TW467902B - Diphenyl heterocycles as potassium channel modulators - Google Patents
Diphenyl heterocycles as potassium channel modulators Download PDFInfo
- Publication number
- TW467902B TW467902B TW086110006A TW86110006A TW467902B TW 467902 B TW467902 B TW 467902B TW 086110006 A TW086110006 A TW 086110006A TW 86110006 A TW86110006 A TW 86110006A TW 467902 B TW467902 B TW 467902B
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- TW
- Taiwan
- Prior art keywords
- phenyl
- chloro
- methyl
- trifluoromethyl
- hydroxyphenyl
- Prior art date
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- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 title claims description 15
- 235000010290 biphenyl Nutrition 0.000 title claims description 9
- 239000004305 biphenyl Substances 0.000 title claims description 5
- 102000004257 Potassium Channel Human genes 0.000 title description 12
- 108020001213 potassium channel Proteins 0.000 title description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 125
- -1 N-methylimidazol-2-yl Chemical group 0.000 claims abstract description 119
- 150000001875 compounds Chemical class 0.000 claims abstract description 101
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 43
- 239000001257 hydrogen Substances 0.000 claims abstract description 33
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 21
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims abstract description 20
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 15
- 150000002367 halogens Chemical class 0.000 claims abstract description 14
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 11
- CAAMSDWKXXPUJR-UHFFFAOYSA-N 3,5-dihydro-4H-imidazol-4-one Chemical group O=C1CNC=N1 CAAMSDWKXXPUJR-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims abstract description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 6
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract 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 abstract 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 142
- 238000011049 filling Methods 0.000 claims description 140
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 133
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 123
- 230000002079 cooperative effect Effects 0.000 claims description 64
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 36
- 239000000460 chlorine Substances 0.000 claims description 33
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 30
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
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- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 19
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- 150000003839 salts Chemical class 0.000 claims description 18
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 14
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 9
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- FFSJPOPLSWBGQY-UHFFFAOYSA-N triazol-4-one Chemical group O=C1C=NN=N1 FFSJPOPLSWBGQY-UHFFFAOYSA-N 0.000 claims description 8
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 7
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- 208000028867 ischemia Diseases 0.000 claims description 7
- 102000005702 Calcium-Activated Potassium Channels Human genes 0.000 claims description 6
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- WNWOTMKHOLCHRJ-UHFFFAOYSA-N 1,4-dihydrotriazol-5-one Chemical compound O=C1CN=NN1 WNWOTMKHOLCHRJ-UHFFFAOYSA-N 0.000 claims description 5
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- MUCRYNWJQNHDJH-OADIDDRXSA-N Ursonic acid Chemical compound C1CC(=O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C MUCRYNWJQNHDJH-OADIDDRXSA-N 0.000 claims description 5
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- HGUFODBRKLSHSI-UHFFFAOYSA-N 2,3,7,8-tetrachloro-dibenzo-p-dioxin Chemical compound O1C2=CC(Cl)=C(Cl)C=C2OC2=C1C=C(Cl)C(Cl)=C2 HGUFODBRKLSHSI-UHFFFAOYSA-N 0.000 claims description 4
- VTNQPKFIQCLBDU-UHFFFAOYSA-N Acetochlor Chemical compound CCOCN(C(=O)CCl)C1=C(C)C=CC=C1CC VTNQPKFIQCLBDU-UHFFFAOYSA-N 0.000 claims description 4
