JP2000516925A - カリウムチャンネル調節物質であるジフェニルヘテロ環化合物 - Google Patents
カリウムチャンネル調節物質であるジフェニルヘテロ環化合物Info
- Publication number
- JP2000516925A JP2000516925A JP10509180A JP50918098A JP2000516925A JP 2000516925 A JP2000516925 A JP 2000516925A JP 10509180 A JP10509180 A JP 10509180A JP 50918098 A JP50918098 A JP 50918098A JP 2000516925 A JP2000516925 A JP 2000516925A
- Authority
- JP
- Japan
- Prior art keywords
- chloro
- phenyl
- hydroxyphenyl
- trifluoromethyl
- methyl
- 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
Links
- -1 Diphenyl heterocyclic compounds Chemical class 0.000 title claims abstract description 154
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 title claims description 11
- 235000010290 biphenyl Nutrition 0.000 title claims description 8
- 102000004257 Potassium Channel Human genes 0.000 title description 9
- 108020001213 potassium channel Proteins 0.000 title description 9
- 239000004305 biphenyl Substances 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 104
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 31
- 239000001257 hydrogen Substances 0.000 claims abstract description 28
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims abstract description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 21
- 201000010099 disease Diseases 0.000 claims abstract description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 15
- 150000002367 halogens Chemical class 0.000 claims abstract description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 15
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims abstract description 13
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims abstract description 9
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 9
- CAAMSDWKXXPUJR-UHFFFAOYSA-N 3,5-dihydro-4H-imidazol-4-one Chemical compound O=C1CNC=N1 CAAMSDWKXXPUJR-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 8
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims abstract description 7
- IQXXEPZFOOTTBA-UHFFFAOYSA-N 1-benzylpiperazine Chemical compound C=1C=CC=CC=1CN1CCNCC1 IQXXEPZFOOTTBA-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims abstract description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 5
- 102000005702 Calcium-Activated Potassium Channels Human genes 0.000 claims abstract description 4
- 108010045489 Calcium-Activated Potassium Channels Proteins 0.000 claims abstract description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 104
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 102
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 92
- 238000000034 method Methods 0.000 claims description 39
- 239000000203 mixture Substances 0.000 claims description 21
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 17
- 239000011575 calcium Substances 0.000 claims description 14
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 13
- WNWOTMKHOLCHRJ-UHFFFAOYSA-N 1,4-dihydrotriazol-5-one Chemical compound O=C1CN=NN1 WNWOTMKHOLCHRJ-UHFFFAOYSA-N 0.000 claims description 12
- 241000124008 Mammalia Species 0.000 claims description 11
- 229910052791 calcium Inorganic materials 0.000 claims description 11
- ZVTQYRVARPYRRE-UHFFFAOYSA-N oxadiazol-4-one Chemical group O=C1CON=N1 ZVTQYRVARPYRRE-UHFFFAOYSA-N 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- FFSJPOPLSWBGQY-UHFFFAOYSA-N triazol-4-one Chemical group O=C1C=NN=N1 FFSJPOPLSWBGQY-UHFFFAOYSA-N 0.000 claims description 9
- 239000012453 solvate Substances 0.000 claims description 8
- 208000028867 ischemia Diseases 0.000 claims description 7
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 6
- 150000002085 enols Chemical class 0.000 claims description 6
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- 206010010904 Convulsion Diseases 0.000 claims description 5
