RU2175319C2 - Дифенильные гетероциклические соединения, фармацевтическая композиция на их основе и способ лечения - Google Patents
Дифенильные гетероциклические соединения, фармацевтическая композиция на их основе и способ лечения Download PDFInfo
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- RU2175319C2 RU2175319C2 RU99104179/04A RU99104179A RU2175319C2 RU 2175319 C2 RU2175319 C2 RU 2175319C2 RU 99104179/04 A RU99104179/04 A RU 99104179/04A RU 99104179 A RU99104179 A RU 99104179A RU 2175319 C2 RU2175319 C2 RU 2175319C2
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- RU
- Russia
- Prior art keywords
- phenyl
- chloro
- trifluoromethyl
- hydroxyphenyl
- methyl
- Prior art date
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- -1 Diphenyl heterocyclic compounds Chemical class 0.000 title claims abstract description 96
- 238000000034 method Methods 0.000 title claims abstract description 56
- 238000011282 treatment Methods 0.000 title claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 12
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 title claims abstract description 10
- 235000010290 biphenyl Nutrition 0.000 title claims abstract description 8
- 239000004305 biphenyl Substances 0.000 title claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 95
- 108010045489 Calcium-Activated Potassium Channels Proteins 0.000 claims abstract description 9
- 102000005702 Calcium-Activated Potassium Channels Human genes 0.000 claims abstract description 9
- 239000012634 fragment Substances 0.000 claims abstract description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 81
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 74
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 72
- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
- 239000001257 hydrogen Substances 0.000 claims description 29
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 17
- 150000002431 hydrogen Chemical class 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- ZVTQYRVARPYRRE-UHFFFAOYSA-N oxadiazol-4-one Chemical group O=C1CON=N1 ZVTQYRVARPYRRE-UHFFFAOYSA-N 0.000 claims description 12
- 241000124008 Mammalia Species 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 208000035475 disorder Diseases 0.000 claims description 10
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical group CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 9
- 239000011575 calcium Substances 0.000 claims description 9
- 231100000252 nontoxic Toxicity 0.000 claims description 8
- 230000003000 nontoxic effect Effects 0.000 claims description 8
- 239000012453 solvate Substances 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- CAAMSDWKXXPUJR-UHFFFAOYSA-N 3,5-dihydro-4H-imidazol-4-one Chemical group O=C1CNC=N1 CAAMSDWKXXPUJR-UHFFFAOYSA-N 0.000 claims description 7
- 229910052791 calcium Inorganic materials 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 6
- IQXXEPZFOOTTBA-UHFFFAOYSA-N 1-benzylpiperazine Chemical group C=1C=CC=CC=1CN1CCNCC1 IQXXEPZFOOTTBA-UHFFFAOYSA-N 0.000 claims description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 5
- FFSJPOPLSWBGQY-UHFFFAOYSA-N triazol-4-one Chemical group O=C1C=NN=N1 FFSJPOPLSWBGQY-UHFFFAOYSA-N 0.000 claims description 5
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 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
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 3
- HWOFQIUXDAXPBK-UHFFFAOYSA-N 3-(5-chloro-2-hydroxyphenyl)-4-phenyl-1h-imidazol-2-one Chemical compound OC1=CC=C(Cl)C=C1N1C(=O)NC=C1C1=CC=CC=C1 HWOFQIUXDAXPBK-UHFFFAOYSA-N 0.000 claims description 3
- FZCVGNHGDUGCFF-UHFFFAOYSA-N 3-[(4-amino-3,5-dichloro-2-hydroxyphenyl)methyl]-5-(3,4-dichlorophenyl)-1,3,4-oxadiazol-2-one Chemical compound OC1=C(Cl)C(N)=C(Cl)C=C1CN1C(=O)OC(C=2C=C(Cl)C(Cl)=CC=2)=N1 FZCVGNHGDUGCFF-UHFFFAOYSA-N 0.000 claims description 3
