WO1995013811A1 - Utilisation de derives de thiazolidine substitues pour le traitement de l'elevation de la pression intra-oculaire - Google Patents

Utilisation de derives de thiazolidine substitues pour le traitement de l'elevation de la pression intra-oculaire Download PDF

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Publication number
WO1995013811A1
WO1995013811A1 PCT/EP1994/003758 EP9403758W WO9513811A1 WO 1995013811 A1 WO1995013811 A1 WO 1995013811A1 EP 9403758 W EP9403758 W EP 9403758W WO 9513811 A1 WO9513811 A1 WO 9513811A1
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WO
WIPO (PCT)
Prior art keywords
thiazolidine
phenyl
carboxy
alkyl
nitroxyethoxy
Prior art date
Application number
PCT/EP1994/003758
Other languages
German (de)
English (en)
Inventor
Jan Bron
Geert Jan Sterk
Hendrik Timmerman
Jan Fetze Van Der Werf
Original Assignee
Byk Nederland Bv
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 Byk Nederland Bv filed Critical Byk Nederland Bv
Priority to AU81076/94A priority Critical patent/AU8107694A/en
Publication of WO1995013811A1 publication Critical patent/WO1995013811A1/fr

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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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles

Definitions

  • the invention relates to the new use of substituted thiazolidine derivatives for the manufacture of medicaments for the treatment of eye diseases.
  • W092 / 04337 known compounds are outstandingly suitable for the treatment of (pathologically increased) intraocular pressure.
  • the invention relates to the use of compounds of the formula I (see attached formula sheet), in which
  • R1 is hydrogen (H) or 1-4C-alkyl
  • R2 is hydrogen (H), 1-6C-alkyl, 4-8C-cycloalkyl, phenyl-1-3C-alkyl or a radical of the formula II (see attached formula sheet), in which
  • R9, R10 and R11 are the same or different and are hydrogen (H), 1-6C-alkyl, 1-6C-alkoxy, 4-8C-cycloalkyl, 4-8C-cycloalkoxy.
  • Halogen. Represent nitro, nitryloxy-2-6C-alkoxy, nitryloxy-4-8C-cycloalkoxy, nitryloxy1-2C-alkyl-4-8C-cycloalkyl-1-2C-alkoxy or a group of the formula -W-C0-Y-R12, in the
  • W is a bond or a group of the formula -OCHp-
  • Y represents an oxygen atom (0) or an imino group (NH) and R12 represents hydrogen (H), 1-4C-alkyl, 4-8C-cycloalkyl, nitryloxy-2-6C-alkyl or nitryloxy-4-8C-cycloalkyl,
  • R3 and R4 are hydrogen (H) or 1-4C-alkyl
  • R5 is hydrogen (H) or a group of the formula -CO-Z-R7, in which Z is an oxygen atom (0) or an imino group (NH) and
  • R7 hydrogen (H), 1-4C-alkyl, 4-8C-cycloalkyl, nitryloxy-2-6C-alkyl, nitryloxy-4-8C-cycloalkyl, nitryloxy-1-2C-alkyl-4-8C-cycloalkyl-1- 2C-alkyl or 4-nitryloxy-2,6-dioxabicyclo [3.3.0] oct-8-yl,
  • R6 is hydrogen (H) or a group of the formula -X-R8 in which
  • R8 represents 1-4C-alkyl, 4-8C-cycloalkyl, nitryloxy-2-6C-alkyl, nitryloxy-4-8C-cycloalkyl, phenyl or 1-4C-AI alkylphenyl,
  • 1-4C-Alkyl stands for straight-chain or branched AI kyl residues with 1 to 4 carbon atoms. Examples include the butyl, iso-butyl, sec-butyl, tert-butyl, propyl, isopropyl, ethyl and especially the methyl radical.
  • 1-6C-Alkyl also includes straight-chain or branched alkyl radicals having 5 or 6 carbon atoms. Examples include the pentyl, isopentyl, neopentyl and hexyl radicals.