- 208000019695 Migraine disease Diseases 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 5
- 206010027599 migraine Diseases 0.000 claims description 5
- 208000010228 Erectile Dysfunction Diseases 0.000 claims description 4
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 4
- 230000036461 convulsion Effects 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 201000001881 impotence Diseases 0.000 claims description 4
- 230000009529 traumatic brain injury Effects 0.000 claims description 4
- PHWHYZMFGGOJEU-UHFFFAOYSA-N 2-(5-chloro-2-hydroxyphenyl)-5-[2-(trifluoromethyl)phenyl]-1h-1,2,4-triazol-3-one Chemical compound OC1=CC=C(Cl)C=C1N1C(=O)NC(C=2C(=CC=CC=2)C(F)(F)F)=N1 PHWHYZMFGGOJEU-UHFFFAOYSA-N 0.000 claims description 3
- XNRWPJIJOVVQRQ-UHFFFAOYSA-N 2-(5-chloro-2-hydroxyphenyl)-5-[4-(trifluoromethyl)phenyl]-1h-1,2,4-triazol-3-one Chemical compound OC1=CC=C(Cl)C=C1N1C(=O)NC(C=2C=CC(=CC=2)C(F)(F)F)=N1 XNRWPJIJOVVQRQ-UHFFFAOYSA-N 0.000 claims description 3
- FTALKIIATXSSFI-UHFFFAOYSA-N 2-[(4-amino-5-chloro-2-hydroxyphenyl)methyl]-5-(3,4-dichlorophenyl)-1h-1,2,4-triazol-3-one Chemical compound C1=C(Cl)C(N)=CC(O)=C1CN1C(=O)NC(C=2C=C(Cl)C(Cl)=CC=2)=N1 FTALKIIATXSSFI-UHFFFAOYSA-N 0.000 claims description 3
- RYJJSCOSTINHIY-UHFFFAOYSA-N 3-[(5-chloro-2-hydroxyphenyl)methyl]-5-(3,5-dichlorophenyl)-1,3,4-oxadiazol-2-one Chemical compound OC1=CC=C(Cl)C=C1CN1C(=O)OC(C=2C=C(Cl)C=C(Cl)C=2)=N1 RYJJSCOSTINHIY-UHFFFAOYSA-N 0.000 claims description 3
- WABFQTRUZJUTES-UHFFFAOYSA-N 3-[(5-chloro-2-hydroxyphenyl)methyl]-5-[2-imidazol-1-yl-4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-one Chemical compound OC1=CC=C(Cl)C=C1CN1C(=O)OC(C=2C(=CC(=CC=2)C(F)(F)F)N2C=NC=C2)=N1 WABFQTRUZJUTES-UHFFFAOYSA-N 0.000 claims description 3
- WHPOKFZAXWSQNX-UHFFFAOYSA-N 3-[(5-chloro-2-hydroxyphenyl)methyl]-5-[4-fluoro-3-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-one Chemical compound OC1=CC=C(Cl)C=C1CN1C(=O)OC(C=2C=C(C(F)=CC=2)C(F)(F)F)=N1 WHPOKFZAXWSQNX-UHFFFAOYSA-N 0.000 claims description 3
- PLLBMGUUHCVCFL-UHFFFAOYSA-N 3-[(5-chloro-2-hydroxyphenyl)methyl]-5-[4-imidazol-1-yl-3-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-one Chemical compound OC1=CC=C(Cl)C=C1CN1C(=O)OC(C=2C=C(C(=CC=2)N2C=NC=C2)C(F)(F)F)=N1 PLLBMGUUHCVCFL-UHFFFAOYSA-N 0.000 claims description 3
- CEPQBUYVEMFRIL-UHFFFAOYSA-N 4-(5-chloro-2-hydroxyphenyl)-3-[3-(trifluoromethyl)phenyl]-1h-1,2,4-triazol-5-one Chemical compound OC1=CC=C(Cl)C=C1N1C(=O)NN=C1C1=CC=CC(C(F)(F)F)=C1 CEPQBUYVEMFRIL-UHFFFAOYSA-N 0.000 claims description 3
- ZHRTXAVKFZEURQ-UHFFFAOYSA-N 4-(5-chloro-2-hydroxyphenyl)-3-[4-(trifluoromethyl)phenyl]-1h-1,2,4-triazole-5-thione Chemical compound OC1=CC=C(Cl)C=C1N1C(=S)NN=C1C1=CC=C(C(F)(F)F)C=C1 ZHRTXAVKFZEURQ-UHFFFAOYSA-N 0.000 claims description 3
- GRDBOUMEDXLDAR-UHFFFAOYSA-N 5-[3,5-bis(trifluoromethyl)phenyl]-3-[(2-hydroxy-5-imidazol-1-ylphenyl)methyl]-1,3,4-oxadiazol-2-one Chemical compound OC1=CC=C(N2C=NC=C2)C=C1CN(C(O1)=O)N=C1C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 GRDBOUMEDXLDAR-UHFFFAOYSA-N 0.000 claims description 3
- XHVYOYZRLCYVPJ-UHFFFAOYSA-N 5-[3,5-bis(trifluoromethyl)phenyl]-3-[(5-chloro-2-hydroxyphenyl)methyl]-1,3,4-oxadiazol-2-one Chemical compound OC1=CC=C(Cl)C=C1CN1C(=O)OC(C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)=N1 XHVYOYZRLCYVPJ-UHFFFAOYSA-N 0.000 claims description 3
- 206010046543 Urinary incontinence Diseases 0.000 claims description 3
- WLYPBMBWKYALCG-UHFFFAOYSA-N [2,4-bis(trifluoromethyl)phenyl]boronic acid Chemical group OB(O)C1=CC=C(C(F)(F)F)C=C1C(F)(F)F WLYPBMBWKYALCG-UHFFFAOYSA-N 0.000 claims description 3
- AJCSNOSWPBAMCW-UHFFFAOYSA-N chembl218582 Chemical compound OC1=CC=C(Cl)C=C1C(OC1=O)=NN1C1=CC=C(C(F)(F)F)C=C1 AJCSNOSWPBAMCW-UHFFFAOYSA-N 0.000 claims description 3