- JBUNVWOOAFSLGG-UHFFFAOYSA-N 3-[(4-amino-5-chloro-2-hydroxyphenyl)methyl]-5-(3,4-dichlorophenyl)-1,3,4-oxadiazol-2-one Chemical compound C1=C(Cl)C(N)=CC(O)=C1CN1C(=O)OC(C=2C=C(Cl)C(Cl)=CC=2)=N1 JBUNVWOOAFSLGG-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
- KOTVBMSCYJKMGP-UHFFFAOYSA-N 3-[(5-chloro-2-hydroxyphenyl)methyl]-5-[2-chloro-5-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-one Chemical compound OC1=CC=C(Cl)C=C1CN1C(=O)OC(C=2C(=CC=C(C=2)C(F)(F)F)Cl)=N1 KOTVBMSCYJKMGP-UHFFFAOYSA-N 0.000 claims description 3
- 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 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
- BNYUSNMOFGIAGK-UHFFFAOYSA-N 3-[3,5-bis(trifluoromethyl)phenyl]-4-(5-chloro-2-hydroxyphenyl)-1h-1,2,4-triazol-5-one Chemical compound OC1=CC=C(Cl)C=C1N1C(=O)NN=C1C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 BNYUSNMOFGIAGK-UHFFFAOYSA-N 0.000 claims description 3
- RXTYWBNEUUKLPB-UHFFFAOYSA-N 3-[[5-chloro-2-hydroxy-4-(2-oxo-1h-imidazol-3-yl)phenyl]methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-one Chemical compound OC1=CC(N2C(NC=C2)=O)=C(Cl)C=C1CN(C(O1)=O)N=C1C1=CC=C(C(F)(F)F)C=C1 RXTYWBNEUUKLPB-UHFFFAOYSA-N 0.000 claims description 3
- 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 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
- 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 3
- IQMKPOSFUJNDSH-UHFFFAOYSA-N 4-chloro-2-[5-[4-(trifluoromethyl)phenyl]imidazol-1-yl]phenol Chemical compound OC1=CC=C(Cl)C=C1N1C(C=2C=CC(=CC=2)C(F)(F)F)=CN=C1 IQMKPOSFUJNDSH-UHFFFAOYSA-N 0.000 claims description 3
- 201000006474 Brain Ischemia Diseases 0.000 claims description 3
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 3
- 206010008118 cerebral infarction Diseases 0.000 claims description 3
- SUHHBZVHXILLQP-UHFFFAOYSA-N chembl328604 Chemical compound OC1=CC=C(Cl)C=C1C1=NC=CN1C1=CC=C(C(F)(F)F)C=C1 SUHHBZVHXILLQP-UHFFFAOYSA-N 0.000 claims description 3
- 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 description 3
- BOFYHEINUMXVSB-UHFFFAOYSA-N 2-(4-benzylpiperazin-1-yl)-n-[2-chloro-5-hydroxy-4-[[2-oxo-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-3-yl]methyl]phenyl]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)CCN1CC1=CC=CC=C1 BOFYHEINUMXVSB-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 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
- LPLFGQAKNUMAQT-UHFFFAOYSA-N 2-(5-chloro-2-hydroxyphenyl)-5-[3-chloro-4-(trifluoromethyl)phenyl]-1h-1,2,4-triazol-3-one Chemical compound OC1=NC(C=2C=C(Cl)C(=CC=2)C(F)(F)F)=NN1C1=CC(Cl)=CC=C1O LPLFGQAKNUMAQT-UHFFFAOYSA-N 0.000 claims description 2
- DXNXQWQRUUJIHA-UHFFFAOYSA-N 2-[3-amino-5-[4-(trifluoromethyl)phenyl]-1,2,4-triazol-4-yl]-4-chlorophenol Chemical compound C=1C(Cl)=CC=C(O)C=1N1C(N)=NN=C1C1=CC=C(C(F)(F)F)C=C1 DXNXQWQRUUJIHA-UHFFFAOYSA-N 0.000 claims description 2
- DQBYAGGQGYYKDW-UHFFFAOYSA-N 3-[(4-amino-5-chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-one Chemical compound C1=C(Cl)C(N)=CC(O)=C1CN1C(=O)OC(C=2C=CC(=CC=2)C(F)(F)F)=N1 DQBYAGGQGYYKDW-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
- OOGYXUJUUXZJKH-UHFFFAOYSA-N 3-[(5-chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazole-2-thione Chemical compound OC1=CC=C(Cl)C=C1CN1C(=S)OC(C=2C=CC(=CC=2)C(F)(F)F)=N1 OOGYXUJUUXZJKH-UHFFFAOYSA-N 0.000 claims description 2
- 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 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
- SJUIMOBXGMTIDW-UHFFFAOYSA-N 4-chloro-2-[2-[4-(trifluoromethyl)phenyl]imidazol-1-yl]phenol Chemical compound OC1=CC=C(Cl)C=C1N1C(C=2C=CC(=CC=2)C(F)(F)F)=NC=C1 SJUIMOBXGMTIDW-UHFFFAOYSA-N 0.000 claims description 2
- HOSIECOQVIJMOH-UHFFFAOYSA-N 5-(4-amino-5-chloro-2-hydroxyphenyl)-3-phenyl-1,3,4-oxadiazol-2-one Chemical compound C1=C(Cl)C(N)=CC(O)=C1C(OC1=O)=NN1C1=CC=CC=C1 HOSIECOQVIJMOH-UHFFFAOYSA-N 0.000 claims description 2
