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ME02847B - Fuzionisana heterociklična jedinjenja kao modulatori jonskih kanala - Google Patents

Fuzionisana heterociklična jedinjenja kao modulatori jonskih kanala

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Publication number
ME02847B
ME02847B MEP-2017-235A MEP23517A ME02847B ME 02847 B ME02847 B ME 02847B ME P23517 A MEP23517 A ME P23517A ME 02847 B ME02847 B ME 02847B
Authority
ME
Montenegro
Prior art keywords
alkyl
heteroaryl
independently selected
halo
cycloalkyl
Prior art date
Application number
MEP-2017-235A
Other languages
German (de)
English (en)
French (fr)
Inventor
Britton Corkey
Elfatih Elzein
Robert Jiang
Rao Kalla
Tetsuya Kobayashi
Dmitry Koltun
Xiaofen Li
Gregory Notte
Eric Parkhill
Thao Perry
Jeff Zablocki
Original Assignee
Gilead Sciences Inc
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 Gilead Sciences Inc filed Critical Gilead Sciences Inc
Publication of ME02847B publication Critical patent/ME02847B/me

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/08Antiepileptics; Anticonvulsants
    • AHUMAN NECESSITIES
    • 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]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • A61P9/10Drugs 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04Ortho-condensed systems

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Diabetes (AREA)
  • Pain & Pain Management (AREA)
  • Neurosurgery (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Emergency Medicine (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Endocrinology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Rheumatology (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Optical Modulation, Optical Deflection, Nonlinear Optics, Optical Demodulation, Optical Logic Elements (AREA)
  • Crystals, And After-Treatments Of Crystals (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Claims (1)

