AR042109A1 - Derivados de acido mandelico, procedimiento de preparacion, composicion farmaceutica que lo comprende, y, usos - Google Patents

Derivados de acido mandelico, procedimiento de preparacion, composicion farmaceutica que lo comprende, y, usos

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Publication number
AR042109A1
AR042109A1 ARP030104302A ARP030104302A AR042109A1 AR 042109 A1 AR042109 A1 AR 042109A1 AR P030104302 A ARP030104302 A AR P030104302A AR P030104302 A ARP030104302 A AR P030104302A AR 042109 A1 AR042109 A1 AR 042109A1
Authority
AR
Argentina
Prior art keywords
alkoxy
carbonyl
lower alkyl
amino
alkyl
Prior art date
Application number
ARP030104302A
Other languages
English (en)
Inventor
Christoph Martin Stahl
David William Banner
Luca Claudio Gobbi
Zbinden Katrin Groebke
Ulrike Obst
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Hoffmann La Roche
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Publication date
Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche
Publication of AR042109A1 publication Critical patent/AR042109A1/es

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    • C07C257/00Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
    • C07C257/10Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
    • C07C257/18Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
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    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P7/02Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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    • A61P9/04Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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    • A61P9/10Drugs 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
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    • C07C259/18Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. N-hydroxyamidines having carbon atoms of hydroxamidine groups bound to carbon atoms of six-membered aromatic rings
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    • C07D213/60Heterocyclic 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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Abstract

La presente se refiere a derivados de ácido mandélico de la fórmula (1), así como a las sales fisiológicamente aceptables de los mismos. Estos compuestos inhiben la formación de los factores de coagulación Xa, IXa y trombina inducida por el factor VIIa y el factor hístico y pueden utilizarse como medicamentos. Reivindicación 1: Compuestos de la fórmula (1) en la que R1 es H, -OH, -NH2, (alcoxi inferior)-carbonilo, aril-(alcoxi inferior)-carbonilo, ariloxi-carbonilo, (alquilo inferior)-carbonilo, aril-carbonilo o (alcoxi inferior)-carbonilo que está sustituido por halógeno; R2, R3, y R4 con independencia entre sí se eligen entre H, halógeno, hidroxi, y alcoxi inferior; cuyo alcoxi inferior puede estar sustituido opcionalmente por hidroxi, carboxi o carbamoilo; R5 es alquilo inferior o cicloalquilo o, si X es O o NR12, R5 puede ser también H; R6 es H, alquilo inferior o flúor-alquilo inferior; Y es N o C-R11; R7, R8, R9, R10 y R11 con independencia entre sí se eligen entre H, hidroxi, halógeno, amino, (alquilo inferior)-amino, di-(alquilo inferior)-amino, (alquilo inferior)-carbonil-amino, NO2, flúor-alquilo inferior, alcoxi inferior, hidroxi-alcoxi inferior, flúor-alcoxi inferior, alquinilo inferior, hidroxi-alquinilo inferior, arilo, aril-alcoxi inferior, ariloxi, ariloxi-alcoxi inferior, heterociclilo, heterocicliloxi, (alcoxi inferior)-carbonil-alcoxi inferior, carbamoil-alcoxi inferior, carboxi-alcoxi inferior, cicloalquiloxi, heteroarilo, amino-alcoxi inferior, (alquilo inferior)-amino-alcoxi inferior y di-(alquilo inferior)-amino-alcoxi inferior; o R8 y R9 o R8 y R7 están unidos entre sí para formar un anillo junto con los átomos de C a los que están unidos y R8 y R9 juntos o R8 y R7 juntos son -O-CH2-O-, -O-CH2-CO-NH-, -O-CH2-CH2-CH2- o -CH=CH-CH=CH-, que pueden estar eventualmente sustituidos por alquilo inferior o alcoxi inferior y R10, R11 y R7 o R9 tienen respectivamente los significados definidos anteriormente; X es O, S, NR12 o SO2; R12 es H, alquilo inferior o (alquilo inferior)-carbonilo; y las sales farmacéuticamente aceptables de los mismos. Reivindicación 37: El uso de los compuestos según una cualquiera de las reivindicaciones 1-26 para la fabricación de medicamentos destinados al tratamiento terapéutico y/o profiláctico de trombosis arteriales y venosas, trombosis de venas profundas, embolia pulmonar, angina de pecho inestable, infarto cardíaco, apoplejía debida a fibrilación atrial, inflamación, arteriosclerosis y/o tumores.
ARP030104302A 2002-11-25 2003-11-21 Derivados de acido mandelico, procedimiento de preparacion, composicion farmaceutica que lo comprende, y, usos AR042109A1 (es)

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