CN102617705A - 抑制丙肝病毒复制的大环类化合物 - Google Patents
抑制丙肝病毒复制的大环类化合物 Download PDFInfo
- Publication number
- CN102617705A CN102617705A CN2012100348720A CN201210034872A CN102617705A CN 102617705 A CN102617705 A CN 102617705A CN 2012100348720 A CN2012100348720 A CN 2012100348720A CN 201210034872 A CN201210034872 A CN 201210034872A CN 102617705 A CN102617705 A CN 102617705A
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- Prior art keywords
- compound
- carbamyl
- cyclopropyl
- ring
- azepine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- QTENRWWVYAAPBI-YCRXJPFRSA-N streptomycin sulfate Chemical compound OS(O)(=O)=O.OS(O)(=O)=O.OS(O)(=O)=O.CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](N=C(N)N)[C@H](O)[C@@H](N=C(N)N)[C@H](O)[C@H]1O.CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](N=C(N)N)[C@H](O)[C@@H](N=C(N)N)[C@H](O)[C@H]1O QTENRWWVYAAPBI-YCRXJPFRSA-N 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 125000000565 sulfonamide group Chemical group 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 125000003375 sulfoxide group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000002512 suppressor factor Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 235000012976 tarts Nutrition 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- BBAWEDCPNXPBQM-GDEBMMAJSA-N telaprevir Chemical compound N([C@H](C(=O)N[C@H](C(=O)N1C[C@@H]2CCC[C@@H]2[C@H]1C(=O)N[C@@H](CCC)C(=O)C(=O)NC1CC1)C(C)(C)C)C1CCCCC1)C(=O)C1=CN=CC=N1 BBAWEDCPNXPBQM-GDEBMMAJSA-N 0.000 description 1
- 108010017101 telaprevir Proteins 0.000 description 1
- 229960002935 telaprevir Drugs 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 108010087967 type I signal peptidase Proteins 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C07K5/1013—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing O or S as heteroatoms, e.g. Cys, Ser
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/005—Enzyme inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/07—Tetrapeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/55—Protease inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0812—Tripeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Virology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Peptides Or Proteins (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
Description
化合物 | EC50 | 化合物 | EC50 | 化合物 | EC50 |
IIa-1 | A | IIa-2 | B | IIa-3 | C |
IIa-4 | D | IIa-5 | C | IIa-6 | C |
IIa-7 | C | IIa-8 | B | IIa-9 | B |
IIa-10 | A | IIa-11 | A | IIa-12 | A |
IIa-13 | B | IIa-14 | C | IIa-15 | A |
IIa-16 | A | IIa-17 | A | IIa-18 | B |
IIa-19 | A | IIa-20 | A | IIa-21 | B |
IIa-22 | A | IIb-1 | A | IIb-2 | A |
IIb-3 | A | IIb-4 | A | IIb-5 | B |
IIb-6 | C | IIb-7 | D | MK7009 | A |
化合物 | t1/2(分钟) |
IIa-1 | 198 |
IIa-16 | 193 |
IIb-3 | 230 |
MK7009 | 26 |
Claims (18)
Priority Applications (11)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201210034872.0A CN102617705B (zh) | 2012-02-16 | 2012-02-16 | 抑制丙肝病毒复制的大环类化合物 |
EP12868766.2A EP2816054A4 (en) | 2012-02-16 | 2012-12-05 | MACROCYCLIC COMPOUNDS FOR SUPPRESSING THE REPLICATION OF HEPATITIS C VIRUS |