- ZOOQSLLVAOEAPI-UHFFFAOYSA-N chembl218692 Chemical compound OC1=CC=C(Cl)C=C1C(NC1=O)=NN1C1=CC=C(C(F)(F)F)C=C1 ZOOQSLLVAOEAPI-UHFFFAOYSA-N 0.000 claims description 3
- XBMRWDFBTQKQES-UHFFFAOYSA-N chembl222070 Chemical compound CN1C=CN=C1C1=CC=C(O)C(CN2C(OC(=N2)C=2C=CC(=CC=2)C(F)(F)F)=O)=C1 XBMRWDFBTQKQES-UHFFFAOYSA-N 0.000 claims description 3
- 229960003887 dichlorophen Drugs 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- ZOHYFQKBEUBQSW-UHFFFAOYSA-N n-[2-chloro-5-hydroxy-4-[(5-naphthalen-2-yl-2-oxo-1,3,4-oxadiazol-3-yl)methyl]phenyl]-2-morpholin-4-ylacetamide Chemical compound ClC=1C=C(CN2C(OC(=N2)C=2C=C3C=CC=CC3=CC=2)=O)C(O)=CC=1NC(=O)CN1CCOCC1 ZOHYFQKBEUBQSW-UHFFFAOYSA-N 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- KWLAYFKMSIOYJS-UHFFFAOYSA-N 2-(5-chloro-2-hydroxyphenyl)-5-[3-(trifluoromethyl)phenyl]-1h-1,2,4-triazol-3-one Chemical compound OC1=CC=C(Cl)C=C1N1C(=O)NC(C=2C=C(C=CC=2)C(F)(F)F)=N1 KWLAYFKMSIOYJS-UHFFFAOYSA-N 0.000 claims description 2
- QJHNYXIRSNWDMG-UHFFFAOYSA-N 3-[(5-chloro-2-hydroxyphenyl)methyl]-5-[2-fluoro-4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-one Chemical compound OC1=CC=C(Cl)C=C1CN1C(=O)OC(C=2C(=CC(=CC=2)C(F)(F)F)F)=N1 QJHNYXIRSNWDMG-UHFFFAOYSA-N 0.000 claims description 2
- MHZFCQSAFRJDIM-UHFFFAOYSA-N 4-(5-chloro-2-hydroxyphenyl)-3-(4-fluorophenyl)-1h-1,2,4-triazol-5-one Chemical compound OC1=CC=C(Cl)C=C1N1C(=O)NN=C1C1=CC=C(F)C=C1 MHZFCQSAFRJDIM-UHFFFAOYSA-N 0.000 claims description 2
- KWAGCRWXUQPLSN-UHFFFAOYSA-N 4-(5-chloro-2-hydroxyphenyl)-3-[4-(trifluoromethyl)phenyl]-1h-1,2,4-triazol-5-one Chemical compound OC1=CC=C(Cl)C=C1N1C(=O)NN=C1C1=CC=C(C(F)(F)F)C=C1 KWAGCRWXUQPLSN-UHFFFAOYSA-N 0.000 claims description 2
- PIWCQADTVIMAOY-UHFFFAOYSA-N 4-chloro-2-(1-phenylimidazol-2-yl)phenol Chemical compound OC1=CC=C(Cl)C=C1C1=NC=CN1C1=CC=CC=C1 PIWCQADTVIMAOY-UHFFFAOYSA-N 0.000 claims description 2
- 201000006474 Brain Ischemia Diseases 0.000 claims description 2
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 2
- 206010008118 cerebral infarction Diseases 0.000 claims description 2
- XAEFRVVUHDAALT-UHFFFAOYSA-N chembl222120 Chemical compound CN1C=CN=C1C1=CC=C(O)C(CN2C(OC(=N2)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)=O)=C1 XAEFRVVUHDAALT-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- UHGSXJOONHIRAJ-UHFFFAOYSA-N 3-phenyl-1,3,4-oxadiazol-2-one Chemical compound O=C1OC=NN1C1=CC=CC=C1 UHGSXJOONHIRAJ-UHFFFAOYSA-N 0.000 claims 2
- MDTUWBLTRPRXBX-UHFFFAOYSA-N 1,2,4-triazol-3-one Chemical compound O=C1N=CN=N1 MDTUWBLTRPRXBX-UHFFFAOYSA-N 0.000 claims 1
- QKOWACXSXTXRKA-UHFFFAOYSA-N 3-[(5-chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-one Chemical compound OC1=CC=C(Cl)C=C1CN1C(=O)OC(C=2C=CC(=CC=2)C(F)(F)F)=N1 QKOWACXSXTXRKA-UHFFFAOYSA-N 0.000 claims 1
- 235000001729 chan in Nutrition 0.000 claims 1
- UOHGUABJZDIZEK-UHFFFAOYSA-N chembl218277 Chemical compound C1=C(Cl)C(N)=CC(O)=C1C(OC1=O)=NN1C1=CC=C(Cl)C(Cl)=C1 UOHGUABJZDIZEK-UHFFFAOYSA-N 0.000 claims 1
- NOTNQGDHIPDABL-UHFFFAOYSA-N n-[2-chloro-5-hydroxy-4-[[2-oxo-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-3-yl]methyl]phenyl]-2-(4-phenylpiperazin-1-yl)acetamide Chemical compound ClC=1C=C(CN2C(OC(=N2)C=2C=CC(=CC=2)C(F)(F)F)=O)C(O)=CC=1NC(=O)CN(CC1)CCN1C1=CC=CC=C1 NOTNQGDHIPDABL-UHFFFAOYSA-N 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 abstract description 13
- WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 112
- 239000000460 chlorine Substances 0.000 description 91
- 239000000243 solution Substances 0.000 description 79
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 66
- 229910001868 water Inorganic materials 0.000 description 46
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 44
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
- 229910052801 chlorine Inorganic materials 0.000 description 38
