=CC2(CCNCC2)Oc2cccc(OC(F)F)c12)=O Chemical compound CCN(CC)C(c(nc1)ccc1C1=CC2(CCNCC2)Oc2cccc(OC(F)F)c12)=O VZMRWCDQCYFJGL-UHFFFAOYSA-N 0.000 description 1
- FRBFXFYMOZCLOJ-UHFFFAOYSA-N CCN(CC)C(c(nc1)ccc1C1=CC2(CCNCCC2)OC2C1=CC(F)=CC2C)=O Chemical compound CCN(CC)C(c(nc1)ccc1C1=CC2(CCNCCC2)OC2C1=CC(F)=CC2C)=O FRBFXFYMOZCLOJ-UHFFFAOYSA-N 0.000 description 1
- GDCHMRACAIKRBC-UHFFFAOYSA-N CCN(CC)C(c(nc1)ccc1C1=CC2(CCNCCC2)Oc2c1cc(C)cc2)=O Chemical compound CCN(CC)C(c(nc1)ccc1C1=CC2(CCNCCC2)Oc2c1cc(C)cc2)=O GDCHMRACAIKRBC-UHFFFAOYSA-N 0.000 description 1
- GUHMAQKAEBUOCY-UHFFFAOYSA-N CCN(CC)C(c(nc1)ccc1C1=CC2(CNCC2)Oc(cc2)c1cc2O)=O Chemical compound CCN(CC)C(c(nc1)ccc1C1=CC2(CNCC2)Oc(cc2)c1cc2O)=O GUHMAQKAEBUOCY-UHFFFAOYSA-N 0.000 description 1
- HUPVDSXHHKLEKN-UHFFFAOYSA-N CCN(CC)C(c1ccc(C(CC2(CCNCC2)OC2CC=C3)C2=C3OC)cn1)=O Chemical compound CCN(CC)C(c1ccc(C(CC2(CCNCC2)OC2CC=C3)C2=C3OC)cn1)=O HUPVDSXHHKLEKN-UHFFFAOYSA-N 0.000 description 1
- ZQRHAVQVARLTEQ-UHFFFAOYSA-N CCN(CC)C(c1ccc(C(CC2(CCNCC2)Oc2ccc3)c2c3OC)cc1)=O Chemical compound CCN(CC)C(c1ccc(C(CC2(CCNCC2)Oc2ccc3)c2c3OC)cc1)=O ZQRHAVQVARLTEQ-UHFFFAOYSA-N 0.000 description 1
- CMOJWHCTKBRKSI-UHFFFAOYSA-N CCN(CC)C(c1ccc(C2=CC3(CCNCC3)Oc3cccc(OC)c23)[s]1)=O Chemical compound CCN(CC)C(c1ccc(C2=CC3(CCNCC3)Oc3cccc(OC)c23)[s]1)=O CMOJWHCTKBRKSI-UHFFFAOYSA-N 0.000 description 1
- KIMAEXWJJNYXKL-UHFFFAOYSA-N CCN(CC)C(c1ccc(C2c(cc(cc3)S(C)(=O)=O)c3NCCCNCCC2)cc1)=O Chemical compound CCN(CC)C(c1ccc(C2c(cc(cc3)S(C)(=O)=O)c3NCCCNCCC2)cc1)=O KIMAEXWJJNYXKL-UHFFFAOYSA-N 0.000 description 1
- HPONIDJWEXQQJT-UHFFFAOYSA-N CCN(CC)C(c1ccc(C2c3cc(O)ccc3CC3(CCNCC3)C2)cc1)=O Chemical compound CCN(CC)C(c1ccc(C2c3cc(O)ccc3CC3(CCNCC3)C2)cc1)=O HPONIDJWEXQQJT-UHFFFAOYSA-N 0.000 description 1
- ITFSWYMUBNGLCY-UHFFFAOYSA-N CCN(CC)Cc1ccc(C(CC2(CCNCC2)Oc2ccc3)c2c3OC)cn1 Chemical compound CCN(CC)Cc1ccc(C(CC2(CCNCC2)Oc2ccc3)c2c3OC)cn1 ITFSWYMUBNGLCY-UHFFFAOYSA-N 0.000 description 1
- DXZSOGQUXFYVLV-UHFFFAOYSA-N CCN(CCCNC)C(c(cc1)ccc1C1=CC2(CCNCC2)Oc2ccccc12)=O Chemical compound CCN(CCCNC)C(c(cc1)ccc1C1=CC2(CCNCC2)Oc2ccccc12)=O DXZSOGQUXFYVLV-UHFFFAOYSA-N 0.000 description 1
- WQLCWHHWRZOJFW-UHFFFAOYSA-N CCN(CCN(C)C)C(c(cc1)ccc1C1=CC2(CCNCC2)Oc2c1cccc2)=O Chemical compound CCN(CCN(C)C)C(c(cc1)ccc1C1=CC2(CCNCC2)Oc2c1cccc2)=O WQLCWHHWRZOJFW-UHFFFAOYSA-N 0.000 description 1
- MAJLLZIJIUXYNA-UHFFFAOYSA-N CCN(CCNC)C(c(cc1)ccc1C1=CC2(CCNCC2)Oc2ccccc12)=O Chemical compound CCN(CCNC)C(c(cc1)ccc1C1=CC2(CCNCC2)Oc2ccccc12)=O MAJLLZIJIUXYNA-UHFFFAOYSA-N 0.000 description 1
- OYGVFIJYXVEFTA-UHFFFAOYSA-N CCN(CCOC)C(c(cc1)ccc1C1=CC2(CCNCC2)Oc2ccccc12)=O Chemical compound CCN(CCOC)C(c(cc1)ccc1C1=CC2(CCNCC2)Oc2ccccc12)=O OYGVFIJYXVEFTA-UHFFFAOYSA-N 0.000 description 1
- HQFSEQHOELVGFI-SOFYXZRVSA-N CCNC(c(nc1)ccc1/C1=C/CCNCCCOc2c1c(O)ccc2)=O Chemical compound CCNC(c(nc1)ccc1/C1=C/CCNCCCOc2c1c(O)ccc2)=O HQFSEQHOELVGFI-SOFYXZRVSA-N 0.000 description 1
