NO317423B1 - Indolderivater, farmasoytisk preparat, middel for a inhibere integrase, antiviralt middel, anti-HIV middel samt anti-HIV medisinsk blanding. - Google Patents
Indolderivater, farmasoytisk preparat, middel for a inhibere integrase, antiviralt middel, anti-HIV middel samt anti-HIV medisinsk blanding. Download PDFInfo
- Publication number
- NO317423B1 NO317423B1 NO20004787A NO20004787A NO317423B1 NO 317423 B1 NO317423 B1 NO 317423B1 NO 20004787 A NO20004787 A NO 20004787A NO 20004787 A NO20004787 A NO 20004787A NO 317423 B1 NO317423 B1 NO 317423B1
- Authority
- NO
- Norway
- Prior art keywords
- optionally substituted
- halogen
- compound
- hydrogen
- hydroxy
- Prior art date
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- 239000000203 mixture Substances 0.000 title claims description 74
- 102100034343 Integrase Human genes 0.000 title claims description 11
- 150000002475 indoles Chemical class 0.000 title claims description 11
- 108010061833 Integrases Proteins 0.000 title claims description 10
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 title claims description 8
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 8
- 230000002401 inhibitory effect Effects 0.000 title claims description 7
- 239000003443 antiviral agent Substances 0.000 title claims description 6
- 230000036436 anti-hiv Effects 0.000 title claims description 3
- 229940124411 anti-hiv antiviral agent Drugs 0.000 title claims description 3
- 229940054051 antipsychotic indole derivative Drugs 0.000 title description 7
- 229940121357 antivirals Drugs 0.000 title description 2
- 239000003795 chemical substances by application Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 165
- -1 azido, phenyl Chemical group 0.000 claims description 74
- 150000002367 halogens Chemical group 0.000 claims description 49
- 229910052736 halogen Inorganic materials 0.000 claims description 47
- 229910052739 hydrogen Inorganic materials 0.000 claims description 42
- 239000001257 hydrogen Substances 0.000 claims description 40
- 239000000460 chlorine Substances 0.000 claims description 38
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 15
- 150000002431 hydrogen Chemical class 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 125000002883 imidazolyl group Chemical group 0.000 claims description 9
- 125000001425 triazolyl group Chemical group 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000000335 thiazolyl group Chemical group 0.000 claims description 7
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 5
- 229940124524 integrase inhibitor Drugs 0.000 claims description 5
- 239000002850 integrase inhibitor Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 4
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000005400 pyridylcarbonyl group Chemical group N1=C(C=CC=C1)C(=O)* 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 234
- 235000019439 ethyl acetate Nutrition 0.000 description 84
- 239000000243 solution Substances 0.000 description 81
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 78
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 76
- 238000000921 elemental analysis Methods 0.000 description 60
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 44
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 41
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
