AU2013303993A1 - Tris(hetero)arylpyrazoles and use thereof - Google Patents
Tris(hetero)arylpyrazoles and use thereof Download PDFInfo
- Publication number
- AU2013303993A1 AU2013303993A1 AU2013303993A AU2013303993A AU2013303993A1 AU 2013303993 A1 AU2013303993 A1 AU 2013303993A1 AU 2013303993 A AU2013303993 A AU 2013303993A AU 2013303993 A AU2013303993 A AU 2013303993A AU 2013303993 A1 AU2013303993 A1 AU 2013303993A1
- Authority
- AU
- Australia
- Prior art keywords
- stands
- alkyl
- alkoxy
- substituted
- halogen
- 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.)
- Abandoned
Links
- 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 6
- 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 99
- 238000011282 treatment Methods 0.000 claims abstract description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 25
- 201000010099 disease Diseases 0.000 claims abstract description 24
- 241001465754 Metazoa Species 0.000 claims abstract description 10
- 238000004519 manufacturing process Methods 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims description 264
- 150000002367 halogens Chemical group 0.000 claims description 153
- 229910052736 halogen Inorganic materials 0.000 claims description 147
- 125000001424 substituent group Chemical group 0.000 claims description 132
- 239000000460 chlorine Substances 0.000 claims description 125
- 229910052799 carbon Inorganic materials 0.000 claims description 110
- 150000003839 salts Chemical class 0.000 claims description 108
- 239000012453 solvate Substances 0.000 claims description 101
- -1 amino, hydroxy, methoxy, methyl Chemical group 0.000 claims description 96
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 92
- 229910052757 nitrogen Inorganic materials 0.000 claims description 74
- 125000004076 pyridyl group Chemical group 0.000 claims description 74
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 72
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 67
- 125000003545 alkoxy group Chemical group 0.000 claims description 64
- 125000000217 alkyl group Chemical group 0.000 claims description 62
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 61
- 229910052739 hydrogen Inorganic materials 0.000 claims description 56
- 239000001257 hydrogen Substances 0.000 claims description 56
- 125000001153 fluoro group Chemical group F* 0.000 claims description 48
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 47
- 150000002431 hydrogen Chemical class 0.000 claims description 46
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 40
- 125000000229 (C1-C4)alkoxy group Chemical group 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 29
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 27
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 26
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 26
- 125000000623 heterocyclic group Chemical group 0.000 claims description 24
- 229910052801 chlorine Inorganic materials 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
- 208000015181 infectious disease Diseases 0.000 claims description 21
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 21
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 20
- 239000011737 fluorine Substances 0.000 claims description 20
- 125000003282 alkyl amino group Chemical group 0.000 claims description 17
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 16
- 150000001204 N-oxides Chemical class 0.000 claims description 16
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 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
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 230000002265 prevention Effects 0.000 claims description 9
- 241000282414 Homo sapiens Species 0.000 claims description 8
- 241001430294 unidentified retrovirus Species 0.000 claims description 7
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- 241000282412 Homo Species 0.000 claims description 6
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 4
- 230000003612 virological effect Effects 0.000 claims description 4
- 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
