WO2003103567A3 - Nitrosodiphenylamine derivatives, compositions comprising them, and the use thereof as antioxidants and spontaneous nitric oxide donors - Google Patents

Nitrosodiphenylamine derivatives, compositions comprising them, and the use thereof as antioxidants and spontaneous nitric oxide donors Download PDF

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Publication number
WO2003103567A3
WO2003103567A3 PCT/EP2003/004919 EP0304919W WO03103567A3 WO 2003103567 A3 WO2003103567 A3 WO 2003103567A3 EP 0304919 W EP0304919 W EP 0304919W WO 03103567 A3 WO03103567 A3 WO 03103567A3
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WO
WIPO (PCT)
Prior art keywords
compositions
antioxidants
nitric oxide
oxide donors
spontaneous
Prior art date
Application number
PCT/EP2003/004919
Other languages
French (fr)
Other versions
WO2003103567A2 (en
Inventor
Claude Lardy
Philippe Guedat
Isabelle Berard
Lidia Caputo
Original Assignee
Merck Patent Gmbh
Claude Lardy
Philippe Guedat
Isabelle Berard
Lidia Caputo
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 Merck Patent Gmbh, Claude Lardy, Philippe Guedat, Isabelle Berard, Lidia Caputo filed Critical Merck Patent Gmbh
Priority to US10/514,410 priority Critical patent/US20050165099A1/en
Priority to AU2003250328A priority patent/AU2003250328A1/en
Publication of WO2003103567A2 publication Critical patent/WO2003103567A2/en
Publication of WO2003103567A3 publication Critical patent/WO2003103567A3/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36—Radicals substituted by singly-bound nitrogen atoms
    • C07D213/40—Acylated substituent nitrogen atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • 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
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
    • C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
    • C07D213/53—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
    • C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
    • C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
    • C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems

Abstract

The invention relates to compounds of the general formula (I) in which R i, A, n, B and Z are as defined in Claim 1. These compounds can be used for the preparation of antioxidant medicinal products that function as free-radical scavengers or are useful in the treatment of pathologies characterised by an oxidative stress condition and a lack of availability of endothelial nitrogen monoxide. The invention also relates to the pharmaceutical compositions comprising them.
PCT/EP2003/004919 2002-05-15 2003-05-12 Nitrosodiphenylamine derivatives, compositions comprising them, and the use thereof as antioxidants and spontaneous nitric oxide donors WO2003103567A2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US10/514,410 US20050165099A1 (en) 2002-05-15 2003-05-12 Method for producing 2-(4-n,n-dialkylamino-2-hydroxybenzol)benzoates
AU2003250328A AU2003250328A1 (en) 2002-06-05 2003-05-12 Nitrosodiphenylamine derivatives, compositions comprising them, and the use thereof as antioxidants and spontaneous nitric oxide donors

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0206923A FR2840609A1 (en) 2002-06-05 2002-06-05 New nitrosodiphenylamine derivatives useful for treating e.g. restenosis, diabetes, atherosclerosis associated ischemias, restenosis after angioplasty and stenosis after vascular surgery
FR0206923 2002-06-05

Publications (2)

Publication Number Publication Date
WO2003103567A2 WO2003103567A2 (en) 2003-12-18
WO2003103567A3 true WO2003103567A3 (en) 2004-04-15

Family

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Family Applications (1)

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PCT/EP2003/004919 WO2003103567A2 (en) 2002-05-15 2003-05-12 Nitrosodiphenylamine derivatives, compositions comprising them, and the use thereof as antioxidants and spontaneous nitric oxide donors

Country Status (4)

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AU (1) AU2003250328A1 (en)
FR (1) FR2840609A1 (en)
UY (1) UY27821A1 (en)
WO (1) WO2003103567A2 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006206521A (en) * 2005-01-28 2006-08-10 Univ Of Tokyo N-nitrosoamine compound as nitrogen monoxide donor
TWI490214B (en) 2008-05-30 2015-07-01 艾德克 上野股份有限公司 Benzene or thiophene derivative and use thereof as vap-1 inhibitor

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0013144A1 (en) * 1978-12-22 1980-07-09 Ici Australia Limited Substituted diphenylamine derivatives, compositions and herbicidal uses thereof, and processes for their preparation
EP0585500A1 (en) * 1992-09-04 1994-03-09 Merrell Dow Pharmaceuticals Inc. Diaryl piperazineacetamides as antimuscarinic agents
JPH1087592A (en) * 1996-09-11 1998-04-07 Ken Fujimori Nitrogen monoxide generating agent
WO2002028820A1 (en) * 2000-10-05 2002-04-11 Merck Patent Gmbh Nitroso diphenylamine derivatives

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0013144A1 (en) * 1978-12-22 1980-07-09 Ici Australia Limited Substituted diphenylamine derivatives, compositions and herbicidal uses thereof, and processes for their preparation
EP0585500A1 (en) * 1992-09-04 1994-03-09 Merrell Dow Pharmaceuticals Inc. Diaryl piperazineacetamides as antimuscarinic agents
JPH1087592A (en) * 1996-09-11 1998-04-07 Ken Fujimori Nitrogen monoxide generating agent
WO2002028820A1 (en) * 2000-10-05 2002-04-11 Merck Patent Gmbh Nitroso diphenylamine derivatives

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
BACH, FREDERICK L., JR. ET AL: "Nonsteroidal hypocholesteremic agents. I. Synthesis and serum sterol lowering properties of substituted 4-(2-dialkylaminoethoxy)diphenylamines and related compounds", JOURNAL OF MEDICINAL CHEMISTRY (1967), 10(5), 802-6, XP002231249 *
BALTZLY R. ET AL.: "SOME PHENOTHIAZINE DERIVATIVES. THE COURSE OF THE FRIEDEL-CRAFTS REACTION", J. AM. CHEM. SOC., vol. 68, 1946, pages 2673 - 2678, XP002231248 *
COUTTS, IAN G. ET AL: "Spirodienones. Part 7. The synthesis of N-arylcyclohexa-2,5-dienimine-4 spirolactones and -spiroacetals", JOURNAL OF CHEMICAL RESEARCH, SYNOPSES (1988), (8), 241, XP008013782 *
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; FUJIMORI, KEN ET AL: "Preparation of dinitrosaminobenezenes as nitric oxide-generating agents", XP002231250, retrieved from STN Database accession no. 128:270433 *

Also Published As

Publication number Publication date
FR2840609A1 (en) 2003-12-12
AU2003250328A1 (en) 2003-12-22
AU2003250328A8 (en) 2003-12-22
WO2003103567A2 (en) 2003-12-18
UY27821A1 (en) 2003-06-30

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