- 239000013078 crystal Substances 0.000 description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- 238000000354 decomposition reaction Methods 0.000 description 29
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 239000002904 solvent Substances 0.000 description 26
- 238000003756 stirring Methods 0.000 description 26
- 239000011541 reaction mixture Substances 0.000 description 24
- 238000002844 melting Methods 0.000 description 23
- 230000008018 melting Effects 0.000 description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 20
- UWOTWBZMCAQHON-UHFFFAOYSA-N benzhydryl 3-acetyl-1-(benzenesulfonyl)indole-5-carboxylate Chemical compound C1=C2C(C(=O)C)=CN(S(=O)(=O)C=3C=CC=CC=3)C2=CC=C1C(=O)OC(C=1C=CC=CC=1)C1=CC=CC=C1 UWOTWBZMCAQHON-UHFFFAOYSA-N 0.000 description 19
- 238000001816 cooling Methods 0.000 description 19
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 17
- 239000000284 extract Substances 0.000 description 16
- 150000002148 esters Chemical group 0.000 description 15
- 125000001424 substituent group Chemical group 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 14
- 239000000725 suspension Substances 0.000 description 13
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- 238000001914 filtration Methods 0.000 description 11
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
- 239000005457 ice water Substances 0.000 description 8
- 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 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- DRPCVGHLXFPJKI-UHFFFAOYSA-N ethyl 2-(oxan-2-yl)tetrazole-5-carboxylate Chemical compound N1=C(C(=O)OCC)N=NN1C1OCCCC1 DRPCVGHLXFPJKI-UHFFFAOYSA-N 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 108020004414 DNA Proteins 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 5
- 235000019270 ammonium chloride Nutrition 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 239000002480 mineral oil Substances 0.000 description 5
- 235000010446 mineral oil Nutrition 0.000 description 5
- 239000013642 negative control Substances 0.000 description 5
- 239000013641 positive control Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- 208000030507 AIDS Diseases 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 125000001041 indolyl group Chemical group 0.000 description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
- GZZAQPFSFSCBPW-UHFFFAOYSA-N 1-(2-benzyl-1h-indol-3-yl)ethanone Chemical compound N1C2=CC=CC=C2C(C(=O)C)=C1CC1=CC=CC=C1 GZZAQPFSFSCBPW-UHFFFAOYSA-N 0.000 description 3
- LEUBXJIHEAWOHZ-UHFFFAOYSA-N 1-(5-chloro-1h-indol-3-yl)ethanone Chemical compound C1=C(Cl)C=C2C(C(=O)C)=CNC2=C1 LEUBXJIHEAWOHZ-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- ITLHXEGAYQFOHJ-UHFFFAOYSA-N [diazo(phenyl)methyl]benzene Chemical compound C=1C=CC=CC=1C(=[N+]=[N-])C1=CC=CC=C1 ITLHXEGAYQFOHJ-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000007810 chemical reaction solvent Substances 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- WHQLQYRFIHPMNA-UHFFFAOYSA-N ethyl acetate;oxolane Chemical compound C1CCOC1.CCOC(C)=O WHQLQYRFIHPMNA-UHFFFAOYSA-N 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000012948 isocyanate Substances 0.000 description 3
- 230000010534 mechanism of action Effects 0.000 description 3
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- 239000011535 reaction buffer Substances 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 2