- 230000006806 disease prevention Effects 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 239000002671 adjuvant Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 16
- 238000002360 preparation method Methods 0.000 abstract description 8
- 230000001177 retroviral effect Effects 0.000 abstract description 4
- 238000011321 prophylaxis Methods 0.000 abstract 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 222
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 67
- 238000005160 1H NMR spectroscopy Methods 0.000 description 64
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- 239000000243 solution Substances 0.000 description 60
- 230000015572 biosynthetic process Effects 0.000 description 58
- 238000003786 synthesis reaction Methods 0.000 description 58
- 239000000126 substance Substances 0.000 description 49
- 239000002904 solvent Substances 0.000 description 47
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 46
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 45
- 239000000047 product Substances 0.000 description 44
- 239000011541 reaction mixture Substances 0.000 description 43
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 37
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 35
- 210000004027 cell Anatomy 0.000 description 35
- 238000012360 testing method Methods 0.000 description 33
- 238000002953 preparative HPLC Methods 0.000 description 30
- 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
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- 229940093499 ethyl acetate Drugs 0.000 description 20
- 235000019439 ethyl acetate Nutrition 0.000 description 20
- 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 18
- 239000003112 inhibitor Substances 0.000 description 17
- 150000003254 radicals Chemical class 0.000 description 17
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 16
- 239000000543 intermediate Substances 0.000 description 16
- 239000000203 mixture Substances 0.000 description 16
- 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
- 239000000725 suspension Substances 0.000 description 13
- 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 12
- KOPFEFZSAMLEHK-UHFFFAOYSA-N 1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1C=CNN=1 KOPFEFZSAMLEHK-UHFFFAOYSA-N 0.000 description 12
- 229940060037 fluorine Drugs 0.000 description 12
- 235000019000 fluorine Nutrition 0.000 description 12
- 208000030507 AIDS Diseases 0.000 description 11
- 101710122864 Major tegument protein Proteins 0.000 description 11
- 101710148592 PTS system fructose-like EIIA component Proteins 0.000 description 11
- 101710169713 PTS system fructose-specific EIIA component Proteins 0.000 description 11
- 101710199973 Tail tube protein Proteins 0.000 description 11
- 229940079593 drug Drugs 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
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 10
- 238000005481 NMR spectroscopy Methods 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 10
- 239000012091 fetal bovine serum Substances 0.000 description 10
- 238000012986 modification Methods 0.000 description 10
- 230000004048 modification Effects 0.000 description 10
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- 125000006519 CCH3 Chemical group 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- 239000003480 eluent Substances 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- RUKDVLFJSMVBLV-UHFFFAOYSA-N 5-iodo-1h-pyrazole Chemical compound IC1=CC=NN1 RUKDVLFJSMVBLV-UHFFFAOYSA-N 0.000 description 8
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 8
- 241000713772 Human immunodeficiency virus 1 Species 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
- 229930182816 L-glutamine Natural products 0.000 description 8
- 239000012980 RPMI-1640 medium Substances 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 238000003556 assay Methods 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
- 208000031886 HIV Infections Diseases 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
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 230000007062 hydrolysis Effects 0.000 description 7
