KR20080005245A - 스피로시클릭 헤테로시클릭 유도체 및 그의 사용 방법 - Google Patents
스피로시클릭 헤테로시클릭 유도체 및 그의 사용 방법 Download PDFInfo
- Publication number
- KR20080005245A KR20080005245A KR1020077025148A KR20077025148A KR20080005245A KR 20080005245 A KR20080005245 A KR 20080005245A KR 1020077025148 A KR1020077025148 A KR 1020077025148A KR 20077025148 A KR20077025148 A KR 20077025148A KR 20080005245 A KR20080005245 A KR 20080005245A
- Authority
- KR
- South Korea
- Prior art keywords
- alkyl
- compound
- formula
- pharmaceutical composition
- 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.)
- Ceased
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- 238000000034 method Methods 0.000 title claims abstract description 202
- 125000000623 heterocyclic group Chemical group 0.000 title claims abstract description 25
- 150000001875 compounds Chemical class 0.000 claims abstract description 548
- 238000011282 treatment Methods 0.000 claims abstract description 94
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 82
- 101100244562 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) oprD gene Proteins 0.000 claims abstract description 57
- 108700023159 delta Opioid Receptors Proteins 0.000 claims abstract description 57
- 102000048124 delta Opioid Receptors Human genes 0.000 claims abstract description 57
- 125000000217 alkyl group Chemical group 0.000 claims description 461
- -1 hydroxy, aminocarbonyl Chemical group 0.000 claims description 406
- 125000003118 aryl group Chemical group 0.000 claims description 132
- 150000003839 salts Chemical class 0.000 claims description 131
- 125000001072 heteroaryl group Chemical group 0.000 claims description 97
- 239000002253 acid Substances 0.000 claims description 83
- 125000005843 halogen group Chemical group 0.000 claims description 81
- 229940002612 prodrug Drugs 0.000 claims description 70
- 239000000651 prodrug Substances 0.000 claims description 70
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 68
- 229910052757 nitrogen Inorganic materials 0.000 claims description 67
- 239000012453 solvate Substances 0.000 claims description 66
- 150000001204 N-oxides Chemical class 0.000 claims description 63
- 125000004432 carbon atom Chemical group C* 0.000 claims description 59
- 125000003545 alkoxy group Chemical group 0.000 claims description 58
- 239000000203 mixture Substances 0.000 claims description 57
- 102000003840 Opioid Receptors Human genes 0.000 claims description 53
- 108090000137 Opioid Receptors Proteins 0.000 claims description 53
- 229910052799 carbon Inorganic materials 0.000 claims description 53
- 230000027455 binding Effects 0.000 claims description 52
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 50
- 230000000694 effects Effects 0.000 claims description 48
- 208000004296 neuralgia Diseases 0.000 claims description 44
- 239000003795 chemical substances by application Substances 0.000 claims description 42
- 210000003169 central nervous system Anatomy 0.000 claims description 40
- 239000003814 drug Substances 0.000 claims description 38
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 29
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 28
- 208000021722 neuropathic pain Diseases 0.000 claims description 28
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 27
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 claims description 27
- 239000000935 antidepressant agent Substances 0.000 claims description 26
- 229940005513 antidepressants Drugs 0.000 claims description 26
- XYYVYLMBEZUESM-UHFFFAOYSA-N dihydrocodeine Natural products C1C(N(CCC234)C)C2C=CC(=O)C3OC2=C4C1=CC=C2OC XYYVYLMBEZUESM-UHFFFAOYSA-N 0.000 claims description 26
- 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 claims description 26
- 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 description 25
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 25
- 229960001797 methadone Drugs 0.000 claims description 25
- 239000003937 drug carrier Substances 0.000 claims description 20
- 150000004677 hydrates Chemical class 0.000 claims description 20
- 230000000202 analgesic effect Effects 0.000 claims description 19
- 206010046543 Urinary incontinence Diseases 0.000 claims description 18
- 239000003242 anti bacterial agent Substances 0.000 claims description 18
- 229940121375 antifungal agent Drugs 0.000 claims description 17
- 230000003444 anaesthetic effect Effects 0.000 claims description 16
- 230000008499 blood brain barrier function Effects 0.000 claims description 16
- 210000001218 blood-brain barrier Anatomy 0.000 claims description 16
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 15
- 229940124597 therapeutic agent Drugs 0.000 claims description 15
- 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 description 14
- 206010021639 Incontinence Diseases 0.000 claims description 14
