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PT2007770E - Compostos imidazo - Google Patents

Compostos imidazo Download PDF

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Publication number
PT2007770E
PT2007770E PT07728052T PT07728052T PT2007770E PT 2007770 E PT2007770 E PT 2007770E PT 07728052 T PT07728052 T PT 07728052T PT 07728052 T PT07728052 T PT 07728052T PT 2007770 E PT2007770 E PT 2007770E
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PT
Portugal
Prior art keywords
alkyl
aryl
compound
alkoxycarbonyl
halogen
Prior art date
Application number
PT07728052T
Other languages
English (en)
Inventor
Peter Herold
Robert Mah
Stefan Stutz
Aleksandar Stojanovic
Stjepan Jelakovic
Vincenzo Tschinke
Christiane Marti
Original Assignee
Novartis Ag
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 Novartis Ag filed Critical Novartis Ag
Publication of PT2007770E publication Critical patent/PT2007770E/pt

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D513/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04Ortho-condensed systems
    • 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
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/02Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • 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
    • A61P3/06Antihyperlipidemics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/12Drugs for disorders of the metabolism for electrolyte homeostasis
    • A61P3/14Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
    • 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
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/24Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/32Antioestrogens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/38Drugs for disorders of the endocrine system of the suprarenal hormones
    • A61P5/40Mineralocorticosteroids, e.g. aldosterone; Drugs increasing or potentiating the activity of mineralocorticosteroids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/38Drugs for disorders of the endocrine system of the suprarenal hormones
    • A61P5/42Drugs for disorders of the endocrine system of the suprarenal hormones for decreasing, blocking or antagonising the activity of mineralocorticosteroids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/04Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives
    • 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
    • C07D498/02Heterocyclic 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 two hetero rings
    • C07D498/04Ortho-condensed systems

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Endocrinology (AREA)
  • Cardiology (AREA)
  • Obesity (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Child & Adolescent Psychology (AREA)
  • Hospice & Palliative Care (AREA)
  • Rheumatology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Claims (10)

