ES2374870T3 - Inhibidores de ns5b de vhc de indolobenzadiazepina fusionada con heterocíclicos aromáticos. - Google Patents
Inhibidores de ns5b de vhc de indolobenzadiazepina fusionada con heterocíclicos aromáticos. Download PDFInfo
- Publication number
- ES2374870T3 ES2374870T3 ES09725965T ES09725965T ES2374870T3 ES 2374870 T3 ES2374870 T3 ES 2374870T3 ES 09725965 T ES09725965 T ES 09725965T ES 09725965 T ES09725965 T ES 09725965T ES 2374870 T3 ES2374870 T3 ES 2374870T3
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- Prior art keywords
- hcv
- compound
- inhibitors
- hydrogen
- alkyl
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- 239000007937 lozenge Substances 0.000 description 1
- 108010026228 mRNA guanylyltransferase Proteins 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- QOQJFUQDXVNLMK-UHFFFAOYSA-N methyl 2-bromo-3-cyclohexyl-1h-indole-6-carboxylate Chemical compound BrC=1NC2=CC(C(=O)OC)=CC=C2C=1C1CCCCC1 QOQJFUQDXVNLMK-UHFFFAOYSA-N 0.000 description 1
- FRSNMANVEIOEQU-UHFFFAOYSA-N methyl 3-cyclohexyl-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]-1-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]indole-6-carboxylate Chemical compound C=1C=CC=C(NC(=O)OC(C)(C)C)C=1C=1N(CC(=O)OC(C)(C)C)C2=CC(C(=O)OC)=CC=C2C=1C1CCCCC1 FRSNMANVEIOEQU-UHFFFAOYSA-N 0.000 description 1
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- JQRYUMGHOUYJFW-UHFFFAOYSA-N pyridine;trihydrobromide Chemical compound [Br-].[Br-].[Br-].C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1 JQRYUMGHOUYJFW-UHFFFAOYSA-N 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 229940038850 rebif Drugs 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 239000003161 ribonuclease inhibitor Substances 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- NHKZSTHOYNWEEZ-AFCXAGJDSA-N taribavirin Chemical compound N1=C(C(=N)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NHKZSTHOYNWEEZ-AFCXAGJDSA-N 0.000 description 1
- 229950006081 taribavirin Drugs 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 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
- C07D487/12—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 three hetero rings
- C07D487/14—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Virology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US39961P | 1997-03-07 | ||
| US3996108P | 2008-03-27 | 2008-03-27 | |
| PCT/US2009/038010 WO2009120650A1 (en) | 2008-03-27 | 2009-03-24 | Aromatic heterocyclic fused indolobenzadiazepine hcv ns5b inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2374870T3 true ES2374870T3 (es) | 2012-02-22 |
Family
ID=40810527
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES09725965T Active ES2374870T3 (es) | 2008-03-27 | 2009-03-24 | Inhibidores de ns5b de vhc de indolobenzadiazepina fusionada con heterocíclicos aromáticos. |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US8431568B2 (enExample) |
| EP (1) | EP2278977B1 (enExample) |
| JP (1) | JP2011517673A (enExample) |
| KR (1) | KR20100124848A (enExample) |
| CN (1) | CN101980711B (enExample) |
| AT (1) | ATE531373T1 (enExample) |
| AU (1) | AU2009228451A1 (enExample) |
| ES (1) | ES2374870T3 (enExample) |
| MX (1) | MX2010010060A (enExample) |
| WO (1) | WO2009120650A1 (enExample) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103288828A (zh) * | 2012-02-24 | 2013-09-11 | 中国科学院大连化学物理研究所 | 一种合成手性二氢-6H-吲哚并[2,1-c][1,4]-苯并二氮杂卓的方法 |
