CA2771988C - Process for the synthesis of 4,5,6,7-tetrachloro-3',6'-dihydroxy-2',4',5',7'-tetraiodo-3h-spiro[isobenzofuran-1,9'-xanthen]-3-one (rose bengal) and related xanthenes - Google Patents

Process for the synthesis of 4,5,6,7-tetrachloro-3',6'-dihydroxy-2',4',5',7'-tetraiodo-3h-spiro[isobenzofuran-1,9'-xanthen]-3-one (rose bengal) and related xanthenes Download PDF

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Publication number
CA2771988C
CA2771988C CA2771988A CA2771988A CA2771988C CA 2771988 C CA2771988 C CA 2771988C CA 2771988 A CA2771988 A CA 2771988A CA 2771988 A CA2771988 A CA 2771988A CA 2771988 C CA2771988 C CA 2771988C
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Prior art keywords
formula
compound
iodine
solution
acid
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CA2771988A
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French (fr)
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CA2771988A1 (en
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Jamie Singer
Eric A. Wachter
Timothy C. Scott
Marlon Lutz
Kevin Babiak
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Provectus Pharmatech Inc
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Provectus Biopharmaceuticals Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/78—Ring systems having three or more relevant rings
    • C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/78—Ring systems having three or more relevant rings
    • C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
    • C07D311/82—Xanthenes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • 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
    • 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
    • A61P31/04—Antibacterial agents
    • 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
    • A61P31/10—Antimycotics
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/10—Spiro-condensed systems

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Endocrinology (AREA)
  • Dermatology (AREA)
  • Pulmonology (AREA)
  • Virology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Diabetes (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Reproductive Health (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Pyrane Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Medicinal Preparation (AREA)
CA2771988A 2009-09-18 2010-09-17 Process for the synthesis of 4,5,6,7-tetrachloro-3',6'-dihydroxy-2',4',5',7'-tetraiodo-3h-spiro[isobenzofuran-1,9'-xanthen]-3-one (rose bengal) and related xanthenes Active CA2771988C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US24370109P 2009-09-18 2009-09-18
US61/243,701 2009-09-18
PCT/US2010/049341 WO2011035161A1 (en) 2009-09-18 2010-09-17 Process for the synthesis of 4,5,6,7-tetrachloro-3',6'-dihydroxy-2',4',5'7'-tetraiodo-3h-spiro[isobenzofuran-1,9'-xanthen]-3-one (rose bengal) and related xanthenes

Publications (2)

Publication Number Publication Date
CA2771988A1 CA2771988A1 (en) 2011-03-24
CA2771988C true CA2771988C (en) 2016-07-05

Family

ID=43757167

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2771988A Active CA2771988C (en) 2009-09-18 2010-09-17 Process for the synthesis of 4,5,6,7-tetrachloro-3',6'-dihydroxy-2',4',5',7'-tetraiodo-3h-spiro[isobenzofuran-1,9'-xanthen]-3-one (rose bengal) and related xanthenes

Country Status (9)

Country Link
US (2) US8530675B2 (en:Method)
EP (1) EP2464225B8 (en:Method)
JP (1) JP5671040B2 (en:Method)
KR (1) KR101494055B1 (en:Method)
CN (1) CN102548406B (en:Method)
CA (1) CA2771988C (en:Method)
ES (1) ES2548575T3 (en:Method)
MX (1) MX2012003063A (en:Method)
WO (1) WO2011035161A1 (en:Method)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012122444A1 (en) * 2011-03-10 2012-09-13 Provectus Pharmaceuticals, Inc. Combination of local and systemic immunomodulative therapies for enhanced treatment of cancer
WO2015059467A1 (en) * 2013-10-22 2015-04-30 SETNA, Rohan Rose bengal for detection of oxidative decomposition of contaminants
JP7015232B2 (ja) * 2018-11-21 2022-02-02 東レ・ファインケミカル株式会社 高純度のフルオレセイン類化合物の製造方法
CN113454088A (zh) * 2019-02-26 2021-09-28 豪夫迈·罗氏有限公司 用于制备(6S)-3-[(4S)-4-氰基-2-氧代-吡咯烷-1-基]-6-甲基-N-(3,4,5-三氟苯基)-6,7-二氢-4H-吡唑并[1,5-a]吡嗪-5-甲酰胺的方法
US11938182B2 (en) 2020-03-26 2024-03-26 Provectus Pharmatech, Inc. Halogenated xanthenes as vaccine adjuvants
EP4103283A4 (en) * 2020-03-26 2024-02-28 Provectus Pharmatech, Inc. NEW USES OF HALOGENATED XANTHENES IN ONCOLOGY AND VIROLOGY
WO2024206220A1 (en) * 2023-03-29 2024-10-03 Provectus Pharmatech, Inc. Anti-bacterial effect of halogenated fluoresceins against colistin-resistant gram-negative bacteria