- FIBQKRNTWLEWHF-WMZJFQQLSA-N (z)-3-(5-chloro-1h-indol-3-yl)-3-hydroxy-1-(2h-tetrazol-5-yl)prop-2-en-1-one Chemical compound C=1NC2=CC=C(Cl)C=C2C=1C(/O)=C/C(=O)C=1N=NNN=1 FIBQKRNTWLEWHF-WMZJFQQLSA-N 0.000 description 2
- MRNWDUGOAUHHPK-UHFFFAOYSA-N 1-[1-(benzenesulfonyl)-5-chloroindol-3-yl]ethanone Chemical compound C12=CC=C(Cl)C=C2C(C(=O)C)=CN1S(=O)(=O)C1=CC=CC=C1 MRNWDUGOAUHHPK-UHFFFAOYSA-N 0.000 description 2
- QEFAOZMRCJYPJB-UHFFFAOYSA-N 1-[2-(benzenesulfonyl)-5-chloro-1h-indol-3-yl]ethanone Chemical compound N1C2=CC=C(Cl)C=C2C(C(=O)C)=C1S(=O)(=O)C1=CC=CC=C1 QEFAOZMRCJYPJB-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- RZNHSEZOLFEFGB-UHFFFAOYSA-N 2-methoxybenzoyl chloride Chemical compound COC1=CC=CC=C1C(Cl)=O RZNHSEZOLFEFGB-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
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- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
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- DGJBKKFGCIDITM-UHFFFAOYSA-N C1=C(Cl)C=C2C(C(=O)C=C(O)C(=O)O)=CNC2=C1 Chemical compound C1=C(Cl)C=C2C(C(=O)C=C(O)C(=O)O)=CNC2=C1 DGJBKKFGCIDITM-UHFFFAOYSA-N 0.000 description 2
- JFWKQHCEQBPMGT-UHFFFAOYSA-N COCOC1=CC=C2N(C(=O)OC(C)(C)C)C=C(C(=O)C=C(O)C(O)=O)C2=C1 Chemical compound COCOC1=CC=C2N(C(=O)OC(C)(C)C)C=C(C(=O)C=C(O)C(O)=O)C2=C1 JFWKQHCEQBPMGT-UHFFFAOYSA-N 0.000 description 2
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 2
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- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 239000007993 MOPS buffer Substances 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
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- LSEYORGBTIEBBP-UHFFFAOYSA-N OC1=CC=C2N(C(=O)OC(C)(C)C)C=C(C(=O)C=C(O)C(O)=O)C2=C1 Chemical compound OC1=CC=C2N(C(=O)OC(C)(C)C)C=C(C(=O)C=C(O)C(O)=O)C2=C1 LSEYORGBTIEBBP-UHFFFAOYSA-N 0.000 description 2
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
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- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical class CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 238000010583 slow cooling Methods 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- MDVJEIQOTLZIDT-UHFFFAOYSA-M sodium;2-amino-4-(1h-indol-3-yl)-4-oxobut-2-enoate Chemical compound [Na+].C1=CC=C2C(C(=O)C=C(N)C([O-])=O)=CNC2=C1 MDVJEIQOTLZIDT-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- PPOODNJLFWUIOY-UHFFFAOYSA-N tert-butyl 3-acetyl-2-benzylindole-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1C2=CC=CC=C2C(C(=O)C)=C1CC1=CC=CC=C1 PPOODNJLFWUIOY-UHFFFAOYSA-N 0.000 description 1
- GNYAQPXKDAGJDK-UHFFFAOYSA-N tert-butyl 3-acetyl-5-hydroxyindole-1-carboxylate Chemical compound C1=C(O)C=C2C(C(=O)C)=CN(C(=O)OC(C)(C)C)C2=C1 GNYAQPXKDAGJDK-UHFFFAOYSA-N 0.000 description 1
- FXWNNNISWSOIKQ-UHFFFAOYSA-N tert-butyl 3-acetyl-5-phenylmethoxyindole-1-carboxylate Chemical compound C1=C2C(C(=O)C)=CN(C(=O)OC(C)(C)C)C2=CC=C1OCC1=CC=CC=C1 FXWNNNISWSOIKQ-UHFFFAOYSA-N 0.000 description 1
- JPHRXDCUOPQYKE-UHFFFAOYSA-N tert-butyl 3-acetylindole-1-carboxylate Chemical compound C1=CC=C2C(C(=O)C)=CN(C(=O)OC(C)(C)C)C2=C1 JPHRXDCUOPQYKE-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical class CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- SYZCZDCAEVUSPM-UHFFFAOYSA-M tetrahexylazanium;bromide Chemical compound [Br-].CCCCCC[N+](CCCCCC)(CCCCCC)CCCCCC SYZCZDCAEVUSPM-UHFFFAOYSA-M 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- 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
