Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
  • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
  • C07D221/04—Ortho- or peri-condensed ring systems
  • C07D221/06—Ring systems of three rings
  • C07D221/14—Aza-phenalenes, e.g. 1,8-naphthalimide
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/26—Psychostimulants, e.g. nicotine, cocaine
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• • 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
  • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• • 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
• • 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
  • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
  • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
  • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
  • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon 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
  • C07D233/56—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 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
  • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
  • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
  • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
  • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
  • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
  • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
  • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
  • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
  • C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Definitions

• Ar 1 and Ar 2 are each independently phenyl
• Het is a saturated, partially or completely unsatura- ted mono- or bicyclic heterocyclic radical having 5 to 10 ring members, where 1 or 2 N and/or 1 or 2 S or O atoms can be present and the heterocyclic radical can be mono- or disubstituted by CN, Hal, OH, OA, CF 3 , A, N0 2 , CO, CO-A or R 5 ,
• Het 1 is an unsaturated mono- or bicyclic heterocyclic radical having 5 to 10 ring members, where 1 or
• 2 N and/or 1 or 2 S or 0 atoms can be present and/or can be mono- or disubstituted by Hal, OH,
• A is unbranched or branched alkyl having 1-6 C atoms
• Hal is F, Cl, Br or I, X,
• Y is 0, S or NH i is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12, m is 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 or 12 , n,o in each case independently of one another are 0,
• GPIblX as an adhesion receptor on platelets, which mediates the primary interaction of platelets with an arteriosclerotically modified vascular wall via binding to the vWF expressed there, has been described by many authors (e.g. Z.M. Ruggeri in Thromb. Hemost. 1997, 78, 611-616).
• GPIIbllla another platelet adhesion receptor, GPIIbllla, following the GPIblX-vWF interaction, leads to platelet aggregation and thus to thrombotic vascular occlusion.
• the disorders are acute coronary syndromes, angina pectoris, myocardial infarct, peripheral circulatory disorders, stroke, transient ischaemic attacks, arteriosclerosis, reocclusion/restenosis after angio- plasty/stent implantation.
• the compounds can furthermore be employed as anti-adhesive substances where the body comes into contact with foreign surfaces such as implants, catheters or cardiac pacemakers.
• R 1 has the meaning indicated in Claim 1 is reacted with a compound of the formula III
• R 9 is Cl, Br, N0 2 or R 1 , where R 1 has the meaning indicated in Claim 1 is reacted with a compound of the formula V L (CHRJi R 2 V in which L is Cl, Br, or I, OH or a reactive esterified
• a radical R and/or R 2 and/or R 9 is converted into another radical R and/or R 2 and/or R 9 by, for example
• the compounds of the formula I can have a chiral centre and therefore occur in a number of stereoisomeric forms. All these forms (e.g. R and S forms) and their mixtures (e.g. the RS forms) are included in the formula I.
• the compounds according to the invention also include so-called prodrug derivatives, i.e. compounds of the formula I modified with, for example, alkyl or acyl groups, sugars or oligopeptides and which are rapidly cleaved in the body to give the active compounds according to the invention.
• prodrug derivatives i.e. compounds of the formula I modified with, for example, alkyl or acyl groups, sugars or oligopeptides and which are rapidly cleaved in the body to give the active compounds according to the invention.
• Solvates of the compounds of the formula I are understood as meaning adducts of inert solvent molecules to the compounds of the formula I which are formed on account of their mutual power of attraction. Solvates are, for example, mono- or dihydrates or alcoholates.
• A is alkyl and has 1 to 6, preferably 1, 2, 3 or 4 C atoms.
• Alkyl is preferably methyl, furthermore ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl or tert-butyl, additionally also pentyl, 1-, 2- or 3-methylbutyl, 1,1-, 1,2- or 2, 2-dimethylpropyl, 1-ethylpropyl, hexyl, 1-, 2-, 3- or 4-methylpentyl, 1,1-, 1 2-, 1,3-, 2,2-, 2,3- or 3,3-dimethylbutyl, 1- or 2-ethylbutyl, 1-ethyl- 1-methylpropyl, l-ethyl-2-methylpropyl, 1,1,2- or 1, 2, 2-trimethylpropyl, .
• Ar is preferentially phenyl, preferably
• phenyl specifically preferentially phenyl, o-, m- or p-methylphenyl, o-, m- or p-ethylphenyl, o-, m- or p-propylphenyl, o-, m- or p-isopropylphenyl, o-, m- or p-tert-butylphenyl, o-, m- or p-aminophenyl, o-, m- or p- (N, N-dimethylamino) phenyl, o-, m- or p-sulfonamoylphenyl, o-, m- or p-nitrophenyl, o-, m- or p-hydroxyphenyl, o-, m- or p-methoxyphenyl, o-, m- or p-ethoxypheny