- 238000006460 hydrolysis reaction Methods 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- CSDTZUBPSYWZDX-UHFFFAOYSA-N n-pentyl nitrite Chemical compound CCCCCON=O CSDTZUBPSYWZDX-UHFFFAOYSA-N 0.000 description 7
- 150000003217 pyrazoles Chemical class 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
- TYRICULVJRGSTL-UHFFFAOYSA-N 4-bromo-2,3-dihydroisoindol-1-one Chemical compound BrC1=CC=CC2=C1CNC2=O TYRICULVJRGSTL-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 125000004494 ethyl ester group Chemical group 0.000 description 6
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 6
- 125000005842 heteroatom Chemical group 0.000 description 6
- 239000013067 intermediate product Substances 0.000 description 6
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 6
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- DWCDDXINAZHRLK-UHFFFAOYSA-N (3-chloro-4-fluorophenyl)hydrazine;hydrochloride Chemical compound [Cl-].[NH3+]NC1=CC=C(F)C(Cl)=C1 DWCDDXINAZHRLK-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical class CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 5
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- 230000036436 anti-hiv Effects 0.000 description 5
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 5
- NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 5
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 5
- 231100000673 dose–response relationship Toxicity 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 5
- 239000002777 nucleoside Substances 0.000 description 5
- 150000003833 nucleoside derivatives Chemical class 0.000 description 5
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- 235000011056 potassium acetate Nutrition 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- 229940086542 triethylamine Drugs 0.000 description 5
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 5
- 239000003643 water by type Substances 0.000 description 5
- ZNGINKJHQQQORD-UHFFFAOYSA-N 2-trimethylsilylethanol Chemical compound C[Si](C)(C)CCO ZNGINKJHQQQORD-UHFFFAOYSA-N 0.000 description 4
- 102100034349 Integrase Human genes 0.000 description 4
- 108060001084 Luciferase Proteins 0.000 description 4
- 239000005089 Luciferase Substances 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 241001494479 Pecora Species 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
- 210000003494 hepatocyte Anatomy 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 4
- YLGXILFCIXHCMC-JHGZEJCSSA-N methyl cellulose Chemical compound COC1C(OC)C(OC)C(COC)O[C@H]1O[C@H]1C(OC)C(OC)C(OC)OC1COC YLGXILFCIXHCMC-JHGZEJCSSA-N 0.000 description 4
- 230000003228 microsomal effect Effects 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 238000000825 ultraviolet detection Methods 0.000 description 4
- UIQNFNIICOIPOM-UHFFFAOYSA-N 1-phenyl-2-(trifluoromethoxy)ethanone Chemical compound FC(F)(F)OCC(=O)C1=CC=CC=C1 UIQNFNIICOIPOM-UHFFFAOYSA-N 0.000 description 3
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 241000283707 Capra Species 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 208000037357 HIV infectious disease Diseases 0.000 description 3
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 3
- 102000000588 Interleukin-2 Human genes 0.000 description 3
- 108010002350 Interleukin-2 Proteins 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 229940122313 Nucleoside reverse transcriptase inhibitor Drugs 0.000 description 3
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 3
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 3
- 241000700157 Rattus norvegicus Species 0.000 description 3
- PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- SWLVFNYSXGMGBS-UHFFFAOYSA-N ammonium bromide Chemical class [NH4+].[Br-] SWLVFNYSXGMGBS-UHFFFAOYSA-N 0.000 description 3
- 230000000798 anti-retroviral effect Effects 0.000 description 3
- 230000000840 anti-viral effect Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
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- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 3
- 235000011167 hydrochloric acid Nutrition 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 229940124524 integrase inhibitor Drugs 0.000 description 3
- 239000002850 integrase inhibitor Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
