JP5031569B2 - Ｈｉｖ阻害剤としてのホスホインドール - Google Patents
Ｈｉｖ阻害剤としてのホスホインドール Download PDFInfo
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- JP5031569B2 JP5031569B2 JP2007531877A JP2007531877A JP5031569B2 JP 5031569 B2 JP5031569 B2 JP 5031569B2 JP 2007531877 A JP2007531877 A JP 2007531877A JP 2007531877 A JP2007531877 A JP 2007531877A JP 5031569 B2 JP5031569 B2 JP 5031569B2
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- JP
- Japan
- Prior art keywords
- alkyl
- hiv
- independently
- optionally substituted
- aryl
- 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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- 239000003112 inhibitor Substances 0.000 title description 13
- 150000003006 phosphoindoles Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 164
- 239000003814 drug Substances 0.000 claims abstract description 66
- 229910052801 chlorine Inorganic materials 0.000 claims description 174
- 229910052731 fluorine Inorganic materials 0.000 claims description 170
- 125000000217 alkyl group Chemical group 0.000 claims description 144
- 229910052739 hydrogen Inorganic materials 0.000 claims description 134
- 229910052736 halogen Inorganic materials 0.000 claims description 88
- 239000001257 hydrogen Substances 0.000 claims description 84
- 150000002367 halogens Chemical class 0.000 claims description 80
- 125000000623 heterocyclic group Chemical group 0.000 claims description 80
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 66
- 150000003839 salts Chemical class 0.000 claims description 66
- -1 benzyloxyl Chemical group 0.000 claims description 58
- 229940079593 drug Drugs 0.000 claims description 52
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- 125000004093 cyano group Chemical group *C#N 0.000 claims description 34
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- 208000031886 HIV Infections Diseases 0.000 claims description 31
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- 125000003545 alkoxy group Chemical group 0.000 claims description 24
- 230000002265 prevention Effects 0.000 claims description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
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- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
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- 238000004519 manufacturing process Methods 0.000 abstract description 8
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- 125000003118 aryl group Chemical group 0.000 description 81
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- 125000005843 halogen group Chemical group 0.000 description 66
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- 125000002947 alkylene group Chemical group 0.000 description 42
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- 125000003342 alkenyl group Chemical group 0.000 description 36
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 32
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 31
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- 125000000547 substituted alkyl group Chemical group 0.000 description 30
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- 238000012360 testing method Methods 0.000 description 22
- 125000002252 acyl group Chemical group 0.000 description 20
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- 210000004027 cell Anatomy 0.000 description 19
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 19
- 125000001424 substituent group Chemical group 0.000 description 19
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
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- 239000002904 solvent Substances 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 17
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- 230000002829 reductive effect Effects 0.000 description 17
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- 238000003786 synthesis reaction Methods 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
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- 238000003556 assay Methods 0.000 description 15
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
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- 125000006850 spacer group Chemical group 0.000 description 10
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- KLLLJCACIRKBDT-UHFFFAOYSA-N 2-phenyl-1H-indole Chemical group N1C2=CC=CC=C2C=C1C1=CC=CC=C1 KLLLJCACIRKBDT-UHFFFAOYSA-N 0.000 description 8
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Images
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom
-
- 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
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- 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
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- 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
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
- C07F9/5728—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
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- Oncology (AREA)
- Communicable Diseases (AREA)
- Tropical Medicine & Parasitology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- AIDS & HIV (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US61106104P | 2004-09-17 | 2004-09-17 | |
| US60/611,061 | 2004-09-17 | ||
| US71144505P | 2005-08-25 | 2005-08-25 | |
| US60/711,445 | 2005-08-25 | ||
| US71156505P | 2005-08-26 | 2005-08-26 | |
| US60/711,565 | 2005-08-26 | ||
| PCT/IB2005/004063 WO2006054182A2 (en) | 2004-09-16 | 2005-09-16 | Phosphoindoles as hiv inhibitors |
Publications (3)
| Publication Number | Publication Date |
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| JP2008515782A JP2008515782A (ja) | 2008-05-15 |
| JP2008515782A5 JP2008515782A5 (https=) | 2008-11-06 |
| JP5031569B2 true JP5031569B2 (ja) | 2012-09-19 |
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| CA (1) | CA2583409C (https=) |
| CY (1) | CY1109440T1 (https=) |
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| NZ (1) | NZ554232A (https=) |
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| DE602005011031D1 (en) | 2004-09-17 | 2008-12-24 | Idenix Pharmaceuticals Inc | Phosphoindole als hiv-inhibitoren |
| KR20090077813A (ko) | 2006-09-29 | 2009-07-15 | 아이데닉스 파마슈티칼스, 인코포레이티드 | Ｈｉｖ 억제제로서의 거울상이성질체적으로 순수한 포스포인돌 |
| US20100113421A1 (en) * | 2006-10-06 | 2010-05-06 | Williams Theresa M | Non-nucleoside reverse transcriptase inhibitors |
| BRPI0811645A2 (pt) | 2007-05-30 | 2014-11-11 | Hoffmann La Roche | Inibidores de transcriptase reversa de não-nucleosídeo |
| TW200946541A (en) * | 2008-03-27 | 2009-11-16 | Idenix Pharmaceuticals Inc | Solid forms of an anti-HIV phosphoindole compound |
| TW200944537A (en) * | 2008-04-03 | 2009-11-01 | Idenix Pharmaceuticals Inc | Formulations comprising a phosphoindole compound and one or more second active agents |
| EP2393822B1 (en) * | 2009-02-03 | 2014-07-16 | IDENIX Pharmaceuticals, Inc. | Phosphinate ruthenium complexes |
| EP2403860B1 (en) * | 2009-03-04 | 2015-11-04 | IDENIX Pharmaceuticals, Inc. | Phosphothiophene and phosphothiazole as hcv polymerase inhibitors |
| PE20121524A1 (es) | 2010-01-27 | 2012-12-03 | Viiv Healthcare Co | Combinaciones de compuestos que comprenden inhibidores de la integrasa de vih y otros agentes terapeuticos |
| CN103275126B (zh) * | 2013-05-28 | 2016-03-23 | 兰州大学 | 一种立体选择性合成3-位膦酰化吲哚的方法 |
| ITMI20131218A1 (it) * | 2013-07-19 | 2015-01-20 | Need Pharma Srl | Nuovi ureido derivati di acidi naftalensolfonici |
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| US4866084A (en) | 1987-07-17 | 1989-09-12 | Harbor Branch Oceanographic Institution, Inc. | Topsentin compounds effective against viruses and certain tumors |
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| WO2002083126A1 (en) * | 2001-04-11 | 2002-10-24 | Idenix (Cayman) Limited | Phenylindoles for the treatment of hiv |
| US6825201B2 (en) | 2001-04-25 | 2004-11-30 | Bristol-Myers Squibb Company | Indole, azaindole and related heterocyclic amidopiperazine derivatives |
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