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DE108838C (en:Method)
US1965842A (en) * 1931-11-21 1934-07-10 Nat Aniline & Chem Co Inc Production of hydroxybenzenephthaleins
US1931049A (en) * 1931-11-21 1933-10-17 Nat Aniline & Chem Co Inc Process of making dihydroxyfluoranes
US3829440A (en) * 1972-12-21 1974-08-13 Richardson Merrell Inc Xanthene derivatives
SU517222A1 (ru) 1974-10-25 1977-06-25 Институт Биофизики Министерства Здравохранения Ссср Способ получени препарата бенгальска роза, меченного радиоизотопами йода
SU792878A1 (ru) 1978-08-29 1982-02-07 Ленинградский институт ядерной физики им. Б.П.Константинова Способ получени галогенированных производных флуоресцеина,меченных радиоизотопом йода
EP0050684B1 (en) 1980-10-27 1986-01-22 Syva Company Novel ether substituted fluorescein compounds as fluorescers and quenchers
SU992516A1 (ru) 1981-06-11 1983-01-30 Ленинградский Институт Ядерной Физики Им.Б.П.Константинова Способ получени галогенированных производных флуоресцеина,меченных радиоизотопом иода -123
ES8606451A1 (es) 1985-10-28 1986-04-16 Zoster Sa Procedimiento para la obtencion de la eritrosina sodica
IN168346B (en:Method) 1987-09-07 1991-03-16 Council Scient Ind Res
US5637733A (en) * 1995-09-27 1997-06-10 Warner-Jenkinson Company, Inc. Syntheses of fluorescein compounds with excess resorcinol as a solvent
EP0862741B1 (en) * 1995-10-23 2001-04-25 Novartis AG Optical sensor system for the determination of ph values independently of ionic strength
US6162931A (en) 1996-04-12 2000-12-19 Molecular Probes, Inc. Fluorinated xanthene derivatives
US5945526A (en) * 1996-05-03 1999-08-31 Perkin-Elmer Corporation Energy transfer dyes with enhanced fluorescence
US6331286B1 (en) * 1998-12-21 2001-12-18 Photogen, Inc. Methods for high energy phototherapeutics
US7648695B2 (en) * 1998-08-06 2010-01-19 Provectus Pharmatech, Inc. Medicaments for chemotherapeutic treatment of disease
US6372907B1 (en) * 1999-11-03 2002-04-16 Apptera Corporation Water-soluble rhodamine dye peptide conjugates
US6448407B1 (en) 2000-11-01 2002-09-10 Pe Corporation (Ny) Atropisomers of asymmetric xanthene fluorescent dyes and methods of DNA sequencing and fragment analysis
AU2002256991A1 (en) * 2001-02-05 2002-08-19 The Government Of The United States Of America, As Represented By The Secretary, Department Of Healt Use of 9h-xanthenes in a method of inhibiting viral replication targeting the nucleocapsid protein
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Also Published As

Publication number Publication date
US9422260B2 (en) 2016-08-23
KR20120091088A (ko) 2012-08-17
HK1172212A1 (zh) 2013-04-19
EP2464225B8 (en) 2017-08-23
WO2011035161A1 (en) 2011-03-24
EP2464225B1 (en) 2015-09-16
ES2548575T3 (es) 2015-10-19
KR101494055B1 (ko) 2015-02-16
EP2464225A1 (en) 2012-06-20
US20110071217A1 (en) 2011-03-24
EP2464225A4 (en) 2013-03-27
CA2771988A1 (en) 2011-03-24
CN102548406B (zh) 2015-04-08
MX2012003063A (es) 2012-07-25
CN102548406A (zh) 2012-07-04
JP5671040B2 (ja) 2015-02-18
US20130274322A1 (en) 2013-10-17
US8530675B2 (en) 2013-09-10
HK1172501A1 (en) 2013-04-26
JP2013505261A (ja) 2013-02-14

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