- 235000019439 ethyl acetate Nutrition 0.000 description 38
- 238000006243 chemical reaction Methods 0.000 description 37
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 35
- 239000012267 brine Substances 0.000 description 29
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 29
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- 239000012299 nitrogen atmosphere Substances 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 239000000047 product Substances 0.000 description 23
- 239000011541 reaction mixture Substances 0.000 description 23
- 108091006146 Channels Proteins 0.000 description 22
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 22
- 239000002904 solvent Substances 0.000 description 21
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 20
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
- 238000010992 reflux Methods 0.000 description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 19
- 102100023073 Calcium-activated potassium channel subunit alpha-1 Human genes 0.000 description 18
- 108010092555 Large-Conductance Calcium-Activated Potassium Channels Proteins 0.000 description 18
- 229910052727 yttrium Inorganic materials 0.000 description 17
- 238000002390 rotary evaporation Methods 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- 239000012074 organic phase Substances 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
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- 238000001953 recrystallisation Methods 0.000 description 12
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- 229920006395 saturated elastomer Polymers 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 239000002253 acid Substances 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 9
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- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 8
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 230000001404 mediated effect Effects 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 7
- 229910001424 calcium ion Inorganic materials 0.000 description 7
- 239000012141 concentrate Substances 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 230000003834 intracellular effect Effects 0.000 description 7
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- 150000001408 amides Chemical class 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 5
- 235000011054 acetic acid Nutrition 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 230000029936 alkylation Effects 0.000 description 5
- 238000005804 alkylation reaction Methods 0.000 description 5
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 5
- 210000000170 cell membrane Anatomy 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
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- 230000008020 evaporation Effects 0.000 description 5
- 229910052731 fluorine Inorganic materials 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
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- 150000002500 ions Chemical class 0.000 description 5
- 230000000302 ischemic effect Effects 0.000 description 5
- 201000007309 middle cerebral artery infarction Diseases 0.000 description 5
- 239000011591 potassium Substances 0.000 description 5
- 229910052700 potassium Inorganic materials 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
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- A61P25/08—Antiepileptics; Anticonvulsants
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/70—One oxygen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C07D233/76—Two oxygen atoms, e.g. hydantoin with substituted hydrocarbon radicals attached to the third ring carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/12—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D249/12—Oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D249/14—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
