KR20150042841A - 트리스(헤테로)아릴피라졸 및 그의 용도 - Google Patents
트리스(헤테로)아릴피라졸 및 그의 용도 Download PDFInfo
- Publication number
- KR20150042841A KR20150042841A KR20157006414A KR20157006414A KR20150042841A KR 20150042841 A KR20150042841 A KR 20150042841A KR 20157006414 A KR20157006414 A KR 20157006414A KR 20157006414 A KR20157006414 A KR 20157006414A KR 20150042841 A KR20150042841 A KR 20150042841A
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- South Korea
- Prior art keywords
- alkyl
- alkoxy
- substituted
- halogen
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- JUHMHPOXZAYYJP-UHFFFAOYSA-N ethyl 5-amino-1-(4-methylphenyl)sulfonylpyrazole-4-carboxylate Chemical class NC1=C(C(=O)OCC)C=NN1S(=O)(=O)C1=CC=C(C)C=C1 JUHMHPOXZAYYJP-UHFFFAOYSA-N 0.000 title abstract description 5
- 239000007983 Tris buffer Substances 0.000 title abstract 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 39
- 238000011282 treatment Methods 0.000 claims abstract description 35
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 23
- 238000002360 preparation method Methods 0.000 claims abstract description 12
- 241001465754 Metazoa Species 0.000 claims abstract description 9
- 230000008569 process Effects 0.000 claims abstract description 5
- 230000006806 disease prevention Effects 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 250
- 150000002367 halogens Chemical group 0.000 claims description 149
- 229910052736 halogen Inorganic materials 0.000 claims description 143
- -1 amino, hydroxy, methoxy, methyl Chemical group 0.000 claims description 117
- 125000001424 substituent group Chemical group 0.000 claims description 110
- 229910052799 carbon Inorganic materials 0.000 claims description 108
- 239000012453 solvate Substances 0.000 claims description 99
- 150000003839 salts Chemical class 0.000 claims description 88
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 85
- 125000003545 alkoxy group Chemical group 0.000 claims description 78
- 125000004076 pyridyl group Chemical group 0.000 claims description 74
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 73
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 70
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 68
- 125000000217 alkyl group Chemical group 0.000 claims description 66
- 229910052757 nitrogen Inorganic materials 0.000 claims description 66
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 65
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 57
- 229910052739 hydrogen Inorganic materials 0.000 claims description 56
- 239000001257 hydrogen Substances 0.000 claims description 56
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 56
- 125000001153 fluoro group Chemical group F* 0.000 claims description 51
- 150000002431 hydrogen Chemical class 0.000 claims description 40
- 150000001721 carbon Chemical group 0.000 claims description 38
- 241000700605 Viruses Species 0.000 claims description 34
- 229910052731 fluorine Inorganic materials 0.000 claims description 30
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 27
- 150000001204 N-oxides Chemical class 0.000 claims description 23
- 208000015181 infectious disease Diseases 0.000 claims description 23
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 23
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 23
- 239000000460 chlorine Substances 0.000 claims description 22
- 229910052801 chlorine Inorganic materials 0.000 claims description 22
- 201000010099 disease Diseases 0.000 claims description 22
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 21
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 21
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 21
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 19
- 239000011737 fluorine Substances 0.000 claims description 18