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- 239000011593 sulfur Chemical group 0.000 claims description 4
- ZZLCFHIKESPLTH-UHFFFAOYSA-N 4-Methylbiphenyl Chemical compound C1=CC(C)=CC=C1C1=CC=CC=C1 ZZLCFHIKESPLTH-UHFFFAOYSA-N 0.000 claims description 3
- CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-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
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 230000033228 biological regulation Effects 0.000 claims description 3
- 206010008118 cerebral infarction Diseases 0.000 claims description 3
- 125000004188 dichlorophenyl group Chemical group 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 3
- 230000004044 response Effects 0.000 claims description 3
- DMDPKUWXJUYFKO-UHFFFAOYSA-N 1,1'-biphenyl;hydrochloride Chemical compound Cl.C1=CC=CC=C1C1=CC=CC=C1 DMDPKUWXJUYFKO-UHFFFAOYSA-N 0.000 claims description 2
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 claims description 2
- VNRJGEMERJZKLQ-UHFFFAOYSA-N 2-piperazin-1-ylacetamide Chemical compound NC(=O)CN1CCNCC1 VNRJGEMERJZKLQ-UHFFFAOYSA-N 0.000 claims description 2
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical group OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 claims description 2
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 claims description 2
- 229940125904 compound 1 Drugs 0.000 claims description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 2
- 229910052722 tritium Inorganic materials 0.000 claims description 2
- VOYADQIFGGIKAT-UHFFFAOYSA-N 1,3-dibutyl-4-hydroxy-2,6-dioxopyrimidine-5-carboximidamide Chemical group CCCCn1c(O)c(C(N)=N)c(=O)n(CCCC)c1=O VOYADQIFGGIKAT-UHFFFAOYSA-N 0.000 claims 5
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 claims 4
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 claims 2
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 claims 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims 2
- 229940050176 methyl chloride Drugs 0.000 claims 2
- SOYANKPFXHJUCE-UHFFFAOYSA-N 1,4-dioxane-2-carbaldehyde Chemical group O=CC1COCCO1 SOYANKPFXHJUCE-UHFFFAOYSA-N 0.000 claims 1
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- MVZDAGSEWKTLMJ-UHFFFAOYSA-N 2-[(5-chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl]-1h-1,2,4-triazol-3-one Chemical compound OC1=CC=C(Cl)C=C1CN1C(=O)NC(C=2C=CC(=CC=2)C(F)(F)F)=N1 MVZDAGSEWKTLMJ-UHFFFAOYSA-N 0.000 claims 1
- VIXOOTOYIUQAMC-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazole Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=NN=CO1 VIXOOTOYIUQAMC-UHFFFAOYSA-N 0.000 claims 1
- SXHKHHXFAQRZOI-UHFFFAOYSA-N 2-fluorofluoren-1-one Chemical compound C1=CC=C2C3=CC=C(F)C(=O)C3=CC2=C1 SXHKHHXFAQRZOI-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
- MOZDKDIOPSPTBH-UHFFFAOYSA-N Benzyl parahydroxybenzoate Chemical compound C1=CC(O)=CC=C1C(=O)OCC1=CC=CC=C1 MOZDKDIOPSPTBH-UHFFFAOYSA-N 0.000 claims 1
- NTYSGXOLWDAQOS-UHFFFAOYSA-N ClC=1C(=NN=NC1)CC1=CC=CC=C1 Chemical compound ClC=1C(=NN=NC1)CC1=CC=CC=C1 NTYSGXOLWDAQOS-UHFFFAOYSA-N 0.000 claims 1
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- 125000000068 chlorophenyl group Chemical group 0.000 claims 1
- QYRFJLLXPINATB-UHFFFAOYSA-N hydron;2,4,5,6-tetrafluorobenzene-1,3-diamine;dichloride Chemical compound Cl.Cl.NC1=C(F)C(N)=C(F)C(F)=C1F QYRFJLLXPINATB-UHFFFAOYSA-N 0.000 claims 1
- 125000000468 ketone group Chemical group 0.000 claims 1
- HWYHDWGGACRVEH-UHFFFAOYSA-N n-methyl-n-(4-pyrrolidin-1-ylbut-2-ynyl)acetamide Chemical compound CC(=O)N(C)CC#CCN1CCCC1 HWYHDWGGACRVEH-UHFFFAOYSA-N 0.000 claims 1
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- 108010092555 Large-Conductance Calcium-Activated Potassium Channels Proteins 0.000 abstract description 14
- 102000016469 Large-Conductance Calcium-Activated Potassium Channels Human genes 0.000 abstract description 14
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- 239000008223 sterile water Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-O sulfonium Chemical compound [SH3+] RWSOTUBLDIXVET-UHFFFAOYSA-O 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000004685 tetrahydrates Chemical class 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- XDLNRRRJZOJTRW-UHFFFAOYSA-N thiohypochlorous acid Chemical compound ClS XDLNRRRJZOJTRW-UHFFFAOYSA-N 0.000 description 1
