WO2003072066A2 - Compositions and methods for the treatment of glaucoma and ocular hypertension - Google Patents

Compositions and methods for the treatment of glaucoma and ocular hypertension Download PDF

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Publication number
WO2003072066A2
WO2003072066A2 PCT/US2003/006685 US0306685W WO03072066A2 WO 2003072066 A2 WO2003072066 A2 WO 2003072066A2 US 0306685 W US0306685 W US 0306685W WO 03072066 A2 WO03072066 A2 WO 03072066A2
Authority
WO
WIPO (PCT)
Prior art keywords
ester
uridine
alkyl
deoxy
trihydrogen diphosphate
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.)
Ceased
Application number
PCT/US2003/006685
Other languages
English (en)
French (fr)
Other versions
WO2003072066A3 (en
Inventor
Jose L. Boyer
Benjamin R. Yerxa
Robert Plourde, Jr.
Edward G. Brown
James G. Douglass Iii
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Inspire Pharmaceuticals Inc
Original Assignee
Inspire Pharmaceuticals Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Inspire Pharmaceuticals Inc filed Critical Inspire Pharmaceuticals Inc
Priority to AU2003223224A priority Critical patent/AU2003223224A1/en
Priority to GB0419174A priority patent/GB2402674B/en
Priority to JP2003570813A priority patent/JP2005535564A/ja
Publication of WO2003072066A2 publication Critical patent/WO2003072066A2/en
Anticipated expiration legal-status Critical
Publication of WO2003072066A3 publication Critical patent/WO2003072066A3/en
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7084—Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06—Pyrimidine radicals
    • C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/16—Purine radicals
    • C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/16—Purine radicals
    • C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
    • C07H19/207—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids the phosphoric or polyphosphoric acids being esterified by a further hydroxylic compound, e.g. flavine adenine dinucleotide or nicotinamide-adenine dinucleotide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids

Definitions

  • Adjunctive therapy includes the intravenous administration of a carbonic anhydrase inhibitor such as acetozolamide to reduce the secretion of aqueous humor, or of an osmotic agent such as mannitol or glycerin to induce intraocular dehydration.
  • a carbonic anhydrase inhibitor such as acetozolamide
  • an osmotic agent such as mannitol or glycerin to induce intraocular dehydration.
  • Therapy of chronic simple glaucoma and secondary glaucoma includes: (1) prostaglandin analogs (e.g. Xalatan ® , Lumigan); (2) beta-adrenergic antagonists such as timolol maleate; (3) sympathomimetic agents (e.g. epinephrine, brimonidine); (4) cholinergic agents (e.g.
  • An effective amount of a nucleoside 5'- pyrophosphate pyranoside or analogue is an amount that reacts with a nucleoside 5'- pyrophosphate pyranoside receptor (a G-protein coupled receptor), leading to a reduction in intraocular pressure and/or amelioration ofthe symptoms of glaucoma.
  • a nucleoside 5'- pyrophosphate pyranoside receptor a G-protein coupled receptor
  • Z O, CH 2 , or CC1 2 ;
  • J 7 are the same as those described in Formula I; provided that the ring formed by the G ⁇ -G 6 ring atoms, in addition to the phosphate moiety, has a minimum of two oxygen-atom-containing substituents (such as hydroxy-, alkoxy-, or acyloxy-) bonded to it, wherein each of said substituents is bonded directly from said oxygen atom of substituent to said ring.
  • substituents such as hydroxy-, alkoxy-, or acyloxy-
  • cyclical orthoesters are prepared by reaction of vicinal hydroxyl groups of a furanose, pyranose, inositol, appropriate nucleoside or appropriate nucleotide derivative with an acylic orthoester in the presence of an acid.

