ES2694001T3 - Moduladores de LXR - Google Patents

Moduladores de LXR Download PDF

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Publication number
ES2694001T3
ES2694001T3 ES14770510T ES14770510T ES2694001T3 ES 2694001 T3 ES2694001 T3 ES 2694001T3 ES 14770510 T ES14770510 T ES 14770510T ES 14770510 T ES14770510 T ES 14770510T ES 2694001 T3 ES2694001 T3 ES 2694001T3
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cycloalkyl
alkyl
monocyclic
ring
independently
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ES2694001T9 (es
Inventor
Ellen K. Kick
Mandar BODAS
Raju Mohan
Brett B. Busch
Claudia Averbuj
Meriah VALENTE
Nicholas Wurtz
Prasanna Savanor Maddu RAO
Jeevanprakash SHETTY
Alla VENU
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Bristol Myers Squibb Co
Exelixis Patent Co LLC
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Bristol Myers Squibb Co
Exelixis Patent Co LLC
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/18—Antioxidants, e.g. antiradicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • 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
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • 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
    • 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
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic 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
    • C07D413/10—Heterocyclic 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 carbon chain containing aromatic rings

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Diabetes (AREA)
  • Immunology (AREA)
  • Dermatology (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Neurosurgery (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Obesity (AREA)
  • Rheumatology (AREA)
  • Emergency Medicine (AREA)
  • Hospice & Palliative Care (AREA)
  • Pain & Pain Management (AREA)
  • Vascular Medicine (AREA)
  • Psychiatry (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Biochemistry (AREA)
  • Endocrinology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Un compuesto de la fórmula I o II,**Fórmula** o una sal o solvato farmacéuticamente aceptable del mismo, en donde el Anillo C se selecciona entre oxazolilo y triazolilo; el Anillo D se selecciona entre fenilo y piridilo; A es fenilo o un heteroarilo de 5 o 6 miembros, en donde el fenilo está opcionalmente condensado con un heterociclilo de 5 o 6 miembros o heteroarilo de 5 o 6 miembros, en donde A está opcionalmente sustituido con 1, 2 o 3 grupos RA, en donde cada RA es independientemente RA1, -alquilo C1-C6-RA1, alquilo C1-C6, haloalquilo C1-C6, alquenilo C2-C6, alquinilo C2-C6, cicloalquilo C3-C8, pirrolidinona o pirrolidinilo, en donde el cicloalquilo está opcionalmente sustituido con 1, 2, 3 o 4 grupos que son independientemente RA1, alquilo C1-C6 o -alquilo C1-C6-RA1, en donde cada RA1 es independientemente halógeno, ciano, nitro, -OR, -NR2, -SR, -C(O)R o -C(O)OR; como alternativa, dos RA en carbonos adyacentes pueden unirse para formar un -O-CH2-O-, -O-CH2-CH2-, - O-CH2-CH2-O-, -CH2-CH2-CH2- u -O-CF2-O-; RB1 es hidrógeno, alquilo C1-3, halo, ciclopropilo, o haloalquilo C1-3; RB2 es hidrógeno, halo, -CN, -C(O)NR2, o alquilo C1-3; RB3 es alquilo C1-6, haloalquilo C1-6, o cicloalquilo C3-6, cada uno de los cuales está sustituido con 0-1 RB5; hidrógeno; ciano; -C(O)-R; -C(O)NR2; -NHC(O)R; -NHSO2R; o un heteroarilo de anillo de 5 miembros, en donde el anillo de heteroarilo consiste en átomos de carbono y 1, 2 o 3 heteroátomos seleccionados independientemente entre el grupo que consiste en N, S y O y está sustituido con 0-1 R; RB4 es H, halógeno, alquilo C1-3, haloalquilo C1-3, -cicloalquilo C3-C6, u -O-alquilo C1-3; RB5 es ciano, -O-R, -C(O)NR2, -C(O)OR, -NR2, -OC(O)-NH2, -S(O)2NR2, o un heteroarilo de anillo de 5 miembros, en donde el anillo de heteroarilo consiste en átomos de carbono y 1, 2 o 3 heteroátomos seleccionados independientemente entre el grupo que consiste en N, S y O; R es hidrógeno, halógeno, ciano o nitro; n es 0, 1, 2, 3 o 4; y cada RD1 y RD2 son independientemente RD3, alquilo C1-C6, -alquilo C1-C6-RD3, haloalquilo C1-C6, alquenilo C2-C6, alquinilo C2-C6, o cicloalquilo C3-C8, en donde el cicloalquilo está cada uno opcionalmente sustituido con 1, 2, 3 o 4 grupos que son independientemente RD3, alquilo C1-C6, cicloalquilo C3-C6, o -alquilo C1-C6-RD3, en donde cada RD3 es independientemente halógeno, ciano, -OR, -NR2, -SR, -C(O)R, -C(O)OR, -C(O)NR2, -S(O)R, -S(O)2R, - S(O)NR2, -S(O)2NR2, -OC(O)R, -OC(O)OR, -OC(O)NR2, -N(R)C(O)R, -N(R)C(O)OR, -N(R)C(O)NR2, -N(R)S(O)2R, - N(R)S(O)2OR, -N(R)S(O)2NR2, o -S(O)2N(R)C(O)NR2; y RL es hidrógeno, alquilo C1-C6, cicloalquilo C3-C6, haloalquilo C1-C6, -C(O)R, -C(O)OR, -C(O)NR2, -S(O)R, - S(O)2R, -S(O)OR, -S(O)2OR, -S(O)NR2, o -S(O)2NR2; en donde cada grupo R es independientemente hidrógeno, alquilo C1-C6, -alquilo C1-C6-R2, haloalquilo C1-C6, -haloalquilo C1-C6-R2, alquenilo C2-C6, alquinilo C2-C6, o cicloalquilo C3-C8, o -alquilo C1-C6-cicloalquilo C3-6; o para cualquier - C(O)NR2 o -NR2, como alternativa, los dos R junto con el N al que estos se unen pueden formar morfolinilo, pirrolidinilo o piperdinilo; y en donde cada R2 es independientemente ciano, -OR3, -C(O)NH2, -N(R3)2, -N(R3)S(O)2R3, -N(R3)S(O)2OR3, o - N(R3)S(O)2N(R3)2, en donde cada R3 es independientemente hidrógeno, alquilo C1-C6, cicloalquilo C3-6 o haloalquilo C1-C6; en donde el término "cicloalquilo" significa un sistema de anillo de cicloalquilo monocíclico o uno bicíclico; en donde los sistemas de anillos de cicloalquilo monocíclico son grupos hidrocarburo cíclico que contienen de 3 a 8 átomos de carbono, que pueden ser saturados o insaturados, pero no aromáticos; los sistemas de anillo de cicloalquilo bicíclico son anillos monocíclicos con puente o anillos bicíclicos condensados; en donde dichos anillos monocíclicos con puente contienen un anillo de cicloalquilo monocíclico en donde dos átomos de carbono no adyacentes del anillo monocíclico están enlazados por un grupo de puente de alquileno de forma -(CH2)w-, en donde w es 1, 2 o 3; y en donde los sistemas de anillo de cicloalquilo bicíclico condensado contienen un anillo de cicloalquilo monocíclico condensado con o bien un fenilo, un cicloalquilo monocíclico, un cicloalquenilo monocíclico, un heterociclilo monocíclico o un heteroarilo monocíclico; en donde el cicloalquilo bicíclico con puente o condensado se une al resto molecular precursor a través de cualquier átomo de carbono contenido dentro del anillo de cicloalquilo monocíclico.
ES14770510T 2013-03-15 2014-03-14 Moduladores de LXR Active ES2694001T3 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201361787422P 2013-03-15 2013-03-15
PCT/US2014/027679 WO2014152738A1 (en) 2013-03-15 2014-03-14 Lxr modulators