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- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 229960004742 raltegravir Drugs 0.000 description 1
- CZFFBEXEKNGXKS-UHFFFAOYSA-N raltegravir Chemical compound O1C(C)=NN=C1C(=O)NC(C)(C)C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1C CZFFBEXEKNGXKS-UHFFFAOYSA-N 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 230000007420 reactivation Effects 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 102200009479 rs141772938 Human genes 0.000 description 1
- 102200131341 rs267607614 Human genes 0.000 description 1
- 102220099575 rs878853725 Human genes 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 231100000747 viability assay Toxicity 0.000 description 1
- 238000003026 viability measurement method Methods 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
-
- C—CHEMISTRY; METALLURGY
- 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
- C07D401/02—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
- 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
-
- C—CHEMISTRY; METALLURGY
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102012016908.6A DE102012016908A1 (de) | 2012-08-17 | 2012-08-17 | Tris-(Hetero)Aryl-Pyrazole und ihre Verwendung |
| DE102012016908.6 | 2012-08-17 | ||
| PCT/EP2013/067201 WO2014027112A1 (de) | 2012-08-17 | 2013-08-16 | Tris-(hetero)aryl-pyrazole und ihre verwendung |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2013303993A1 true AU2013303993A1 (en) | 2015-03-12 |
Family
ID=48986151
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2013303993A Abandoned AU2013303993A1 (en) | 2012-08-17 | 2013-08-16 | Tris(hetero)arylpyrazoles and use thereof |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US9249148B2 (https=) |
| EP (1) | EP2885300A1 (https=) |
| JP (1) | JP2015524835A (https=) |
| KR (1) | KR20150042841A (https=) |
| CN (1) | CN104684913B (https=) |
| AP (1) | AP2015008325A0 (https=) |
| AR (1) | AR092145A1 (https=) |
| AU (1) | AU2013303993A1 (https=) |
| BR (1) | BR112015003115A2 (https=) |
| CA (1) | CA2881997A1 (https=) |
| CL (1) | CL2015000362A1 (https=) |
| CU (1) | CU20150015A7 (https=) |
| DE (1) | DE102012016908A1 (https=) |
| EA (1) | EA201500232A1 (https=) |
| HK (1) | HK1212327A1 (https=) |
| IL (1) | IL237298A0 (https=) |
| MA (1) | MA37928A1 (https=) |
| MX (1) | MX2015002046A (https=) |
| NZ (1) | NZ704727A (https=) |
| PE (1) | PE20150869A1 (https=) |
| PH (1) | PH12015500322B1 (https=) |
| SG (1) | SG11201501183VA (https=) |
| TN (1) | TN2015000045A1 (https=) |
| TW (1) | TW201412720A (https=) |
| UA (1) | UA112488C2 (https=) |
| WO (1) | WO2014027112A1 (https=) |
| ZA (1) | ZA201501078B (https=) |
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 |
| MX2020010433A (es) * | 2018-04-04 | 2020-10-28 | Japan Tobacco Inc | Compuestos de pirazol sustituidos con heteroarilo y uso farmaceutico de los mismos. |
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| Publication number | Priority date | Publication date | Assignee | Title |
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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 |
| AU2002363250A1 (en) | 2001-11-01 | 2003-05-12 | 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 |
| KR20050083761A (ko) | 2002-12-02 | 2005-08-26 | 후지사와 야꾸힝 고교 가부시키가이샤 | Ｃｏｘ－ｉ저해제로서 유용한 피라졸 유도체 |
| KR20050096956A (ko) | 2003-02-07 | 2005-10-06 | 다이이찌 세이야꾸 가부시기가이샤 | 피라졸 유도체 |
| ATE440085T1 (de) | 2004-02-20 | 2009-09-15 | Astrazeneca Ab | 3-substituierte 1,5-diphenylpyrazolderivate, die sich als cb1-modulatoren eignen |
| PT1732892E (pt) | 2004-03-26 | 2008-12-22 | Hoffmann La Roche | Tetra-hidrocarbazóis e os seus derivados |
| US20080064682A1 (en) | 2004-07-01 | 2008-03-13 | 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 |
| US8703805B2 (en) | 2005-06-27 | 2014-04-22 | Exelixis Patent Company Llc | Modulators of LXR |
| 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 |
| NZ566036A (en) | 2005-09-13 | 2010-06-25 | Janssen Pharmaceutica Nv | 2-Aniline-4-aryl substituted thiazole derivatives that modulate the alpha7 nicotinic receptor |
