JP5669749B2 - ウイルス複製の阻害剤である４−アミノ−４−オキソブタノイルペプチド環状類似体 - Google Patents
ウイルス複製の阻害剤である４−アミノ−４−オキソブタノイルペプチド環状類似体 Download PDFInfo
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- JP5669749B2 JP5669749B2 JP2011540890A JP2011540890A JP5669749B2 JP 5669749 B2 JP5669749 B2 JP 5669749B2 JP 2011540890 A JP2011540890 A JP 2011540890A JP 2011540890 A JP2011540890 A JP 2011540890A JP 5669749 B2 JP5669749 B2 JP 5669749B2
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- Prior art keywords
- dioxo
- pyrrolo
- alkyl
- carboxamide
- yloxy
- Prior art date
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- -1 4-amino-4-oxobutanoyl Chemical group 0.000 title claims description 308
- 125000004122 cyclic group Chemical group 0.000 title description 12
- 108090000765 processed proteins & peptides Proteins 0.000 title description 9
- 239000003112 inhibitor Substances 0.000 title description 7
- 230000029812 viral genome replication Effects 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims description 187
- 125000000217 alkyl group Chemical group 0.000 claims description 145
- 150000003839 salts Chemical class 0.000 claims description 74
- 125000001424 substituent group Chemical group 0.000 claims description 64
- 229910052739 hydrogen Inorganic materials 0.000 claims description 57
- 239000001257 hydrogen Substances 0.000 claims description 57
- 229910052736 halogen Inorganic materials 0.000 claims description 52
- 150000002367 halogens Chemical class 0.000 claims description 51
- 125000004432 carbon atom Chemical group C* 0.000 claims description 49
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 49
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 45
- 125000003118 aryl group Chemical group 0.000 claims description 44
- 238000000034 method Methods 0.000 claims description 43
- 125000003545 alkoxy group Chemical group 0.000 claims description 39
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 34
- 229910052717 sulfur Inorganic materials 0.000 claims description 34
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 32
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 31
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 29
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 29
- 208000005176 Hepatitis C Diseases 0.000 claims description 28
- 229910052760 oxygen Inorganic materials 0.000 claims description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 24
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- 125000001183 hydrocarbyl group Chemical group 0.000 claims 2
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 1
- XKNGSLFFWBWACL-UHFFFAOYSA-N 1,4-diazacyclopentadeca-2,4,6,8,10,12,14-heptaen-2-yl 4-fluoro-1,3-dihydroisoindole-2-carboxylate Chemical compound FC1=C2CN(CC2=CC=C1)C(=O)OC=1NC=CC=CC=CC=CC=CC=NC=1 XKNGSLFFWBWACL-UHFFFAOYSA-N 0.000 claims 1
- DLPDBBPTTGBGRX-UHFFFAOYSA-N 3,4-dihydro-1h-isoquinoline-2-carboxylic acid Chemical compound C1=CC=C2CN(C(=O)O)CCC2=C1 DLPDBBPTTGBGRX-UHFFFAOYSA-N 0.000 claims 1
- ATIAQHBVRPNWGE-UHFFFAOYSA-N N1C=C(N=CC=CC=CC=CC=CC=C1)C(=O)O Chemical compound N1C=C(N=CC=CC=CC=CC=CC=C1)C(=O)O ATIAQHBVRPNWGE-UHFFFAOYSA-N 0.000 claims 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
- RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 claims 1
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Classifications
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- 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
- C07K5/12—Cyclic peptides with only normal peptide bonds in the ring
-
- 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
- C07D403/14—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 three or more hetero rings
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
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- 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
- A61K38/05—Dipeptides
-
- A—HUMAN NECESSITIES
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- 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