• Ar is also preferentially unsubstituted biphenyl - as indicated - or alternatively monosubstituted biphenyl, specifically preferentially biphenyl-4-yl or biphenyl-3-yl, 2 ' -methylbiphenyl-4-yl, 3 ' -methylbiphenyl-4-yl, 4 ' -methylbiphenyl-4-yl, 2 ' -methylbiphenyl-3-yl,
• Ar' is preferably unsubstituted or substituted phenylene or cycloalkylene, where R 8 is preferentially an amido, an alkylamido or dialkylamido group or -CONH- (CH 2 ) 0 -Ar,
• Cycloalkylene having 3 to 8 carbon atoms is preferentially cyclobutylene, cyclopentylene, cyclohexylene, or cycloheptylene; particularly preferred cyclohexylene.
• Hal is preferably F, Cl, Br or iodine.
• Het 1 is preferentially substituted or unsubstituted 2-, 3-, or 4-pyridyl, 2- or 3-benzo[b] thiophenyl, lH-indol-2-yl, lH-indol-3-yl, 4-, 5-, 6-, 7-fluoro-lH-indol-2-yl, 4-, 5-, 6-, 7-fluoro- lH-indol-3-yl, 4-, 5-, 6-, 7-methyl-lH-indo-2-yl, 4-, 5-, 6-, 7-methyl-lH-indol-3-yl, 4-, 5-, 6-, methoxy-lH- indol-2-yl or 4-, 5-, 6-, 7-methoxy-lH-indol-3-yl, 4-Pyridyl, 3-benzo [b] thiophenyl, lH-indol-3
• Het is preferably substituted or unsubstituted 2- or 3-furyl, 2- or 3-thienyl, 2-chloro-thienyl-5-yl, 2-acetyl-thienyl-5-yl, 1-, 2- or 3-pyrrolyl, 1-, 2-, 4- or 5-imidazolyl, 1-, 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-oxazolyl, 3-, 4- or 5-isoxazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-isothiazolyl, 2-, 3- or 4-pyridyl, 2-, 4-, 5- or 6-pyrimidinyl, furthermore preferably 1, 2, 3-triazol-l-, -4- or -5-yl, 1, 2, 4-triazol-l-, -4- or -5-yl, 1- or 5-tetrazolyl, 1, 2, 3-oxadiazol-4- or -5-yl, 1, 2, -oxadiazol-3- or -5-yl, 1, 3, 4-thiadia
• heterocyclic radicals can also be partially or completely hydrogenated. Het can thus also be 2,3-dihydro-2-, -3-, -4- or -5-furyl, 2, 5-dihydro-2-, -3-, -4- or -5-furyl, tetrahydro-2- or -3-furyl, 1, 3-dioxolan-4-yl, tetrahydro-2- or -3-thienyl, 2, 3-dihydro-l-, -2-, -3-, -4- or -5-pyrrolyl, 2, 5-dihydro-l-, -2-, -3-, -4- or -5-pyrrolyl, 1-, 2- or 3-pyrrolidinyl, pyrrolidine-2-on-l-yl, tetrahydro-1-, -2- or -3-pyrrolyl, tetrahydro-1-, -2- or 4-imidazolyl, 2, 3-dihydro-l-, -2-
• 2-, 3- or 4-pyridyl 1-imidazolyl, 2-methyl-l-imidazolyl, 2-pyrimidinyl, 5-fluoro-lH- indol-2-yl, 2, 3-dihydro-l-, -2-, -3-, -4-, -5-, -6-, -7-lH-indolyl, 1-quinolinyl, 1-isoquinolinyl, 1, 2, 3, 4-tetrahydroisoquinoline-l-yl, tetrahydro- 1-pyrrolyl, 1-piperidinyl, 2, 6-tetramethyl- piperidine-4-yl, 1-azepanyl, 4-morpholinyl, 1- piperazinyl, 4-methyl-piperazin-l-yl, 4-phenyl- piperazin-1-yl or 4-phenylmethylpiperazin-l-yl is particularly preferred.
• Het and Ar have one of the preferred meanings indicated above, where Het is preferably piperidine-1, 4-diyl or piperazine-1, 4-diyl and n can be 0, 1, 2, 3, or 4.
• Het has one of the preferred meanings indicated above, where in -Het-Het the first heterocycle is preferably piperidine-1, 4-diyl or
• Y is preferably 0, S or NH, where Het has one of the preferred meanings indicated above and R 6 is preferentially H, amino or alkylamino.
• n and o independently of one another are preferably 0, 1, 2, 3 or 4.
• NH-(CH 2 ) 3 —N N—(CH 2 ) 3 NH 2 are particularly preferred for -Y- (CH 2 ) n -Het (CH 2 ) 0 -R 6 .
• Y is preferentially 0, S, or NH, where Ar' has a preferred meaning indicated beforehand and R 6 is preferably H, amino or alkylamino and n and o independently of one another are 0, 1, 2, 3 or 4.
• Y is preferentially O, S, or NH, where Ar' has a preferred meaning indicated beforehand and R 11 is preferably -NH-
• Y is preferentially 0, S or NH, where X, X 1 and X 2 have a preferred meaning indicated beforehand.
• R 5 is preferably amino, alkylamino or dialkylamino, t is 0, 1 or 2 and u is 1 or 2.
• -NH-(CH 2 ) 3 -0-(CH 2 ) -0-(CH 2 ) 3 -NH 2 is particularly preferred for -Y- [X-O] t - [X 1 -0] U -X 2 -R 5 .
• R 1 is preferably -Het, -N- [ (CH 2 ) s -OH] 2 . -N-[(CH 2 ) s -OA] 2 , -NA-(CH 2 ) S -Ar, -NA- (CH 2 ) m ⁇ R 5 , -Y-(CH 2 ) ra -R 5 , -Y-(CH 2 ) 2 -NHA, -Y- (CH 2 ) 2 -NA 2 ,
• s in -N-[ (CH 2 ) s -OH] 2 and -N- [ (CH 2 ) ⁇ -OA] 2 is preferably 1, 2, 3 or 4 and A has the preferred meaning indicated beforehand.
• -N- [ (CH 2 ) 2 -OH] 2 is particularly preferred for -N-[(CH 2 ) s -OH] 2 .
• a and Ar have a preferred meaning indicated beforehand and s is preferably 1, 2,
• Y is preferably 0, S or NH, where m is 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12.
• -NH- (CH 2 ) 5 ⁇ OH is particularly preferred for -Y- (CH 2 ) m -0H.
• Y is preferentially 0, S, NH, where A has a preferred meaning indicated beforehand, R 5 is preferably amino, alkylamino or dialkylamino and n and o in each case independently of one another are 0, 1, 2, 3 or 4.
• -NH-(CH 2 )3-N(CH 3 )-(CH 2 ) 3 -NH 2 is particularly preferred for -Y- (CH 2 ) n -NA- (CH 2 ) 0 -R 5 .
• i is preferentially 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12, particularly preferentially 1, 2, 3, 5, 7, 10 or 11.
• R 7 is preferentially -Ar' - (CH 2 ) n -R 8 or -Ar'-(CH 2 ) n -R 5 , where -Ar' - (CH 2 ) n -R 8 and -Ar' - (CH 2 ) n -R 5 have a preferred or particularly preferred meaning indicated beforehand.
• R 1 is -Het, -NA-(CH 2 ) S -Ar, -Y- (CH 2 ) m -R 5 , -Y-(CH 2 ) m -OH, -Y-(CH 2 ) n -(CHR )-R 3 , -Y-(CH 2 ) n -Ar' (CH 2 ) 0 -R 6 or -Het- (CH 2 ) n -Ar and i is 1 or 2;
• R 2 is Ar'-(CH 2 ) n -R 8 ,
• the starting substances can also be formed in situ such that they are not isolated from the reaction mixture, but immediately reacted further to give the compounds of the formula I.
• Example B Suppositories