  1. ΡΕ2007770 1 REIVINDICAÇÕES 1. Um composto da fórmula geral
    (l) na qual R é deutério, halogéneo ou hidrogénio; R1 é aril-alquilo C0-C4 ou heterociclil-alquilo C0-C4, grupos esses que podem ser substituídos por 1-4 alcoxi C1-C8, (alcoxi Ci-Cs) carbonilo, alquilo Ci-Cs, (alquil C0-C8)carbonilo, (alquil Ci-Cs)sulfonilo, arilo facultativamente substituído, aril-(alcoxi C0-C4)carbonilo, ciano, halogéneo, heterociclilo não substituído ou substituído, hidroxi, nitro, óxido, oxo, tri-(alquil C1-C4) sililo, tri-fluorometoxi ou trifluorometilo; pelo que heterociclilo representa um sistema em anel monocíclico, de 4-8 membros, saturado, parcialmente saturado ou insaturado, um sistema em anel bicíclico, de 7-12 membros, parcialmente saturado ou insaturado, e também um sistema em anel tricíclico, de 9-12 membros, parcialmente saturado ou insaturado, o qual compreende um átomo de N, 0 ou S em pelo menos um dos anéis, sendo possível para um átomo de N, 0 ou S adicional estar presente num anel, e pelo que arilo representa um hidrocarboneto aromático mono, bi ou tricíclico concordando com a regra de Huckel que geralmente compreende 6-14 átomos de carbono, 2 ΡΕ2007770 R2 é a) deutério, halogéneo, hidroxi, ciano ou hidrogénio; ou b) alcenilo C2-Cs, alcinilo C2-C8, alcoxi Ci-C8, (alcoxi C1-C4) carbonil-alquilo C1-C4, alquilo Ci-C8, (alquil C0-C4) carbonilo, aril-alquilo C0-C4, carboxi-alquilo C1-C4, cicloalquilo C3-C8 ou heterociclil-alquilo C0-C4, grupos esses que podem ser substituídos por 1-4 alcoxi Ci-Cg, (alcoxi Ci-C8) carbonilo, alquilo Ci-Cs, (alquil Co-C8) carbonilo, (alquil Ci-Cs)-sulfonilo, arilo não substituído ou substituído, aril-(alcoxi C0-C4)carbonilo, ciano, halogéneo, heterociclilo não substituído ou substituído, hidroxi, nitro, óxido, oxo, tri-(alquil C1-C4)-sililo, trifluorometoxi ou trifluorometilo; Q é oxigénio ou enxofre; m é um número 0, 1 ou 2; n é um número 0, 1 ou 2; onde m e n não são simultaneamente 0; pelo que os substituintes nos grupos arilo ou grupos fenilo ou naftilo preferidos são: alcoxi Ci-C8, (alcoxi Ci-C8)-carbonilo, alquilo Ci-C8, (alquil C0-C8) carbonilo, (alquil Ci-Cs) sulfonilo, arilo facultativamente substituído, aril-(alcoxi C0-C4) carbonilo, ciano, halogéneo, heterociclilo facultativamente substituído, hidroxi, nitro, tri-(Ci-C4 alquil)sililo, trifluorometoxi ou trifluorometilo, os substituintes nos grupos heterociclilo são: alcoxi Ci-Cs, (alcoxi Ci-Cs) carbonilo, alquilo Ci-Cs, (alquil Cq-Cs)- 3 ΡΕ2007770 carbonilo, (alquil Ci-Ce)sulfonilo, arilo facultativamente substituído, aril-(alcoxi C0-C4)carbonilo, ciano, halogé-neo, heterociclilo facultativamente substituído, hidroxi, nitro, óxido, oxo, tri-(alquil C1-C4)sililo, trifluorometo-xi ou trifluorometilo, e um seu sal, preferivelmente um sal farmaceuticamente aceitável.
  2. 2. Um composto de acordo com a Reivindicação 1, o qual corresponde à fórmula geral
    onde os significados dos substituintes R, R1, R2, Q, m e n são conforme indicado para os compostos da fórmula (I) de acordo com a Reivindicação 1, e * designa um átomo de carbono assimétrico e em que o composto mostra uma actividade inibidora de aldosterona-sintase e/ou ΙΙ-β-hidroxilase pelo menos 10 vezes mais alta, mas preferivelmente 20 vezes mais alta, ou mais preferivelmente 40 vezes mais alta, do que o composto da fórmula (Ia) com a configuração oposta à volta do átomo de carbono assimétrico assinalado .
  3. 3. Um composto de acordo com a Reivindicação 1 ou 2, onde R é deutério ou hidrogénio. Um composto de acordo com qualquer uma das 4 .
  4. 4 ΡΕ2007770 Reivindicações 1 a 3, onde R1 é fenilo facultativamente mono, di ou trissubstituido ou facultativamente mono, di ou trissubstituido benzofuranilo, benzo[b]tiofenilo, benzimi-dazolilo, benzo[d]isotiazolilo, benzo[d]isoxazolilo, benzo-[b]tiofenilo, imidazolilo, indazolilo, oxazolilo, piridilo, pirrolilo, tiazolilo ou tiofenilo.
  5. 5. Um composto de acordo com qualquer uma das Reivindicações 1 a 4, onde R2 é alcoxi Ci-Cs, hidroxi, alquilo Ci-C8, aril-alquilo C0-C4, deutério, halogéneo, ciano ou hidrogénio.
  6. 6. 0 uso de um composto da fórmula geral (I) ou (Ia) ou um seu sal farmaceuticamente aceitável de acordo com qualquer uma das Reivindicações 1 a 5 para o fabrico de um medicamento.
  7. 7. 0 uso de um composto da fórmula geral (I) ou (Ia) ou um seu sal farmaceuticamente aceitável de acordo com qualquer uma das Reivindicações 1 a 5 para o fabrico de um medicamento humano para a prevenção, para o retardamento da progressão ou para o tratamento de estados patológicos que são causados ou parcialmente causados por hiperal-dosteronismo.
  8. 8. 0 uso de um composto da fórmula geral (I) ou (Ia) ou um seu sal farmaceuticamente aceitável de acordo com qualquer uma das Reivindicações 1 a 5 para o fabrico de um medicamento humano para a prevenção, para o retardamento 5 ΡΕ2007770 da progressão ou para o tratamento de estados patológicos que são causados ou parcialmente causados pela libertação excessiva de cortisol.
  9. 9. Um produto farmacêutico compreendendo um composto da fórmula geral (I) ou (Ia) ou um seu sal farmaceuticamente aceitável de acordo com qualquer uma das Reivindicações 1 a 5, e excipientes convencionais.
  10. 10. Uma combinação farmacêutica na forma de um produto ou de um kit composto de componentes individuais consistindo a) de um composto da fórmula geral (I) ou (Ia) ou um seu sal farmaceuticamente aceitável de acordo com qualquer uma das Reivindicações 1 a 5, e b) de pelo menos uma forma farmacêutica cujo ingrediente activo tem um efeito de abaixamento da pressão sanguínea, inotrópico, antidiabético, de redução da obesidade ou de abaixamento de lípido. Lisboa, 15 de Outubro de 2011
PT07728052T 2006-04-12 2007-04-12 Compostos imidazo PT2007770E (pt)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CH6202006 2006-04-12