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- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D403/12—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 chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- 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
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- C07K5/06165—Dipeptides with the first amino acid being heterocyclic and Pro-amino acid; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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Landscapes
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- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
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- Public Health (AREA)
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- Genetics & Genomics (AREA)
- Biophysics (AREA)
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- General Chemical & Material Sciences (AREA)
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- Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Oncology (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
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| US61/226,323 | 2009-07-17 | ||
| PCT/US2009/067507 WO2010068761A2 (en) | 2008-12-10 | 2009-12-10 | 4-amino-4-oxobutanoyl peptide cyclic analogues, inhibitors of viral replication |
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| WO2009142842A2 (en) | 2008-04-15 | 2009-11-26 | Intermune, Inc. | Novel macrocyclic inhibitors of hepatitis c virus replication |
| WO2010045266A1 (en) * | 2008-10-15 | 2010-04-22 | Intermune, Inc. | Therapeutic antiviral peptides |
| AR075584A1 (es) * | 2009-02-27 | 2011-04-20 | Intermune Inc | COMPOSICIONES TERAPEUTICAS QUE COMPRENDEN beta-D-2'-DESOXI-2'-FLUORO-2'-C-METILCITIDINA Y UN DERIVADO DE ACIDO ISOINDOL CARBOXILICO Y SUS USOS. COMPUESTO. |
| US8835456B1 (en) | 2011-03-18 | 2014-09-16 | Achillion Pharmaceuticals, Inc. | NS5A inhibitors useful for treating HCV |
| US8957203B2 (en) | 2011-05-05 | 2015-02-17 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| RS55123B1 (sr) | 2011-05-27 | 2016-12-30 | Achillion Pharmaceuticals Inc | Supstituisani alifani, ciklofani, heterafani, heterofani, hetero-heterafani i metaloceni korisni za lečenje infekcija hepatitis c virusa |
| UA119315C2 (uk) | 2012-07-03 | 2019-06-10 | Гіліад Фармассет Елелсі | Інгібітори вірусу гепатиту с |
| JP6154474B2 (ja) | 2012-10-19 | 2017-06-28 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | Ｃ型肝炎ウイルス阻害剤 |
| US9643999B2 (en) | 2012-11-02 | 2017-05-09 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| WO2014071007A1 (en) | 2012-11-02 | 2014-05-08 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| EP2914613B1 (en) | 2012-11-02 | 2017-11-22 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| EP2914614B1 (en) | 2012-11-05 | 2017-08-16 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| EP2964664B1 (en) | 2013-03-07 | 2017-01-11 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| EP3782638A1 (en) | 2013-03-13 | 2021-02-24 | President and Fellows of Harvard College | Stapled and stitched polypeptides and uses thereof |
| JP6511432B2 (ja) | 2013-03-15 | 2019-05-15 | ギリアード サイエンシーズ， インコーポレイテッド | Ｃ型肝炎ウイルスの大環状二環式阻害剤 |
| WO2014145600A1 (en) * | 2013-03-15 | 2014-09-18 | Achillion Pharmaceuticals, Inc. | Ach-0142684 sodium salt polymorphs, composition including the same, and method of manufacture thereof |
| WO2014145507A1 (en) | 2013-03-15 | 2014-09-18 | Achillion Pharmaceuticals, Inc. | A process for making a 4-amino-4-oxobutanoyl peptide cyclic analogue, an inhibitor of viral replication, and intermediates thereof |
| AU2014250762A1 (en) | 2013-04-12 | 2015-10-29 | Achillion Pharmaceuticals, Inc. | Highly active nucleoside derivative for the treatment of HCV |
| WO2014201370A1 (en) | 2013-06-14 | 2014-12-18 | President And Fellows Of Harvard College | Stabilized polypeptide insulin receptor modulators |
| CN114805527A (zh) | 2014-05-21 | 2022-07-29 | 哈佛大学的校长及成员们 | Ras抑制肽和其用途 |
| BR112020004555A2 (pt) | 2017-09-07 | 2020-09-24 | Fog Pharmaceuticals, Inc. | agentes que modulam funções de beta-catenina e métodos dos mesmos |
