UA72244C2 - Aryl-substituted pyrazols, imidazols, oxazols, thiazols, pyrrols and their use - Google Patents
Aryl-substituted pyrazols, imidazols, oxazols, thiazols, pyrrols and their use Download PDFInfo
- Publication number
- UA72244C2 UA72244C2 UA2001107227A UA2001107227A UA72244C2 UA 72244 C2 UA72244 C2 UA 72244C2 UA 2001107227 A UA2001107227 A UA 2001107227A UA 2001107227 A UA2001107227 A UA 2001107227A UA 72244 C2 UA72244 C2 UA 72244C2
- Authority
- UA
- Ukraine
- Prior art keywords
- alkyl
- phenyl
- group
- hydrogen
- fluorophenoxy
- Prior art date
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- -1 thiazols Chemical class 0.000 title claims description 117
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical class C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 title claims description 30
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical class C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 title description 11
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical class C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 title description 6
- 125000002971 oxazolyl group Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 229
- 238000011282 treatment Methods 0.000 claims abstract description 40
- 150000003839 salts Chemical class 0.000 claims abstract description 29
- 208000002193 Pain Diseases 0.000 claims abstract description 22
- 229940002612 prodrug Drugs 0.000 claims abstract description 18
- 239000000651 prodrug Substances 0.000 claims abstract description 18
- 239000012453 solvate Substances 0.000 claims abstract description 16
- 230000002265 prevention Effects 0.000 claims abstract description 14
- 208000028867 ischemia Diseases 0.000 claims abstract description 11
- 230000003961 neuronal insult Effects 0.000 claims abstract description 7
- 230000000626 neurodegenerative effect Effects 0.000 claims abstract description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 176
- 125000000217 alkyl group Chemical group 0.000 claims description 121
- 229910052739 hydrogen Inorganic materials 0.000 claims description 106
- 239000001257 hydrogen Substances 0.000 claims description 94
- 150000002431 hydrogen Chemical class 0.000 claims description 77
- 239000000203 mixture Substances 0.000 claims description 53
- 125000003342 alkenyl group Chemical group 0.000 claims description 51
- 125000003118 aryl group Chemical group 0.000 claims description 50
- 125000000304 alkynyl group Chemical group 0.000 claims description 48
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 46
- 125000001072 heteroaryl group Chemical group 0.000 claims description 46
- 125000000623 heterocyclic group Chemical group 0.000 claims description 42
- 238000000034 method Methods 0.000 claims description 37
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 36
- 125000005843 halogen group Chemical group 0.000 claims description 34
- 125000001188 haloalkyl group Chemical group 0.000 claims description 30
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 29
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 29
- 125000003545 alkoxy group Chemical group 0.000 claims description 27
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 26
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 26
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 25
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 25
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 25
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 24
- 125000003282 alkyl amino group Chemical group 0.000 claims description 23
- 150000001408 amides Chemical class 0.000 claims description 22
- 125000004432 carbon atom Chemical group C* 0.000 claims description 22
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 21
- 125000004442 acylamino group Chemical group 0.000 claims description 20
- 125000004423 acyloxy group Chemical group 0.000 claims description 20
- 150000001356 alkyl thiols Chemical class 0.000 claims description 20
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 20
- 239000011734 sodium Substances 0.000 claims description 20
- 150000003573 thiols Chemical class 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 19
- 241001465754 Metazoa Species 0.000 claims description 18
- 108010052164 Sodium Channels Proteins 0.000 claims description 17
- 102000018674 Sodium Channels Human genes 0.000 claims description 17
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 17
- 229910052760 oxygen Inorganic materials 0.000 claims description 17
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- 125000004414 alkyl thio group Chemical group 0.000 claims description 16
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 16
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 16
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 15
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 14
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 14
- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 14
- 125000005015 aryl alkynyl group Chemical group 0.000 claims description 14
- 241000124008 Mammalia Species 0.000 claims description 13
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 13
- 230000015572 biosynthetic process Effects 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 229920006395 saturated elastomer Polymers 0.000 claims description 11
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
- 229910052783 alkali metal Inorganic materials 0.000 claims description 10
- 150000001340 alkali metals Chemical class 0.000 claims description 10
- 125000006323 alkenyl amino group Chemical group 0.000 claims description 10