- RGMGGXDMTJTYPP-UHFFFAOYSA-N CCc(cc1)ccc1C(N(C)C(C)C)=O Chemical compound CCc(cc1)ccc1C(N(C)C(C)C)=O RGMGGXDMTJTYPP-UHFFFAOYSA-N 0.000 description 1
- HLXJBOURBWLEQR-UHFFFAOYSA-N CN(C)C(c(cc1)cc(O)c1S1(C)CC1)=O Chemical compound CN(C)C(c(cc1)cc(O)c1S1(C)CC1)=O HLXJBOURBWLEQR-UHFFFAOYSA-N 0.000 description 1
- ONAKURCWCNFQTK-UHFFFAOYSA-N CN(C)CCCNC(c1ccc(C2c3ccccc3OC3(CCNCC3)C2)cc1)=O Chemical compound CN(C)CCCNC(c1ccc(C2c3ccccc3OC3(CCNCC3)C2)cc1)=O ONAKURCWCNFQTK-UHFFFAOYSA-N 0.000 description 1
- CPJJVIXIQNCTHK-UHFFFAOYSA-O CS(C(CCCCCCN1N=C(c(cc2)ccc2C2=CC3(CCNCC3)Oc3c2cccc3)[NH2+]N1)=C)(=O)=O Chemical compound CS(C(CCCCCCN1N=C(c(cc2)ccc2C2=CC3(CCNCC3)Oc3c2cccc3)[NH2+]N1)=C)(=O)=O CPJJVIXIQNCTHK-UHFFFAOYSA-O 0.000 description 1
- VSQSVUWMFMHRIS-UHFFFAOYSA-N CSNCCCC[n]1nnc(-c(cc2)ccc2C2=CC3(CCNCC3)Oc3ccccc23)n1 Chemical compound CSNCCCC[n]1nnc(-c(cc2)ccc2C2=CC3(CCNCC3)Oc3ccccc23)n1 VSQSVUWMFMHRIS-UHFFFAOYSA-N 0.000 description 1
- SBZOARJKACTJLN-UHFFFAOYSA-M C[IH]N(C=C)C(c(nc1)ccc1[Cs](C)I)=O Chemical compound C[IH]N(C=C)C(c(nc1)ccc1[Cs](C)I)=O SBZOARJKACTJLN-UHFFFAOYSA-M 0.000 description 1
- ULKWBVNMJZUEBD-UHFFFAOYSA-N Cc(cc1)ccc1C(N(C)C)=O Chemical compound Cc(cc1)ccc1C(N(C)C)=O ULKWBVNMJZUEBD-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
- ROHFNLRQFUQHCH-RXMQYKEDSA-N D-leucine Chemical compound CC(C)C[C@@H](N)C(O)=O ROHFNLRQFUQHCH-RXMQYKEDSA-N 0.000 description 1
- URLZCHNOLZSCCA-VABKMULXSA-N Leu-enkephalin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 URLZCHNOLZSCCA-VABKMULXSA-N 0.000 description 1
- RJTSILCJEPOBNH-UHFFFAOYSA-N NCCCCCC[n]1nnc(-c(cc2)ccc2C2=CC3(CCNCC3)Oc3ccccc23)n1 Chemical compound NCCCCCC[n]1nnc(-c(cc2)ccc2C2=CC3(CCNCC3)Oc3ccccc23)n1 RJTSILCJEPOBNH-UHFFFAOYSA-N 0.000 description 1
- IBUNXJGYYGKNEG-UHFFFAOYSA-N NCCCCC[n]1nnc(-c(cc2)ccc2C2=CC3(CCNCC3)Oc3ccccc23)n1 Chemical compound NCCCCC[n]1nnc(-c(cc2)ccc2C2=CC3(CCNCC3)Oc3ccccc23)n1 IBUNXJGYYGKNEG-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229940127450 Opioid Agonists Drugs 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 108010003581 Ribulose-bisphosphate carboxylase Proteins 0.000 description 1
- 208000026723 Urinary tract disease Diseases 0.000 description 1
- 239000000370 acceptor Substances 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000005961 cardioprotection Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000006266 hibernation Effects 0.000 description 1
- 208000008384 ileus Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000008991 intestinal motility Effects 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000005056 memory consolidation Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- UZHSEJADLWPNLE-GRGSLBFTSA-N naloxone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 0.000 description 1
