ME02603B - Nove 5 - aminotetrahidrohinolin-2-karbonske kiseline i njihova upotreba - Google Patents

Nove 5 - aminotetrahidrohinolin-2-karbonske kiseline i njihova upotreba

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Publication number
ME02603B
ME02603B MEP-2017-30A MEP201730A ME02603B ME 02603 B ME02603 B ME 02603B ME P201730 A MEP201730 A ME P201730A ME 02603 B ME02603 B ME 02603B
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ME
Montenegro
Prior art keywords
formula
compound
salts
solvates
fluorine
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Application number
MEP-2017-30A
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German (de)
English (en)
French (fr)
Inventor
Michael Hahn
Markus Follmann
Walter Hübsch
Eva-Maria Becker-Pelster
Johannes-Peter Stasch
Joerg Keldenich
Martina Delbeck
Hanna Tinel
Frank Wunder
Joachim Mittendorf
Ildiko Terebesi
Dieter Lang
René Martin
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Bayer Pharma AG
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Publication of ME02603B publication Critical patent/ME02603B/me

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D215/00Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
    • C07D215/48Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • 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
    • A61K31/47Quinolines; Isoquinolines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • 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
    • A61K31/47Quinolines; Isoquinolines
    • A61K31/47064-Aminoquinolines; 8-Aminoquinolines, e.g. chloroquine, primaquine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • 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
    • A61K31/47Quinolines; Isoquinolines
    • A61K31/4709Non-condensed quinolines and containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/04Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D217/00Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
    • C07D217/26Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Hospice & Palliative Care (AREA)
  • Hematology (AREA)
  • Vascular Medicine (AREA)
  • Diabetes (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Quinoline Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Claims (13)