- C07D403/06—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 linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/20—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals substituted additionally by nitrogen atoms, e.g. tryptophane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/22—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an aralkyl radical attached to the ring nitrogen atom
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7820398 | 1998-03-26 | ||
| PCT/JP1999/001547 WO1999050245A1 (fr) | 1998-03-26 | 1999-03-26 | Derives d'indole exerçant une activite antivirale |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20004787D0 NO20004787D0 (no) | 2000-09-25 |
| NO20004787L NO20004787L (no) | 2000-11-27 |
| NO317423B1 true NO317423B1 (no) | 2004-10-25 |
Family
ID=13655476
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20004787A NO317423B1 (no) | 1998-03-26 | 2000-09-25 | Indolderivater, farmasoytisk preparat, middel for a inhibere integrase, antiviralt middel, anti-HIV middel samt anti-HIV medisinsk blanding. |
Country Status (17)
| Country | Link |
|---|---|
| US (3) | US6333323B1 (xx) |
| EP (1) | EP1069111A4 (xx) |
| JP (1) | JP3794469B2 (xx) |
| KR (1) | KR20010041705A (xx) |
| CN (1) | CN1142909C (xx) |
| AU (1) | AU752005B2 (xx) |
| BR (1) | BR9909146A (xx) |
| CA (1) | CA2326166A1 (xx) |
| HU (1) | HUP0103460A3 (xx) |
| ID (1) | ID26031A (xx) |
| IL (1) | IL137974A0 (xx) |
| NO (1) | NO317423B1 (xx) |
| NZ (1) | NZ506435A (xx) |
| PL (1) | PL343249A1 (xx) |
| RU (1) | RU2217421C2 (xx) |
| WO (1) | WO1999050245A1 (xx) |
| ZA (1) | ZA200004047B (xx) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6142163A (en) * | 1996-03-29 | 2000-11-07 | Lam Research Corporation | Method and apparatus for pressure control in vacuum processors |
| JP3794469B2 (ja) * | 1998-03-26 | 2006-07-05 | 塩野義製薬株式会社 | 抗ウイルス作用を有するインドール誘導体 |
| AU757409B2 (en) * | 1998-06-03 | 2003-02-20 | Merck & Co., Inc. | Hiv integrase inhibitors |
| EP1082121A4 (en) * | 1998-06-03 | 2003-02-05 | Merck & Co Inc | INTEGRASE HIV INHIBITORS |
| WO2000039086A1 (fr) | 1998-12-25 | 2000-07-06 | Shionogi & Co., Ltd. | Composes heterocycliques aromatiques possedant des activites inhibitrices de l'integrase du vih |
| US7294481B1 (en) * | 1999-01-05 | 2007-11-13 | Immunex Corporation | Method for producing recombinant proteins |
| TR200202129T2 (tr) * | 1999-06-02 | 2003-03-21 | Shionogi & Co., Ltd. | Yeni ikameli propenon türevlerinin hazırlanması için prosesler. |
| WO2001000578A1 (en) * | 1999-06-25 | 2001-01-04 | Merck & Co., Inc. | 1-(aromatic- or heteroaromatic-substituted)-3-(heteroaromatic substituted)-1,3-propanediones and uses thereof |
| ATE504572T1 (de) * | 1999-09-02 | 2011-04-15 | Shionogi & Co | Derivate von aromatische heterocyclen enthaltende integraseinhibitoren |
| CZ20023940A3 (cs) * | 2000-06-13 | 2003-05-14 | Shionogi & Co., Ltd. | Lékařské směsi zahrnující propenonové deriváty |
| WO2001095905A1 (en) * | 2000-06-14 | 2001-12-20 | Shionogi & Co., Ltd. | Inhibitor for enzyme having two divalent metal ions as active centers |
| AU4322802A (en) * | 2000-11-16 | 2002-06-24 | Univ California | Marine actinomycete taxon for drug and fermentation product dicovery |
| US7067539B2 (en) | 2001-02-08 | 2006-06-27 | Schering Corporation | Cannabinoid receptor ligands |
