JP2012533569A - フラビウイルス感染症を治療又は予防するためのベンゾイミダゾール類似体 - Google Patents
フラビウイルス感染症を治療又は予防するためのベンゾイミダゾール類似体 Download PDFInfo
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- JP2012533569A JP2012533569A JP2012520823A JP2012520823A JP2012533569A JP 2012533569 A JP2012533569 A JP 2012533569A JP 2012520823 A JP2012520823 A JP 2012520823A JP 2012520823 A JP2012520823 A JP 2012520823A JP 2012533569 A JP2012533569 A JP 2012533569A
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- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title claims description 3
- 206010054261 Flavivirus infection Diseases 0.000 title abstract description 19
- 150000003839 salts Chemical class 0.000 claims abstract description 59
- 229910052796 boron Inorganic materials 0.000 claims abstract description 33
- 125000000217 alkyl group Chemical group 0.000 claims description 576
- 150000001875 compounds Chemical class 0.000 claims description 470
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 326
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 309
- 125000000623 heterocyclic group Chemical group 0.000 claims description 309
- 229910052799 carbon Inorganic materials 0.000 claims description 294
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 286
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 259
- 125000003342 alkenyl group Chemical group 0.000 claims description 251
- 229910052736 halogen Inorganic materials 0.000 claims description 238
- 150000002367 halogens Chemical class 0.000 claims description 238
- 229910052739 hydrogen Inorganic materials 0.000 claims description 236
- 125000001072 heteroaryl group Chemical group 0.000 claims description 234
- 125000000304 alkynyl group Chemical group 0.000 claims description 231
- 125000003118 aryl group Chemical group 0.000 claims description 227
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 206
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 186
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 169
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 146
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 137
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 136
- -1 — (CH 2 ) 1-6 OH Chemical group 0.000 claims description 117
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 105
- DYMRYCZRMAHYKE-UHFFFAOYSA-N n-diazonitramide Chemical compound [O-][N+](=O)N=[N+]=[N-] DYMRYCZRMAHYKE-UHFFFAOYSA-N 0.000 claims description 99
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 80
- 125000004429 atom Chemical group 0.000 claims description 79
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 71
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- 239000003795 chemical substances by application Substances 0.000 claims description 55
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 50
- 125000003545 alkoxy group Chemical group 0.000 claims description 49
- 230000003612 virological effect Effects 0.000 claims description 47
- QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 claims description 45
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 44
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 41
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 39
- 239000003112 inhibitor Substances 0.000 claims description 35
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 27
- 150000001350 alkyl halides Chemical class 0.000 claims description 26
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- 125000004193 piperazinyl group Chemical group 0.000 claims description 25
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 25
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 24
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 23
- 125000001153 fluoro group Chemical group F* 0.000 claims description 22
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 21
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 21
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 21
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 19
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 18
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 18
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 17
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
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- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 14
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 13
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- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical group N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 13
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- 125000002971 oxazolyl group Chemical group 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
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- 229960000329 ribavirin Drugs 0.000 claims description 13
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 13
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- 125000002883 imidazolyl group Chemical group 0.000 claims description 12
- 229940021747 therapeutic vaccine Drugs 0.000 claims description 12
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 12
- 125000001425 triazolyl group Chemical group 0.000 claims description 12
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- 125000005874 benzothiadiazolyl group Chemical group 0.000 claims description 11
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
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- 125000003226 pyrazolyl group Chemical group 0.000 claims description 11
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 11
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 11
- 125000004587 thienothienyl group Chemical group S1C(=CC2=C1C=CS2)* 0.000 claims description 11
- 230000000692 anti-sense effect Effects 0.000 claims description 10
- 230000003078 antioxidant effect Effects 0.000 claims description 10
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 10
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 10
- 208000010710 hepatitis C virus infection Diseases 0.000 claims description 10
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- 125000003373 pyrazinyl group Chemical group 0.000 claims description 10
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
- 108010047761 Interferon-alpha Proteins 0.000 claims description 9
- 102000006992 Interferon-alpha Human genes 0.000 claims description 9
- 125000006001 difluoroethyl group Chemical group 0.000 claims description 9
- 125000005433 dihydrobenzodioxinyl group Chemical group O1C(COC2=C1C=CC=C2)* 0.000 claims description 9
- 125000001624 naphthyl group Chemical group 0.000 claims description 9
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 9
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 7
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 7
- 239000002552 dosage form Substances 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 7
- 125000003072 pyrazolidinyl group Chemical group 0.000 claims description 7
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 6
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 6
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 6
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- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 125000001041 indolyl group Chemical group 0.000 claims description 5
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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
- C07K5/06—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
- C07K5/06052—Val-amino acid
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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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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- 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
- C07D401/14—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 three or more hetero rings
-
- 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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
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- Hematology (AREA)
- Obesity (AREA)
- Communicable Diseases (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Applications Claiming Priority (5)
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- 2010-07-16 IN IN999DEN2012 patent/IN2012DN00999A/en unknown
- 2010-07-16 JP JP2012520823A patent/JP2012533569A/ja not_active Withdrawn
- 2010-07-16 US US12/838,350 patent/US8354419B2/en not_active Expired - Fee Related
- 2010-07-16 CN CN2010800415480A patent/CN102656160A/zh active Pending
-
2012
- 2012-01-12 IL IL217503A patent/IL217503A0/en unknown
- 2012-11-16 US US13/678,854 patent/US8765731B2/en not_active Expired - Fee Related
-
2014
- 2014-05-08 US US14/272,699 patent/US20140243257A1/en not_active Abandoned
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013514982A (ja) * | 2009-12-18 | 2013-05-02 | イデニク プハルマセウティカルス，インコーポレイテッド | ５，５−縮合アリーレン又はヘテロアリーレンｃ型肝炎ウイルス阻害剤 |
| JP2017008058A (ja) * | 2009-12-18 | 2017-01-12 | イデニク プハルマセウティカルス，インコーポレイテッド | ５，５−縮合アリーレン又はヘテロアリーレンｃ型肝炎ウイルス阻害剤 |
| WO2016159082A1 (ja) * | 2015-03-30 | 2016-10-06 | 塩野義製薬株式会社 | ９員縮合環誘導体 |
| KR20170131568A (ko) * | 2015-03-30 | 2017-11-29 | 시오노기 앤드 컴파니, 리미티드 | 9원 축합환 유도체 |
| AU2016240715B2 (en) * | 2015-03-30 | 2020-10-08 | Shionogi & Co., Ltd. | 9-membered fused ring derivative |
| KR102633911B1 (ko) * | 2015-03-30 | 2024-02-05 | 시오노기 앤드 컴파니, 리미티드 | 9원 축합환 유도체 |
Also Published As
| Publication number | Publication date |
|---|---|
| US20140243257A1 (en) | 2014-08-28 |
| IN2012DN00999A (https=) | 2015-04-10 |
| WO2011009084A2 (en) | 2011-01-20 |
| AU2010274001A1 (en) | 2012-02-23 |
| CA2767887A1 (en) | 2011-01-20 |
| IL217503A0 (en) | 2012-03-01 |
| US8354419B2 (en) | 2013-01-15 |
| MX2012000695A (es) | 2012-06-12 |
| US20110172238A1 (en) | 2011-07-14 |
| US20130157997A1 (en) | 2013-06-20 |
| EP2454254A2 (en) | 2012-05-23 |
| US8765731B2 (en) | 2014-07-01 |
| CN102656160A (zh) | 2012-09-05 |
| WO2011009084A3 (en) | 2011-04-28 |
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