ES2650372T3 - Compuestos tricíclicos como inhibidores de CFTR - Google Patents

Compuestos tricíclicos como inhibidores de CFTR Download PDF

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Publication number
ES2650372T3
ES2650372T3 ES13826624T ES13826624T ES2650372T3 ES 2650372 T3 ES2650372 T3 ES 2650372T3 ES 13826624 T ES13826624 T ES 13826624T ES 13826624 T ES13826624 T ES 13826624T ES 2650372 T3 ES2650372 T3 ES 2650372T3
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carbon atoms
alkyl
amino
atoms
alkoxy
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Mahbub AHMED
Alexander ASHALL-KELLY
Graham Charles Bloomfield
Louisa GUERITZ
Jeffrey Mckenna
Joseph Mckenna
Simon MUTTON
Rakesh PARMAR
Jon SHEPHERD
Paul Wright
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Novartis AG
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Novartis AG
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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
    • C07D487/12Heterocyclic 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 three hetero rings
    • C07D487/14Ortho-condensed systems
    • 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
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • 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
    • A61K31/535Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53831,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
    • 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
    • A61K31/55Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/553Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
    • 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
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/12Antidiarrhoeals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • 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
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D498/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/14Ortho-condensed systems

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pulmonology (AREA)
  • Urology & Nephrology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Un compuesto de la fórmula (I), o una sal farmacéuticamente aceptable del mismo:**Fórmula** en donde R1 representa fenilo, cicloalquenilo (de 4 a 7 átomos de carbono) o Het1, cuyo grupo R1 puede estar insustituido o sustituido sobre uno o dos átomos de carbono por sustituyentes Ra, y puede estar además sustituido sobre un átomo de nitrógeno con un sustituyente Ra1; cada Ra independientemente representa alquilo (de 1 a 4 átomos de carbono), halógeno, halo-alquilo (de 1 a 4 átomos de carbono), ciano, hidroxi-alquilo (de 1 a 4 átomos de carbono), alcoxilo (de 1 a 4 átomos de carbono), halo-alcoxilo (de 1 a 4 átomos de carbono), alcoxilo (de 1 a 4 átomos de carbono)-alquilo (de 1 a 4 átomos de carbono)-, R6OC(O)-, o R6OC(O)alquilo (de 1 a 4 átomos de carbono)-; Ra1 representa alquilo (de 1 a 4 átomos de carbono), hidroxi-alquilo (de 1 a 4 átomos de carbono), alcoxilo (de 1 a 4 átomos de carbono)-alquilo (de 1 a 4 átomos de carbono)-, alquilo (de 1 a 4 átomos de carbono)-aminoalquilo (de 1 a 4 átomos de carbono)-, di-[alquilo (de 1 a 4 átomos de carbono)]-amino-alquilo (de 1 a 4 átomos de carbono)-, aril-alquilo (de 1 a 4 átomos de carbono)- o R6OC(O)alquilo (de 1 a 4 átomos de carbono)-; R2 representa alquilo (de 1 a 6 átomos de carbono), cicloalquilo (de 3 a 7 átomos de carbono), cicloalquenilo (de 4 a 7 átomos de carbono), fenilo, furanilo, tiazolilo, tienilo o pirazolilo, cuyo R2 puede estar insustituido