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)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Ophthalmology & Optometry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
PCT/US2003/006685 2002-02-27 2003-02-27 Compositions and methods for the treatment of glaucoma and ocular hypertension Ceased WO2003072066A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU2003223224A AU2003223224A1 (en) 2002-02-27 2003-02-27 Compositions and methods for the treatment of glaucoma and ocular hypertension
GB0419174A GB2402674B (en) 2002-02-27 2003-02-27 Compositions and methods for the treatment of glaucoma or ocular hypertension
JP2003570813A JP2005535564A (ja) 2002-02-27 2003-02-27 緑内障または高眼圧症の治療のための組成物および方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US10/087,551 2002-02-27
US10/087,551 US6897201B2 (en) 2000-08-21 2002-02-27 Compositions and methods for the treatment of glaucoma or ocular hypertension

Publications (2)

Publication Number Publication Date
WO2003072066A2 true WO2003072066A2 (en) 2003-09-04
WO2003072066A3 WO2003072066A3 (en) 2004-11-11

Family

ID=27765359

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2003/006685 Ceased WO2003072066A2 (en) 2002-02-27 2003-02-27 Compositions and methods for the treatment of glaucoma and ocular hypertension

Country Status (6)

Country Link
US (1) US6897201B2 (https=)
JP (1) JP2005535564A (https=)
AU (1) AU2003223224A1 (https=)
GB (1) GB2402674B (https=)
TW (1) TW200305427A (https=)
WO (1) WO2003072066A2 (https=)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6897201B2 (en) 2000-08-21 2005-05-24 Inspire Pharmaceuticals, Inc. Compositions and methods for the treatment of glaucoma or ocular hypertension

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2345657A1 (en) * 2003-05-30 2011-07-20 Pharmasset, Inc. Modified fluorinated nucleoside analogues
US7488100B2 (en) * 2003-09-03 2009-02-10 Samuel Roberts Bicycle light
CN101023094B (zh) * 2004-07-21 2011-05-18 法莫赛特股份有限公司 烷基取代的2-脱氧-2-氟代-d-呋喃核糖基嘧啶和嘌呤及其衍生物的制备
AU2005285045B2 (en) * 2004-09-14 2011-10-13 Gilead Sciences, Inc. Preparation of 2'fluoro-2'- alkyl- substituted or other optionally substituted ribofuranosyl pyrimidines and purines and their derivatives
EP1863826A1 (en) * 2005-03-30 2007-12-12 Inspire Pharmaceuticals, Inc. Process for the preparation of 4,6-disubstituted-tetrahydro-furo, thieno, pyrrolo and cyclopenta-[3,4][1,3]dioxoles
US7964580B2 (en) 2007-03-30 2011-06-21 Pharmasset, Inc. Nucleoside phosphoramidate prodrugs
US8173621B2 (en) 2008-06-11 2012-05-08 Gilead Pharmasset Llc Nucleoside cyclicphosphates
KR20110098849A (ko) 2008-12-23 2011-09-01 파마셋 인코포레이티드 뉴클레오시드 유사체
PT2376088T (pt) 2008-12-23 2017-05-02 Gilead Pharmasset Llc Fosforamidatos de nucleósidos de 2-amino-purina 6-osubstituída
SG194404A1 (en) 2008-12-23 2013-11-29 Gilead Pharmasset Llc Synthesis of purine nucleosides
TWI598358B (zh) 2009-05-20 2017-09-11 基利法瑪席特有限責任公司 核苷磷醯胺
US8618076B2 (en) 2009-05-20 2013-12-31 Gilead Pharmasset Llc Nucleoside phosphoramidates
PL3290428T3 (pl) 2010-03-31 2022-02-07 Gilead Pharmasset Llc Tabletka zawierająca krystaliczny (S)-2-(((S)-(((2R,3R,4R,5R)-5-(2,4-diokso-3,4-dihydropirymidyn-1(2H)-ylo)-4-fluoro-3-hydroksy-4-metylotetrahydrofuran-2-ylo)metoksy)(fenoksy)fosforylo)amino)propanian izopropylu
PT2609923T (pt) 2010-03-31 2017-08-30 Gilead Pharmasset Llc Processo para a cristalização de 2-(((s)- (perfluorofenoxi)(fenoxi)fosforil)amino)propanoato de (s)-isopropilo
AU2011336632B2 (en) 2010-11-30 2015-09-03 Gilead Pharmasset Llc Compounds
US8889159B2 (en) 2011-11-29 2014-11-18 Gilead Pharmasset Llc Compositions and methods for treating hepatitis C virus
EA201690473A1 (ru) 2013-08-27 2017-03-31 ГАЙЛИД ФАРМАССЕТ ЭлЭлСи Комбинированный состав двух противовирусных соединений
US9808531B2 (en) 2015-09-22 2017-11-07 Graybug Vision, Inc. Compounds and compositions for the treatment of ocular disorders
ES2981607T3 (es) * 2015-09-23 2024-10-09 Eyepoint Pharmaceuticals Inc Activadores de Tie-2 para uso en el tratamiento de la presión intraocular
CA3056923A1 (en) 2017-03-23 2018-09-27 Graybug Vision, Inc. Drugs and compositions for the treatment of ocular disorders
US11160870B2 (en) 2017-05-10 2021-11-02 Graybug Vision, Inc. Extended release microparticles and suspensions thereof for medical therapy
AU2018385762A1 (en) * 2017-12-14 2020-06-04 Graybug Vision, Inc. Drugs and compositions for ocular delivery