1. Jednjenje sa formulom III:gde:R1 je aril ili heteroaril odabran iz grupe koja se sastoji od:gde pomenuti aril ili heteroaril su supstituisani sa jednim dva, ili tri supstituenta nezavisno odabranih iz grupe koja se sastoji od hidroksi!, halo, -NO2, CN, -SF5, -Si(CH3)3 -O-CF3, -O-R20, -S-R20, -C(O)-R20, C(O)OH,-N(R20)(R22), -C(O)-N(R20)(R22), -N(R20)-C(O)-R22,-N(R20)-S(=O)2-R26, -S(=O)2- R20, -S(=O)2-N(R20)(R22), C1-C3 alkoksi, C1-4 alkil, C2-4 alkenil, C2-4 alkinil, cikloalkil, heteroaril, i heterociklil;gde pomenuti alkoksi, alkil, alkenil, alkinil, heteroaril, cikloalkil, ili heterociklil su po izboru supstituisani sa jednim, dva, ili tri supstituenta nezavisno odabranih od hidroksil, halo, -NO2 , -O-CF3, -O-CHF2, fenil, heterociklil, heteroaril, cikloalkil, -N(R 20)(R22), -C(O)-R20, -C(O)-O-R20, -C(O)-N(R20)(R22), -CN, i -O-R20,ili gde R1 je supstituisan sa jednim, dva, ili tri supstituenta nezavisno odabranih odR2 je nezavisno odabran iz grupe koja se sastoji od vodonika, po izboru supstituisanog alkila, amino, po izboru supstituisanog alkoksi, -CF3, -O-CF3, -CN, i -N(R 20)C(O)-R22 ;R3 je nezavisno odabran iz grupe koja se sastoji od vodonika, alkila,- CF3, -halo, i -O-R4 je nezavisno odabran iz grupe koja se sastoji od vodonika, hidroksila, halo, C1-4 alkila, C1-C3 alkoksi, -R25-N(R20)(R22), -R25-O-R20, -R25-C(O)-O-R20, -R25-C(O)-N(R20)(R22),-R25-C(O)-O-N(R20)(R22), -R25-N(R20)-C(O)-R22, i -R25-O-C(O)-N(R20)(R22),gde pomenuti alkil su po izboru supstituisani sa jednim, dva, ili tri supstituenta nezavisno odabranih od hidroksil i halo,Q je odabran od kovalentne veze ili C2-4 alkinilena;Ra je vodonik, C1-15 alkil, C1-4 alkoksi, -C(O)-O-R26, -C(O)-N(R26)(R28), -N(R20)-S(=O)2-R20, cikloalkil, aril, heteroaril, i heterociklil, gde pomenuti alkil je po izboru supstituisan sa jedan, dva, ili tri supstituenta nezavisno odabranih od hidroksil, halo, -NO2, -O-CF3, -O-CHF2, cikloalkil, -CN, i C1-4 alkoksi; ipomenuti alkoksi, cikloalkil, aril, heterociklil, ili heteroaril su po izboru supstituisani sa jednim, dva, ili tri supstituenta nezavisno odabranih od hidroksila, halo, -NO2, -O-CF3, -O-CHF2, fenila, heterociklila, heteroarila, cikloalkila, -N(R20)(R22), -C(O)-R20, -C(O)-O-R20, -C(O)-N(R20)(R22), -CN, i -O-R20; iliRa je-Y-Z-R25-R23-R2o, gde,Y je kovalentna veza ili odabran od C1-C3 alkilena po izboru supstituisanog sa jedan ili dva C1-C3 alkila ili fluora grupe;Z je C2-4 alkinilen, -O-, -S-, -NR", -NR"-, -NR5'-C(O), -NR"-C(O)-NR5'- ili -C(O)-NR3-, gde svako R" i R5' je nezavisno vodonik ili C1-6 niži alkil; idalje gde pomenuti alkil su po izboru supstituisani sa jednim, dva, ili tri supstituenta nezavisno odabranih od hidroksila, halo, -NO2, -O-CF3, -O-CHF2, fenila, heterociklila, heteroarila, cikloalkila, -N(R2O)(R22), -C(O)-R20, -C(O)-O-R20, -C(O)-N(R20)(R22), -CN, i -O- R2o ,iligde Ra je odabran iz grupe koja se sastoji odR20 i R22 su u svakom slučaju nezavisno odabrani iz grupe koja se sastoji od vodonika, C1-C15 alkila, C2-C15 alkenila, C2-C15 alkinila, cikloalkila, heterociklila, arila, i heteroarila,gde alkil, alkenil, alkinil, heterociklil, aril, i heteroaril su po izboru supstituisani sa jednim, dva, ili tri supstituenta nezavisno odabranih od hidroksila, halo, alkila, mono- ili dialkilamino, alkil ili aril ili heteroaril amida, -NO2, -SO2R26, -CN, C1-3 alkoksi, -CF3, -OCF3, arila, cikloalkila, i heteroarila; ili;kada R20 i R22 su vezani za zajednički atom azota R20 i R22 se mogu spojiti da formiraju heterociklični prsten koji je zatim po izboru supstituisan sa jedan, dva, ili tri supstituenta nezavisno odabranih od hidroksila, halo, alkila, mono- ili dialkilamino, alkil ili aril ili heteroaril amida, -NO2, -SO2R26, -CN, C1-3 alkoksi, -CF3, i -OCF3, arila, i cikloalkila;R23 je kovalentna veza ili je odabrana iz grupe koja se sastoji od cikloalkilena, heterociklilena, arilena, i heteroarilena,gde cikloalkilen, heterociklilen, arilen, i heteroarilen su po izboru supstituisani sa jednim do tri supstituenta nezavisno odabranih od hidroksila, halo, alkil.a, mono- ili dialkilamino, alkil ili aril ili heteroaril amida, -NO2, -SO2R26, -CN, C1-3 alkoksi, - CF3, -OCF3, arila, cikloalkila, i heteroarila;R24 je u svakom slučaju nezavisno odabran od alkila i l i arila od kojih svaki može po izboru biti supstituisan sa 1, 2, ili 3 grupe nezavisno odabrane od hidroksi la, -OCF3, halo, C1-C3 alkoksi, -O-R20, ili alkila po izboru supstituisanog sa halo, -NO2, -CF3, -O-CF3, -N(R20)(R22), -C(O)-R20, -C(O)-O-R20, -C(O)-N(R20)(R22), -CN, ili -O-R20 ;R25 je u svakom slučaju nezavisno kovalentna veza ili odabran od C1-C3 alkilena po izboru supstituisanog sa jednom ili dve C1 -C3 alkil grupe; iR26 i R28 su u svakom slučaju nezavisno odabrani od vodonika, alki la, ili cikloalkila, gde alkil i cikloalki l mogu dalje biti supstituisani sa od 1 do 3 supstituenta nezavisno odabranih od hidroksil, halo, C1 -4 alkoksi, -CF3, i -OCF3;ili njegove farmaceutski prihvatljive soli, estra, ili solvata,pod uslovima daa. kada Ra je -Y-Z-R25-R23-R20, Y nije kovalentna veza i Z je -0-, -S-, -C(O)-NR3-, -NR5 -C(O)-, ili NR"-, onda R25 ne može biti veza;b. kada Raje -Y-Z-R 25-R23-R20,Y je kovalentna veza i Z je -O-, -S-, ili NR"-, onda R25 je kovalentna veza i R23 nije cikloalkilen;c. kada Z je -NR 5'-C(O)-, onda Y nije kovalentna veza;d. R23 i R25 ne mogu oba biti kovalentne veze; ie. kada Q je veza, i R1 je heteroaril, onda R1 heteroaril možda neće dalje biti supstituisan sa fenilom; if. kada R2 je supstituisan alkil, onda Ra nije alkil, cikloalkil, ili heterociklil.
2. Jedinjenje patentnog zahteva 1 , gde Q je C2-4 alkinilen.
4. Jedinjenje patentnog zahteva 1, gde R1 je heteroaril.
8. Jedinjenje patentnog zahteva 1 , gde R1 je aril po izboru supstituisan sa halo, hidroksil, metoksi, etoksi, -OCF3, ili amino.
11. Jedinjenje bilo kog od patentnih zahteva l do l O za primenu u metodi za lečenje stanja bolesti kod sisara koje je olakšana tretmanom sa agensom koji je sposoban da smanji kasnu struju natrijuma.
12. Primena jedinjenja bilo kog od patentnih zahteva l do l O za pripremanje farmaceutske kompozicije za lečenje stanja bolesti kod sisara koje je olakšano tretmanom sa agensom koji je sposoban da smanji kasnu struju natrijuma.
13. Jedinjenje patentnog zahteva ll ili primena prema patentnom zahtevu 12, gde stanje bolesti je kardiovaskulama bolest odabrana od jedne ili više od atrijalnih i ventrikulamih aritmija, srčane insuficijencije (uključujući kongestivnu srčanu insuficijenciju, dijastolnu srčanu insuficijenciju, sistolnu srčanu insuficijenciju, akutnu srčanu insuficijenciju), Princmetalove (varijantu) angine, stabilne i nestabilne angine, angine izazvane vežbanjem, kongestivne srčane bolesti, ishemije, rekurentne ishemije, reperfuzione povrede, infarktamiokarda, akutnog koronarnog sindroma, periferne arterijske bolesti, plućne hipertenzije, intermitentne klaudikacije; ili stanje bolesti je dijabetes ili dijabetička periferna neuropatija; ili stanje bolesti rezultira u jednom ili više od neuropatskog bola, epilepsije, napada ili paralize.
14. Farmaceutska kompozicija koja sadrži farmaceutski prihvatljiv ekscipijens i terapijski efikasnu količinujedinjenja bilo kog od patentnih zahteva l do 10 ili farmaceutski prihvaljivu so, estar ili hidrat togjedinjenja.
MEP-2017-235A 2009-07-27 2010-07-26 Fuzionisana heterociklična jedinjenja kao modulatori jonskih kanala ME02847B (me)