- 229940123685 Monoamine oxidase inhibitor Drugs 0.000 claims description 14
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 14
- 230000000648 anti-parkinson Effects 0.000 claims description 14
- 239000001961 anticonvulsive agent Substances 0.000 claims description 14
- 239000000939 antiparkinson agent Substances 0.000 claims description 14
- 229960004126 codeine Drugs 0.000 claims description 14
- 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 description 14
- 125000001153 fluoro group Chemical group F* 0.000 claims description 14
- 239000002899 monoamine oxidase inhibitor Substances 0.000 claims description 14
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 claims description 14
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 claims description 14
- LGFMXOTUSSVQJV-NEYUFSEYSA-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;(4r,4ar,7s,7ar,12bs)-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7,9-diol;1-[(3,4-dimethoxyphenyl)methyl]-6 Chemical compound Cl.Cl.Cl.O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC.C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 LGFMXOTUSSVQJV-NEYUFSEYSA-N 0.000 claims description 13
- 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 description 13
- 229940127291 Calcium channel antagonist Drugs 0.000 claims description 13
- 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 description 13
- OGDVEMNWJVYAJL-LEPYJNQMSA-N Ethyl morphine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OCC OGDVEMNWJVYAJL-LEPYJNQMSA-N 0.000 claims description 13
- OGDVEMNWJVYAJL-UHFFFAOYSA-N Ethylmorphine Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OCC OGDVEMNWJVYAJL-UHFFFAOYSA-N 0.000 claims description 13
- 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 description 13
- ALFGKMXHOUSVAD-UHFFFAOYSA-N Ketobemidone Chemical compound C=1C=CC(O)=CC=1C1(C(=O)CC)CCN(C)CC1 ALFGKMXHOUSVAD-UHFFFAOYSA-N 0.000 claims description 13
- XADCESSVHJOZHK-UHFFFAOYSA-N Meperidine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 XADCESSVHJOZHK-UHFFFAOYSA-N 0.000 claims description 13
- 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 description 13
- 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 description 13
- 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 description 13
- 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 description 13
- 229940123445 Tricyclic antidepressant Drugs 0.000 claims description 13
- 229960001391 alfentanil Drugs 0.000 claims description 13
- KGYFOSCXVAXULR-UHFFFAOYSA-N allylprodine Chemical compound C=1C=CC=CC=1C1(OC(=O)CC)CCN(C)CC1CC=C KGYFOSCXVAXULR-UHFFFAOYSA-N 0.000 claims description 13
- 229950004361 allylprodine Drugs 0.000 claims description 13
- UVAZQQHAVMNMHE-XJKSGUPXSA-N alphaprodine Chemical compound C=1C=CC=CC=1[C@@]1(OC(=O)CC)CCN(C)C[C@@H]1C UVAZQQHAVMNMHE-XJKSGUPXSA-N 0.000 claims description 13
- 229960001349 alphaprodine Drugs 0.000 claims description 13
- 230000000843 anti-fungal effect Effects 0.000 claims description 13
- 230000000840 anti-viral effect Effects 0.000 claims description 13
- 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 description 13
- 229940125388 beta agonist Drugs 0.000 claims description 13
- FLKWNFFCSSJANB-UHFFFAOYSA-N bezitramide Chemical compound O=C1N(C(=O)CC)C2=CC=CC=C2N1C(CC1)CCN1CCC(C#N)(C=1C=CC=CC=1)C1=CC=CC=C1 FLKWNFFCSSJANB-UHFFFAOYSA-N 0.000 claims description 13
- 229960004611 bezitramide Drugs 0.000 claims description 13
- 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 description 13
- 229960001736 buprenorphine Drugs 0.000 claims description 13
- 239000000480 calcium channel blocker Substances 0.000 claims description 13
- XBRXTUGRUXGBPX-DLBZAZTESA-N cyclazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N([C@@H]1CCCC[C@@H]11)CCN1C(=O)C1=CC=CO1 XBRXTUGRUXGBPX-DLBZAZTESA-N 0.000 claims description 13
- 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 description 13
- XLMALTXPSGQGBX-GCJKJVERSA-N dextropropoxyphene Chemical group 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 description 13
- 229960004193 dextropropoxyphene Drugs 0.000 claims description 13
- 229960002069 diamorphine Drugs 0.000 claims description 13
- 229960000920 dihydrocodeine Drugs 0.000 claims description 13
- 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 description 13
- 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 description 13
- 229950011187 dimenoxadol Drugs 0.000 claims description 13
- CANBGVXYBPOLRR-UHFFFAOYSA-N dimethylthiambutene Chemical compound C=1C=CSC=1C(=CC(C)N(C)C)C1=CC=CS1 CANBGVXYBPOLRR-UHFFFAOYSA-N 0.000 claims description 13
- 229950005563 dimethylthiambutene Drugs 0.000 claims description 13
- 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 description 13
- 229960002500 dipipanone Drugs 0.000 claims description 13