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 16
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 16
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 15
- 125000003282 alkyl amino group Chemical group 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 11
- 229910052794 bromium Inorganic materials 0.000 claims description 11
- 241000282414 Homo sapiens Species 0.000 claims description 8
- 235000012054 meals Nutrition 0.000 claims description 7
- 230000002265 prevention Effects 0.000 claims description 7
- 241001430294 unidentified retrovirus Species 0.000 claims description 7
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- 230000003612 virological effect Effects 0.000 claims description 6
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 5
- 238000011321 prophylaxis Methods 0.000 claims description 5
- 230000000840 anti-viral effect Effects 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 231100000252 nontoxic Toxicity 0.000 claims description 3
- 230000003000 nontoxic effect Effects 0.000 claims description 3
- 229910052720 vanadium Inorganic materials 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 abstract description 10
- 230000001177 retroviral effect Effects 0.000 abstract description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 216
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 66
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- 239000000243 solution Substances 0.000 description 60
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 58
- 230000015572 biosynthetic process Effects 0.000 description 57
- 238000003786 synthesis reaction Methods 0.000 description 56
- 239000002904 solvent Substances 0.000 description 45
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 42
- 239000011541 reaction mixture Substances 0.000 description 41
- 210000004027 cell Anatomy 0.000 description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 35
- 238000012360 testing method Methods 0.000 description 35
- 238000000746 purification Methods 0.000 description 34
- 238000004128 high performance liquid chromatography Methods 0.000 description 29
- 239000000126 substance Substances 0.000 description 26
- 239000012043 crude product Substances 0.000 description 25
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000000047 product Substances 0.000 description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- 239000000463 material Substances 0.000 description 19
- 239000012074 organic phase Substances 0.000 description 19
- 229910052938 sodium sulfate Inorganic materials 0.000 description 19
- 235000011152 sodium sulphate Nutrition 0.000 description 19
- 241000725303 Human immunodeficiency virus Species 0.000 description 17
- 206010057190 Respiratory tract infections Diseases 0.000 description 17
- 239000000203 mixture Substances 0.000 description 17
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 16
- 239000003112 inhibitor Substances 0.000 description 16
- 239000000543 intermediate Substances 0.000 description 16
- 102100034349 Integrase Human genes 0.000 description 15
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- PGAJYUDRKAPMPA-UHFFFAOYSA-N trimethylsilyl n-ethylcarbamate Chemical compound CCNC(=O)O[Si](C)(C)C PGAJYUDRKAPMPA-UHFFFAOYSA-N 0.000 description 15
- JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical compound NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 14
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 14
- 150000003217 pyrazoles Chemical class 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- 208000030507 AIDS Diseases 0.000 description 12
- KOPFEFZSAMLEHK-UHFFFAOYSA-N 1h-pyrazole-5-carboxylic acid Chemical class OC(=O)C=1C=CNN=1 KOPFEFZSAMLEHK-UHFFFAOYSA-N 0.000 description 11
- 235000019000 fluorine Nutrition 0.000 description 11