  • 4-8C-Cycloalkyl stands for cyclic alkyl radicals with 4 to 8 carbon atoms, that is for the cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl radical.
  • Phenyl-1-3C-alkyl stands for 1-3C-alkyl radicals which are substituted by a phenyl radical.
  • a phenyl radical for example, the phenyl propyl, the phenylethyl and the benzyl radical may be mentioned.
  • 1-6C-alkoxy radicals contain one of the 1-6C-alkyl radicals mentioned above. The methoxy and ethoxy radicals are preferred.
  • 4-8C-cycloalkoxy radicals contain one of the 4-8C-cycloalkyl radicals mentioned above.
  • the cyclopentyloxy and the cyclohexyloxy radical may be mentioned.
  • Halogen in the sense of the present invention is bromine, chlorine and fluorine.
  • Nitryloxy-2-6C-alkoxy radicals are straight-chain or branched 2-6C-alkoxy radicals to which a nitryloxy group (-O-NO 2 ) is attached.
  • Exemplary preferred nitryloxy-2-6C-alkoxy radicals are the 2-nitryloxyethoxy group (-OCH 2 CH 2 -O-NO 2 ), the 3-nitryloxypropoxy group (-O- (CH 2 ) 3 -O-NO 2 ), the 4th -Nitryloxybutoxyrios (-O- (CH 2 ) 4 -O-NO 2 ), the 2-nitryloxypropoxy group [-O-CH 2 -CH (CH 3 ) -O-NO 2 ] and the 2,2-dimethyl-3- nitryloxypropoxy group
  • Nitryloxy-4-8C-cycloalkoxy radicals are 4-8C-cycloalkoxy radicals to which a nitryloxy group is attached.
  • the 4-nitryloxycyclohexyloxy radical may be mentioned.
  • Nitryloxy-1-2C-alkyl-4-8C-cycloalkyl-1-2C-alkoxy radicals are 4-8C-cycloalkyl radicals which are bonded to a 1-2C-alkoxy radical and to which a nitryloxy-1-2C-alkyl radical is bound is.
  • An exemplary preferred nitryloxy-1-2C-alkyl-4-8C-cycloalkyl-1-2C-alkoxy radical is the nitroxymethyl - (trans) -cyclohexylmethoxy radical [-OCH 2 - (C 6 H 10 ) -CH 2 -O-NO 2 ].
  • Suitable pharmacologically acceptable salts for compounds of the formula I are preferably all acid addition salts with inorganic and organic acids commonly used in galenics. Suitable as such are water-soluble and water-insoluble acid addition salts with acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, Nitric acid, sulfuric acid, acetic acid, citric acid, D-gluconic acid, benzoic acid, 2- (4-hydroxybenzoyl) -benzoic acid, butyric acid, sulfosalicylic acid, maleic acid, lauric acid, malic acid, fumaric acid, succinic acid, oxalic acid, tartaric acid, embonic acid, stearic acid, toluenic acid, toluenic acid 3-hydroxy-2-naphthoic acid, the acids used in salt production - depending on whether it is a mono- or polybasic acid and which salt is desired - in an equimolar or a different quantity ratio.
  • acids
  • the compounds of the formula I are used in particular in the form of those medicaments which are suitable for the treatment of eye diseases.
  • suitable pharmaceutical formulations include, for example, emulsions, suspensions, ointments or solutions (e.g. eye drops) in which the active substance content is advantageously between 0.01 and 99%.
  • auxiliaries suitable for the desired pharmaceutical formulations on the basis of his specialist knowledge.
  • solvents and other active ingredient carriers for example antioxidants, dispersants, emulsifiers, preservatives, solubilizers or permeation promoters can be used.
  • the reduction in intraocular pressure in female New Zealand albino rabbits was determined using conventional methods.
  • the substances to be examined were dropped in 0.05% solution (50 ⁇ l) into one eye, while a solution of the

