AR053778A1 - Compuestos de quinazolina para el tratamiento de desordenes mediados por la proteina quinasa - Google Patents

Compuestos de quinazolina para el tratamiento de desordenes mediados por la proteina quinasa

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Publication number
AR053778A1
AR053778A1 ARP050104700A ARP050104700A AR053778A1 AR 053778 A1 AR053778 A1 AR 053778A1 AR P050104700 A ARP050104700 A AR P050104700A AR P050104700 A ARP050104700 A AR P050104700A AR 053778 A1 AR053778 A1 AR 053778A1
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Argentina
Prior art keywords
group
ring
atoms
optionally
hydrocarbyl
Prior art date
Application number
ARP050104700A
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English (en)
Inventor
Valerio Berdini
Robert George Boyle
Gordon Saxty
Marinus L Verdonk
Steven Woodhead
Paul Graham Wyatt
Hannah Fiona Sore
David Winter Walker
John Caldwell
Ian Collins
Original Assignee
Cancer Res Inst Royal
Cancer Rec Tech Ltd
Astex Therapeutics Ltd
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Priority claimed from GB0424742A external-priority patent/GB0424742D0/en
Application filed by Cancer Res Inst Royal, Cancer Rec Tech Ltd, Astex Therapeutics Ltd filed Critical Cancer Res Inst Royal
Publication of AR053778A1 publication Critical patent/AR053778A1/es

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    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic 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
    • C07D403/12Heterocyclic 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 chain containing hetero atoms as chain links
    • 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/06Antiasthmatics
    • 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
    • A61P25/00Drugs for disorders of the nervous system
    • 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/04Anorexiants; Antiobesity agents
    • 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
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/08Antiallergic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • 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
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72Quinazolines; Hydrogenated quinazolines
    • C07D239/86Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
    • C07D239/88Oxygen atoms
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
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    • C07D239/72Quinazolines; Hydrogenated quinazolines
    • C07D239/86Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
    • C07D239/88Oxygen atoms
    • C07D239/91Oxygen atoms with aryl or aralkyl radicals attached in position 2 or 3
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
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    • C07D239/70Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72Quinazolines; Hydrogenated quinazolines
    • C07D239/95Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
    • C07D239/96Two oxygen atoms
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    • 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
    • C07D401/04Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D401/06Heterocyclic 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 carbon chain containing only aliphatic carbon atoms
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    • 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
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic 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
    • C07D403/04Heterocyclic 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 directly linked by a ring-member-to-ring-member bond