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- 229960002428 fentanyl Drugs 0.000 claims description 13
- 125000005842 heteroatom Chemical group 0.000 claims description 13
- 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 description 13
- 229960000240 hydrocodone Drugs 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 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 description 13
- 229960001410 hydromorphone Drugs 0.000 claims description 13
- 229960003029 ketobemidone Drugs 0.000 claims description 13
- 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 description 13
- 229950010274 lofentanil Drugs 0.000 claims description 13
- 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 description 13
- 229960001571 loperamide Drugs 0.000 claims description 13
- YEOTYALSMRNXLJ-UHFFFAOYSA-N metazosin Chemical compound C1CN(C(=O)C(C)OC)CCN1C1=NC(N)=C(C=C(OC)C(OC)=C2)C2=N1 YEOTYALSMRNXLJ-UHFFFAOYSA-N 0.000 claims description 13
- 229960005181 morphine Drugs 0.000 claims description 13
- 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 description 13
- 229960000805 nalbuphine Drugs 0.000 claims description 13
- 229960004300 nicomorphine Drugs 0.000 claims description 13
- 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 description 13
- 229950006134 normorphine Drugs 0.000 claims description 13
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- 229960005118 oxymorphone Drugs 0.000 claims description 13
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- 229960000482 pethidine Drugs 0.000 claims description 13
- 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 description 13
- 229950004540 phenadoxone Drugs 0.000 claims description 13
- CFBQYWXPZVQQTN-QPTUXGOLSA-N phenomorphan Chemical compound C([C@]12CCCC[C@H]1[C@H]1CC3=CC=C(C=C32)O)CN1CCC1=CC=CC=C1 CFBQYWXPZVQQTN-QPTUXGOLSA-N 0.000 claims description 13
- 229950011496 phenomorphan Drugs 0.000 claims description 13
- 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 description 13
- 229950004345 properidine Drugs 0.000 claims description 13
- 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 description 13
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- 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 description 13
- LLPOLZWFYMWNKH-UHFFFAOYSA-N trans-dihydrocodeinone Natural products C1C(N(CCC234)C)C2CCC(=O)C3OC2=C4C1=CC=C2OC LLPOLZWFYMWNKH-UHFFFAOYSA-N 0.000 claims description 13
- 239000003029 tricyclic antidepressant agent Substances 0.000 claims description 13
- 150000003536 tetrazoles Chemical class 0.000 claims description 12
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 10
- 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 claims description 9
- 125000003282 alkyl amino group Chemical group 0.000 claims description 7
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 7
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- SQQWBSBBCSFQGC-JLHYYAGUSA-N ubiquinone-2 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CCC=C(C)C)=C(C)C1=O SQQWBSBBCSFQGC-JLHYYAGUSA-N 0.000 claims description 6
- 208000000921 Urge Urinary Incontinence Diseases 0.000 claims description 5
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- 125000001544 thienyl group Chemical group 0.000 claims description 4
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- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
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- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 2
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
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- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 39
- 150000003018 phosphorus compounds Chemical class 0.000 claims 35
- 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
- 230000001430 anti-depressive effect Effects 0.000 claims 24
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 claims 12
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- 208000020401 Depressive disease Diseases 0.000 claims 12
- 230000001004 anti-acetylcholinic effect Effects 0.000 claims 12
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- 230000003115 biocidal effect Effects 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
- 239000004084 narcotic analgesic agent Substances 0.000 claims 12
- 230000002981 neuropathic effect Effects 0.000 claims 12
- LKYQLAWMNBFNJT-UHFFFAOYSA-N anileridine Chemical compound C1CC(C(=O)OCC)(C=2C=CC=CC=2)CCN1CCC1=CC=C(N)C=C1 LKYQLAWMNBFNJT-UHFFFAOYSA-N 0.000 claims 5
- 229960002512 anileridine Drugs 0.000 claims 5
- 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 5
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 77
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- 208000018522 Gastrointestinal disease Diseases 0.000 abstract description 4
- 230000001404 mediated effect Effects 0.000 abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 52