- 208000035475 disorder Diseases 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 208000009205 Tinnitus Diseases 0.000 claims description 9
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 230000036407 pain Effects 0.000 claims description 9
- 231100000886 tinnitus Toxicity 0.000 claims description 9
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 8
- 125000005125 aryl alkyl amino carbonyl group Chemical group 0.000 claims description 7
- 125000004658 aryl carbonyl amino group Chemical group 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 7
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 6
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 6
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 5
- 125000005126 aryl alkyl carbonyl amino group Chemical group 0.000 claims description 5
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 5
- 125000004447 heteroarylalkenyl group Chemical group 0.000 claims description 5
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 5
- 125000005312 heteroarylalkynyl group Chemical group 0.000 claims description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
- 208000020925 Bipolar disease Diseases 0.000 claims description 4
- 208000028683 bipolar I disease Diseases 0.000 claims description 4
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000002287 radioligand Substances 0.000 claims description 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 3
- VAELWSLNTRVXQS-UHFFFAOYSA-N 1,3-oxazole-4-carboxamide Chemical compound NC(=O)C1=COC=N1 VAELWSLNTRVXQS-UHFFFAOYSA-N 0.000 claims description 3
- IIFSJFXZWQFZER-UHFFFAOYSA-N 5-methylsulfinyl-3-(4-phenoxyphenyl)pyrazole-1-carboxamide Chemical compound NC(=O)N1C(S(=O)C)=CC(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=N1 IIFSJFXZWQFZER-UHFFFAOYSA-N 0.000 claims description 3
- 206010003119 arrhythmia Diseases 0.000 claims description 3
- 230000006793 arrhythmia Effects 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 229910052698 phosphorus Inorganic materials 0.000 claims description 3
- 229940080818 propionamide Drugs 0.000 claims description 3
- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 claims description 3
- WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical compound OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 claims description 3
- 230000002285 radioactive effect Effects 0.000 claims description 3
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
- FTVGTSUFLFFSDY-UHFFFAOYSA-N 3-(4-phenoxyphenyl)pyrazole-1-carboxamide Chemical compound NC(=O)N1C=CC(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=N1 FTVGTSUFLFFSDY-UHFFFAOYSA-N 0.000 claims description 2
- OQKGTYKILXDSGY-UHFFFAOYSA-N 5-(4-phenoxyphenyl)-1h-pyrrole-2-carboxamide Chemical compound N1C(C(=O)N)=CC=C1C(C=C1)=CC=C1OC1=CC=CC=C1 OQKGTYKILXDSGY-UHFFFAOYSA-N 0.000 claims description 2
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 2
- 230000001684 chronic effect Effects 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 230000002981 neuropathic effect Effects 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 17
- 238000002690 local anesthesia Methods 0.000 claims 2
- 230000000116 mitigating effect Effects 0.000 claims 2
- 229910002091 carbon monoxide Inorganic materials 0.000 claims 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims 1
- 229910052759 nickel Inorganic materials 0.000 claims 1
- 229910052718 tin Inorganic materials 0.000 claims 1
- 229910052720 vanadium Inorganic materials 0.000 claims 1
- 229910052727 yttrium Inorganic materials 0.000 claims 1
- 239000001961 anticonvulsive agent Substances 0.000 abstract description 13
- 208000000094 Chronic Pain Diseases 0.000 abstract description 9
- 229940125681 anticonvulsant agent Drugs 0.000 abstract description 9
- 239000003416 antiarrhythmic agent Substances 0.000 abstract description 7
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 abstract description 6
- 239000003589 local anesthetic agent Substances 0.000 abstract description 6
- 229960005015 local anesthetics Drugs 0.000 abstract description 6
- 230000001154 acute effect Effects 0.000 abstract description 5
- 208000005298 acute pain Diseases 0.000 abstract description 4
- 230000003288 anthiarrhythmic effect Effects 0.000 abstract description 4
- 208000032131 Diabetic Neuropathies Diseases 0.000 abstract description 3
- 239000003795 chemical substances by application Substances 0.000 abstract description 3
- 230000003561 anti-manic effect Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 177
- 239000000243 solution Substances 0.000 description 112
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 87
- 235000019439 ethyl acetate Nutrition 0.000 description 70
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 61
- 239000007787 solid Substances 0.000 description 49
- 239000011541 reaction mixture Substances 0.000 description 42
- 239000010410 layer Substances 0.000 description 36
- 108091006146 Channels Proteins 0.000 description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
- 238000006243 chemical reaction Methods 0.000 description 25
- 238000010992 reflux Methods 0.000 description 25
- 238000004440 column chromatography Methods 0.000 description 23
- 230000000694 effects Effects 0.000 description 22
- 238000012360 testing method Methods 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 19
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 17
- 239000012044 organic layer Substances 0.000 description 17
- 230000002829 reductive effect Effects 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 16