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• General Health & Medical Sciences (AREA)
• Veterinary Medicine (AREA)
• General Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Pharmacology & Pharmacy (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Public Health (AREA)
• Cardiology (AREA)
• Heart & Thoracic Surgery (AREA)
• Psychiatry (AREA)
• Hematology (AREA)
• Urology & Nephrology (AREA)
• Vascular Medicine (AREA)
• Diabetes (AREA)
• Biomedical Technology (AREA)
• Neurology (AREA)
• Neurosurgery (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Plural Heterocyclic Compounds (AREA)
• Other In-Based Heterocyclic Compounds (AREA)
• Nitrogen Condensed Heterocyclic Rings (AREA)

Applications Claiming Priority (5)

Publications (1)

Family

ID=26894739

Family Applications (1)

Country Status (15)

Families Citing this family (14)

Family Cites Families (9)

• 1999
  • 1999-11-09 EP EP99957291A patent/EP1133475A1/en not_active Withdrawn
  • 1999-11-09 CN CN99813608A patent/CN1328549A/zh active Pending
  • 1999-11-09 CZ CZ20011792A patent/CZ20011792A3/cs unknown
  • 1999-11-09 CA CA002351348A patent/CA2351348A1/en not_active Abandoned
  • 1999-11-09 JP JP2000583867A patent/JP2002530379A/ja active Pending
  • 1999-11-09 MX MXPA01005228A patent/MXPA01005228A/es unknown
  • 1999-11-09 BR BR9915611-3A patent/BR9915611A/pt not_active IP Right Cessation
  • 1999-11-09 SK SK701-2001A patent/SK7012001A3/sk unknown
  • 1999-11-09 HU HU0104469A patent/HUP0104469A3/hu unknown
  • 1999-11-09 WO PCT/EP1999/008560 patent/WO2000031039A1/en not_active Application Discontinuation
  • 1999-11-09 ID IDW00200101390A patent/ID29425A/id unknown
  • 1999-11-09 PL PL99347766A patent/PL347766A1/xx unknown
  • 1999-11-09 AU AU15049/00A patent/AU1504900A/en not_active Abandoned
  • 1999-11-24 AR ARP990105972A patent/AR029152A1/es not_active Application Discontinuation
• 2001
  • 2001-05-23 NO NO20012543A patent/NO20012543D0/no not_active Application Discontinuation

Non-Patent Citations (1)

Also Published As

Similar Documents

Legal Events