PCT/CN2012/085912 WO2013120371A1 (zh) | 2012-02-16 | 2012-12-05 | 抑制丙肝病毒复制的大环类化合物 |
US14/375,418 US9321809B2 (en) | 2012-02-16 | 2012-12-05 | Macrocyclic compounds for suppressing replication of hepatitis C virus |
KR1020147022579A KR102004381B1 (ko) | 2012-02-16 | 2012-12-05 | C형 간염 바이러스의 복제를 억제하기 위한 거대고리 화합물 |
JP2014556905A JP6105632B2 (ja) | 2012-02-16 | 2012-12-05 | C型肝炎ウイルスの複製を抑制するための大環状化合物 |
AU2012370125A AU2012370125A1 (en) | 2012-02-16 | 2012-12-05 | Macrocyclic compounds for suppressing replication of hepatitis C virus |
CN201280069837.0A CN104169293A (zh) | 2012-02-16 | 2012-12-05 | 抑制丙肝病毒复制的大环类化合物 |
IN1637MUN2014 IN2014MN01637A (zh) | 2012-02-16 | 2012-12-05 | |
CA2864488A CA2864488A1 (en) | 2012-02-16 | 2012-12-05 | Macrocyclic compounds for suppressing replication of hepatitis c virus |
IL233899A IL233899A0 (en) | 2012-02-16 | 2014-07-31 | Macrocyclic compounds for suppression of hepatitis C virus replication |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201210034872.0A CN102617705B (zh) | 2012-02-16 | 2012-02-16 | 抑制丙肝病毒复制的大环类化合物 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN102617705A true CN102617705A (zh) | 2012-08-01 |
CN102617705B CN102617705B (zh) | 2014-12-31 |
Family
ID=46557956
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201210034872.0A Expired - Fee Related CN102617705B (zh) | 2012-02-16 | 2012-02-16 | 抑制丙肝病毒复制的大环类化合物 |
CN201280069837.0A Pending CN104169293A (zh) | 2012-02-16 | 2012-12-05 | 抑制丙肝病毒复制的大环类化合物 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201280069837.0A Pending CN104169293A (zh) | 2012-02-16 | 2012-12-05 | 抑制丙肝病毒复制的大环类化合物 |
Country Status (10)
Country | Link |
---|---|
US (1) | US9321809B2 (zh) |
EP (1) | EP2816054A4 (zh) |
JP (1) | JP6105632B2 (zh) |
KR (1) | KR102004381B1 (zh) |
CN (2) | CN102617705B (zh) |
AU (1) | AU2012370125A1 (zh) |
CA (1) | CA2864488A1 (zh) |
IL (1) | IL233899A0 (zh) |
IN (1) | IN2014MN01637A (zh) |
WO (1) | WO2013120371A1 (zh) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013120371A1 (zh) * | 2012-02-16 | 2013-08-22 | 银杏树药业(苏州)有限公司 | 抑制丙肝病毒复制的大环类化合物 |
CN104447952A (zh) * | 2014-12-11 | 2015-03-25 | 上海唐润医药科技有限公司 | 丙肝病毒蛋白酶抑制剂及其合成方法 |
CN110963986A (zh) * | 2018-09-28 | 2020-04-07 | 北京瑞莱博基医药科技有限公司 | 一种糖尿病治疗药物中间体的新合成工艺 |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8957203B2 (en) | 2011-05-05 | 2015-02-17 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
US9499550B2 (en) | 2012-10-19 | 2016-11-22 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
WO2014071007A1 (en) | 2012-11-02 | 2014-05-08 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
US9643999B2 (en) | 2012-11-02 | 2017-05-09 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
WO2014070964A1 (en) | 2012-11-02 | 2014-05-08 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
US9409943B2 (en) | 2012-11-05 | 2016-08-09 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
CN105164148A (zh) | 2013-03-07 | 2015-12-16 | 百时美施贵宝公司 | 丙型肝炎病毒抑制剂 |
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CN101228181A (zh) * | 2005-07-20 | 2008-07-23 | 默克公司 | Hcv ns3蛋白酶抑制剂 |