- XHZWFUVEKDDQPF-UHFFFAOYSA-N 5-bromo-1h-pyrazole Chemical compound BrC1=CC=NN1 XHZWFUVEKDDQPF-UHFFFAOYSA-N 0.000 description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 239000003480 eluent Substances 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
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- 238000011534 incubation Methods 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- RUKDVLFJSMVBLV-UHFFFAOYSA-N 5-iodo-1h-pyrazole Chemical compound IC1=CC=NN1 RUKDVLFJSMVBLV-UHFFFAOYSA-N 0.000 description 8
- 208000031886 HIV Infections Diseases 0.000 description 8
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 8
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 8
- 239000012980 RPMI-1640 medium Substances 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 238000012986 modification Methods 0.000 description 8
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- 150000003254 radicals Chemical class 0.000 description 8
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 7
- 235000019253 formic acid Nutrition 0.000 description 7
- 230000007062 hydrolysis Effects 0.000 description 7
- 238000006460 hydrolysis reaction Methods 0.000 description 7
- RJSAWRPVTKYGIZ-UHFFFAOYSA-N pyridin-3-ylhydrazine;hydrochloride Chemical compound Cl.NNC1=CC=CN=C1 RJSAWRPVTKYGIZ-UHFFFAOYSA-N 0.000 description 7
- 238000001953 recrystallisation Methods 0.000 description 7
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 6
- TYRICULVJRGSTL-UHFFFAOYSA-N 4-bromo-2,3-dihydroisoindol-1-one Chemical compound BrC1=CC=CC2=C1CNC2=O TYRICULVJRGSTL-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 6
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- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
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- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Public Health (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Tropical Medicine & Parasitology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102012016908.6 | 2012-08-17 | ||
| DE102012016908.6A DE102012016908A1 (de) | 2012-08-17 | 2012-08-17 | Tris-(Hetero)Aryl-Pyrazole und ihre Verwendung |
| PCT/EP2013/067201 WO2014027112A1 (de) | 2012-08-17 | 2013-08-16 | Tris-(hetero)aryl-pyrazole und ihre verwendung |
Publications (1)
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|---|---|
| KR20150042841A true KR20150042841A (ko) | 2015-04-21 |
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| WO (1) | WO2014027112A1 (enExample) |
| ZA (1) | ZA201501078B (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102012016908A1 (de) | 2012-08-17 | 2014-02-20 | Aicuris Gmbh & Co. Kg | Tris-(Hetero)Aryl-Pyrazole und ihre Verwendung |
| AR099428A1 (es) * | 2014-02-14 | 2016-07-20 | Aicuris Gmbh & Co Kg | Combinaciones de principios activos farmacéuticos con compuestos basados en tri(hetero)aril pirazoles |
| EP3263567A1 (en) * | 2016-07-01 | 2018-01-03 | AiCuris Anti-infective Cures GmbH | Carboxamide-substituted pyrazoles and tri(hetero)aryl-pyrazoles for use in methods of treating and / or preventing cardiovascular diseases and / or comorbidities thereof |
| WO2019194207A1 (ja) * | 2018-04-04 | 2019-10-10 | 日本たばこ産業株式会社 | ヘテロアリールで置換されたピラゾール化合物及びその医薬用途 |
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| PH27357A (en) | 1989-09-22 | 1993-06-21 | Fujisawa Pharmaceutical Co | Pyrazole derivatives and pharmaceutical compositions comprising the same |
| IL104311A (en) | 1992-02-05 | 1997-07-13 | Fujisawa Pharmaceutical Co | Pyrazole derivatives, processes for the preparation thereof and pharmaceutical compositions containing the same |
| FR2692575B1 (fr) | 1992-06-23 | 1995-06-30 | Sanofi Elf | Nouveaux derives du pyrazole, procede pour leur preparation et compositions pharmaceutiques les contenant. |