- KZJHVTHAPNKQRE-UHFFFAOYSA-N 5-[2,4-bis(trifluoromethyl)phenyl]-2-(5-chloro-2-hydroxyphenyl)-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)C(F)(F)F)=N1 KZJHVTHAPNKQRE-UHFFFAOYSA-N 0.000 claims description 2
- BTIBUAQSOJYXGU-UHFFFAOYSA-N 5-[3,5-bis(trifluoromethyl)phenyl]-2-(5-chloro-2-hydroxyphenyl)-1h-1,2,4-triazol-3-one Chemical compound OC1=CC=C(Cl)C=C1N1C(=O)NC(C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)=N1 BTIBUAQSOJYXGU-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 2
- 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 description 2
- 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 2
- AWIUQNHZMIVVPC-UHFFFAOYSA-N chembl221809 Chemical compound C1=C(Cl)C(N)=CC(O)=C1C(OC1=O)=NN1C1=CC=C(C(F)(F)F)C=C1 AWIUQNHZMIVVPC-UHFFFAOYSA-N 0.000 claims description 2
- QIDPZRGUHWOOQN-UHFFFAOYSA-N chembl327279 Chemical compound OC1=CC=C(Cl)C=C1C1=NNC(=O)N1C1=CC=C(C(F)(F)F)C=C1 QIDPZRGUHWOOQN-UHFFFAOYSA-N 0.000 claims description 2
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 2
- 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 2
- ZHMLTARLBSXVPP-UHFFFAOYSA-N n-[2-chloro-5-hydroxy-4-[[2-oxo-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-3-yl]methyl]phenyl]-2-(4-methylpiperazin-1-yl)acetamide Chemical compound C1CN(C)CCN1CC(=O)NC(C(=C1)Cl)=CC(O)=C1CN1C(=O)OC(C=2C=CC(=CC=2)C(F)(F)F)=N1 ZHMLTARLBSXVPP-UHFFFAOYSA-N 0.000 claims description 2
- 230000009529 traumatic brain injury Effects 0.000 claims description 2
- GHBAXDKJRNXYNL-UHFFFAOYSA-N 3-methyl-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-one Chemical compound O1C(=O)N(C)N=C1C1=CC=C(C(F)(F)F)C=C1 GHBAXDKJRNXYNL-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
- VDQXPESZCDZQGU-UHFFFAOYSA-N 2-(4-amino-5-chloro-2-hydroxyphenyl)-5-[4-(trifluoromethyl)phenyl]-1h-1,2,4-triazol-3-one Chemical compound C1=C(Cl)C(N)=CC(O)=C1N1C(=O)N=C(C=2C=CC(=CC=2)C(F)(F)F)N1 VDQXPESZCDZQGU-UHFFFAOYSA-N 0.000 claims 1
- WZELXJBMMZFDDU-UHFFFAOYSA-N Imidazol-2-one Chemical group O=C1N=CC=N1 WZELXJBMMZFDDU-UHFFFAOYSA-N 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 13
- 208000028867 ischemia Diseases 0.000 abstract description 8
- 239000000126 substance Substances 0.000 abstract description 8
- 210000002569 neuron Anatomy 0.000 abstract description 6
- 150000002391 heterocyclic compounds Chemical class 0.000 abstract 1
- 230000007721 medicinal effect Effects 0.000 abstract 1
- 238000011321 prophylaxis Methods 0.000 abstract 1
- 238000004458 analytical method Methods 0.000 description 138
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 137
- 239000000460 chlorine Substances 0.000 description 78
- 239000000243 solution Substances 0.000 description 71
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 70
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 51
- 235000019439 ethyl acetate Nutrition 0.000 description 47
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 41
- 229910052801 chlorine Inorganic materials 0.000 description 39
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
- 239000012267 brine Substances 0.000 description 34
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 34
- 108091006146 Channels Proteins 0.000 description 32
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 26
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 25
- 239000011541 reaction mixture Substances 0.000 description 25
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 23
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
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Images
Classifications
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- 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
-
- 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
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- 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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- 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
