ES2700117T3 - Derivados de éster de fosfonato y métodos de síntesis de los mismos - Google Patents
Derivados de éster de fosfonato y métodos de síntesis de los mismos Download PDFInfo
- Publication number
- ES2700117T3 ES2700117T3 ES15193479T ES15193479T ES2700117T3 ES 2700117 T3 ES2700117 T3 ES 2700117T3 ES 15193479 T ES15193479 T ES 15193479T ES 15193479 T ES15193479 T ES 15193479T ES 2700117 T3 ES2700117 T3 ES 2700117T3
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- Prior art keywords
- virus
- compound
- hexadecyloxy
- methyl
- cmx001
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- 239000002253 acid Substances 0.000 description 19
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 19
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- 125000001424 substituent group Chemical group 0.000 description 16
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- FESYLDKBOOCXRD-UHFFFAOYSA-N hexadecyl methanesulfonate Chemical compound CCCCCCCCCCCCCCCCOS(C)(=O)=O FESYLDKBOOCXRD-UHFFFAOYSA-N 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 125000003342 alkenyl group Chemical group 0.000 description 14
- 238000004128 high performance liquid chromatography Methods 0.000 description 14
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 14
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 14
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 239000003826 tablet Substances 0.000 description 14
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- 125000001183 hydrocarbyl group Chemical group 0.000 description 13
- 239000001257 hydrogen Substances 0.000 description 12
- 229910052739 hydrogen Inorganic materials 0.000 description 12
- RTKCPZYOLXPARI-UHFFFAOYSA-N magnesium;2-methylpropan-2-olate Chemical compound [Mg+2].CC(C)(C)[O-].CC(C)(C)[O-] RTKCPZYOLXPARI-UHFFFAOYSA-N 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- LVOASXNJWPROPP-UHFFFAOYSA-N (4-methylphenyl)sulfonyloxymethylphosphonic acid Chemical compound CC1=CC=C(S(=O)(=O)OCP(O)(O)=O)C=C1 LVOASXNJWPROPP-UHFFFAOYSA-N 0.000 description 11
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- XFSXUCMYFWZRAF-UHFFFAOYSA-N 2-(trityloxymethyl)oxirane Chemical compound C1OC1COC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 XFSXUCMYFWZRAF-UHFFFAOYSA-N 0.000 description 7
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- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 description 6
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- UXQPXWNAHMNXOR-UHFFFAOYSA-N diethoxyphosphorylmethyl phenylmethanesulfonate Chemical compound CCOP(=O)(OCC)COS(=O)(=O)CC1=CC=CC=C1 UXQPXWNAHMNXOR-UHFFFAOYSA-N 0.000 description 5
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- HLZGLPITPIPRNZ-UHFFFAOYSA-N phosphonatomethyl phenylmethanesulfonate pyridin-1-ium Chemical compound C(C1=CC=CC=C1)S(=O)(=O)OCP([O-])([O-])=O.[NH+]1=CC=CC=C1.[NH+]1=CC=CC=C1 HLZGLPITPIPRNZ-UHFFFAOYSA-N 0.000 description 4
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- 125000000547 substituted alkyl group Chemical group 0.000 description 4
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- QVBNCXBDAWUGEA-UHFFFAOYSA-N 6-[methoxy(trityl)amino]-1h-pyrimidin-2-one Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)N(OC)C1=CC=NC(=O)N1 QVBNCXBDAWUGEA-UHFFFAOYSA-N 0.000 description 3
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- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
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- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- 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
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4021—Esters of aromatic acids (P-C aromatic linkage)
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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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
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- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
-
- 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
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- C07F9/28—Phosphorus compounds with one or more P—C bonds
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- C07F9/40—Esters thereof
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- C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6509—Six-membered rings
- C07F9/6512—Six-membered rings having the nitrogen atoms in positions 1 and 3
-
- 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
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
- C07F9/657163—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms the ring phosphorus atom being bound to at least one carbon atom