| US6277847B1 (en) | 1999-04-02 | 2001-08-21 | Fmc Corporation | Herbicidal isoindolinonyl-and 3,4-dihydroisoquinolonyl-substituted heterocycles |
| WO2003037274A2 (en) | 2001-11-01 | 2003-05-08 | Icagen, Inc. | Pyrazole-amides and-sulfonamides |
| US6649638B1 (en) * | 2002-08-14 | 2003-11-18 | Ppd Discovery, Inc. | Prenylation inhibitors and methods of their synthesis and use |
| CA2505945A1 (en) | 2002-12-02 | 2004-06-17 | Fujisawa Pharmaceutical Co., Ltd. | Pyrazole derivatives useful as cox-i inhibitors |
| KR20050096956A (ko) | 2003-02-07 | 2005-10-06 | 다이이찌 세이야꾸 가부시기가이샤 | 피라졸 유도체 |
| EP1718617B1 (en) | 2004-02-20 | 2009-08-19 | AstraZeneca AB | 3-substituted 1,5-diphenylpyrazole derivatives useful as cb1 modulators |
| AU2005225524B2 (en) | 2004-03-26 | 2007-11-22 | F. Hoffmann-La Roche Ag | Tetrahydrocarbazoles and derivatives |
| EP1762568A1 (en) | 2004-07-01 | 2007-03-14 | Daiichi Pharmaceutical Co., Ltd. | Pyrazole derivatives |
| GB0417910D0 (en) | 2004-08-11 | 2004-09-15 | Novartis Ag | Organic compounds |
| DE102004054666A1 (de) | 2004-11-12 | 2006-05-18 | Bayer Cropscience Gmbh | Substituierte Pyrazol-3-carboxamide, Verfahren zur Herstellung und Verwendung als Herbizide und Pflanzenwachstumsregulatoren |
| WO2007002559A1 (en) | 2005-06-27 | 2007-01-04 | Exelixis, Inc. | Pyrazole based lxr modulators |
| EP1743637A1 (en) | 2005-07-15 | 2007-01-17 | Laboratorios Del Dr. Esteve, S.A. | Use of substituted pyrazole compounds and combinations thereof for the treatment of the metabolic syndrome |
| WO2007009701A2 (en) | 2005-07-15 | 2007-01-25 | Laboratorios Del Dr. Esteve, S.A. | Use of substituted pyrazole compounds and combinations thereof for the treatment of the metabolic syndrome |
| GB0516661D0 (en) | 2005-08-13 | 2005-09-21 | Astrazeneca Ab | Therapeutic agents |
| JP5341516B2 (ja) | 2005-09-13 | 2013-11-13 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ２−アニリン−４−アリール置換チアゾール誘導体 |
| WO2007064553A2 (en) | 2005-11-29 | 2007-06-07 | Merck & Co., Inc. | Thiazole derivatives as cxcr3 receptor modulators |
| US20110195110A1 (en) | 2005-12-01 | 2011-08-11 | Roger Smith | Urea compounds useful in the treatment of cancer |
| JP2010500336A (ja) | 2006-08-09 | 2010-01-07 | ファイザー・プロダクツ・インク | 炭酸脱水酵素阻害剤として有用な複素環 |
| US8188113B2 (en) | 2006-09-14 | 2012-05-29 | Deciphera Pharmaceuticals, Inc. | Dihydropyridopyrimidinyl, dihydronaphthyidinyl and related compounds useful as kinase inhibitors for the treatment of proliferative diseases |
| GB0625196D0 (en) | 2006-12-18 | 2007-01-24 | 7Tm Pharma As | Modulators of cannabinoid receptor |
| JP4994295B2 (ja) * | 2007-04-20 | 2012-08-08 | 田辺三菱製薬株式会社 | 医薬組成物 |
| US8648085B2 (en) | 2007-11-30 | 2014-02-11 | Boehringer Ingelheim International Gmbh | 1, 5-dihydro-pyrazolo (3, 4-D) pyrimidin-4-one derivatives and their use as PDE9A mudulators for the treatment of CNS disorders |
| AR069650A1 (es) | 2007-12-14 | 2010-02-10 | Actelion Pharmaceuticals Ltd | Derivados de aminopirazol como agonistas no peptidicos del receptor alx humano |
| AU2009216825A1 (en) | 2008-02-18 | 2009-08-27 | F. Hoffmann-La Roche Ag | 4, 5-dihydro-oxazol-2-yl amine derivatives |
| DE102008015032A1 (de) | 2008-03-17 | 2009-09-24 | Aicuris Gmbh & Co. Kg | Substituierte Pyrazolamide und ihre Verwendung |
| DE102008015033A1 (de) | 2008-03-17 | 2009-09-24 | Aicuris Gmbh & Co. Kg | Substituierte (Pyrazolyl-carbonyl)imidazolidinone und ihre Verwendung |
| TW201041888A (en) * | 2009-05-06 | 2010-12-01 | Plexxikon Inc | Compounds and methods for kinase modulation, and indications therefor |
| TW201100441A (en) * | 2009-06-01 | 2011-01-01 | Osi Pharm Inc | Amino pyrimidine anticancer compounds |
| WO2011033018A1 (en) | 2009-09-17 | 2011-03-24 | Janssen Pharmaceutica Nv | Substituted n-phenyl-1-(4-pyridinyl)-1h-pyrazol-3-amines |