Applications Claiming Priority (4)

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US22886409P 2009-07-27 2009-07-27
US36003710P 2010-06-30 2010-06-30
EP10737724.4A EP2464645B1 (en) 2009-07-27 2010-07-26 Fused heterocyclic compounds as ion channel modulators
PCT/US2010/043264 WO2011014462A1 (en) 2009-07-27 2010-07-26 Fused heterocyclic compounds as ion channel modulators

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AU2010276537A1 (en) 2012-05-24
SI2464645T1 (sl) 2017-10-30
CN102725290B (zh) 2016-03-09
WO2011014462A1 (en) 2011-02-03
CN102725290A (zh) 2012-10-10
TW201542545A (zh) 2015-11-16
TWI490217B (zh) 2015-07-01
LT2464645T (lt) 2017-10-25
HRP20171454T1 (hr) 2017-12-01
EP2464645B1 (en) 2017-07-05
US8952034B2 (en) 2015-02-10
HRP20171454T8 (hr) 2018-01-12
ES2642586T3 (es) 2017-11-16
NZ598942A (en) 2014-02-28
US20110021521A1 (en) 2011-01-27
EA025824B1 (ru) 2017-02-28
HUE034911T2 (hu) 2018-03-28
CY1119584T1 (el) 2018-03-07
SMT201700456T1 (it) 2017-11-15
UY32805A (es) 2011-02-28
PL2464645T3 (pl) 2017-12-29
TW201116528A (en) 2011-05-16
US9371329B2 (en) 2016-06-21
RS56410B1 (sr) 2018-01-31
US20140303158A1 (en) 2014-10-09
AU2010276537B2 (en) 2015-04-16
CA2774715A1 (en) 2011-02-03
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DK2464645T3 (en) 2017-10-23
AR077598A1 (es) 2011-09-07

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