| US7507767B2 (en) | 2001-02-08 | 2009-03-24 | Schering Corporation | Cannabinoid receptor ligands |
| EP2033952B1 (en) | 2001-03-01 | 2012-08-29 | Shionogi&Co., Ltd. | Nitrogen-containing Heteroaryl compounds having HIV Integrase Inhibitory Activity |
| ATE550320T1 (de) | 2001-08-10 | 2012-04-15 | Shionogi & Co | Antivirales mittel |
| ITMI20012060A1 (it) * | 2001-10-05 | 2003-04-05 | Recordati Chem Pharm | Nuovi eterocilcli n-acilati |
| RS51542B (sr) * | 2001-10-26 | 2011-06-30 | Istituto Di Ricerche Di Biologia Molecolare P.Angeletti Spa. | N-supstituisani hidroksipirimidinon karboksamidni inhibitori hiv integraze |
| JP2005509032A (ja) | 2001-11-14 | 2005-04-07 | シェーリング コーポレイション | カンナビノイドレセプターリガンド |
| WO2003049695A2 (en) * | 2001-12-07 | 2003-06-19 | The Government Of The United States Of America As Represented By The Secretary, Department Of Healthand Human Services | Compounds to treat hiv infection and aids |
| US20030236277A1 (en) | 2002-02-14 | 2003-12-25 | Kadow John F. | Indole, azaindole and related heterocyclic pyrrolidine derivatives |
| EP1539693B9 (en) | 2002-06-19 | 2008-10-08 | Schering Corporation | Cannabinoid receptor agonists |
| US7176232B2 (en) | 2002-06-24 | 2007-02-13 | The Regents Of The University Of California | Salinosporamides and methods for use thereof |
| PT1529044E (pt) * | 2002-08-02 | 2008-01-14 | Nereus Pharmaceuticals Inc | Desidrofenila-histinas e os seus análogos e a síntese de desidrofenila-histinas e os seus análogos |
| US7919497B2 (en) * | 2002-08-02 | 2011-04-05 | Nereus Pharmaceuticals, Inc. | Analogs of dehydrophenylahistins and their therapeutic use |
| US7935704B2 (en) * | 2003-08-01 | 2011-05-03 | Nereus Pharmaceuticals, Inc. | Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof |
| JP3908248B2 (ja) | 2002-08-13 | 2007-04-25 | 塩野義製薬株式会社 | Ｈｉｖインテグラーゼ阻害活性を有するヘテロ環化合物 |
| WO2004034970A2 (en) * | 2002-09-27 | 2004-04-29 | Nereus Pharmaceuticals, Inc. | Macrocyclic lactams |
| TW200505902A (en) | 2003-03-20 | 2005-02-16 | Schering Corp | Cannabinoid receptor ligands |
| CA2532066C (en) * | 2003-06-20 | 2015-07-28 | Nereus Pharmaceuticals, Inc. | Methods of using [3.2.0] heterocyclic compounds and analogs thereof |
| CN101791306A (zh) * | 2003-06-20 | 2010-08-04 | 加利福尼亚大学董事会 | 盐孢菌酰胺及其使用方法 |
| JP2007519727A (ja) * | 2004-01-23 | 2007-07-19 | ネレアス ファーマシューティカルズ インコーポレイテッド | 抗菌薬として有用なビス−インドールピロール |
| ATE482208T1 (de) | 2004-03-10 | 2010-10-15 | Us Of America Represented By T | Chinolin-4-one als inhibitoren der retroviralen integrase zur behandlung von hiv, aids und aids- related complex (arc) |
| US7579371B2 (en) | 2004-04-30 | 2009-08-25 | Nereus Pharmaceuticals, Inc. | Methods of using [3.2.0] heterocyclic compounds and analogs thereof |
| WO2006028525A2 (en) * | 2004-04-30 | 2006-03-16 | Nereus Pharmaceuticals, Inc. | [3.2.0] heterocyclic compounds and methods of using the same |
| EP1799696B1 (en) | 2004-09-17 | 2008-11-12 | IDENIX Pharmaceuticals, Inc. | Phosphoindoles as hiv inhibitors |
| US20060100432A1 (en) | 2004-11-09 | 2006-05-11 | Matiskella John D | Crystalline materials of 1-(4-benzoyl-piperazin-1-yl)-2-[4-methoxy-7-(3-methyl-[1,2,4]triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-ethane-1,2-dione |
| CN101155582B (zh) * | 2004-12-03 | 2013-04-24 | 达纳-法伯癌症研究公司 | 治疗肿瘤性疾病的组合物和方法 |
| CN1316968C (zh) * | 2005-09-30 | 2007-05-23 | 青岛大学 | 吲哚－2,3－二酮在制备抗病毒或免疫增强剂药物中的应用 |