- 229960004127 naloxone Drugs 0.000 description 1
- 230000001962 neuropharmacologic effect Effects 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 208000014001 urinary system disease Diseases 0.000 description 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US66717705P | 2005-03-31 | 2005-03-31 | |
| US60/667,177 | 2005-03-31 | ||
| US11/393,133 US7598261B2 (en) | 2005-03-31 | 2006-03-30 | Spirocyclic heterocyclic derivatives and methods of their use |
| US11/393,133 | 2006-03-30 | ||
| PCT/US2006/012081 WO2006105442A2 (en) | 2005-03-31 | 2006-03-31 | Spirocyclic heterocyclic derivatives and methods of their use |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2008534613A JP2008534613A (ja) | 2008-08-28 |
| JP2008534613A5 true JP2008534613A5 (https=) | 2009-05-21 |
| JP5118788B2 JP5118788B2 (ja) | 2013-01-16 |
Family
ID=37054196
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008504447A Expired - Fee Related JP5118788B2 (ja) | 2005-03-31 | 2006-03-31 | スピロ複素環式誘導体およびその使用方法 |
Country Status (11)
| Country | Link |
|---|---|
| US (3) | US7598261B2 (https=) |
| EP (1) | EP1871761A4 (https=) |
| JP (1) | JP5118788B2 (https=) |
| KR (1) | KR20080005245A (https=) |
| AU (1) | AU2006230517B2 (https=) |
| BR (1) | BRPI0612189A2 (https=) |
| CA (1) | CA2603126A1 (https=) |
| IL (1) | IL186342A0 (https=) |
| MX (1) | MX2007011962A (https=) |
| NZ (1) | NZ562144A (https=) |
| WO (1) | WO2006105442A2 (https=) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ546834A (en) * | 2003-10-01 | 2010-03-26 | Adolor Corp | Spirocyclic heterocyclic derivatives and methods of their use |
| US7598261B2 (en) * | 2005-03-31 | 2009-10-06 | Adolor Corporation | Spirocyclic heterocyclic derivatives and methods of their use |
| US7576207B2 (en) * | 2006-04-06 | 2009-08-18 | Adolor Corporation | Spirocyclic heterocyclic derivatives and methods of their use |
| WO2008033299A2 (en) * | 2006-09-12 | 2008-03-20 | Adolor Corporation | Use of n-containing spirocompounds for the enhancement of cognitive function |
| US8258131B2 (en) * | 2007-08-01 | 2012-09-04 | Mitsubishi Tanabe Pharma Corporation | Fused bicyclic compound |
| WO2009143299A1 (en) | 2008-05-20 | 2009-11-26 | Neurogesx, Inc. | Hepatoprotectant acetaminophen mutual prodrugs |
| US8598164B2 (en) | 2010-05-06 | 2013-12-03 | Vertex Pharmaceuticals Incorporated | Heterocyclic chromene-spirocyclic piperidine amides as modulators of ion channels |
| KR101923367B1 (ko) | 2011-02-02 | 2018-12-04 | 버텍스 파마슈티칼스 인코포레이티드 | 이온 채널의 조절제로서의 피롤로피라진―스피로사이클릭 피페리딘 아미드 |
| MX2013009393A (es) * | 2011-02-18 | 2013-08-29 | Vertex Pharma | Piperidinamidas cromano-espirociclicas como moduladores de canales de iones. |
| CN103517910B (zh) | 2011-03-14 | 2016-12-14 | 沃泰克斯药物股份有限公司 | 作为离子通道调节剂的吗啉-螺环哌啶酰胺 |
| GB201113538D0 (en) | 2011-08-04 | 2011-09-21 | Karobio Ab | Novel estrogen receptor ligands |