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Utilisation de composés de la formule (I), dans laquelle les substituants ont la signification indiquée dans la description, et utilisation de leurs sels compatibles sur le plan pharmacologique pour la fabrication de produits pharmaceutiques destinés au traitement de l'élévation pathologique de la pression intra-oculaire.
PCT/EP1994/003758 1993-11-17 1994-11-12 Utilisation de derives de thiazolidine substitues pour le traitement de l'elevation de la pression intra-oculaire WO1995013811A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU81076/94A AU8107694A (en) 1993-11-17 1994-11-12 Use of substituted thiazolidine derivatives in the treatment of raised intraocular pressure

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH342893 1993-11-17
CH3428/93-4 1993-11-17

Publications (1)

Publication Number Publication Date
WO1995013811A1 true WO1995013811A1 (fr) 1995-05-26

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PCT/EP1994/003758 WO1995013811A1 (fr) 1993-11-17 1994-11-12 Utilisation de derives de thiazolidine substitues pour le traitement de l'elevation de la pression intra-oculaire

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AU (1) AU8107694A (fr)
WO (1) WO1995013811A1 (fr)

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000009106A2 (fr) * 1998-08-14 2000-02-24 Gpi Nil Holdings, Inc. Acides carboxyliques et isosteres de composes a noyau heterocyclique possedant plusieurs heteroatomes et destines a des troubles de la vision et de la memoire
US6093696A (en) * 1997-05-30 2000-07-25 Celltech Therapeutics, Limited Tyrosine derivatives
US6110945A (en) * 1998-06-03 2000-08-29 Celltech Therapeutics Limited Aromatic amine derivatives
US6274577B1 (en) 1998-09-30 2001-08-14 Celltech Therapeutics Limited Benzodiazepines
US6319922B1 (en) 1998-11-23 2001-11-20 Celltech Therapeutics Limited Propanoic acid derivatives
US6329372B1 (en) 1998-01-27 2001-12-11 Celltech Therapeutics Limited Phenylalanine derivatives
US6329362B1 (en) 1998-03-16 2001-12-11 Celltech Therapeutics Limited Cinnamic acid derivatives
US6348463B1 (en) 1998-09-28 2002-02-19 Celltech Therapeutics Limited Phenylalanine derivatives
US6362204B1 (en) 1998-05-22 2002-03-26 Celltech Therapeutics, Ltd Phenylalanine derivatives
US6403608B1 (en) 2000-05-30 2002-06-11 Celltech R&D, Ltd. 3-Substituted isoquinolin-1-yl derivatives
US6455539B2 (en) 1999-12-23 2002-09-24 Celltech R&D Limited Squaric acid derivates
US6465471B1 (en) 1998-07-03 2002-10-15 Celltech Therapeutics Limited Cinnamic acid derivatives
US6469025B1 (en) 2000-08-02 2002-10-22 Celltech R&D Ltd. 3-substituted isoquinolin-1-yl derivatives
US6518283B1 (en) 1999-05-28 2003-02-11 Celltech R&D Limited Squaric acid derivatives
US6521626B1 (en) 1998-03-24 2003-02-18 Celltech R&D Limited Thiocarboxamide derivatives
US6534513B1 (en) 1999-09-29 2003-03-18 Celltech R&D Limited Phenylalkanoic acid derivatives
US6545013B2 (en) 2000-05-30 2003-04-08 Celltech R&D Limited 2,7-naphthyridine derivatives
US6555562B1 (en) 1998-02-26 2003-04-29 Celltech R&D Limited Phenylalanine derivatives
US6610700B2 (en) 2000-04-17 2003-08-26 Celltech R & D Limited Enamine derivatives
US6740654B2 (en) 2000-07-07 2004-05-25 Celltech R & D Limited Squaric acid derivatives
US6953798B1 (en) 1998-11-30 2005-10-11 Celltech R&D Limited β-alanine derivates
US20100183629A1 (en) * 2006-07-25 2010-07-22 Alcon Research, Ltd. Antagonists of endothelial differentiation gene subfamily 3 (edg-3, s1p3) receptors for prevention and treatment of ocular disorders

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992004337A1 (fr) * 1990-09-05 1992-03-19 Cedona Pharmaceuticals Bv Derives de thiazolidine