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WO2011009961A1 (en) * | 2009-07-24 | 2011-01-27 | Virologik Gmbh | Combination of proteasome inhibitors and anti-hepatitis medication for treating hepatitis |
CN102112486A (zh) * | 2008-05-29 | 2011-06-29 | 百时美施贵宝公司 | 丙型肝炎病毒抑制剂 |
CN102300871A (zh) * | 2008-12-19 | 2011-12-28 | 吉里德科学公司 | Hcv ns3蛋白酶抑制剂 |
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CA2369711A1 (en) * | 2002-01-30 | 2003-07-30 | Boehringer Ingelheim (Canada) Ltd. | Macrocyclic peptides active against the hepatitis c virus |
PE20050953A1 (es) * | 2003-09-26 | 2005-11-19 | Schering Corp | Compuestos macrociclicos como inhibidores de la serina proteasa ns3 del virus de la hepatitis c |
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GB0612423D0 (en) * | 2006-06-23 | 2006-08-02 | Angeletti P Ist Richerche Bio | Therapeutic agents |
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CN102617705B (zh) * | 2012-02-16 | 2014-12-31 | 上海纬诺医药科技有限公司 | 抑制丙肝病毒复制的大环类化合物 |
-
2012
- 2012-02-16 CN CN201210034872.0A patent/CN102617705B/zh not_active Expired - Fee Related
- 2012-12-05 KR KR1020147022579A patent/KR102004381B1/ko active IP Right Grant
- 2012-12-05 WO PCT/CN2012/085912 patent/WO2013120371A1/zh active Application Filing
- 2012-12-05 IN IN1637MUN2014 patent/IN2014MN01637A/en unknown
- 2012-12-05 US US14/375,418 patent/US9321809B2/en active Active
- 2012-12-05 EP EP12868766.2A patent/EP2816054A4/en not_active Withdrawn
- 2012-12-05 CA CA2864488A patent/CA2864488A1/en not_active Abandoned
- 2012-12-05 JP JP2014556905A patent/JP6105632B2/ja not_active Expired - Fee Related
- 2012-12-05 CN CN201280069837.0A patent/CN104169293A/zh active Pending
- 2012-12-05 AU AU2012370125A patent/AU2012370125A1/en not_active Abandoned
-
2014
- 2014-07-31 IL IL233899A patent/IL233899A0/en unknown
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013120371A1 (zh) * | 2012-02-16 | 2013-08-22 | 银杏树药业(苏州)有限公司 | 抑制丙肝病毒复制的大环类化合物 |
CN104447952A (zh) * | 2014-12-11 | 2015-03-25 | 上海唐润医药科技有限公司 | 丙肝病毒蛋白酶抑制剂及其合成方法 |
CN110963986A (zh) * | 2018-09-28 | 2020-04-07 | 北京瑞莱博基医药科技有限公司 | 一种糖尿病治疗药物中间体的新合成工艺 |
CN110963986B (zh) * | 2018-09-28 | 2022-03-29 | 北京瑞莱博基医药科技有限公司 | 一种糖尿病治疗药物中间体的合成工艺 |
Also Published As
Publication number | Publication date |
---|---|
IL233899A0 (en) | 2014-09-30 |
CN104169293A (zh) | 2014-11-26 |
US20150031603A1 (en) | 2015-01-29 |
KR102004381B1 (ko) | 2019-10-01 |
WO2013120371A1 (zh) | 2013-08-22 |
AU2012370125A1 (en) | 2014-07-31 |
CN102617705B (zh) | 2014-12-31 |
JP2015508761A (ja) | 2015-03-23 |
US9321809B2 (en) | 2016-04-26 |
EP2816054A1 (en) | 2014-12-24 |
EP2816054A4 (en) | 2015-07-29 |
JP6105632B2 (ja) | 2017-03-29 |
KR20140134273A (ko) | 2014-11-21 |
IN2014MN01637A (zh) | 2015-07-03 |
CA2864488A1 (en) | 2013-08-22 |
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Inventor after: Li Ben Inventor after: Chen Li Inventor after: Zhai Peibin Inventor after: Jiang Tao Inventor before: Li Ben Inventor before: Chen Li Inventor before: Zhai Peibin Inventor before: He Songtao Inventor before: Jiang Tao Inventor before: Gan Libin Inventor before: Xiao Benliang Inventor before: Wen Xiaowei Inventor before: Sun Li |
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