| CA2882038A1 (en) | 2012-08-16 | 2014-02-20 | Janssen Pharmaceutica Nv | Substituted pyrazoles as n-type calcium channel blockers |
| KR20160043047A (ko) * | 2013-08-16 | 2016-04-20 | 얀센 파마슈티카 엔.브이. | N형 칼슘 채널 차단제로서의 치환된 이미다졸 |
| US9453002B2 (en) | 2013-08-16 | 2016-09-27 | Janssen Pharmaceutica Nv | Substituted imidazoles as N-type calcium channel blockers |
| 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 |
| CA3225945A1 (en) * | 2021-07-16 | 2023-01-19 | Tuan Trang | Sulfamoyl benzene derivatives and uses thereof |
Family Cites Families (70)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5387587A (en) | 1986-12-23 | 1995-02-07 | Merck Patent Gesellschaft Mit Beschrankter Haftung | Chroman derivatives |
| BR8904728A (pt) | 1988-09-26 | 1990-05-01 | Goodyear Tire & Rubber | Processo para a sintese catalisada de acrilamidas n-substituidas |
| DE3837809A1 (de) | 1988-11-08 | 1990-05-10 | Merck Patent Gmbh | Tetralinderivate |
| ATE120459T1 (de) | 1988-12-13 | 1995-04-15 | Beecham Group Plc | Benzopyran und verwandte verbindungen. |
| IT1230062B (it) * | 1989-04-18 | 1991-09-27 | Enichem Sintesi | Nuovi silani contenenti almeno due gruppi oxazolidinici, loro preparazione ed impiego. |
| EP0401958B1 (en) | 1989-06-05 | 1995-01-11 | Tokuyama Corporation | Photochromic compound, composition and use thereof |
| CA2026389A1 (en) | 1989-09-29 | 1991-03-30 | Hideo Nakai | Chromene or thiochromene derivatives, process for preparing the same and intermediate therefor |
| JP2985322B2 (ja) | 1991-03-01 | 1999-11-29 | 東レ株式会社 | イソキノリン誘導体およびその医薬用途 |
| US5354863A (en) | 1992-01-21 | 1994-10-11 | G. D. Searle & Co. | Opioid agonist compounds |
| GB9202238D0 (en) | 1992-02-03 | 1992-03-18 | Wellcome Found | Compounds |
| GB9203596D0 (en) | 1992-02-20 | 1992-04-08 | Smithkline Beecham Plc | Novel process |
| GB9207400D0 (en) | 1992-04-02 | 1992-05-13 | Smithkline Beecham Plc | Novel use |
| CA2100514C (en) | 1992-07-29 | 2005-03-29 | Johannes A. M. Hamersma | 17-spiromethylene steroids |
| ES2064228B1 (es) | 1992-10-19 | 1995-09-01 | Uriach & Cia Sa J | Nuevas tetralonas con actividad farmacologica, composiciones que las contienen y procedimiento para su preparacion. |
| CA2154569A1 (en) | 1993-01-28 | 1994-08-04 | Jeffrey J. Hale | Spiro-substituted azacycles as tachykinin receptor antagonists |
| US6031115A (en) | 1993-05-14 | 2000-02-29 | Smithkline Beecham Plc | Process for preparing epoxides |
| JPH09505030A (ja) | 1993-08-06 | 1997-05-20 | スミスクライン・ビーチャム・ソシエタ・ペル・アチオニ | ヒドロイソキノリン誘導体 |
| US5403846A (en) | 1993-11-22 | 1995-04-04 | Merck & Co., Inc. | Spirocycles |
| SE9401727D0 (sv) | 1994-05-18 | 1994-05-18 | Astra Ab | New compounds I |
| US5683628A (en) | 1994-10-17 | 1997-11-04 | Seiko Epson Corp. | Photochromic composition and photochromic resin obtainable by using the same |