- 239000003921 oil Substances 0.000 description 16
- 235000019198 oils Nutrition 0.000 description 16
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
- 239000007864 aqueous solution Substances 0.000 description 15
- 229910052938 sodium sulfate Inorganic materials 0.000 description 15
- 235000011152 sodium sulphate Nutrition 0.000 description 15
- 239000000047 product Substances 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 13
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 241000699670 Mus sp. Species 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 238000013504 emergency use authorization Methods 0.000 description 12
- 241000700159 Rattus Species 0.000 description 11
- 208000005923 otitis media with effusion Diseases 0.000 description 10
- 150000003217 pyrazoles Chemical class 0.000 description 10
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 9
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000005557 antagonist Substances 0.000 description 9
- 239000003195 sodium channel blocking agent Substances 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 150000002460 imidazoles Chemical class 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 7
- 150000002916 oxazoles Chemical class 0.000 description 7
- 239000000546 pharmaceutical excipient Substances 0.000 description 7
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- 150000003557 thiazoles Chemical class 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
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- 208000004454 Hyperalgesia Diseases 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 125000002252 acyl group Chemical group 0.000 description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 238000010828 elution Methods 0.000 description 6
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- 239000002244 precipitate Substances 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
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- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 5
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- 229920002472 Starch Polymers 0.000 description 5
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- 229910052794 bromium Inorganic materials 0.000 description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
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- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 4
- SGQSMRQYEPPNIA-UHFFFAOYSA-N 5-(4-phenoxyphenyl)-1h-pyrazole Chemical compound C=1C=C(C=2NN=CC=2)C=CC=1OC1=CC=CC=C1 SGQSMRQYEPPNIA-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
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- 206010026749 Mania Diseases 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
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- 239000002253 acid Substances 0.000 description 4
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- 239000002585 base Substances 0.000 description 4
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- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 4
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- 229910052740 iodine Inorganic materials 0.000 description 4
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
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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
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- 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
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- 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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- 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
- C07D235/18—Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2
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- C—CHEMISTRY; METALLURGY
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- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three 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
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Physical Education & Sports Medicine (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US12655399P | 1999-03-26 | 1999-03-26 | |
PCT/US2000/007944 WO2000057877A1 (en) | 1999-03-26 | 2000-03-24 | Aryl substituted pyrazoles, imidazoles, oxazoles, thiazoles and pyrroles, and the use thereof |
Publications (1)
Publication Number | Publication Date |
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UA72244C2 true UA72244C2 (en) | 2005-02-15 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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UA2001107227A UA72244C2 (en) | 1999-03-26 | 2000-03-24 | Aryl-substituted pyrazols, imidazols, oxazols, thiazols, pyrrols and their use |
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US (2) | US6414011B1 (no) |
EP (2) | EP2266960B1 (no) |
JP (2) | JP4832647B2 (no) |
KR (1) | KR20020015308A (no) |
CN (1) | CN1353605A (no) |
AR (1) | AR023171A1 (no) |
AT (1) | ATE467620T1 (no) |
AU (1) | AU782353B2 (no) |
BR (1) | BR0009322A (no) |
CA (1) | CA2368631A1 (no) |
CY (1) | CY1111163T1 (no) |
CZ (1) | CZ20013435A3 (no) |
DE (2) | DE60044395D1 (no) |
DK (1) | DK1173169T3 (no) |
ES (1) | ES2345921T3 (no) |
HU (1) | HUP0201314A3 (no) |
IL (1) | IL145508A0 (no) |
MX (1) | MXPA01009655A (no) |
NO (1) | NO20014659L (no) |
NZ (2) | NZ514756A (no) |
PL (1) | PL351439A1 (no) |
PT (1) | PT1173169E (no) |
RU (1) | RU2001129155A (no) |
TR (1) | TR200102790T2 (no) |
TW (1) | TW502019B (no) |
UA (1) | UA72244C2 (no) |
WO (1) | WO2000057877A1 (no) |
YU (1) | YU68701A (no) |
ZA (1) | ZA200108807B (no) |
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