- C07D271/113—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Veterinary Medicine (AREA)
- Neurosurgery (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2298396P | 1996-07-31 | 1996-07-31 | |
| US60/022,983 | 1996-07-31 | ||
| PCT/US1997/014352 WO1998004135A1 (en) | 1996-07-31 | 1997-07-30 | Diphenyl heterocycles as potassium channel modulators |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2000516925A true JP2000516925A (ja) | 2000-12-19 |
| JP2000516925A5 JP2000516925A5 (enExample) | 2005-02-10 |
Family
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Family Applications (1)
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|---|---|---|---|
| JP10509180A Ceased JP2000516925A (ja) | 1996-07-31 | 1997-07-30 | カリウムチャンネル調節物質であるジフェニルヘテロ環化合物 |
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| EP (1) | EP0915856A4 (enExample) |
| JP (1) | JP2000516925A (enExample) |
| KR (1) | KR20000029735A (enExample) |
| CN (1) | CN1116287C (enExample) |
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| BR (1) | BR9710793A (enExample) |
| CZ (1) | CZ32199A3 (enExample) |
| HU (1) | HUP0000063A3 (enExample) |
| IL (1) | IL128308A (enExample) |
| NO (1) | NO990428L (enExample) |
| NZ (1) | NZ334403A (enExample) |
| PL (1) | PL331385A1 (enExample) |
| RU (1) | RU2175319C2 (enExample) |
| TW (1) | TW467902B (enExample) |
| WO (1) | WO1998004135A1 (enExample) |
| ZA (1) | ZA976554B (enExample) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009125870A1 (en) | 2008-04-09 | 2009-10-15 | Mitsubishi Tanabe Pharma Corporation | Pyrimidine, pyridine and triazine derivatives as maxi-k channel openers. |
| JP2022550640A (ja) * | 2019-10-07 | 2022-12-02 | ディー.イー.ショウ リサーチ,エルエルシー | Kv1.3カリウムシェーカーチャネル遮断薬としてのアリール複素環式化合物 |
| JP2022552445A (ja) * | 2019-10-07 | 2022-12-15 | ディー.イー.ショウ リサーチ,エルエルシー | Kv1.3カリウムシェーカーチャネル遮断薬としてのアリールメチレン芳香族化合物 |
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|---|---|---|---|---|
| TW467902B (en) * | 1996-07-31 | 2001-12-11 | Bristol Myers Squibb Co | Diphenyl heterocycles as potassium channel modulators |
| ID26909A (id) | 1998-01-29 | 2001-02-15 | Bristol Myers Squibb Co | Turunan-turunan 1,3,4-oksadiazolon |
| JP2002501926A (ja) * | 1998-01-29 | 2002-01-22 | ブリストル−マイヤーズ スクイブ カンパニー | ジアリール1、3、4−オキサジアゾロンのホスフェート誘導体 |
| EP1056730A4 (en) * | 1998-01-29 | 2003-01-02 | Bristol Myers Squibb Co | Diaryl-1,3,4-oxadiazolone benzoate |
| JP2003525199A (ja) * | 1998-01-29 | 2003-08-26 | ブリストル−マイヤーズ スクイブ カンパニー | ジアリール1,3,4−オキサジアゾロンアミノ酸誘導体 |
| DE19816882A1 (de) * | 1998-04-17 | 1999-10-21 | Boehringer Ingelheim Pharma | Triazolone mit neuroprotektiver Wirkung |
| US6919366B2 (en) * | 1998-05-22 | 2005-07-19 | Avanir Pharmaceuticals | Benzimidazole derivatives as modulators of IgE |
| US6911462B2 (en) * | 1998-05-22 | 2005-06-28 | Avanir Pharmaceuticals | Benzimidazole compounds for regulating IgE |
| SE9802937D0 (sv) * | 1998-09-01 | 1998-09-01 | Astra Pharma Prod | Novel compounds |
| US6632836B1 (en) | 1998-10-30 | 2003-10-14 | Merck & Co., Inc. | Carbocyclic potassium channel inhibitors |
| US6194458B1 (en) | 1998-10-30 | 2001-02-27 | Merck & Co., Inc. | Benzamide potassium channel inhibitors |
| US6303637B1 (en) * | 1998-10-30 | 2001-10-16 | Merck & Co., Inc. | Heterocyclic potassium channel inhibitors |
| US6297241B1 (en) | 1999-01-29 | 2001-10-02 | Bristol-Myers Squibb Company | Carbamate derivatives of diaryl 1,3,4-oxadiazolone |
| WO2000044745A1 (en) * | 1999-01-29 | 2000-08-03 | Bristol-Myers Squibb Company | Carbamate derivatives of diaryl 1,3,4-oxadiazolone |
| GB9915414D0 (en) * | 1999-07-01 | 1999-09-01 | Glaxo Group Ltd | Medical use |