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
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- A—HUMAN NECESSITIES
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- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/20—Spiro-condensed ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/96—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings spiro-condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/10—Spiro-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
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- Neurosurgery (AREA)
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- Endocrinology (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyrane Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US66717705P | 2005-03-31 | 2005-03-31 | |
| US60/667,177 | 2005-03-31 | ||
| US11/393,133 | 2006-03-30 | ||
| US11/393,133 US7598261B2 (en) | 2005-03-31 | 2006-03-30 | Spirocyclic heterocyclic derivatives and methods of their use |
Publications (1)
| Publication Number | Publication Date |
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| KR20080005245A true KR20080005245A (ko) | 2008-01-10 |
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| Application Number | Title | Priority Date | Filing Date |
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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=) |
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| CN101921279A (zh) * | 2003-10-01 | 2010-12-22 | 阿得罗公司 | 螺环杂环衍生物及其应用方法 |
| 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 |
| KR101717145B1 (ko) | 2008-05-20 | 2017-03-16 | 노이로제스엑스, 인코포레이티드 | 간보호제 아세트아미노펜 공통 프로드러그 |
| US8598164B2 (en) | 2010-05-06 | 2013-12-03 | Vertex Pharmaceuticals Incorporated | Heterocyclic chromene-spirocyclic piperidine amides as modulators of ion channels |
| MX355907B (es) | 2011-02-02 | 2018-05-04 | Vertex Pharma | Pirrolopirazina-piperidina espirociclica-amidas como moduladores de canales de ionicos. |
| JP5940562B2 (ja) * | 2011-02-18 | 2016-06-29 | バーテックス ファーマシューティカルズ インコーポレイテッドVertex Pharmaceuticals Incorporated | イオンチャネルのモジュレーターとしてのクロマン−スピロ環式ピペリジンアミド |
| MX347982B (es) | 2011-03-14 | 2017-05-22 | Vertex Pharma | Morfolina-piperidina espirociclica-amidas como moduladores de canales ionicos. |
| GB201113538D0 (en) | 2011-08-04 | 2011-09-21 | Karobio Ab | Novel estrogen receptor ligands |
| SG11201501130PA (en) | 2012-08-16 | 2015-04-29 | Janssen Pharmaceutica Nv | Substituted pyrazoles as n-type calcium channel blockers |
| US9453002B2 (en) | 2013-08-16 | 2016-09-27 | Janssen Pharmaceutica Nv | Substituted imidazoles as N-type calcium channel blockers |
| AU2013397913B2 (en) * | 2013-08-16 | 2018-07-19 | 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 |
| WO2023283743A1 (en) * | 2021-07-16 | 2023-01-19 | Aphiotx Inc. | Sulfamoyl benzene derivatives and uses thereof |
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| 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 |
| WO2004082612A2 (en) | 2003-03-14 | 2004-09-30 | Optime Therapeutics Inc. | Liposomal formulations and methods of use |
| CN101921279A (zh) * | 2003-10-01 | 2010-12-22 | 阿得罗公司 | 螺环杂环衍生物及其应用方法 |
| US7598261B2 (en) | 2005-03-31 | 2009-10-06 | Adolor Corporation | Spirocyclic heterocyclic derivatives and methods of their use |
-
2006
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- 2006-03-31 JP JP2008504447A patent/JP5118788B2/ja not_active Expired - Fee Related
- 2006-03-31 NZ NZ562144A patent/NZ562144A/en not_active IP Right Cessation
- 2006-03-31 EP EP06749077A patent/EP1871761A4/en not_active Withdrawn
- 2006-03-31 CA CA002603126A patent/CA2603126A1/en not_active Abandoned
- 2006-03-31 KR KR1020077025148A patent/KR20080005245A/ko not_active Ceased
- 2006-03-31 AU AU2006230517A patent/AU2006230517B2/en not_active Ceased
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2007
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2009
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2011
- 2011-04-29 US US13/097,940 patent/US20110218186A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| BRPI0612189A2 (pt) | 2009-01-20 |
| IL186342A0 (en) | 2008-01-20 |
| CA2603126A1 (en) | 2006-10-05 |
| JP5118788B2 (ja) | 2013-01-16 |
| NZ562144A (en) | 2011-04-29 |
| EP1871761A4 (en) | 2011-10-19 |
| AU2006230517A1 (en) | 2006-10-05 |
| US20100029614A1 (en) | 2010-02-04 |
| US20110218186A1 (en) | 2011-09-08 |
| US20060270695A1 (en) | 2006-11-30 |
| JP2008534613A (ja) | 2008-08-28 |
| US7598261B2 (en) | 2009-10-06 |
| US8022060B2 (en) | 2011-09-20 |
| WO2006105442A3 (en) | 2007-08-02 |
| WO2006105442A2 (en) | 2006-10-05 |
| MX2007011962A (es) | 2007-12-13 |
| AU2006230517B2 (en) | 2012-09-13 |
| EP1871761A2 (en) | 2008-01-02 |
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