| ES2607952T3 (es) | 2009-11-13 | 2017-04-04 | Merck Serono S.A. | Derivados tricíclicos de Pirazol Amina |
| WO2012009009A2 (en) * | 2010-07-14 | 2012-01-19 | Addex Pharma S.A. | Novel 2-amino-4-pyrazolyl-thiazole derivatives and their use as allosteric modulators of metabotropic glutamate receptors |
| WO2012058133A1 (en) * | 2010-10-29 | 2012-05-03 | Merck Sharp & Dohme Corp. | Isoindolinone pde10 inhibitors |
| US9938269B2 (en) | 2011-06-30 | 2018-04-10 | Abbvie Inc. | Inhibitor compounds of phosphodiesterase type 10A |
| DE102012016908A1 (de) | 2012-08-17 | 2014-02-20 | Aicuris Gmbh & Co. Kg | Tris-(Hetero)Aryl-Pyrazole und ihre Verwendung |
| AR099428A1 (es) | 2014-02-14 | 2016-07-20 | Aicuris Gmbh & Co Kg | Combinaciones de principios activos farmacéuticos con compuestos basados en tri(hetero)aril pirazoles |
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2012
- 2012-08-17 DE DE102012016908.6A patent/DE102012016908A1/de not_active Withdrawn
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2013
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- 2013-08-16 PE PE2015000171A patent/PE20150869A1/es not_active Application Discontinuation
- 2013-08-16 BR BR112015003115A patent/BR112015003115A2/pt not_active IP Right Cessation
- 2013-08-16 NZ NZ704727A patent/NZ704727A/en not_active IP Right Cessation
- 2013-08-16 US US14/422,191 patent/US9249148B2/en not_active Expired - Fee Related
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- 2013-08-16 EA EA201500232A patent/EA201500232A1/ru unknown
- 2013-08-16 EP EP13750087.2A patent/EP2885300A1/de not_active Withdrawn
- 2013-08-16 MX MX2015002046A patent/MX2015002046A/es unknown
- 2013-08-16 TW TW102129567A patent/TW201412720A/zh unknown
- 2013-08-16 JP JP2015527004A patent/JP2015524835A/ja not_active Ceased
- 2013-08-16 AU AU2013303993A patent/AU2013303993A1/en not_active Abandoned
- 2013-08-16 CN CN201380044128.1A patent/CN104684913B/zh not_active Expired - Fee Related
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- 2013-08-16 WO PCT/EP2013/067201 patent/WO2014027112A1/de not_active Ceased
- 2013-08-16 MA MA37928A patent/MA37928A1/fr unknown
- 2013-08-16 CA CA2881997A patent/CA2881997A1/en not_active Abandoned
- 2013-08-16 KR KR20157006414A patent/KR20150042841A/ko not_active Withdrawn
- 2013-08-16 UA UAA201502210A patent/UA112488C2/uk unknown
-
2015
- 2015-02-12 TN TNP2015000045A patent/TN2015000045A1/fr unknown
- 2015-02-13 PH PH12015500322A patent/PH12015500322B1/en unknown
- 2015-02-16 ZA ZA2015/01078A patent/ZA201501078B/en unknown
- 2015-02-16 CL CL2015000362A patent/CL2015000362A1/es unknown
- 2015-02-17 IL IL237298A patent/IL237298A0/en unknown
- 2015-02-17 CU CUP2015000015A patent/CU20150015A7/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US9249148B2 (en) | 2016-02-02 |
| ZA201501078B (en) | 2017-11-29 |
| BR112015003115A2 (pt) | 2017-07-04 |
| DE102012016908A1 (de) | 2014-02-20 |
| CU20150015A7 (es) | 2015-11-27 |
| AP2015008325A0 (en) | 2015-03-31 |
| AR092145A1 (es) | 2015-03-25 |
| CL2015000362A1 (es) | 2015-07-10 |
| EA201500232A1 (ru) | 2015-07-30 |
| PH12015500322B1 (en) | 2019-03-25 |
| MA37928A1 (fr) | 2017-11-30 |
| UA112488C2 (uk) | 2016-09-12 |
| TW201412720A (zh) | 2014-04-01 |
| AU2013303993A1 (en) | 2015-03-12 |
| CN104684913B (zh) | 2016-11-23 |
| TN2015000045A1 (en) | 2016-06-29 |
| WO2014027112A1 (de) | 2014-02-20 |
| PH12015500322A1 (en) | 2015-03-30 |
| CN104684913A (zh) | 2015-06-03 |
| HK1212327A1 (en) | 2016-06-10 |
| MX2015002046A (es) | 2015-06-05 |
| PE20150869A1 (es) | 2015-05-27 |
| IL237298A0 (en) | 2015-04-30 |
| CA2881997A1 (en) | 2014-02-20 |
| NZ704727A (en) | 2016-07-29 |
| US20150203500A1 (en) | 2015-07-23 |
| JP2015524835A (ja) | 2015-08-27 |
| SG11201501183VA (en) | 2015-05-28 |
| EP2885300A1 (de) | 2015-06-24 |
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