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  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
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  • Obesity (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Reivindicacion 1: Un compuesto para usar en el tratamiento o profilaxis de un estado de enfermedad o condicion mediado por la proteína quinasa A y/o proteína quinasa B, caracterizado porque es un compuesto de la formula (1), o una sal, solvato, tautomero o N-oxido del mismo, en donde: el anillo Q es un anillo benceno; J2-J1 es un grupo N=CR7 un grupo R1aN-CO; G es OH o NR5R6; E es un átomo o un grupo ligante que se seleccionan entre CONR7, NR7CO, C(R8)=C(R8), (X)m(CR8R8a)n donde X se selecciona entre O, S y NR7; con la salvedad de que cuando J2-J1 es un grupo R1aN-C, E es distinto de NR7CO; m y n son cada uno 0 o 1, con la salvedad de que la suma de m y n es 1 o 2; A es un enlace y R4 y R4a están ausentes, o A es un grupo ligante de hidrocarburo saturado que contiene entre 1 y 7 átomos de C, donde el grupo ligante tiene una longitud máxima de cadena de 5 átomos que se extiende entre E y G, en donde uno de los átomos de C en el grupo ligante A optativamente puede reemplazarse con un átomo de O o N; y en donde los átomos de C del grupo ligante A optativamente pueden tener uno o más sustituyentes que se seleccionan entre oxo, F y hidroxi, con la salvedad de que el grupo hidroxi y el grupo oxo cuando están presentes no estén ubicados en un átomo de C alfa con respecto al grupo G; R1, R1a, R2, y R3 se seleccionan cada uno en forma independiente entre H, halogeno; C1-6 hidrocarbilo opcionalmente sustituido con halogeno, hidroxi o 1-2 alcoxi; ciano, CONHR8, NH2, NHCOR10 y NHCONHR10; R4 es H o alquilo C1-4; R4a es H, alquilo C1-4 o un grupo R9; R5 y R6 se seleccionan cada uno entre H, un grupo R9 y hidrocarbilo C1-4 opcionalmente sustituido con halogeno o alcoxi C1-2 o por un grupo R9; o NR5R6 forma un grupo monocíclico heterocíclico saturado que tiene 4-7miembros en el anillo y que contiene optativamente un segundo heteroátomo en el anillo que se seleccionan entre O y N; R7 se selecciona entre H y alquilo C1-4; R8 y R8a se seleccionan entre H y hidrocarbilo C1-4 saturado opcionalmente sustituido con uno o más átomos de F; R9 es un grupo monocíclico o bicíclico carbocíclico o heterocíclico que contiene hasta 3 heteroátomos en el anillo que se seleccionan entre N, O y S; o R4 y R4a junto con el o los átomos intervinientes del grupo A forman un grupo monocíclico heterocíclico saturado que tiene 4-7 miembros en el anillo y que contiene optativamente un segundo heteroátomo en el anillo que se seleccionan entre O y N, o uno de R5 y R6 junto con el átomo de N al cual están unidos y R4 y uno o más átomos del grupo ligante A forman un grupo monocíclico heterocíclico saturado que tiene 4-7 miembros en el anillo y que contiene optativamente un segundo heteroátomo en el anillo que se seleccionan entre O y n; o R4 junto con R7 o R8 y los átomos intervinientes de los grupos A y E forman un grupo monocíclico heterocíclico saturado que tiene 4-7 miembros en el anillo y que contiene optativamente un segundo heteroátomo en el anillo que se seleccionan entre O y N; o uno de R5 y R6 junto con el átomo de N al cual están unidos y R7 o R8 y, los átomos intervinientes de los grupos A y E forman un grupo monocíclico heterocíclico saturado que tiene 4-7 miembros en el anillo y que contiene optativamente un segundo heteroátomo en el anillo que se seleccionan entre O y N; R10 es fenilo o bencilo cada uno opcionalmente sustituido con uno o más sustituyentes que se seleccionan entre halogeno, hidroxi, trifluorometilo, ciano, nitro, carboxi, amino, mono- o di-C1-4hidrocarbilamino; un grupo Ra-Rb en donde Ra es un enlace, O, CO, X1C(X2), C(X2)X1, X1C(X2)X1, S, SO, SO2, NRc, SO2NRc o NRcSO2; y Rb se selecciona entre H, grupos heterocíclicos que tienen entre 3 y 12 miembros en el anillo, y un grupo C1-8 hidrocarbilo opcionalmente sustituido con uno o más sustituyentes que se seleccionan entre hidroxi, oxo, halogeno, ciano, nitro, carboxi, amino, mono- o di-C14 hidrocarbilamino, grupos carbocíclicos y heterocíclicos que tienen entre 3 y 12 miembros en el anillo y en donde uno o más átomos de C del grupo C1-8 hidrocarbilo optativamente pueden reemplazarse con O, S, SO, SO2, NRc, X1C(X2), C(X2)X1 o X1C(X2)X1; Rc se selecciona entre H e hidrocarbilo C1-4; y X1 es O, S o NRc y X2 es =O, =S o =NRc.
ARP050104700A 2004-11-09 2005-11-09 Compuestos de quinazolina para el tratamiento de desordenes mediados por la proteina quinasa AR053778A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US62640304P 2004-11-09 2004-11-09
GB0424742A GB0424742D0 (en) 2004-11-09 2004-11-09 Pharmaceutical compounds

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AR053778A1 true AR053778A1 (es) 2007-05-23

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ARP050104700A AR053778A1 (es) 2004-11-09 2005-11-09 Compuestos de quinazolina para el tratamiento de desordenes mediados por la proteina quinasa