| US5628935A (en) | 1994-10-28 | 1997-05-13 | Vision-Ease Lens, Inc. | Photochromic spironaphthopyran compounds |
| WO1996022276A1 (en) | 1995-01-20 | 1996-07-25 | Nippon Shinyaku Co., Ltd. | Ethylamine derivatives and drugs |
| US5656420A (en) | 1995-02-24 | 1997-08-12 | University Of Kentucky Research Foundation | Method for employing the delta opioid dadle to extend tissue survival time during ischemia |
| IT1307327B1 (it) | 1995-09-12 | 2001-10-30 | Smithkline Beecham Spa | Derivati idroisochinolinici sostituiti |
| SE9504661D0 (sv) * | 1995-12-22 | 1995-12-22 | Astra Pharma Inc | New compounds |
| JPH09301973A (ja) | 1996-05-09 | 1997-11-25 | Kumiai Chem Ind Co Ltd | クロメン誘導体及びこれを有効成分とする除草剤 |
| US6218424B1 (en) | 1996-09-25 | 2001-04-17 | Gpi Nil Holdings, Inc. | Heterocyclic ketone and thioester compounds and uses |
| US5786378A (en) | 1996-09-25 | 1998-07-28 | Gpi Nil Holdings, Inc. | Heterocyclic thioesters |
| DE19805370A1 (de) * | 1997-03-14 | 1998-09-17 | Gruenenthal Gmbh | Substituierte Aminoverbindungen und ihre Verwendung als analgetisch wirksame Substanzen |
| US6103722A (en) | 1997-07-23 | 2000-08-15 | The Medical College Of Wisconsin Research Foundation Inc. | Ischemic preconditioning |
| DK1037880T3 (da) | 1997-12-11 | 2004-11-15 | Janssen Pharmaceutica Nv | Anilider som retinsyremimetika |
| GB9804734D0 (en) | 1998-03-05 | 1998-04-29 | Pfizer Ltd | Compounds |
| US6436959B1 (en) | 1998-12-23 | 2002-08-20 | Ortho-Mcneil Pharmaceutical, Inc. | 4-[aryl(piperidin-4-yl)]aminobenzamides |
| FR2787789B1 (fr) | 1998-12-29 | 2002-06-14 | Lipha | Benzopyranes et benzoxepines utilisables dans le traitement de dyslipidemies, de l'atherosclerose et du diabete, compositions pharmaceutiques les contenant et procedes de preparations |
| GB9912413D0 (en) * | 1999-05-28 | 1999-07-28 | Pfizer Ltd | Compounds useful in therapy |
| TWI243173B (en) | 1999-11-17 | 2005-11-11 | Akzo Nobel Nv | Spiro[2H-1-benzopyran-2,4'-piperidine] derivatives |
| JP2005231995A (ja) | 1999-12-22 | 2005-09-02 | Meiji Seika Kaisha Ltd | オピオイドδ受容体アゴニスト／アンタゴニストとして有用なスピロ化合物 |
| CA2404280A1 (en) * | 2000-03-24 | 2002-09-23 | Meiji Seika Kaisha, Ltd. | Diphenylalkylamine derivatives useful as opioid .delta. receptor agonists |
| JP4275288B2 (ja) | 2000-03-31 | 2009-06-10 | 新明和工業株式会社 | ダンプ車輌の油圧制御装置 |
| KR20020093966A (ko) * | 2000-04-27 | 2002-12-16 | 바실리어 파마슈티카 아게 | 항균제로서의 크로메닐메틸 피리미딘디아민 |
| KR20020012346A (ko) | 2000-08-07 | 2002-02-16 | 유현식 | 신디오탁틱 폴리스티렌을 고수율로 제조하고 반응기부착물을 감소시키는 담지촉매 |
| WO2002048122A2 (en) | 2000-12-14 | 2002-06-20 | Ortho-Mcneil Pharmaceutical, Inc. | Benzamidine derivatives |
| PT1395567E (pt) | 2001-05-18 | 2009-03-26 | Astrazeneca Ab | Derivados de 4(fenil-piperazinil-metil)benzamida e sua utilização para o tratamento da ansiedade da dor ou de distúrbios gastrointestinais |