| US20050153940A1 (en) * | 2000-01-26 | 2005-07-14 | Cedars-Sinai Medical Center | Method for using potassium channel activation for delivering a medicant to an abnormal brain region and/or a malignant tumor |
| US7018979B1 (en) | 2000-01-26 | 2006-03-28 | Cedars-Sinai Medical Center | Method for using potassium channel agonists for delivering a medicant to an abnormal brain region and/or a malignant tumor |
| GB2361003A (en) * | 2000-04-07 | 2001-10-10 | Astrazeneca Ab | Novel compounds |
| HUP0303559A3 (en) * | 2000-10-13 | 2006-02-28 | Bristol Myers Squibb Co | Selective maxi-k-potassium channel openers functional under conditions of high intracellular calcium concentration and uses thereof |
| DE10056344A1 (de) * | 2000-11-14 | 2002-05-16 | Degussa | n-Propylethoxysiloxane, Verfahren zu deren Herstellung und deren Verwendung |
| DE10058461A1 (de) * | 2000-11-24 | 2002-09-19 | Bayer Ag | Substituierte Cyclohexanderivate und ihre Verwendung |
| US6855829B2 (en) | 2001-02-20 | 2005-02-15 | Bristol-Myers Squibb Company | 3-fluoro-2-oxindole modulators of KCNQ potassium channels and use thereof in treating migraine and mechanistically related disease |
| ES2291455T3 (es) * | 2001-03-12 | 2008-03-01 | Avanir Pharmaceuticals | Compuestos de bencimidazol para modular ige e inhibir la proliferacion celular. |
| WO2002083111A2 (en) * | 2001-04-16 | 2002-10-24 | Tanabe Seiyaku Co., Ltd. | Imidazole, thiazole and oxazole derivatives and their use for the manufacture of a medicament for the treatment and/or prevention of pollakiuria or urinary incontinence |
| US7022480B1 (en) | 2001-10-11 | 2006-04-04 | The Regents Of The University Of California | Exons of the hSKCa3/KCNN3 gene |
| US7211561B2 (en) * | 2001-10-12 | 2007-05-01 | Cedars-Sinai Medical Center | Method for inducing selective cell death of malignant cells by activation of calcium-activated potassium channels (KCa) |
| US6613786B2 (en) | 2001-11-02 | 2003-09-02 | Bristol-Myers Squibb Company | Thiophenyl triazol-3-one derivatives as smooth muscle relaxants |
| US7846671B2 (en) * | 2002-01-28 | 2010-12-07 | Bristol-Myers Squibb Company | Methods of screening for agents that modulate the interaction of RGS and Gαq and urinary incontinence |
| TW200304820A (en) * | 2002-03-25 | 2003-10-16 | Avanir Pharmaceuticals | Use of benzimidazole analogs in the treatment of cell proliferation |
| WO2004024655A2 (en) | 2002-09-12 | 2004-03-25 | Avanir Pharmaceuticals | Phenyl-indole compounds for modulating ige and inhibiting cellular proliferation |
| TWI276631B (en) * | 2002-09-12 | 2007-03-21 | Avanir Pharmaceuticals | Phenyl-aza-benzimidazole compounds for modulating IgE and inhibiting cellular proliferation |
| TWI271402B (en) * | 2002-10-15 | 2007-01-21 | Tanabe Seiyaku Co | Large conductance calcium-activated K channel opener |
| TW200505441A (en) | 2003-03-24 | 2005-02-16 | Hoffmann La Roche | Non-nucleoside reverse transcriptase inhibitorsⅠ |
| RU2005134670A (ru) * | 2003-04-10 | 2006-06-10 | Аванир Фармасьютикалс (Us) | Производные имидазола для лечения аллергических и гиперпролиферативных нарушений |
| GB0315111D0 (en) * | 2003-06-27 | 2003-07-30 | Cancer Rec Tech Ltd | Substituted 5-membered ring compounds and their use |
| CA2533990A1 (en) * | 2003-08-08 | 2005-02-17 | Avanir Pharmaceuticals | Selective pharmacologic inhibition of protein trafficking and related methods of treating human diseases |
| AU2005230867A1 (en) * | 2004-03-26 | 2005-10-20 | Amphora Discovery Corporation | Certain triazole-based compounds, compositions, and uses thereof |
| CA2561718A1 (en) * | 2004-04-13 | 2005-10-27 | Icagen, Inc. | Polycyclic pyridines as potassium ion channel modulators |
| EP1773790B1 (en) * | 2004-07-27 | 2012-08-15 | F.Hoffmann-La Roche Ag | Benzyltriazolone compounds as non-nucleoside reverse transcriptase inhibitors |