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US (1) US20080275029A1 (es)
EP (1) EP1814552A2 (es)
JP (1) JP2008519087A (es)
AR (1) AR053778A1 (es)
UY (1) UY29198A1 (es)
WO (1) WO2006051290A2 (es)

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WO2007008926A1 (en) 2005-07-11 2007-01-18 Aerie Pharmaceuticals, Inc. Isoquinoline compounds
US7618985B2 (en) 2005-12-08 2009-11-17 N.V. Organon Isoquinoline derivatives
US7893088B2 (en) 2006-08-18 2011-02-22 N.V. Organon 6-substituted isoquinoline derivatives
CA2664335C (en) * 2006-09-20 2014-12-02 Boehringer Ingelheim International Gmbh Rho kinase inhibitors
US8455513B2 (en) 2007-01-10 2013-06-04 Aerie Pharmaceuticals, Inc. 6-aminoisoquinoline compounds
US8455514B2 (en) 2008-01-17 2013-06-04 Aerie Pharmaceuticals, Inc. 6-and 7-amino isoquinoline compounds and methods for making and using the same
US8450344B2 (en) 2008-07-25 2013-05-28 Aerie Pharmaceuticals, Inc. Beta- and gamma-amino-isoquinoline amide compounds and substituted benzamide compounds
EP3828172A1 (en) 2009-05-01 2021-06-02 Aerie Pharmaceuticals, Inc. Dual mechanism inhibitors for the treatment of disease
RU2451010C1 (ru) * 2011-01-11 2012-05-20 Закрытое Акционерное Общество "Ива Фарм" Палладиево-медные катализаторы гомогенного селективного окисления тиольных групп, комбинация и композиция на их основе и способ терапевтического воздействия
ES2852377T3 (es) 2013-03-15 2021-09-13 Aerie Pharmaceuticals Inc Sales dimesilato de 4-(3-amino-1-(isoquinolin-6-ilamino)-1-oxopropan-2-il)bencilo, sus combinaciones con prostaglandinas y el uso de las mismas en el tratamiento de trastornos oculares
CN103524431B (zh) * 2013-09-24 2016-01-13 西安交通大学 3-苄基-4-喹唑啉酮类化合物及其合成方法和应用
AU2015295405B2 (en) 2014-08-01 2020-04-09 Nuevolution A/S Compounds active towards bromodomains
WO2016126726A1 (en) 2015-02-02 2016-08-11 Forma Therapeutics, Inc. Bicyclic [4,6,0] hydroxamic acids as hdac6 inhibitors
WO2016126721A1 (en) 2015-02-02 2016-08-11 Forma Therapeutics, Inc. 3-aryl-bicyclic [4,5,0] hydroxamic acids as hdac inhibitors
US9643927B1 (en) 2015-11-17 2017-05-09 Aerie Pharmaceuticals, Inc. Process for the preparation of kinase inhibitors and intermediates thereof
JP6832946B2 (ja) 2015-11-17 2021-02-24 アエリエ ファーマシューティカルズ インコーポレイテッド キナーゼ阻害剤およびその中間体の調製方法
EP3472131B1 (en) 2016-06-17 2020-02-19 Forma Therapeutics, Inc. 2-spiro-5- and 6-hydroxamic acid indanes as hdac inhibitors
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CN110506037A (zh) 2017-03-31 2019-11-26 爱瑞制药公司 芳基环丙基-氨基-异喹啉酰胺化合物
US20220089609A1 (en) 2018-07-26 2022-03-24 Domain Therapeutics Substituted quinazolinone derivatives and their use as positive allosteric modulators of mglur4
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UA73993C2 (uk) * 2000-06-06 2005-10-17 Астразенека Аб Хіназолінові похідні для лікування пухлин та фармацевтична композиція
TW200301123A (en) * 2001-12-21 2003-07-01 Astrazeneca Uk Ltd New use

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US20080275029A1 (en) 2008-11-06
UY29198A1 (es) 2006-05-31
EP1814552A2 (en) 2007-08-08
WO2006051290A3 (en) 2006-09-14
JP2008519087A (ja) 2008-06-05

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