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0492903A1 (en) 1990-12-21 1992-07-01 MERCK SHARP & DOHME LTD. Substituted pyrazines, pyrimidines and pyridazines for use in the treatment of glaucoma
US5654285A (en) 1991-04-06 1997-08-05 Astra Pharmaceuticals Limited ADP and ATP analogues, process for making and administration to inhibit ADP-induced platelet aggregation
EP0508687B1 (en) 1991-04-06 1995-09-13 Astra Pharmaceuticals Limited ATP analogues
SK281309B6 (sk) 1993-02-10 2001-02-12 Astra Pharmaceuticals Limited N-alkyl-2-substituované adenozíntrifosfátové deriváty, spôsob ich prípravy, farmaceutické prostriedky obsahujúce tieto deriváty a použitie týchto derivátov
US5545626A (en) * 1994-01-19 1996-08-13 The Trustees Of Columbia University In The City Of New York Method of treating glaucoma with oligonucleotides
TR199800019T1 (xx) 1995-07-11 1998-05-21 Astra Pharmaceuticals Limited Trombosit topaklanmas�n� �nleyici yeni maddeler.
EP0946561B1 (en) 1996-12-20 2002-02-13 AstraZeneca AB Triazolo(4,5-d)pyrimidinyl derivatives and their use as medicaments
SE9702774D0 (sv) 1997-07-22 1997-07-22 Astra Pharma Prod Novel compounds
CA2332540A1 (en) * 1998-05-22 1999-12-02 Benjamin R. Yerxa Therapeutic dinucleotide and derivatives
US6528516B1 (en) 1998-07-16 2003-03-04 Trustees Of The University Of Pennsylvania, The Center For Technology Transfer Methods for reducing intraocular pressure using A3 adenosine receptor antagonists
SE9804175D0 (sv) 1998-12-02 1998-12-02 Astra Pharma Prod New assay
TWI229674B (en) 1998-12-04 2005-03-21 Astra Pharma Prod Novel triazolo[4,5-d]pyrimidine compounds, pharmaceutical composition containing the same, their process for preparation and uses
SE9903290D0 (sv) 1999-09-15 1999-09-15 Astra Pharma Prod Novel compounds
SE9904129D0 (sv) 1999-11-15 1999-11-15 Astra Pharma Prod Novel compounds
SE9904377D0 (sv) 1999-12-01 1999-12-01 Astra Pharma Prod Pharmaceutical combinations
US6897201B2 (en) 2000-08-21 2005-05-24 Inspire Pharmaceuticals, Inc. Compositions and methods for the treatment of glaucoma or ocular hypertension
WO2002079150A2 (en) * 2001-03-30 2002-10-10 Sloan-Kettering Institute For Cancer Research Glycorandomization and the production of novel erythronolide and coumarin analogs

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6897201B2 (en) 2000-08-21 2005-05-24 Inspire Pharmaceuticals, Inc. Compositions and methods for the treatment of glaucoma or ocular hypertension

Also Published As

Publication number Publication date
US6897201B2 (en) 2005-05-24
AU2003223224A1 (en) 2003-09-09
GB0419174D0 (en) 2004-09-29
TW200305427A (en) 2003-11-01
JP2005535564A (ja) 2005-11-24
US20020128224A1 (en) 2002-09-12
GB2402674B (en) 2005-08-03
GB2402674A (en) 2004-12-15
AU2003223224A8 (en) 2003-09-09
WO2003072066A3 (en) 2004-11-11

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