| EP1957076A2 (en) | 2005-11-29 | 2008-08-20 | Merck & Co., Inc. | Thiazole derivatives as cxcr3 receptor modulators |
| JP2009518298A (ja) | 2005-12-01 | 2009-05-07 | バイエル ヘルスケア リミティド ライアビリティ カンパニー | 癌治療に有用な尿素化合物 |
| US20100256357A1 (en) | 2006-08-09 | 2010-10-07 | Agouron Pharmaceuticals, Inc. | Heterocycles useful as inhibitors of carbonic anhydrase |
| 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 |
| JP5498392B2 (ja) | 2007-11-30 | 2014-05-21 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | １，５−ジヒドロ−ピラゾロ［３，４−ｄ］ピリミジン−４−オン誘導体及びｃｎｓ障害の治療のためのｐｄｅ９ａモジュレーターとしてのそれらの使用 |
| 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 |
| DE102008015033A1 (de) | 2008-03-17 | 2009-09-24 | Aicuris Gmbh & Co. Kg | Substituierte (Pyrazolyl-carbonyl)imidazolidinone und ihre Verwendung |
| DE102008015032A1 (de) | 2008-03-17 | 2009-09-24 | Aicuris Gmbh & Co. Kg | Substituierte Pyrazolamide 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 |
| BR112012005960A2 (pt) | 2009-09-17 | 2016-03-15 | Janssen Pharmaceutica Nv | n-fenil-1-(4-piridinil)-1h-pirazol-3-aminas substituídas |
| KR20130049766A (ko) | 2009-11-13 | 2013-05-14 | 메르크 세로노 에스. 에이. | 트리사이클릭 피라졸 아민 유도체 |
| US20130210809A1 (en) | 2010-07-14 | 2013-08-15 | Christelle Boléa | Novel 2-amino-4-pyrazolyl-thiazole derivatives and their use as allosteric modulators of metabotropic glutamate receptors |
| EP2632461A4 (en) | 2010-10-29 | 2014-04-02 | Merck Sharp & Dohme | 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 |
-
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 NZ NZ704727A patent/NZ704727A/en not_active IP Right Cessation
- 2013-08-16 MX MX2015002046A patent/MX2015002046A/es unknown
- 2013-08-16 EA EA201500232A patent/EA201500232A1/ru unknown
- 2013-08-16 JP JP2015527004A patent/JP2015524835A/ja not_active Ceased
- 2013-08-16 MA MA37928A patent/MA37928A1/fr unknown
- 2013-08-16 KR KR20157006414A patent/KR20150042841A/ko not_active Withdrawn
- 2013-08-16 SG SG11201501183VA patent/SG11201501183VA/en unknown
- 2013-08-16 HK HK15112600.0A patent/HK1212327A1/xx unknown
- 2013-08-16 AU AU2013303993A patent/AU2013303993A1/en not_active Abandoned
- 2013-08-16 BR BR112015003115A patent/BR112015003115A2/pt not_active IP Right Cessation
- 2013-08-16 WO PCT/EP2013/067201 patent/WO2014027112A1/de not_active Ceased
- 2013-08-16 UA UAA201502210A patent/UA112488C2/uk unknown
- 2013-08-16 CN CN201380044128.1A patent/CN104684913B/zh not_active Expired - Fee Related
- 2013-08-16 PE PE2015000171A patent/PE20150869A1/es not_active Application Discontinuation
- 2013-08-16 AP AP2015008325A patent/AP2015008325A0/xx unknown
- 2013-08-16 US US14/422,191 patent/US9249148B2/en not_active Expired - Fee Related
- 2013-08-16 CA CA2881997A patent/CA2881997A1/en not_active Abandoned
- 2013-08-16 TW TW102129567A patent/TW201412720A/zh unknown
- 2013-08-16 EP EP13750087.2A patent/EP2885300A1/de not_active Withdrawn
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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
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- 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 |
|---|---|
| PH12015500322B1 (en) | 2019-03-25 |
| UA112488C2 (uk) | 2016-09-12 |
| MA37928A1 (fr) | 2017-11-30 |
| CN104684913B (zh) | 2016-11-23 |
| CA2881997A1 (en) | 2014-02-20 |
| DE102012016908A1 (de) | 2014-02-20 |
| MX2015002046A (es) | 2015-06-05 |
| JP2015524835A (ja) | 2015-08-27 |
| EA201500232A1 (ru) | 2015-07-30 |
| TN2015000045A1 (en) | 2016-06-29 |
| EP2885300A1 (de) | 2015-06-24 |
| AP2015008325A0 (en) | 2015-03-31 |
| PE20150869A1 (es) | 2015-05-27 |
| WO2014027112A1 (de) | 2014-02-20 |
| CU20150015A7 (es) | 2015-11-27 |
| ZA201501078B (en) | 2017-11-29 |
| CN104684913A (zh) | 2015-06-03 |
| CL2015000362A1 (es) | 2015-07-10 |
| NZ704727A (en) | 2016-07-29 |
| TW201412720A (zh) | 2014-04-01 |
| AR092145A1 (es) | 2015-03-25 |
| US20150203500A1 (en) | 2015-07-23 |
| US9249148B2 (en) | 2016-02-02 |
| HK1212327A1 (en) | 2016-06-10 |
| IL237298A0 (en) | 2015-04-30 |
| PH12015500322A1 (en) | 2015-03-30 |
| SG11201501183VA (en) | 2015-05-28 |
| BR112015003115A2 (pt) | 2017-07-04 |
| KR20150042841A (ko) | 2015-04-21 |
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