| US7851476B2 (en) | 2005-12-14 | 2010-12-14 | Bristol-Myers Squibb Company | Crystalline forms of 1-benzoyl-4-[2-[4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-YL)-1-[(phosphonooxy)methyl]-1H-pyrrolo[2,3-C]pyridin-3-YL]-1,2-dioxoethyl]-piperazine |
| JP5093096B2 (ja) * | 2006-03-02 | 2012-12-05 | アステラス製薬株式会社 | １７βＨＳＤｔｙｐｅ５阻害剤 |
| TR200806911T1 (tr) * | 2006-03-17 | 2009-01-21 | Cipla Limited | 4-[1-(4-siyano fenil)-1-(1,2,4-triazol-1-il)metil] benzonitril ile 4[1-(1h-1,2,4-triazol-1-il)metilen benzonitril ara maddesinin sentezi. |
| BRPI0709474A2 (pt) | 2006-04-06 | 2011-07-12 | Nerus Pharmaceuticals Inc | sìntese total de salinosporamida a e seus análogos |
| US7807671B2 (en) | 2006-04-25 | 2010-10-05 | Bristol-Myers Squibb Company | Diketo-piperazine and piperidine derivatives as antiviral agents |
| CA2664396A1 (en) * | 2006-09-29 | 2008-04-10 | Idenix Pharmaceuticals, Inc. | Enantiomerically pure phosphoindoles as hiv inhibitors |
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| US8394816B2 (en) * | 2007-12-07 | 2013-03-12 | Irene Ghobrial | Methods of using [3.2.0] heterocyclic compounds and analogs thereof in treating Waldenstrom's Macroglobulinemia |
| EP2234608A2 (en) | 2007-12-11 | 2010-10-06 | Viamet Pharmaceuticals, Inc. | Metalloenzyme inhibitors using metal binding moieties in combination with targeting moieties |
| CA2723465A1 (en) * | 2008-05-12 | 2009-11-19 | Nereus Pharmaceuticals, Inc. | Proteasome inhibitors |
| WO2013123658A1 (en) | 2012-02-23 | 2013-08-29 | Empire Technology Development Llc | Azobenzene compounds with cholesterol group and their sunscreen compositions |
| CN103420894A (zh) * | 2012-05-22 | 2013-12-04 | 中国科学院上海药物研究所 | 丁-2-烯-1,4-二酮类化合物及其制备方法和用途 |
| CN117427077A (zh) | 2014-09-14 | 2024-01-23 | 阿瓦尼尔制药股份有限公司 | 用于治疗痴呆中的激越行为的包含右美沙芬化合物和奎尼丁的药物组合物 |
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| CA2980221C (en) * | 2015-03-31 | 2024-03-12 | The Royal Institution For The Advancement Of Learning/Mcgill University | Indole analogs as 5-oxo-ete receptor antagonists and method of use thereof |
| EP3334726B1 (en) | 2015-07-13 | 2022-03-16 | Beyondspring Pharmaceuticals, Inc. | Plinabulin compositions |
| MY192703A (en) | 2016-02-08 | 2022-09-02 | Beyondspring Pharmaceuticals Inc | Compositions containing tucaresol or its analogs |
| MX2018015100A (es) | 2016-06-06 | 2019-09-04 | Beyondspring Pharmaceuticals Inc | Composicion y metodo para reducir la neutropenia. |
| JP2020503363A (ja) | 2017-01-06 | 2020-01-30 | ビヨンドスプリング ファーマシューティカルズ，インコーポレイテッド | チューブリン結合化合物およびその治療的使用 |
| WO2018144764A1 (en) | 2017-02-01 | 2018-08-09 | Beyondspring Pharmaceuticals, Inc. | Method of reducing neutropenia |
| CN106995400B (zh) * | 2017-04-10 | 2019-08-06 | 湘潭大学 | 一种化合物及其盐及其合成方法 |
| CN107226810B (zh) * | 2017-06-16 | 2020-04-28 | 郑州大学 | 吲哚衍生物及其制备方法和其抗流感病毒作用 |
| KR20200112881A (ko) | 2018-01-24 | 2020-10-05 | 비욘드스프링 파마수티컬스, 인코포레이티드. | 플리나불린의 투여를 통해 혈소판감소증을 감소시키는 조성물 및 방법 |
| CN109810044B (zh) * | 2019-02-27 | 2022-05-03 | 贵州医科大学 | 一种具有hiv-1整合酶抑制活性的化合物及其制备和应用 |
| WO2023115203A1 (en) * | 2021-12-20 | 2023-06-29 | Fairhaven Pharmaceuticals Inc. | Oxer1 antagonists and uses thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US4377698A (en) * | 1976-01-22 | 1983-03-22 | Sterling Drug Inc. | 2,4 Bis(2-indolyl-3)-4-oxobutanoic acids |
| WO1993005020A1 (en) * | 1991-09-06 | 1993-03-18 | Merck & Co., Inc. | Indoles as inhibitors of hiv reverse transcriptase |