| WO2022232025A1 (en) * | 2021-04-26 | 2022-11-03 | Alkermes, Inc. | Substituted amide macrocyclic compounds with orexin-2 receptor agonist activity |
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| 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 |
| MXPA03004299A (es) * | 2000-11-20 | 2004-02-12 | Bristol Myers Squibb Co | Inhibidores de tripeptido de hepatitis c. |
| US6867185B2 (en) * | 2001-12-20 | 2005-03-15 | Bristol-Myers Squibb Company | Inhibitors of hepatitis C virus |
| US7119072B2 (en) * | 2002-01-30 | 2006-10-10 | Boehringer Ingelheim (Canada) Ltd. | Macrocyclic peptides active against the hepatitis C virus |
| US20060199773A1 (en) * | 2002-05-20 | 2006-09-07 | Sausker Justin B | Crystalline forms of (1R,2S)-N-[(1,1-dimethylethoxy)carbonyl]-3-methyl-L-valyl-(4R)-4-[(6-methoxy-1-isoquinolinyl)oxy]-L-prolyl-1-amino-N-(cyclopropylsulfonyl)-2-ethenyl-cyclopropanecarboxamide, monopotassium salt |
| ES2315568T3 (es) * | 2002-05-20 | 2009-04-01 | Bristol-Myers Squibb Company | Inhibidores del virus de la hepatitis c basados en cicloalquilo p1' sustituido. |
| PL215228B1 (pl) * | 2002-05-20 | 2013-11-29 | Bristol Myers Squibb Co | Zwiazki tripeptydowe, ich zastosowanie i kompozycja farmaceutyczna je zawierajaca oraz jej zastosowanie |
| MY140680A (en) * | 2002-05-20 | 2010-01-15 | Bristol Myers Squibb Co | Hepatitis c virus inhibitors |
| US7601709B2 (en) * | 2003-02-07 | 2009-10-13 | Enanta Pharmaceuticals, Inc. | Macrocyclic hepatitis C serine protease inhibitors |
| US20040180815A1 (en) * | 2003-03-07 | 2004-09-16 | Suanne Nakajima | Pyridazinonyl macrocyclic hepatitis C serine protease inhibitors |
| CN1771050A (zh) * | 2003-02-07 | 2006-05-10 | 益安药业 | 丙型肝炎丝氨酸蛋白酶的大环抑制剂 |
| DE602004029866D1 (de) * | 2003-03-05 | 2010-12-16 | Boehringer Ingelheim Pharma | Peptidanaloga mit inhibitorischer wirkung auf hepatitis c |
| US7176208B2 (en) * | 2003-04-18 | 2007-02-13 | Enanta Pharmaceuticals, Inc. | Quinoxalinyl macrocyclic hepatitis C serine protease inhibitors |
| UY29016A1 (es) * | 2004-07-20 | 2006-02-24 | Boehringer Ingelheim Int | Analogos de dipeptidos inhibidores de la hepatitis c |
| JP4914355B2 (ja) * | 2004-07-20 | 2012-04-11 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｃ型肝炎インヒビターペプチド類似体 |
| CN101039947A (zh) * | 2004-08-09 | 2007-09-19 | 布里斯托尔-迈尔斯斯奎布公司 | Hcv复制抑制剂 |
| US7153848B2 (en) * | 2004-08-09 | 2006-12-26 | Bristol-Myers Squibb Company | Inhibitors of HCV replication |
| US7659263B2 (en) * | 2004-11-12 | 2010-02-09 | Japan Tobacco Inc. | Thienopyrrole compound and use thereof as HCV polymerase inhibitor |
| US7601686B2 (en) * | 2005-07-11 | 2009-10-13 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US7772183B2 (en) * | 2005-10-12 | 2010-08-10 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US7741281B2 (en) * | 2005-11-03 | 2010-06-22 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| ES2448494T3 (es) * | 2006-07-13 | 2014-03-14 | Achillion Pharmaceuticals, Inc. | Péptidos de 4-amino-4-oxobutanoilo en calidad de inhibidores de la replicación viral |
| ES2527166T3 (es) * | 2008-12-10 | 2015-01-21 | Achillion Pharmaceuticals, Inc. | Nuevos péptidos de 4-amino-4-oxobutanoílo como inhibidores de la replicación viral |
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| US20140206604A1 (en) | 2014-07-24 |
| NZ592705A (en) | 2013-02-22 |
| WO2010068761A2 (en) | 2010-06-17 |
| KR20110096557A (ko) | 2011-08-30 |
| EA201100927A1 (ru) | 2011-12-30 |
| IL212787A0 (en) | 2011-07-31 |
| CN102245598B (zh) | 2014-01-29 |
| CN102245598A (zh) | 2011-11-16 |
| EP2364310A2 (en) | 2011-09-14 |
| JP2012511588A (ja) | 2012-05-24 |
| CA2746265A1 (en) | 2010-06-17 |
| US20100152103A1 (en) | 2010-06-17 |
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| AU2009324644A1 (en) | 2010-06-17 |
| ZA201104383B (en) | 2012-03-28 |
| BRPI0922913A2 (pt) | 2015-08-18 |
| AU2009324644B2 (en) | 2013-12-05 |
| EP2364310A4 (en) | 2012-05-16 |
| EA021794B1 (ru) | 2015-09-30 |
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