AR081117A1 - Derivados de quinazolina como moduladores de la hsp90 y su preparacion - Google Patents

Derivados de quinazolina como moduladores de la hsp90 y su preparacion

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Publication number
AR081117A1
AR081117A1 ARP100104277A ARP100104277A AR081117A1 AR 081117 A1 AR081117 A1 AR 081117A1 AR P100104277 A ARP100104277 A AR P100104277A AR P100104277 A ARP100104277 A AR P100104277A AR 081117 A1 AR081117 A1 AR 081117A1
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AR
Argentina
Prior art keywords
conh
hal
atoms
ncooa
ncooh
Prior art date
Application number
ARP100104277A
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English (en)
Inventor
Hans-Michael Eggenweiler
Hans-Peter Buchstaller
Christian Sirrenberg
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Merck Patent Gmbh
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Publication date
Application filed by Merck Patent Gmbh filed Critical Merck Patent Gmbh
Publication of AR081117A1 publication Critical patent/AR081117A1/es

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    • 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
    • C07D403/14—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 three or more hetero rings
    • 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
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • 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
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/02—Antidotes
    • 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
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
    • C07D239/84—Nitrogen atoms
    • 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
    • C07D403/06—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 only aliphatic carbon atoms
    • 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

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Urology & Nephrology (AREA)
  • Virology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Transplantation (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Cardiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Vascular Medicine (AREA)
  • Toxicology (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Derivados de quinazolina de la formula (1) en donde R1, R2 son cada uno, de modo independiente entre sí, H, A, (CH2)nHet o (CH2)nAr, R1 y R2 junto con el átomo de N al que están unidos, también son un heterociclo mono- o bicíclico saturado, insaturado o aromático no sustituido o mono-, di- o trisustituido con Hal, A, (CH2)nHet, (CH2)nAr, (CH2)nOH, (CH2)nOA, (CH2)nNH2, (CH2)nCOOH, (CH2)nCOOA, NHCOA, NA'COA, CONH2, CONHA, CONAA', OC(=O) (CH2)pNH2 y/u =O (oxígeno de carbonilo), que puede contener otros 1 a 3 átomos de N, O y/o S, R3, R4 son cada uno, de modo independiente entre sí, H, Hal, A, (CH2)nHet, (CH2)nAr, (CH2)nCOHet o (CH2)nC(=CH2)CONR5R6, R3 y R4 junto con el átomo de C al que están unidos, también son un carbociclo C3-10 monocíclico saturado o insaturado no sustituido o mono-, di- o trisustituido con Hal, A, (CH2)nOH, (CH2)nOA, (CH2)nNH2, (CH2)nCOOH, (CH2)nCOOA, NHCOA, NA'COA, CONH2, CONHA, CONAA', OC(=O) (CH2)pNH2 y/u =O (oxígeno de carbonilo), que puede contener otros 1 a 3 átomos de N, O y/o S, X es NR5R6, CONR5R6, CH2NR5R6, COOR5, -OR5, CH2OR5, COHet, Het, CONH(CH2)pCN o CONH(CH2)pNR5R6, R5, R6 son cada uno, de modo independiente entre sí, H, A, (CH2)nHet o (CH2)nAr, Ar es fenilo, naftilo, tetrahidronaftilo o bifenilo no sustituido o monodi-, tri-, tetra- o pentasustituido con