Publications (1)

Publication Number Publication Date
PT2007770E true PT2007770E (pt) 2010-10-21

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ID=38462029

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PT07728052T PT2007770E (pt) 2006-04-12 2007-04-12 Compostos imidazo
PT07728054T PT2007771E (pt) 2006-04-12 2007-04-12 Compostos imidazo

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Country Status (15)

Country Link
US (3) US20090192149A1 (pt)
EP (2) EP2007771B1 (pt)
JP (2) JP2009534319A (pt)
CN (2) CN101421279B (pt)
AR (1) AR060590A1 (pt)
AT (2) ATE463498T1 (pt)
BR (2) BRPI0711540A2 (pt)
CA (2) CA2649213A1 (pt)
DE (2) DE602007005788D1 (pt)
ES (2) ES2352358T3 (pt)
IL (2) IL194584A0 (pt)
PL (2) PL2007770T3 (pt)
PT (2) PT2007770E (pt)
TW (1) TW200808813A (pt)
WO (2) WO2007116099A1 (pt)

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TW200616623A (en) * 2004-05-28 2006-06-01 Speedel Experimenta Ag Organic compounds
AR056888A1 (es) * 2005-12-09 2007-10-31 Speedel Experimenta Ag Derivados de heterociclil imidazol
TW200808812A (en) * 2006-04-12 2008-02-16 Speedel Experimenta Ag Imidazo compounds
TW200808813A (en) * 2006-04-12 2008-02-16 Speedel Experimenta Ag Imidazo compounds
UY32660A (es) 2009-05-28 2010-12-31 Novartis Ag Derivados aminobutricos sustituidos como inhibidores de neprilisina
ME01923B (me) 2009-05-28 2015-05-20 Novartis Ag Supstituisani derivati aminopropionske kiseline kao inhibitori neprilizina
JO2967B1 (en) 2009-11-20 2016-03-15 نوفارتس ايه جي Acetic acid derivatives of carbamoyl methyl amino are substituted as new NEP inhibitors
US8877815B2 (en) 2010-11-16 2014-11-04 Novartis Ag Substituted carbamoylcycloalkyl acetic acid derivatives as NEP
US8673974B2 (en) 2010-11-16 2014-03-18 Novartis Ag Substituted amino bisphenyl pentanoic acid derivatives as NEP inhibitors
TWI627167B (zh) 2011-07-08 2018-06-21 諾華公司 用於高三酸甘油酯個體治療動脈粥狀硬化之方法
UY35144A (es) 2012-11-20 2014-06-30 Novartis Ag Miméticos lineales sintéticos de apelina para el tratamiento de insuficiencia cardiaca
LT2956464T (lt) 2013-02-14 2018-07-10 Novartis Ag Pakeisti bisfenilbutanoinės fosfonrūgšties dariniai, kaip nep (neutralios endopeptidazės) inhibitoriai
AP2016009019A0 (en) 2013-07-25 2016-02-29 Novartis Ag Bioconjugates of synthetic apelin polypeptides
JP6501775B2 (ja) 2013-07-25 2019-04-17 ノバルティス アーゲー 心不全治療用の環状ポリペプチド
RS57570B1 (sr) * 2014-07-24 2018-10-31 Boehringer Ingelheim Int Inhibitori aldosteron sintaze
PE20171328A1 (es) 2015-01-23 2017-09-12 Novartis Ag Conjugados de acidos grasos y apelina sintetica con mayor vida media
JOP20190086A1 (ar) 2016-10-21 2019-04-18 Novartis Ag مشتقات نافثيريدينون جديدة واستخدامها في معالجة عدم انتظام ضربات القلب
UY38072A (es) 2018-02-07 2019-10-01 Novartis Ag Compuestos derivados de éster butanoico sustituido con bisfenilo como inhibidores de nep, composiciones y combinaciones de los mismos
US20230089867A1 (en) 2018-11-27 2023-03-23 Novartis Ag Cyclic pentamer compounds as proprotein convertase subtilisin/kexin type 9 (pcsk9) inhibitors for the treatment of metabolic disorder
UY38485A (es) 2018-11-27 2020-06-30 Novartis Ag Compuestos tetrámeros cíclicos como inhibidores de proproteína convertasa subtilisina/kexina tipo 9 (pcsk9), método de tratamiento, uso y su preparación
EP3887388A1 (en) 2018-11-27 2021-10-06 Novartis AG Cyclic peptides as proprotein convertase subtilisin/kexin type 9 (pcsk9) inhibitors for the treatment of metabolic disorders
US11958818B2 (en) 2019-05-01 2024-04-16 Boehringer Ingelheim International Gmbh (R)-(2-methyloxiran-2-yl)methyl 4-bromobenzenesulfonate
TW202333563A (zh) 2021-11-12 2023-09-01 瑞士商諾華公司 用於治療疾病或障礙之二胺基環戊基吡啶衍生物
AR127698A1 (es) 2021-11-23 2024-02-21 Novartis Ag Derivados de naftiridinona para el tratamiento de una enfermedad o un trastorno
WO2023114170A1 (en) 2021-12-14 2023-06-22 Boehringer Ingelheim International Gmbh Aldosterone synthase inhibitors for treating chronic kidney disease
WO2024241229A1 (en) 2023-05-24 2024-11-28 Novartis Ag Naphthyridinone derivatives for the treatment of a disease or disorder