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- QPDUQKTYZRXRBC-UHFFFAOYSA-N triazole-4-thione Chemical compound S=C1C=NN=N1 QPDUQKTYZRXRBC-UHFFFAOYSA-N 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
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Classifications
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
-
- 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
-
- 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
Landscapes
- 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)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- 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)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
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| US2298396P | 1996-07-31 | 1996-07-31 |
Publications (1)
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| TW467902B true TW467902B (en) | 2001-12-11 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW086110006A TW467902B (en) | 1996-07-31 | 1997-07-15 | Diphenyl heterocycles as potassium channel modulators |
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| EP (1) | EP0915856A4 (enExample) |
| JP (1) | JP2000516925A (enExample) |
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| CN (1) | CN1116287C (enExample) |
| AR (1) | AR008110A1 (enExample) |
| AU (1) | AU711736B2 (enExample) |
| 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) |
Families Citing this family (70)
| Publication number | Priority date | Publication date | Assignee | Title |
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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) |
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| 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 |
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| US10681909B2 (en) | 2014-08-29 | 2020-06-16 | Fmc Corporation | Herbicidal triazoles |
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| 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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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1545646B1 (de) * | 1965-12-15 | 1969-09-18 | Boehringer Sohn Ingelheim | 1,3-Dimethyl-4-(2',4'-dichlorphenyl)-1,2,4-triazolon-(5) und Verfahren zu dessen Herstellung |
| CH583213A5 (enExample) * | 1973-05-21 | 1976-12-31 | Ciba Geigy Ag | |
| DE2940709A1 (de) * | 1979-10-08 | 1981-04-16 | Basf Ag, 6700 Ludwigshafen | Verfahren zur herstellung von in 1-stellung substituierten imidazolen |
| US5436252A (en) * | 1986-12-19 | 1995-07-25 | Merrell Dow Pharmaceuticals Inc. | 5-aryl-3H-1,2,4-triazol-3-ones and their use in the treatment of neurodegenerative disorders |
| CA2014537A1 (en) * | 1989-04-26 | 1990-10-26 | Yoshio Hayashi | 4-imidazoline derivatives |
| 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 |
| IT1251488B (it) * | 1991-09-17 | 1995-05-15 | Mini Ricerca Scient Tecnolog | Ossa(tia)diazol- e triazol-oni(tioni) ad attivita' acaricida ed insetticida |
| 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 |
| US5612363A (en) * | 1995-06-02 | 1997-03-18 | Berlex Laboratories, Inc. | N,N-di(aryl) cyclic urea derivatives as anti-coagulants |
| IL124364A (en) * | 1995-11-09 | 2001-08-08 | Synthelabo | 5-phenyl-3-(piperidin-4-yl)-1,3,4-oxadiazol -2(3h)- one derivatives, their preparation and pharmaceutical compositions comprising them |
| TW467902B (en) * | 1996-07-31 | 2001-12-11 | Bristol Myers Squibb Co | Diphenyl heterocycles as potassium channel modulators |
-
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
-
1998
- 1998-11-23 US US09/197,887 patent/US6077861A/en not_active Expired - Fee Related
-
1999
- 1999-01-29 NO NO990428A patent/NO990428L/no unknown
-
2000
- 2000-03-29 US US09/538,520 patent/US6271249B1/en not_active Expired - Lifetime
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 |
| 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 |
| RU2175319C2 (ru) | 2001-10-27 |
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