A, Hal, (CH2)nOA, (CH2)nOH, (CH2)nCN, SA, SOA, SO2A, NO2, C:::CH, (CH2)nCOOH, CHO, (CH2)nCOOA, CONH2, CONHA, CONAA', NHCOA, CH(OH)A, (CH2)nNH2, (CH2)nNHA, (CH2)nNAA', (CH2)nNHSO2A, SO2NH(CH2)nNH2, SO2NH2, SO2NHA, SO2NAA', CONH(CH2)nCOOA, CONH(CH2)nCOOH, NHCO(CH2)nCOOA, NHCO(CH2)nCOOH, CONH(CH2)nNH2, CONH(CH2)nNHA, CONH(CH2)nNAA', CONH(CH2)nCN y/o (CH2)nCH(NH2)COOH, Het es un heterociclo saturado, insaturado o aromático mono- o bicíclico con 1 a 4 átomos de N, O y/o S, que no está sustituido o que puede estar mono-, di- o trisustituido con A, OA, OH, fenilo, SH, S(O)mA, Hal, NO2, CN, COA, COOA, COObencilo, CONH2, CONHA, CONAA', SO2NH2, NH2, NHA, NAA', NHCOA, NHSO2A y/u =O (oxígeno de carbonilo) A, A' son cada uno, de modo independiente entre sí, alquilo no ramificado o ramificado con 1-10 átomos de C, en donde 1-3 grupos CH2 no adyacentes pueden estar reemplazados por O, S, SO, SO2, NH, NMe o NEt y/o también 1-5 átomos de H pueden estar reemplazados por F y/o Cl, o alquilo cíclico con 3-8 átomos de C, Hal es F, Cl, Br o I, n es 0, 1, 2, 3 o 4, p es 1, 2, 3 o 4, así como sus sales y estereoisomeros farmacéuticamente aceptables, incluyendo sus mezclas en todas las proporciones. Son inhibidores de la HSP90 y pueden ser utilizados para preparar un medicamento para el tratamiento de enfermedades en las que la inhibicion, la regulacion y/o la modulacion de la HSP90 desempena un papel importante. Un método para la preparacion de los mismos. Reivindicacion 16: Compuestos de la formula (2) en donde R1, R2 son cada uno, de modo independiente entre si, H, A, (CH2)nHet o (CH2)nAr, R1 y R2 junto con el átomo de N al que están unidos, también son un heterociclo mono- o bicíclico saturado, insaturado o aromático no sustituido o mono-, di- o trisustituido con Hal, A, (CH2)nHet, (CH2)nAr, (CH2)nOH, (CH2)nOA, (CH2)nNH2, (CH2)nCOOH, (CH2)nCOOA, NHCOA, NA'COA, CONH2, CONHA, CONAA', OC(=O)(CH2)pNH2 y/u =O (oxígeno de carbonilo), que puede contener otros 1 a 3 átomos de N, O y/o S, R3, R4 son cada uno, de modo independiente entre sí, H, Hal, A, (CH2)nHet, (CH2)nAr, (CH2)nCOHet o (CH2)nC(=CH2)CONR5R6, R3 y R4 junto con el átomo de C al que están unidos, también son un carbociclo C3-10 monocíclico saturado o insaturado no sustituido o mono-, di- o trisustituido con Hal, A, (CH2)nOH, (CH2)nOA, (CH2)nNH2, (CH2)nCOOH, (CH2)nCOOA, NHCOA, NA'COA, CONH2, CONHA, CONAA', OC(=O)(CH2)pNH2 y/u =O (oxígeno de carbonilo), que puede contener otros 1 a 3 átomos de N, O y/o S, R es ter.-butiloxicarbonilo, X es COOR5, R5 es A, Ar es fenilo, naftilo, tetrahidronaftilo o bifenilo no sustituido o mono-, di-, tri-, tetra- o pentasustituido con A, Hal, (CH2)nOA, (CH2)nOH, (CH2)nCN, SA, SOA, SO2A, NO2, C:::CH, (CH2)nCOOH, CHO, (CH2)nCOOA, CONH2, CONHA, CONAA', NHCOA, CH(OH)A, (CH2)nNH2, (CH2)nNHA, (CH2)nNAA', (CH2)nNHSO2A, SO2NH(CH2)nNH2, SO2NH2, SO2NHA, SO2NAA', CONH(CH2)nCOOA, CONH(CH2)nCOOH, NHCO(CH2)nCOOA, NHCO(CH2)nCOOH, CONH(CH2)nNH2, CONH(CH2)nNHA, CONH(CH2)nNAA', CONH(CH2)nCN y/o (CH2)nCH(NH2)COOH, Het es un heterociclo saturado, insaturado o aromático mono- o bicíclico con 1 a 4 átomos de N, O y/o S, que no está sustituido o que puede estar mono-, di- o trisustituido con A, OA, OH, fenilo, SH, S(O)mA, Hal, NO2, CN, COA, COOA, COObencilo, CONH2, CONHA, CONAA', SO2NH2, NH2, NHA, NAA', NHCOA, NHSO2A y/u =O (oxígeno de carbonilo), A, A' son cada uno, de modo independiente entre sí, alquilo no ramificado o ramificado con 1-10 átomos de C, en donde 1-3 grupos CH2 no adyacentes pueden estar reemplazados O, S, SO, SO2, NH, NMe o NEt y/o también 1-5 átomos de H pueden estar reemplazados por F y/o CI, o alquilo cíclico con 3-8 átomos de C, Hal es F, CI, Br o I, n es 0,1, 2, 3 o 4, p es 1, 2, 3 o 4, así como sus sales.
ARP100104277A 2009-11-23 2010-11-19 Derivados de quinazolina como moduladores de la hsp90 y su preparacion AR081117A1 (es)