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Publication number Priority date Publication date Assignee Title
JPH0670064B2 (ja) * 1986-12-08 1994-09-07 三井石油化学工業株式会社 二環性イミダゾ−ル誘導体
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AR032316A1 (es) * 2000-04-12 2003-11-05 Novartis Ag Uso de una composicion farmaceutica para la fabricacion de medicamentos y una composicion farmaceutica
AU2003253387A1 (en) * 2002-08-07 2004-02-25 Novartis Ag Organic compounds as agents for the treatment of aldosterone mediated conditions
TW200616623A (en) * 2004-05-28 2006-06-01 Speedel Experimenta Ag Organic compounds
CN1956987A (zh) 2004-05-28 2007-05-02 斯皮德尔实验股份公司 杂环化合物及其作为醛固酮合酶抑制剂的应用
EP1748986B1 (en) * 2004-05-28 2010-12-01 Novartis AG Heterocyclic compounds and their use as aldosterone synthase inhibitors
WO2006005726A2 (en) * 2004-07-09 2006-01-19 Speedel Experimenta Ag Heterocyclic compounds
AR056888A1 (es) * 2005-12-09 2007-10-31 Speedel Experimenta Ag Derivados de heterociclil imidazol
TW200808812A (en) * 2006-04-12 2008-02-16 Speedel Experimenta Ag Imidazo compounds
TW200808813A (en) * 2006-04-12 2008-02-16 Speedel Experimenta Ag Imidazo compounds

Also Published As

Publication number Publication date
AR060590A1 (es) 2008-07-02
US7879847B2 (en) 2011-02-01
WO2007116101A1 (en) 2007-10-18
PL2007770T3 (pl) 2011-03-31
EP2007770A1 (en) 2008-12-31
EP2007771B1 (en) 2010-04-07
CN101421277A (zh) 2009-04-29
PT2007771E (pt) 2010-05-11
EP2007771A1 (en) 2008-12-31
BRPI0711540A2 (pt) 2011-11-01
BRPI0710614A2 (pt) 2011-08-16
ATE480545T1 (de) 2010-09-15
CN101421279B (zh) 2012-08-15
JP2009533395A (ja) 2009-09-17
US20110092492A1 (en) 2011-04-21
JP2009534319A (ja) 2009-09-24
IL194584A0 (en) 2009-08-03
ES2342689T3 (es) 2010-07-12
DE602007009074D1 (de) 2010-10-21
WO2007116099A1 (en) 2007-10-18
US20090192144A1 (en) 2009-07-30
US8138176B2 (en) 2012-03-20
US20090192149A1 (en) 2009-07-30
CA2649217A1 (en) 2007-10-18
IL194583A0 (en) 2009-08-03
ATE463498T1 (de) 2010-04-15
JP5260496B2 (ja) 2013-08-14
PL2007771T3 (pl) 2010-10-29
TW200808813A (en) 2008-02-16
CN101421279A (zh) 2009-04-29
CA2649213A1 (en) 2007-10-18
DE602007005788D1 (de) 2010-05-20
ES2352358T3 (es) 2011-02-17
EP2007770B1 (en) 2010-09-08

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