| US8293778B2 (en) | 2004-07-27 | 2012-10-23 | Roche Palo Alto Llc | Heterocyclic antiviral compounds |
| CA2583177A1 (en) * | 2004-10-13 | 2006-04-27 | Ptc Therapeutics, Inc. | Compounds for nonsense suppression, and methods for their use |
| DK1817295T3 (da) | 2004-11-18 | 2013-02-18 | Synta Pharmaceuticals Corp | Triazolforbindelser, der modulerer HSP90-aktivitet |
| WO2006091542A2 (en) * | 2005-02-22 | 2006-08-31 | Cedars-Sinai Medical Center | Use of sildenafil, vardenafil and other 5-phosphodiesterase inhibitors to enhance permeability of the abnormal blood-brain barrier |
| JP5178515B2 (ja) | 2005-08-12 | 2013-04-10 | シンタ ファーマシューティカルズ コーポレーション | Hsp90活性を調節するピラゾール化合物 |
| US8629285B2 (en) * | 2005-08-18 | 2014-01-14 | Synta Pharmaceuticals Corp. | Imidazole compounds that modulate HSP90 activity |
| CA2618628C (en) * | 2005-08-18 | 2014-11-18 | Synta Pharmaceuticals Corp. | Triazole compounds that modulate hsp90 activity |
| DE102006024024A1 (de) * | 2006-05-23 | 2007-11-29 | Bayer Healthcare Aktiengesellschaft | Substituierte Arylimidazolone und -triazolone sowie ihre Verwendung |
| AU2007267852A1 (en) * | 2006-05-25 | 2007-12-06 | Synta Pharmaceuticals Corp. | Compounds that modulate Hsp90 activity and methods for identifying same |
| TW200804314A (en) | 2006-05-25 | 2008-01-16 | Synta Pharmaceuticals Corp | Triazole compounds that modulate Hsp90 activity |
| AU2007267847B2 (en) * | 2006-05-25 | 2012-04-12 | Synta Pharmaceuticals Corp. | Triazole compounds that modulate Hsp90 activity |
| JP5410965B2 (ja) * | 2006-05-25 | 2014-02-05 | シンタ ファーマシューティカルズ コーポレーション | Hsp90活性を調節するトリアゾール化合物 |
| EP2121640A1 (en) * | 2007-01-18 | 2009-11-25 | NeuroSearch AS | Novel semicarbazide and carbonylhydrazide derivatives useful as potassium channel modulators |
| BRPI0809617A2 (pt) | 2007-03-29 | 2014-09-16 | Hoffmann La Roche | Inibidores não-nucleosídicos da transcriptase reversa |
| WO2008135447A1 (en) * | 2007-05-03 | 2008-11-13 | Neurosearch A/S | Acetamide derivatives as potassium channel modulators |
| US20090281089A1 (en) * | 2008-04-11 | 2009-11-12 | Genentech, Inc. | Pyridyl inhibitors of hedgehog signalling |
| PE20091953A1 (es) * | 2008-05-08 | 2010-01-09 | Du Pont | Azoles sustituidos como fungicidas |
| US9205086B2 (en) | 2010-04-19 | 2015-12-08 | Synta Pharmaceuticals Corp. | Cancer therapy using a combination of a Hsp90 inhibitory compounds and a EGFR inhibitor |
| WO2013067165A1 (en) | 2011-11-02 | 2013-05-10 | Synta Pharmaceuticals Corp. | Combination therapy of hsp90 inhibitors with platinum-containing agents |
| US9439899B2 (en) | 2011-11-02 | 2016-09-13 | Synta Pharmaceuticals Corp. | Cancer therapy using a combination of HSP90 inhibitors with topoisomerase I inhibitors |
| US9402831B2 (en) | 2011-11-14 | 2016-08-02 | Synta Pharmaceutical Corp. | Combination therapy of HSP90 inhibitors with BRAF inhibitors |
| EP2822931B1 (en) | 2012-03-09 | 2017-05-03 | Inception 2, Inc. | Triazolone compounds and uses thereof |
| DK2935228T3 (en) | 2012-12-20 | 2017-10-30 | Inception 2 Inc | TRIAZOLONE COMPOUNDS AND APPLICATIONS THEREOF |
| JP2016529311A (ja) | 2013-09-06 | 2016-09-23 | インセプション 2、 インコーポレイテッド | トリアゾロン化合物類及びそれらの使用 |
| US10681909B2 (en) | 2014-08-29 | 2020-06-16 | Fmc Corporation | Herbicidal triazoles |
| CN104710379B (zh) * | 2015-03-09 | 2017-01-18 | 华南理工大学 | 一种bms‑191011的合成方法 |
| US12194026B2 (en) * | 2018-10-26 | 2025-01-14 | University Of South Florida | Drug for treating tinnitus |
| CN115504940A (zh) * | 2021-06-23 | 2022-12-23 | 中国科学院上海药物研究所 | 一种酰胺类化合物、其制备方法和制药用途 |
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| DE2940709A1 (de) * | 1979-10-08 | 1981-04-16 | Basf Ag, 6700 Ludwigshafen | Verfahren zur herstellung von in 1-stellung substituierten imidazolen |