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ES2694001T3 true ES2694001T3 (es) 2018-12-17
ES2694001T9 ES2694001T9 (es) 2019-07-12

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US (1) US9751869B2 (es)
EP (1) EP2967073B9 (es)
JP (1) JP6456909B2 (es)
CN (1) CN105188380B (es)
ES (1) ES2694001T3 (es)
WO (1) WO2014152738A1 (es)

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EP2968275B1 (en) 2013-03-15 2017-11-29 Bristol-Myers Squibb Company Lxr modulators
ITUA20164199A1 (it) * 2016-06-08 2017-12-08 Univ Degli Studi Del Piemonte Orientale Amedeo Avogadro Modulatori di soce compisizioni e relativi usi
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WO2023240267A2 (en) * 2022-06-10 2023-12-14 Sionna Therapeutics Compounds, compositions, and methods of using thereof

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US9751869B2 (en) 2017-09-05
JP6456909B2 (ja) 2019-01-23
ES2694001T9 (es) 2019-07-12
EP2967073A4 (en) 2016-10-12
US20160289222A1 (en) 2016-10-06
JP2016518334A (ja) 2016-06-23
EP2967073A1 (en) 2016-01-20
WO2014152738A1 (en) 2014-09-25
EP2967073B9 (en) 2019-04-10
CN105188380A (zh) 2015-12-23
CN105188380B (zh) 2017-08-15
EP2967073B1 (en) 2018-08-01

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