ES2281170T3 - Inhibidores de serina proteasas, particularmente proteasa ns3 del virus de la hepatitis c. - Google Patents
Inhibidores de serina proteasas, particularmente proteasa ns3 del virus de la hepatitis c. Download PDFInfo
- Publication number
- ES2281170T3 ES2281170T3 ES99915185T ES99915185T ES2281170T3 ES 2281170 T3 ES2281170 T3 ES 2281170T3 ES 99915185 T ES99915185 T ES 99915185T ES 99915185 T ES99915185 T ES 99915185T ES 2281170 T3 ES2281170 T3 ES 2281170T3
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- Prior art keywords
- compound according
- alkyl
- compound
- aryl
- resin
- 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.)
- Expired - Lifetime
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- 108091005804 Peptidases Proteins 0.000 title abstract description 16
- 102000035195 Peptidases Human genes 0.000 title abstract description 15
- 239000004365 Protease Substances 0.000 title abstract description 15
- 241000700605 Viruses Species 0.000 title abstract description 10
- 239000003112 inhibitor Substances 0.000 title description 22
- 208000006454 hepatitis Diseases 0.000 title description 5
- 231100000283 hepatitis Toxicity 0.000 title description 4
- MTCFGRXMJLQNBG-UHFFFAOYSA-N serine Chemical compound OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 title description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 133
- 239000000203 mixture Substances 0.000 claims abstract description 47
- 238000000034 method Methods 0.000 claims abstract description 39
- 102000012479 Serine Proteases Human genes 0.000 claims abstract description 22
- 108010022999 Serine Proteases Proteins 0.000 claims abstract description 22
- 101800001838 Serine protease/helicase NS3 Proteins 0.000 claims abstract description 12
- 239000011347 resin Substances 0.000 claims description 95
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- -1 aralkoxy Chemical group 0.000 claims description 77
- 125000003118 aryl group Chemical group 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 125000000623 heterocyclic group Chemical group 0.000 claims description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 23
- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
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- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 1
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- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
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- 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
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- 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
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Virology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8006098P | 1998-03-31 | 1998-03-31 | |
| US80060P | 1998-03-31 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2281170T3 true ES2281170T3 (es) | 2007-09-16 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES99915185T Expired - Lifetime ES2281170T3 (es) | 1998-03-31 | 1999-03-31 | Inhibidores de serina proteasas, particularmente proteasa ns3 del virus de la hepatitis c. |
Country Status (9)
| Country | Link |
|---|---|
| US (3) | US6608067B1 (enExample) |
| EP (1) | EP1066247B1 (enExample) |
| JP (1) | JP4690545B2 (enExample) |
| AT (1) | ATE346035T1 (enExample) |
| AU (1) | AU3376699A (enExample) |
| DE (1) | DE69934104T2 (enExample) |
| DK (1) | DK1066247T3 (enExample) |
| ES (1) | ES2281170T3 (enExample) |
| WO (1) | WO1999050230A1 (enExample) |
Families Citing this family (127)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ335276A (en) * | 1996-10-18 | 2000-09-29 | Vertex Pharma | Inhibitors of serine proteases, particularly hepatitis C virus (HCV) NS3 (Non Structural Protein 3) protease |
| AU1324300A (en) * | 1998-10-26 | 2000-05-15 | Vertex Pharmaceuticals Incorporated | Pentacyclic compounds useful as inhibitors of hepatitis c virus ns3 helicase |