Applications Claiming Priority (1)

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DE102009054302A DE102009054302A1 (de) 2009-11-23 2009-11-23 Chinazolinderivate

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AR081117A1 true AR081117A1 (es) 2012-06-27

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US (1) US8906930B2 (es)
EP (1) EP2504314B1 (es)
JP (1) JP5841059B2 (es)
KR (1) KR20120101085A (es)
CN (1) CN102648178B (es)
AR (1) AR081117A1 (es)
AU (1) AU2010321264B2 (es)
BR (1) BR112012012000A2 (es)
CA (1) CA2781380C (es)
DE (1) DE102009054302A1 (es)
EA (1) EA201200764A1 (es)
ES (1) ES2548027T3 (es)
IL (1) IL219872A (es)
MX (1) MX2012005811A (es)
WO (1) WO2011060873A1 (es)

Families Citing this family (4)

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Publication number Priority date Publication date Assignee Title
JP5583751B2 (ja) 2009-03-21 2014-09-03 クイ ニング アミノエステル誘導体、その塩、及び使用方法
US10138212B2 (en) 2015-02-06 2018-11-27 Merck Sharp & Dohme Corp. Aminoquinazoline compounds as A2A antagonist
EP3317278B1 (en) 2015-07-01 2021-04-14 Crinetics Pharmaceuticals, Inc. Somatostatin modulators and uses thereof
US11028068B2 (en) 2017-07-25 2021-06-08 Crinetics Pharmaceuticals, Inc. Somatostatin modulators and uses thereof

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US5968921A (en) 1997-10-24 1999-10-19 Orgegon Health Sciences University Compositions and methods for promoting nerve regeneration
AU3378599A (en) 1998-04-03 1999-10-25 University Of Pittsburgh Benzoquinoid ansamycins for the treatment of cardiac arrest and stroke
AU776652B2 (en) 1999-03-12 2004-09-16 United States Of America, Represented By The Secretary, Department Of Health And Human Services, The Method of inhibiting a chaperone protein
WO2001072779A1 (en) 2000-03-24 2001-10-04 Duke University Characterization of grp94-ligand interactions and purification, screening, and therapeutic methods relating thereto
WO2002002123A1 (en) 2000-06-29 2002-01-10 Trustees Of Boston University Use of geldanamycin and related compounds for prophylaxis or treatment of fibrogenic disorders
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CN101027053A (zh) 2004-07-27 2007-08-29 诺瓦提斯公司 Hsp90抑制剂
US20070054916A1 (en) * 2004-10-01 2007-03-08 Amgen Inc. Aryl nitrogen-containing bicyclic compounds and methods of use
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Publication number Publication date
KR20120101085A (ko) 2012-09-12
JP2013511477A (ja) 2013-04-04
EA201200764A1 (ru) 2012-12-28
EP2504314A1 (de) 2012-10-03
CA2781380C (en) 2017-07-25
EP2504314B1 (de) 2015-08-05
IL219872A0 (en) 2012-07-31
AU2010321264B2 (en) 2016-05-26
US8906930B2 (en) 2014-12-09
US20120238582A1 (en) 2012-09-20
AU2010321264A1 (en) 2012-07-12
BR112012012000A2 (pt) 2016-05-10
MX2012005811A (es) 2012-06-12
CN102648178B (zh) 2015-01-07
WO2011060873A1 (de) 2011-05-26
DE102009054302A1 (de) 2011-05-26
ES2548027T3 (es) 2015-10-13
CN102648178A (zh) 2012-08-22
CA2781380A1 (en) 2011-05-26
IL219872A (en) 2017-06-29
JP5841059B2 (ja) 2016-01-06

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