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992004337A1 (fr) * 1990-09-05 1992-03-19 Cedona Pharmaceuticals Bv Derives de thiazolidine

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
J.A. NATHANSON: "Nitrovasodilators as a new class of ocular hypertensives.", J. PHARMACOL. EXP. THER, vol. 260, no. 3, 1992, pages 956 - 965 *
L.Z. BITO: "Comparison of the ocular hypotensive efficacy of eicosanoids and related compounds.", EXP. EYE RES., vol. 38, no. 2, 1984, pages 181 - 194 *

Cited By (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6093696A (en) * 1997-05-30 2000-07-25 Celltech Therapeutics, Limited Tyrosine derivatives
US6329372B1 (en) 1998-01-27 2001-12-11 Celltech Therapeutics Limited Phenylalanine derivatives
US6555562B1 (en) 1998-02-26 2003-04-29 Celltech R&D Limited Phenylalanine derivatives
US6329362B1 (en) 1998-03-16 2001-12-11 Celltech Therapeutics Limited Cinnamic acid derivatives
US6521626B1 (en) 1998-03-24 2003-02-18 Celltech R&D Limited Thiocarboxamide derivatives
US6362204B1 (en) 1998-05-22 2002-03-26 Celltech Therapeutics, Ltd Phenylalanine derivatives
US6110945A (en) * 1998-06-03 2000-08-29 Celltech Therapeutics Limited Aromatic amine derivatives
US6369229B1 (en) 1998-06-03 2002-04-09 Celltech Therapeutics, Limited Pyridylalanine derivatives
US6465471B1 (en) 1998-07-03 2002-10-15 Celltech Therapeutics Limited Cinnamic acid derivatives
WO2000009106A2 (fr) * 1998-08-14 2000-02-24 Gpi Nil Holdings, Inc. Acides carboxyliques et isosteres de composes a noyau heterocyclique possedant plusieurs heteroatomes et destines a des troubles de la vision et de la memoire
WO2000009106A3 (fr) * 1998-08-14 2000-10-12 Guilford Pharm Inc Acides carboxyliques et isosteres de composes a noyau heterocyclique possedant plusieurs heteroatomes et destines a des troubles de la vision et de la memoire
US6348463B1 (en) 1998-09-28 2002-02-19 Celltech Therapeutics Limited Phenylalanine derivatives
US6677339B2 (en) 1998-09-28 2004-01-13 Celltech R & D Limited Phenylalanine derivatives
US6274577B1 (en) 1998-09-30 2001-08-14 Celltech Therapeutics Limited Benzodiazepines
US6319922B1 (en) 1998-11-23 2001-11-20 Celltech Therapeutics Limited Propanoic acid derivatives
US6953798B1 (en) 1998-11-30 2005-10-11 Celltech R&D Limited β-alanine derivates
US6518283B1 (en) 1999-05-28 2003-02-11 Celltech R&D Limited Squaric acid derivatives
US6534513B1 (en) 1999-09-29 2003-03-18 Celltech R&D Limited Phenylalkanoic acid derivatives
US6455539B2 (en) 1999-12-23 2002-09-24 Celltech R&D Limited Squaric acid derivates
US6610700B2 (en) 2000-04-17 2003-08-26 Celltech R & D Limited Enamine derivatives
US6545013B2 (en) 2000-05-30 2003-04-08 Celltech R&D Limited 2,7-naphthyridine derivatives
US6403608B1 (en) 2000-05-30 2002-06-11 Celltech R&D, Ltd. 3-Substituted isoquinolin-1-yl derivatives
US6740654B2 (en) 2000-07-07 2004-05-25 Celltech R & D Limited Squaric acid derivatives
US6469025B1 (en) 2000-08-02 2002-10-22 Celltech R&D Ltd. 3-substituted isoquinolin-1-yl derivatives
US20100183629A1 (en) * 2006-07-25 2010-07-22 Alcon Research, Ltd. Antagonists of endothelial differentiation gene subfamily 3 (edg-3, s1p3) receptors for prevention and treatment of ocular disorders

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Publication number Publication date
AU8107694A (en) 1995-06-06

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