o sustituido sobre uno a tres átomos de carbono con sustituyentes Rb, y puede estar además sustituido sobre un átomo de nitrógeno con alquilo (de 1 a 4 átomos de carbono); cada Rb independientemente representa alquilo (de 1 a 4 átomos de carbono), halógeno, halo-alquilo (de 1 a 4 átomos de carbono), ciano, alquilo (de 1 a 4 átomos de carbono)-amino-alquilo (de 1 a 4 átomos de carbono)-, di-[alquilo (de 1 a 4 átomos de carbono)]- amino-alquilo (de 1 a 4 átomos de carbono)-, (R6)2NC(O)alquilo (de 1 a 4 átomos de carbono)- o R6OC(O)alquilo (de 1 a 4 átomos de carbono)-; X representa O, NH o NMe; o X representa -CH2-O-, en donde el átomo de oxígeno (O) se une al átomo de -C(R4)(R4') del anillo; cada R3 independientemente representa metilo o etilo; R4 representa hidrógeno, alquilo (de 1 a 4 átomos de carbono), halo-alquilo (de 1 a 4 átomos de carbono), hidroxi-alquilo (de 1 a 4 átomos de carbono), alcoxilo (de 1 a 4 átomos de carbono)-alquilo (de 1 a 4 átomos de carbono)-, amino-alquilo (de 1 a 4 átomos de carbono)-, alquilo (de 1 a 4 átomos de carbono)-amino-alquilo (de 1 a 4 átomos de carbono)-, di-[alquilo (de 1 a 4 átomos de carbono)]-amino-alquilo (de 1 a 4 átomos de carbono)- , fenilo, Het1alquilo (de 1 a 4 átomos de carbono)-, Het2alquilo (de 1 a 4 átomos de carbono)-, alquilo (de 1 a 4 átomos de carbono)S(O)2NH-alquilo (de 1 a 4 átomos de carbono)-, o R7C(O)NH-alquilo (de 1 a 4 átomos de carbono)-; R4' representa H o metilo; R4a representa hidrógeno, alquilo (de 1 a 4 átomos de carbono), halo-alquilo (de 1 a 4 átomos de carbono), amino-alquilo (de 1 a 4 átomos de carbono)-, alquilo (de 1 a 4 átomos de carbono)-amino-alquilo (de 1 a 4 átomos de carbono)-, di-[alquilo (de 1 a 4 átomos de carbono)]-amino-alquilo (de 1 a 4 átomos de carbono)-, Het1alquilo (de 1 a 4 átomos de carbono)-, Het2alquilo (de 1 a 4 átomos de carbono)-, o R6OC(O)-; R6 representa hidrógeno, alquilo (de 1 a 4 átomos de carbono); R7 representa alquilo (de 1 a 2 átomos de carbono), alcoxilo (de 1 a 2 átomos de carbono), alcoxilo (de 1 a 2 átomos de carbono)-alquilo (de 1 a 2 átomos de carbono) o fenilo; Het1 representa un anillo de heteroarilo de 5 o 6 miembros que comprende: a) un átomo de oxígeno o de azufre, y opcionalmente uno o dos átomos de nitrógeno; o b) de uno a cuatro átomos de nitrógeno; y Het2 representa un anillo heterocíclico de 4 a 7 miembros que comprende: a) 1 o 2 heteroátomos seleccionados a partir de N, O y S; o b) -C(O)- y 1 o 2 heteroátomos seleccionados a partir de N y O.
ES13826624T 2012-12-19 2013-12-17 Compuestos tricíclicos como inhibidores de CFTR Active ES2650372T3 (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201261739337P 2012-12-19 2012-12-19
US201361906154P 2013-11-19 2013-11-19
PCT/IB2013/061041 WO2014097147A1 (en) 2012-12-19 2013-12-17 Tricyclic compounds as cftr inhibitors

Publications (1)

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ES2650372T3 true ES2650372T3 (es) 2018-01-18

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ES13826624T Active ES2650372T3 (es) 2012-12-19 2013-12-17 Compuestos tricíclicos como inhibidores de CFTR

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US (1) US9303035B2 (es)
EP (1) EP2935277B1 (es)
JP (1) JP6284545B2 (es)
KR (1) KR20150095925A (es)
CN (1) CN105008370B (es)
AR (1) AR094123A1 (es)
AU (1) AU2013365827A1 (es)
BR (1) BR112015014433A2 (es)
CA (1) CA2895656A1 (es)
EA (1) EA201591175A1 (es)
ES (1) ES2650372T3 (es)
MX (1) MX2015007940A (es)
TW (1) TW201429976A (es)
UY (1) UY35209A (es)
WO (1) WO2014097147A1 (es)