| US6608027B1 (en) | 1999-04-06 | 2003-08-19 | Boehringer Ingelheim (Canada) Ltd | Macrocyclic peptides active against the hepatitis C virus |
| UA74546C2 (en) * | 1999-04-06 | 2006-01-16 | Boehringer Ingelheim Ca Ltd | Macrocyclic peptides having activity relative to hepatitis c virus, a pharmaceutical composition and use of the pharmaceutical composition |
| AU2001251165A1 (en) | 2000-04-03 | 2001-10-15 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases, particularly hepatitis c virus ns3 protease |
| US6613801B2 (en) | 2000-05-30 | 2003-09-02 | Transtech Pharma, Inc. | Method for the synthesis of compounds of formula I and their uses thereof |
| AR034127A1 (es) * | 2000-07-21 | 2004-02-04 | Schering Corp | Imidazolidinonas como inhibidores de ns3-serina proteasa del virus de hepatitis c, composicion farmaceutica, un metodo para su preparacion, y el uso de las mismas para la manufactura de un medicamento |
| SV2003000617A (es) | 2000-08-31 | 2003-01-13 | Lilly Co Eli | Inhibidores de la proteasa peptidomimetica ref. x-14912m |
| US6846806B2 (en) | 2000-10-23 | 2005-01-25 | Bristol-Myers Squibb Company | Peptide inhibitors of Hepatitis C virus NS3 protein |
| WO2002048157A2 (en) * | 2000-12-13 | 2002-06-20 | Bristol-Myers Squibb Pharma Company | Imidazolidinones and their related derivatives as hepatitis c virus ns3 protease inhibitors |
| MXPA03006514A (es) | 2001-01-22 | 2004-12-02 | Merck & Co Inc | Derivados de nucleosidos como inhibidores de polimerasa de acido ribonucleico viral dependiente de acido ribonucleico. |
| CN1235583C (zh) | 2001-03-05 | 2006-01-11 | 特兰斯泰克制药公司 | 用作治疗剂的苯并咪唑衍生物 |
| CA2440042C (en) | 2001-03-05 | 2011-09-27 | Transtech Pharma, Inc. | Carboxamide derivatives as therapeutic agents |
| KR100926244B1 (ko) | 2001-07-11 | 2009-11-12 | 버텍스 파마슈티칼스 인코포레이티드 | 브릿지된 바이사이클릭 세린 프로테아제 억제제 |
| MXPA04003825A (es) | 2001-10-24 | 2004-07-08 | Vertex Pharma | Inhibidores de serina proteasa, en particular la ns3-ns4a proteasa del virus de hepatitis c, que incorpora un sistema de anillo fusionado. |
| US7119072B2 (en) | 2002-01-30 | 2006-10-10 | Boehringer Ingelheim (Canada) Ltd. | Macrocyclic peptides active against the hepatitis C virus |
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| US5798442A (en) * | 1995-04-21 | 1998-08-25 | Merck Frosst Canada, Inc. | Peptidyl derivatives as inhibitors of pro-apoptotic cysteine proteinases |
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| NZ335276A (en) * | 1996-10-18 | 2000-09-29 | Vertex Pharma | Inhibitors of serine proteases, particularly hepatitis C virus (HCV) NS3 (Non Structural Protein 3) protease |
| DE19648793A1 (de) * | 1996-11-26 | 1998-05-28 | Basf Ag | Neue Benzamide und deren Anwendung |
| PT1012180E (pt) * | 1997-08-11 | 2005-04-29 | Boehringer Ingelheim Ca Ltd | Analogos de peptidos inibidores da hepatite c |
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- 1999-03-31 WO PCT/US1999/007149 patent/WO1999050230A1/en not_active Ceased
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- 1999-03-31 DE DE69934104T patent/DE69934104T2/de not_active Expired - Lifetime
- 1999-03-31 DK DK99915185T patent/DK1066247T3/da active
- 1999-03-31 AT AT99915185T patent/ATE346035T1/de not_active IP Right Cessation
- 1999-03-31 JP JP2000541139A patent/JP4690545B2/ja not_active Expired - Fee Related
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2003
- 2003-07-07 US US10/614,432 patent/US20040077600A1/en not_active Abandoned
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2010
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| JP2002509910A (ja) | 2002-04-02 |
| DE69934104D1 (de) | 2007-01-04 |
| EP1066247A1 (en) | 2001-01-10 |
| WO1999050230A1 (en) | 1999-10-07 |
| DK1066247T3 (da) | 2007-04-02 |
| AU3376699A (en) | 1999-10-18 |
| EP1066247B1 (en) | 2006-11-22 |
| JP4690545B2 (ja) | 2011-06-01 |
| DE69934104T2 (de) | 2007-06-28 |
| US6608067B1 (en) | 2003-08-19 |
| ATE346035T1 (de) | 2006-12-15 |
| US20040077600A1 (en) | 2004-04-22 |
| US20110112114A1 (en) | 2011-05-12 |
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