| CN103539723A (zh) * | 2013-10-29 | 2014-01-29 | 南方医科大学 | 一种3-氨基-2-芳甲酰基-1h-吲哚类衍生物的合成方法 |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4897392A (en) * | 1989-07-03 | 1990-01-30 | Hoechst-Roussel Pharmaceuticals, Inc. | 4H-indolo(1,2-d)(1,2,4)triazolo(4,3-A)(1,4)benzodiazepines |
| DE602005013922D1 (de) * | 2004-02-24 | 2009-05-28 | Japan Tobacco Inc | Kondensierte heterotetracyclische verbindungen und deren verwendung als hcv-polymerase-inhibitor |
| US7153848B2 (en) * | 2004-08-09 | 2006-12-26 | Bristol-Myers Squibb Company | Inhibitors of HCV replication |
| US7348425B2 (en) | 2004-08-09 | 2008-03-25 | Bristol-Myers Squibb Company | Inhibitors of HCV replication |
| AU2005298403A1 (en) | 2004-10-26 | 2006-05-04 | Istituto Di Ricerche Di Biologia Molecolare P Angeletti Spa | Tetracyclic indole derivatives as antiviral agents |
| GB0518390D0 (en) * | 2005-09-09 | 2005-10-19 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
| US7399758B2 (en) | 2005-09-12 | 2008-07-15 | Meanwell Nicholas A | Cyclopropyl fused indolobenzazepine HCV NS5B inhibitors |
| US7473688B2 (en) | 2005-09-13 | 2009-01-06 | Bristol-Myers Squibb Company | Indolobenzazepine HCV NS5B inhibitors |
| US7456165B2 (en) | 2006-02-08 | 2008-11-25 | Bristol-Myers Squibb Company | HCV NS5B inhibitors |
| GB0608928D0 (en) * | 2006-05-08 | 2006-06-14 | Angeletti P Ist Richerche Bio | Therapeutic agents |
| US7521442B2 (en) | 2006-05-25 | 2009-04-21 | Bristol-Myers Squibb Company | Cyclopropyl fused indolobenzazepine HCV NS5B inhibitors |
| CN101490054B (zh) | 2006-05-25 | 2012-05-16 | 百时美施贵宝公司 | 环丙基稠合的吲哚并苯并氮杂*hcv ns5b抑制剂 |
| US7452876B2 (en) | 2006-06-08 | 2008-11-18 | Bristol-Myers Squibb Company | Cyclopropyl fused indolobenzazepine HCV NS5B inhibitors |
| KR20090029827A (ko) * | 2006-07-20 | 2009-03-23 | 제네랩스 테크놀로지스, 인코포레이티드 | 폴리사이클릭 바이러스 억제제 |
| US7642251B2 (en) | 2007-08-09 | 2010-01-05 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| US7652004B2 (en) | 2007-08-09 | 2010-01-26 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| US8143243B2 (en) | 2007-08-09 | 2012-03-27 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| US8138171B2 (en) | 2008-03-27 | 2012-03-20 | Bristol-Myers Squibb Company | Dioxolane and dioxolanone fused indolobenzadiazepine HCV NS5B inhibitors |
| US8133884B2 (en) | 2008-05-06 | 2012-03-13 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
-
2009
- 2009-03-24 JP JP2011501963A patent/JP2011517673A/ja active Pending
- 2009-03-24 MX MX2010010060A patent/MX2010010060A/es active IP Right Grant
- 2009-03-24 CN CN2009801109761A patent/CN101980711B/zh not_active Expired - Fee Related
- 2009-03-24 KR KR1020107023917A patent/KR20100124848A/ko not_active Withdrawn
- 2009-03-24 AT AT09725965T patent/ATE531373T1/de active
- 2009-03-24 EP EP09725965A patent/EP2278977B1/en not_active Not-in-force
- 2009-03-24 US US12/922,801 patent/US8431568B2/en active Active
- 2009-03-24 AU AU2009228451A patent/AU2009228451A1/en not_active Abandoned
- 2009-03-24 WO PCT/US2009/038010 patent/WO2009120650A1/en not_active Ceased
- 2009-03-24 ES ES09725965T patent/ES2374870T3/es active Active
Also Published As
| Publication number | Publication date |
|---|---|
| MX2010010060A (es) | 2010-09-30 |
| WO2009120650A1 (en) | 2009-10-01 |
| KR20100124848A (ko) | 2010-11-29 |
| JP2011517673A (ja) | 2011-06-16 |
| AU2009228451A1 (en) | 2009-10-01 |
| EP2278977B1 (en) | 2011-11-02 |
| CN101980711A (zh) | 2011-02-23 |
| US20110014154A1 (en) | 2011-01-20 |
| CN101980711B (zh) | 2012-10-31 |
| EP2278977A1 (en) | 2011-02-02 |
| US8431568B2 (en) | 2013-04-30 |
| ATE531373T1 (de) | 2011-11-15 |
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