1.Jedinjenje sa formulom (I) naznačeno time što R1 predstavlja vodonik ili fluor, L1 predstavlja etan-1,2-diil ili 1,4-fenilen, i A predstavlja grupu sa formulom u kojoj * označava odgovarajuću tačku vezivanja na ostatak molekula, L3 predstavlja vezu, -O-, -CH2-, -CH2-CH2- ili -CH=CH-, i R3C predstavlja supstituent izabran iz grupe koju čine fluor, hlor, brom, cijano, (C1-C4)-alkil, difluormetil, trifluormetil, (C1-C4)-alkoksi, difluormetoksi i trifluormetoksi, i R3D predstavlja supstituent izabran iz grupe koju čine vodonik, fluor, hlor, brom, cijano, (C1-C4)-alkil, difluormetil, trifluormetil, (C1-C4)-alkoksi, difluormetoksi i trifluormetoksi, i soli, solvati i solvati njihovih soli.
2.Jedinjenje sa formulom (I) prema zahtevu 1 naznačeno time što R1 predstavlja vodonik ili fluor, L1 predstavlja etan-1,2-diil ili 1,4-fenilen, i A predstavlja grupu sa formulom u kojoj * označava odgovarajuću tačku vezivanja na ostatak molekula, L3 predstavlja vezu, -CH2-CH2- ili -CH=CH-, R3C predstavlja fluor, hlor, metil ili trifluormetil, i R3D predstavlja vodonik, fluor, hlor, cijano, metil, trifluormetil, metoksi ili trifluormetoksi, i soli, solvati i solvati njihovih soli.
3.Jedinjenje sa formulom (I) prema zahtevu 1 ili 2 naznačeno time što R1 predstavlja vodonik ili fluor, L1 predstavlja etan-1,2-diil ili 1,4-fenilen, i A predstavlja grupu sa formulom u kojoj * označava odgovarajuću tačku vezivanja na ostatak molekula, L3 predstavlja vezu, -CH2-CH2- ili -CH=CH-, R3C predstavlja fluor, hlor, metil ili trifluormetil, i R3D predstavlja vodonik, fluor, hlor, cijano, metil, trifluormetil ili trifluormetoksi, i soli, solvati i solvati njihovih soli.
4.Jedinjenje sa formulom (I) prema zahtevu 1, 2 ili 3 naznačeno time što R1 predstavlja vodonik ili fluor, L1 predstavlja etan-1,2-diil ili 1,4-fenilen, i A predstavlja grupu sa formulom u kojoj * označava odgovarajuću tačku vezivanja na ostatak molekula, L3 predstavlja vezu ili -CH2-CH2-, R3C predstavlja hlor, i R3D predstavlja vodonik, fluor ili trifluormetil, i soli, solvati i solvati njihovih soli.
5.5-{[2-(4-karboksifenil)etil][2-(2-{[3-hlor-4'-(trifluormetil)bifenil-4-il]metoksi}fenil)etil]amino}-5,6,7,8-tetrahidrokinolin-2-karboksilna kiselina prema formuli u nastavku i soli, solvati i solvati njihovih soli.
6.5-{(4-karboksibutil)[2-(2-{[3-hlor-4'-(trifluormetil)bifenil-4-il]metoksi}fenil)etil]amino}-5,6,7,8-tetrahidrokinolin-2-karboksilna kiselina prema formuli u nastavku i soli, solvati i solvati njihovih soli.
7.Postupak za pripremanje jedinjenja sa formulom (I) kako je definisano u bilo kom od zahteva 1 do 6, naznačen time što ili [A] jedinjenje sa formulom (II) u kojoj R1 i L1 imaju značenja data u bilo kom od zahteva 1 do 6 i T1 i T2 su identični ili različiti i predstavljaju (C1-C4)-alkil, reaguje u prisustvu baze sa jedinjenjem sa formulom (III) u kojoj A ima značenja data u bilo kom od zahteva 1 do 6 i X1 predstavlja odlazeću grupu kao što je, na primer, hlor, brom, jod, mesilat, triflat ili tosilat, ili [B] jedinjenje sa formulom (IV) u kojoj R1 i A imaju značenja data u bilo kom od zahteva 1 do 6 i T2 predstavlja (C1-C4)-alkil, reaguje u prisustvu baze sa jedinjenjem sa formulom (V) u kojoj L1 ima značenja data u bilo kom od zahteva 1 do 6, T1 predstavlja (C1-C4)-alkil, i X2 predstavlja odlazeću grupu kao što je, na primer, hlor, brom, jod, mesilat, triflat ili tosilat, i odgovarajuće dobijeno jedinjenje sa formulom (VI) u kojoj R1, A, L1, T1 i T2 imaju gore navedena značenja, se zatim konvertuje hidrolizom grupa estra -C(O)OT1 i -C(O)OT2 u odgovarajuću dikarboksilnu kiselinu sa formulom (I) i na ovaj način dobivena jedinjenja sa formulom (I) se opciono rastavljaju na njihove enantiomere i/ili dijastereomere i/ili se opciono konvertuju sa odgovarajućim (i) rastvaračima i/ili (ii) bazama ili kiselinama u njihove solvate, soli i/ili solvate soli.
8.Jedinjenje kako je definisano u bilo kom od zahteva 1 do 6 naznačeno time što je za lečenje i/ili prevenciju bolesti.
9.Jedinjenje kako je definisano u bilo kom od zahteva 1 do 6 naznačeno time što je za upotrebu u postupku lečenja i/ili prevencije primarnih i sekundarnih oblika plućne hipertenzije, zatajenja srca, angine pektoris, hipertenzije, tromboembolijskih poremećaja, ishemija, vaskularnih poremećaja, oštećenja mikrocirkulacije, insuficijencije bubrega, fibroznih poremećaja i arterioskleroze.
10.Upotreba jedinjenja kako je definisano u bilo kom od zahteva 1 do 6 naznačena time da je za dobivanje leka za lečenje i/ili prevenciju primarnih i sekundarnih oblika plućne hipertenzije, zatajenja srca, angine pektoris, hipertenzije, tromboembolijskih poremećaja, ishemija, vaskularnih poremećaja, oštećenja mikrocirkulacije, insuficijencije bubrega, fibroznih poremećaja i arterioskleroze.
11.Lek, naznačen time što sadrži jedinjenje kako je definisano u bilo kom od zahteva 1 do 6 u kombinaciji sa jednom ili više inertnih netoksičnih farmaceutski prihvatljivih pomoćnih supstanci.
12.Lek, naznačen time što sadrži jedinjenje kako je definisano u bilo kom od zahteva 1 do 6 u kombinaciji sa jednim ili više daljnjih aktivnih jedinjenja koja su izabrana iz grupe koju čine organski nitrati, donori NO, inhibitori PDE 5, analozi prostaciklina, agonisti IP receptora, antagonisti receptora endotelina, stimulatori gvanilat ciklaze, inhibitori tirozin kinaze, anti-opstruktivna sredstva, anti-inflamatorna i/ili imunosupresivna sredstva, antitrombotička sredstva, sredstva za snižavanje krvnog pritiska i sredstva koja menjaju metabolizam masti.
13. Lek prema zahtevu 11 ili 12 naznačen time što je za lečenje i/ili prevenciju primarnih i sekundarnih oblika plućne hipertenzije, zatajenja srca, angine pektoris, hipertenzije, tromboembolijskih poremećaja, ishemija, vaskularnih poremećaja, oštećenja mikrocirkulacije, insuficijencije bubrega, fibroznih poremećaja i arterioskleroze.
MEP-2017-30A 2012-07-20 2013-07-16 Nove 5 - aminotetrahidrohinolin-2-karbonske kiseline i njihova upotreba ME02603B (me)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP12177284 2012-07-20
EP13167967 2013-05-16
EP13744464.2A EP2875003B1 (de) 2012-07-20 2013-07-16 Neue 5-aminotetrahydrochinolin-2-carbonsäuren und ihre verwendung
PCT/EP2013/065017 WO2014012934A1 (de) 2012-07-20 2013-07-16 Neue 5-aminotetrahydrochinolin-2-carbonsäuren und ihre verwendung

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