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| US4966909A (en) * | 1989-12-20 | 1990-10-30 | Merrell Dow Pharmaceuticals | 4-benzyl-5-phenyl-2,4-dihydro-3H-1,2,4-triazol-3-ones and their use as anticonvulsants |
| US5331002A (en) * | 1990-04-19 | 1994-07-19 | Merrell Dow Pharmaceuticals Inc. | 5-aryl-4-alkyl-3H-1,2,4-triazole-3-thiones useful as memory enhancers |
| DE4015535A1 (de) * | 1990-05-15 | 1991-11-21 | Basf Ag | Verfahren zur herstellung von n-substituierten imidazolen |
| IL99372A0 (en) * | 1990-09-10 | 1992-08-18 | Ciba Geigy Ag | Azacyclic compounds |
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| US5234947A (en) * | 1991-11-07 | 1993-08-10 | New York University | Potassium channel activating compounds and methods of use thereof |
| DK28893D0 (da) * | 1993-03-15 | 1993-03-15 | Neurosearch As | Benzimidazole derivater, deres fremstilling og anvendelse |
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| TW467902B (en) * | 1996-07-31 | 2001-12-11 | Bristol Myers Squibb Co | Diphenyl heterocycles as potassium channel modulators |
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1997
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- 1997-07-23 ZA ZA976554A patent/ZA976554B/xx unknown
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- 1997-07-30 BR BR9710793A patent/BR9710793A/pt not_active Application Discontinuation
- 1997-07-30 RU RU99104179/04A patent/RU2175319C2/ru not_active IP Right Cessation
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- 1997-07-30 NZ NZ334403A patent/NZ334403A/xx unknown
- 1997-07-30 PL PL97331385A patent/PL331385A1/xx unknown
- 1997-07-30 WO PCT/US1997/014352 patent/WO1998004135A1/en not_active Ceased
- 1997-07-30 AU AU40679/97A patent/AU711736B2/en not_active Ceased
- 1997-07-30 EP EP97938316A patent/EP0915856A4/en not_active Withdrawn
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1998
- 1998-11-23 US US09/197,887 patent/US6077861A/en not_active Expired - Fee Related
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1999
- 1999-01-29 NO NO990428A patent/NO990428L/no unknown
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2000
- 2000-03-29 US US09/538,520 patent/US6271249B1/en not_active Expired - Lifetime
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009125870A1 (en) | 2008-04-09 | 2009-10-15 | Mitsubishi Tanabe Pharma Corporation | Pyrimidine, pyridine and triazine derivatives as maxi-k channel openers. |
| US8575338B2 (en) | 2008-04-09 | 2013-11-05 | Mitsubishi Tanabe Pharma Corporation | Pyrimidine, pyridine and triazine derivatives as maxi-K channel openers |
| JP2022550640A (ja) * | 2019-10-07 | 2022-12-02 | ディー.イー.ショウ リサーチ,エルエルシー | Kv1.3カリウムシェーカーチャネル遮断薬としてのアリール複素環式化合物 |
| JP2022552445A (ja) * | 2019-10-07 | 2022-12-15 | ディー.イー.ショウ リサーチ,エルエルシー | Kv1.3カリウムシェーカーチャネル遮断薬としてのアリールメチレン芳香族化合物 |
| JP7697954B2 (ja) | 2019-10-07 | 2025-06-24 | ディー.イー.ショウ リサーチ,エルエルシー | Kv1.3カリウムシェーカーチャネル遮断薬としてのアリールメチレン芳香族化合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| NO990428D0 (no) | 1999-01-29 |
| AU711736B2 (en) | 1999-10-21 |
| BR9710793A (pt) | 1999-08-17 |
| US6271249B1 (en) | 2001-08-07 |
| HUP0000063A3 (en) | 2001-04-28 |
| EP0915856A1 (en) | 1999-05-19 |
| NZ334403A (en) | 2000-09-29 |
| US6077861A (en) | 2000-06-20 |
| TW467902B (en) | 2001-12-11 |
| ZA976554B (en) | 1999-01-25 |
| KR20000029735A (ko) | 2000-05-25 |
| WO1998004135A1 (en) | 1998-02-05 |
| HUP0000063A2 (hu) | 2001-01-29 |
| NO990428L (no) | 1999-01-29 |
| EP0915856A4 (en) | 2006-04-12 |
| IL128308A (en) | 2004-09-27 |
| IL128308A0 (en) | 1999-11-30 |
| PL331385A1 (en) | 1999-07-05 |
| CN1226803A (zh) | 1999-08-25 |
| US5869509A (en) | 1999-02-09 |
| AU4067997A (en) | 1998-02-20 |
| CZ32199A3 (cs) | 1999-06-16 |
| CN1116287C (zh) | 2003-07-30 |
| AR008110A1 (es) | 1999-12-09 |
| RU2175319C2 (ru) | 2001-10-27 |
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