| SE0101770D0 (sv) | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| SE0101766D0 (sv) | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| SE0101773D0 (sv) | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| SE0101767D0 (sv) | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| SE0101768D0 (sv) | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| SE0101765D0 (sv) | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| SE0101769D0 (sv) * | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| SE0101771D0 (sv) | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| EP1279666A1 (en) | 2001-07-24 | 2003-01-29 | Pfizer Products Inc. | 1-diphenylmethyl-pyrazole derivatives as opioid receptor ligands |
| SE0103313D0 (sv) | 2001-10-03 | 2001-10-03 | Astrazeneca Ab | Novel compounds |
| EA006507B1 (ru) | 2001-10-15 | 2005-12-29 | Янссен Фармацевтика Н.В. | Новые замещенные 4-фенил-4-[1h-имидазол-2-ил] пиперидиновые производные и их применение в качестве селективных непептидных агонистов дельта-опиоидов |
| CN1596113B (zh) | 2001-10-29 | 2010-05-26 | 蒙特库克生物科学公司 | δ受体激动剂化合物在制备治疗抑郁症的药物中的应用 |
| EP1469850B1 (en) | 2002-01-02 | 2013-01-02 | Versi Group, LLC | Method of treating sexual dysfunctions with delta opioid receptor agonist compounds |
| US7164021B2 (en) | 2002-09-18 | 2007-01-16 | The Curators Of The University Of Missouri | Opiate analogs selective for the δ-opioid receptor |
| WO2004035541A1 (en) | 2002-10-15 | 2004-04-29 | Janssen Pharmaceutica, N.V. | Benzyl substituted (piperidin-4-yl) aminobenzamido derivatives as delta-opiod receptor modulators |
| ES2300626T3 (es) | 2002-10-15 | 2008-06-16 | Janssen Pharmaceutica Nv | Compuestos de aminoquinuclidina sustituida y su uso como ligandos del receptor delta-opioide. |
| SE0203301D0 (sv) | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Compounds |
| SE0203303D0 (sv) | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Compounds |
| SE0203300D0 (sv) | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Compounds |
| SE0203302D0 (sv) | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Compounds |
| US7314880B2 (en) | 2003-01-02 | 2008-01-01 | Mount Cook Biosciences, Inc. | Cardioprotective delta opioid receptor agonists and methods of using same |
| SE0300103D0 (sv) | 2003-01-16 | 2003-01-16 | Astrazeneca Ab | Diarylmethylidene piperidine derivatives, preparations thereof and uses thereof |
| SE0300104D0 (sv) | 2003-01-16 | 2003-01-16 | Astrazeneca Ab | Diarylmethylidene piperidine derivatives, preparations thereof and uses thereof |
| SE0300105D0 (sv) | 2003-01-16 | 2003-01-16 | Astrazeneca Ab | Diarylmethylidene piperdine derivatives, preparations thereof and uses thereof |
| US20050095281A1 (en) | 2003-03-14 | 2005-05-05 | Optime Therapeutics, Inc. | Liposomal formulations and methods of use |