- C07D233/64—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
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- 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
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- 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
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- 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
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- 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
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- 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
Landscapes
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
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- 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)
- Plural Heterocyclic Compounds (AREA)
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| US2298396P | 1996-07-31 | 1996-07-31 | |
| US60/022,983 | 1996-07-31 |
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| RU99104179A RU99104179A (ru) | 2001-02-20 |
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| TW (1) | TW467902B (enExample) |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2394028C2 (ru) * | 2004-07-27 | 2010-07-10 | Ф.Хоффманн-Ля Рош Аг | Производные бензилтриазолона в качестве ненуклеозидных ингибиторов обратной транскриптазы |
| RU2460724C2 (ru) * | 2006-05-23 | 2012-09-10 | Байер Шеринг Фарма Акциенгезельшафт | Замещенные арилимидазолоны и -триазолоны в качестве ингибиторов рецепторов вазопрессина |
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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 |
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| 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. |
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| 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) |
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| TW200505441A (en) | 2003-03-24 | 2005-02-16 | Hoffmann La Roche | Non-nucleoside reverse transcriptase inhibitorsⅠ |
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1997
- 1997-07-15 TW TW086110006A patent/TW467902B/zh not_active IP Right Cessation
- 1997-07-23 ZA ZA976554A patent/ZA976554B/xx unknown
- 1997-07-30 IL IL12830897A patent/IL128308A/en not_active IP Right Cessation
- 1997-07-30 US US08/902,684 patent/US5869509A/en not_active Expired - Fee Related
- 1997-07-30 HU HU0000063A patent/HUP0000063A3/hu unknown
- 1997-07-30 JP JP10509180A patent/JP2000516925A/ja not_active Ceased
- 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
- 1997-07-30 CZ CZ99321A patent/CZ32199A3/cs unknown
- 1997-07-30 AR ARP970103438A patent/AR008110A1/es not_active Application Discontinuation
- 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
- 1997-07-30 CN CN97196891A patent/CN1116287C/zh not_active Expired - Fee Related
- 1997-07-30 KR KR1019997000839A patent/KR20000029735A/ko not_active Ceased
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- 1998-11-23 US US09/197,887 patent/US6077861A/en not_active Expired - Fee Related
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- 1999-01-29 NO NO990428A patent/NO990428L/no unknown
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| EP0533276A1 (en) * | 1991-09-17 | 1993-03-24 | Ministero Dell' Universita' E Della Ricerca Scientifica E Tecnologica | Oxa(thia)diazol - and triazol-ones (thiones) having a miticide and insecticide activity |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| RU2394028C2 (ru) * | 2004-07-27 | 2010-07-10 | Ф.Хоффманн-Ля Рош Аг | Производные бензилтриазолона в качестве ненуклеозидных ингибиторов обратной транскриптазы |
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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 |
| JP2000516925A (ja) | 2000-12-19 |
| 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 |
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