| US5475109A (en) | 1994-10-17 | 1995-12-12 | Merck & Co., Inc. | Dioxobutanoic acid derivatives as inhibitors of influenza endonuclease |
| EP0820441B1 (en) * | 1995-04-10 | 2002-06-26 | Fujisawa Pharmaceutical Co., Ltd. | INDOLE DERIVATIVES AS cGMP-PDE INHIBITORS |
| US5858738A (en) * | 1996-11-07 | 1999-01-12 | Merck & Co., Inc. | Ermophilane sesquiterpenoids as HIV intergrase inhibitors |
| JP3794469B2 (ja) * | 1998-03-26 | 2006-07-05 | 塩野義製薬株式会社 | 抗ウイルス作用を有するインドール誘導体 |
| EP1082121A4 (en) | 1998-06-03 | 2003-02-05 | Merck & Co Inc | INTEGRASE HIV INHIBITORS |
| AU757409B2 (en) | 1998-06-03 | 2003-02-20 | Merck & Co., Inc. | Hiv integrase inhibitors |
| CA2329134A1 (en) | 1998-06-03 | 1999-12-09 | David L. Clark | Hiv integrase inhibitors |
| WO2001000578A1 (en) | 1999-06-25 | 2001-01-04 | Merck & Co., Inc. | 1-(aromatic- or heteroaromatic-substituted)-3-(heteroaromatic substituted)-1,3-propanediones and uses thereof |
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- 1999-03-26 JP JP2000541150A patent/JP3794469B2/ja not_active Expired - Fee Related
- 1999-03-26 RU RU2000126474/04A patent/RU2217421C2/ru not_active IP Right Cessation
- 1999-03-26 CN CNB998044180A patent/CN1142909C/zh not_active Expired - Fee Related
- 1999-03-26 IL IL13797499A patent/IL137974A0/xx unknown
- 1999-03-26 WO PCT/JP1999/001547 patent/WO1999050245A1/ja not_active Application Discontinuation
- 1999-03-26 US US09/622,543 patent/US6333323B1/en not_active Expired - Fee Related
- 1999-03-26 EP EP99910719A patent/EP1069111A4/en not_active Withdrawn
- 1999-03-26 ID IDW20001898A patent/ID26031A/id unknown
- 1999-03-26 BR BR9909146-1A patent/BR9909146A/pt not_active IP Right Cessation
- 1999-03-26 HU HU0103460A patent/HUP0103460A3/hu unknown
- 1999-03-26 CA CA002326166A patent/CA2326166A1/en not_active Abandoned
- 1999-03-26 NZ NZ506435A patent/NZ506435A/xx unknown
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- 1999-03-26 PL PL99343249A patent/PL343249A1/xx unknown
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- 2000-09-25 NO NO20004787A patent/NO317423B1/no not_active IP Right Cessation
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2002
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| US6716605B2 (en) | 2004-04-06 |
| CA2326166A1 (en) | 1999-10-07 |
| WO1999050245A1 (fr) | 1999-10-07 |
| US6506787B2 (en) | 2003-01-14 |
| NO20004787D0 (no) | 2000-09-25 |
| NO20004787L (no) | 2000-11-27 |
| JP3794469B2 (ja) | 2006-07-05 |
| BR9909146A (pt) | 2000-12-05 |
| AU2958199A (en) | 1999-10-18 |
| US20030181499A1 (en) | 2003-09-25 |
| CN1294580A (zh) | 2001-05-09 |
| CN1142909C (zh) | 2004-03-24 |
| HUP0103460A2 (hu) | 2002-01-28 |
| NZ506435A (en) | 2002-08-28 |
| AU752005B2 (en) | 2002-09-05 |
| EP1069111A1 (en) | 2001-01-17 |
| ID26031A (id) | 2000-11-16 |
| IL137974A0 (en) | 2001-10-31 |
| US20020019434A1 (en) | 2002-02-14 |
| EP1069111A4 (en) | 2001-06-06 |
| US6333323B1 (en) | 2001-12-25 |
| KR20010041705A (ko) | 2001-05-25 |
| PL343249A1 (en) | 2001-07-30 |
| HUP0103460A3 (en) | 2002-11-28 |
| ZA200004047B (en) | 2001-04-25 |
| RU2217421C2 (ru) | 2003-11-27 |
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Free format text: INDOLDERIVATER, FARMASOYTISK PREPARAT, MIDDEL FOR A INHIBERE INTEGRASE, ANTIVIRALT MIDDEL, ANTI-HIVMIDDEL SAMT ANTI-HIV MEDISINSK BLANDING. |
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| MM1K | Lapsed by not paying the annual fees |