| NZ546834A (en) * | 2003-10-01 | 2010-03-26 | Adolor Corp | Spirocyclic heterocyclic derivatives and methods of their use |
| US7598261B2 (en) * | 2005-03-31 | 2009-10-06 | Adolor Corporation | Spirocyclic heterocyclic derivatives and methods of their use |
-
2006
- 2006-03-30 US US11/393,133 patent/US7598261B2/en not_active Expired - Fee Related
- 2006-03-31 WO PCT/US2006/012081 patent/WO2006105442A2/en not_active Ceased
- 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 CA CA002603126A patent/CA2603126A1/en not_active Abandoned
- 2006-03-31 EP EP06749077A patent/EP1871761A4/en not_active Withdrawn
- 2006-03-31 NZ NZ562144A patent/NZ562144A/en not_active IP Right Cessation
- 2006-03-31 KR KR1020077025148A patent/KR20080005245A/ko not_active Ceased
- 2006-03-31 BR BRPI0612189-6A patent/BRPI0612189A2/pt not_active IP Right Cessation
- 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
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2008534613A5 (https=) | ||
| US20200345718A1 (en) | Morphinan Derivatives for the Treatment of Drug Overdose | |
| US20080176885A1 (en) | Novel synergistic opioid-cannabinoid codrug for pain management | |
| JP6279547B2 (ja) | オピオイド誘発性有害薬力学的応答を治療するためのシステムおよび方法 | |
| JP2009526793A5 (https=) | ||
| JP2003528819A5 (https=) | ||
| JP5751831B2 (ja) | 鎮痛耐性抑制剤 | |
| JP2009533353A5 (https=) | ||
| EP2529739A1 (en) | Therapeutic or prophylactic agent for biliary diseases | |
| WO2020055725A4 (en) | Dopamine d3 receptor selective antagonists/partial agonists and uses thereof | |
| US20030166670A1 (en) | Use of an opioid compound to treat a neurologic or neurogenic disorder | |
| JP2003518119A (ja) | ４−［アリール（８−アザビシクロ［３．２．１］オクタン−３−イル）］アミノ安息香酸誘導体 | |
| US20200352917A1 (en) | Medicated spray for treatment of substance abuse, overdose, addiction and impulse control disorders | |
| EP1904068A1 (en) | Synergistic combination for the treatment of pain (cannabioid receptor agonist and opiod receptor agonist) | |
| US20170217976A1 (en) | 6-(amino acid)-morphinan derivatives in combination with permeation enhancers for use as an orally, rectally, transdermally or nasally administered medicament | |
| JP2010532315A5 (https=) | ||
| Le Bourdonnec et al. | Novel trans-3, 4-dimethyl-4-(3-hydroxyphenyl) piperidines as μ opioid receptor antagonists with improved opioid receptor selectivity profiles | |
| AU2004233582B2 (en) | Pharmaceutical compositon comprising a cathepsin S inhibitor and an opioid | |
| WO2004078178A1 (en) | Buprenorphine compounds for treatment of alcohol dependence and excessive alcohol use | |
| HK1174496A (en) | Morphinan derivatives for the treatment of drug overdose | |
| HK1174496B (en) | Morphinan derivatives for the treatment of drug overdose | |
| EP1797883A2 (en) | Pharmaceutical composition comprising a cathepsin S inhibitor and an opioid | |
| JP2011513278A5 (https=) |