- C07F9/657181—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms the ring phosphorus atom being bound to at least one carbon atom the ring phosphorus atom and, at least, one ring oxygen atom being part of a (thio)phosphonic acid derivative
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Virology (AREA)
- Biochemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Epidemiology (AREA)
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- Biotechnology (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Pulmonology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (1)
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| WO2012031045A2 (en) * | 2010-08-31 | 2012-03-08 | Chimerix, Inc. | Phosphonate ester derivatives and methods of synthesis thereof |
| SG10201800188SA (en) | 2013-03-15 | 2018-02-27 | Univ California | Acyclic nucleoside phosphonate diesters |
| US8962829B1 (en) * | 2013-11-15 | 2015-02-24 | Chimerix, Inc. | Morphic forms of hexadecyloxypropyl-phosphonate esters and methods of synthesis thereof |
| EP3077403A4 (en) * | 2013-12-05 | 2017-08-02 | Chimerix, Inc. | Branched chain acyclic nucleoside phosphonate esters and methods of synthesis and uses thereof |
| CN103951703A (zh) * | 2014-04-28 | 2014-07-30 | 中国人民解放军军事医学科学院微生物流行病研究所 | 制备膦酯衍生物的方法 |
| CN111808136B (zh) | 2014-09-15 | 2024-06-11 | 加利福尼亚大学董事会 | 核苷酸类似物 |
| US10160778B2 (en) | 2014-10-27 | 2018-12-25 | Concert Pharmaceuticals, Inc. | Pyrimidine phosphonic acid esters |
| EP3350191B9 (en) | 2015-09-15 | 2021-12-22 | The Regents of the University of California | Nucleotide analogs |
| AU2017290703B2 (en) | 2016-06-28 | 2023-03-30 | Emergent Biodefense Operations Lansing Llc | Formulations of brincidofovir |
| WO2020006050A1 (en) | 2018-06-26 | 2020-01-02 | Tsrl, Inc. | Metabolically stable prodrugs |
| CN109021011A (zh) * | 2018-08-14 | 2018-12-18 | 山东沾化永浩医药科技有限公司 | 一种合成对甲苯磺酰氧甲基膦酸二乙酯的方法 |
| KR20250052378A (ko) | 2022-07-21 | 2025-04-18 | 안티바 바이오사이언시즈, 인크. | Hpv 감염 및 hpv-유도 신생물의 치료를 위한 조성물 및 투여 형태 |
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| US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
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| CA2747954C (en) | 1999-12-03 | 2014-02-25 | The Regents Of The University Of California | Phosphonate compounds |
| NZ543864A (en) * | 2003-06-16 | 2009-10-30 | Leuven K U Res & Dev | Pyrimidine compounds having phosphonate groups as antiviral nucleotide analogs |
| JP2005045073A (ja) | 2003-07-23 | 2005-02-17 | Hamamatsu Photonics Kk | 裏面入射型光検出素子 |
| WO2005090370A1 (en) * | 2004-02-05 | 2005-09-29 | The Regents Of The University Of California | Pharmacologically active agents containing esterified phosphonates and methods for use thereof |
| WO2005087788A2 (en) * | 2004-03-04 | 2005-09-22 | The Regents Of The University Of California | Methods for preparation of nucleoside phosphonate esters |
| ES2401285T3 (es) * | 2004-12-16 | 2013-04-18 | The Regents Of The University Of California | Fármacos con el pulmón como diana |
| US8642577B2 (en) * | 2005-04-08 | 2014-02-04 | Chimerix, Inc. | Compounds, compositions and methods for the treatment of poxvirus infections |
| EP2842559A3 (en) | 2005-04-08 | 2015-03-18 | Chimerix, Inc. | Compounds, compositions and methods for the treatment of viral infections and other medical disorders |
| WO2007130783A2 (en) * | 2006-05-03 | 2007-11-15 | Chimerix, Inc. | Metabolically stable alkoxyalkyl esters of antiviral or antiproliferative phosphonates, nucleoside phosphonates and nucleoside phosphates |
| AU2008246195B2 (en) * | 2007-04-27 | 2014-06-05 | Emergent Biodefence Operations Lansing Llc | Methods of Reducing Nephrotoxicity in Subjects Administered with Nucleoside Phosphonates |
| WO2011011519A1 (en) | 2009-07-21 | 2011-01-27 | Chimerix, Inc. | Compounds, compositions and methods for treating ocular conditions |
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| CA2779473C (en) | 2009-10-30 | 2016-08-16 | Chimerix, Inc. | Methods of treating viral associated diseases |
| US20110263536A1 (en) | 2010-04-22 | 2011-10-27 | Chimerix, Inc. | Methods of Treating Orthopox Virus Infections and Associated Diseases |
| WO2012031045A2 (en) * | 2010-08-31 | 2012-03-08 | Chimerix, Inc. | Phosphonate ester derivatives and methods of synthesis thereof |
| US20140303092A1 (en) * | 2011-10-26 | 2014-10-09 | Chimerix, Inc | Hexadecyloxypropyl cidofovir for the treatment of double-stranded dna virus infection |
| WO2013163509A1 (en) * | 2012-04-27 | 2013-10-31 | Chimerix, Inc. | A method of mitigating virus associated end-organ damage |
| US8962829B1 (en) * | 2013-11-15 | 2015-02-24 | Chimerix, Inc. | Morphic forms of hexadecyloxypropyl-phosphonate esters and methods of synthesis thereof |
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