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Publication number Priority date Publication date Assignee Title
ES2882807T3 (es) 2011-09-16 2021-12-02 Novartis Ag Heterociclil carboxamidas N-sustituidas
WO2014097147A1 (en) 2012-12-19 2014-06-26 Novartis Ag Tricyclic compounds as cftr inhibitors
EP2935278B1 (en) 2012-12-19 2017-03-15 Novartis AG Tricyclic compounds for inhibiting the cftr channel
ES3066112T3 (en) 2015-12-24 2026-05-11 The Regents Of The Univ Of California Cftr regulators and methods of use thereof
RU2730855C2 (ru) 2015-12-24 2020-08-26 Дзе Риджентс Оф Дзе Юниверсити Оф Калифорниа Кфтр регуляторы и способы их применения
EP3672598A4 (en) 2017-08-24 2021-04-28 The Regents of The University of California OCULAR PHARMACEUTICAL COMPOSITIONS
CN112724157B (zh) * 2021-01-23 2022-04-19 中国科学院新疆理化技术研究所 二氢噁唑并[5,4-d]吡咯并[1,2-a]嘧啶-9(5H)-酮类衍生物及用途
IL307863A (en) 2021-04-29 2023-12-01 Novartis Ag Diubiquitinase-directed chimeras and related methods

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TW224974B (es) * 1991-07-02 1994-06-11 Hoffmann La Roche
AU6729600A (en) 1999-08-25 2001-03-19 Banyu Pharmaceutical Co., Ltd. Novel isoindole derivatives
JP2002255967A (ja) 2001-02-27 2002-09-11 Banyu Pharmaceut Co Ltd イソインドール誘導体を有効成分とする糖尿病の治療剤、糖尿病の慢性合併症の予防剤又は肥満の治療剤。
CA2514733A1 (en) 2003-02-28 2004-09-16 Transform Pharmaceuticals, Inc. Pharmaceutical co-crystal compositions of drugs such as carbamazepine, celecoxib, olanzapine, itraconazole, topiramate, modafinil, 5-fluorouracil, hydrochlorothiazide, acetaminophen, aspirin, flurbiprofen, phenytoin and ibuprofen
JP2010512389A (ja) 2006-12-12 2010-04-22 シェーリング コーポレイション アスパルチルプロテアーゼ阻害剤
US20110015137A1 (en) * 2007-07-05 2011-01-20 Trustees Of Boston University Reca inhibitors and their uses as microbial inhibitors or potentiators of antibiotic activity
US8642660B2 (en) 2007-12-21 2014-02-04 The University Of Rochester Method for altering the lifespan of eukaryotic organisms
EP2464354B1 (en) * 2009-08-10 2015-04-01 The Regents of The University of California Pyrimido-pyrrolo-quinoxalinedione inhibitors of cystic fibrosis transmembrane conductance regulator protein and uses therefor
USRE48842E1 (en) * 2011-05-27 2021-12-07 The Regents Of The University Of California Pyrimido-pyrrolo-oxazine-dione compound inhibitors of the cystic fibrosis transmembrane conductance regulator protein and uses therefor
WO2014097147A1 (en) 2012-12-19 2014-06-26 Novartis Ag Tricyclic compounds as cftr inhibitors
EP2935278B1 (en) * 2012-12-19 2017-03-15 Novartis AG Tricyclic compounds for inhibiting the cftr channel

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TW201429976A (zh) 2014-08-01
CA2895656A1 (en) 2014-06-26
CN105008370A (zh) 2015-10-28
EP2935277A1 (en) 2015-10-28
WO2014097147A1 (en) 2014-06-26
AR094123A1 (es) 2015-07-08
US20140171412A1 (en) 2014-06-19
EA201591175A1 (ru) 2015-11-30
CN105008370B (zh) 2017-06-09
EP2935277B1 (en) 2017-08-30
UY35209A (es) 2014-07-31
MX2015007940A (es) 2016-03-11
AU2013365827A1 (en) 2015-07-09
KR20150095925A (ko) 2015-08-21
BR112015014433A2 (pt) 2017-07-11
US9303035B2 (en) 2016-04-05
JP6284545B2 (ja) 2018-02-28
JP2016507498A (ja) 2016-03-10

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