[go: up one dir, main page]

WO2011046991A2 - Certaines urées substituées comme modulateurs de l'activité de kinases - Google Patents

Certaines urées substituées comme modulateurs de l'activité de kinases Download PDF

Info

Publication number
WO2011046991A2
WO2011046991A2 PCT/US2010/052420 US2010052420W WO2011046991A2 WO 2011046991 A2 WO2011046991 A2 WO 2011046991A2 US 2010052420 W US2010052420 W US 2010052420W WO 2011046991 A2 WO2011046991 A2 WO 2011046991A2
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutically acceptable
compound
acceptable salt
phenyl
chloro
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US2010/052420
Other languages
English (en)
Other versions
WO2011046991A3 (fr
Inventor
David R. Brittelli
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Gilead Connecticut Inc
Original Assignee
Gilead Connecticut Inc
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 Gilead Connecticut Inc filed Critical Gilead Connecticut Inc
Publication of WO2011046991A2 publication Critical patent/WO2011046991A2/fr
Publication of WO2011046991A3 publication Critical patent/WO2011046991A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4409—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides

Definitions

  • R 2 is chosen from fluoro, chloro, methoxy, and difluoromethoxy
  • n 0 or 1 ;
  • the compounds are deuterated.
  • Such deuterated forms can be made by the procedure described in U.S. Patent Nos. 5,846,514 and 6,334,997.
  • deuteration may improve the efficacy and increase the duration of action of drugs.
  • Deuterium substituted compounds can be synthesized using various methods such as described in: Dean, Dennis C; Editor. Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development.
  • a "chelate” is formed by the coordination of a compound to a metal ion at two (or more) points.
  • the term “compound” is intended to include chelates of compounds.
  • salts includes chelates of salts.
  • a detection Mix which includes 1 nM LANCE Eu-W1024 labeled anti-phosphotyrosine antibody PT66 (Perkin-Elmer, cat #AD0068) and 20 nM SA- APC (based on the SA moiety), is added.
  • the reaction plates are incubated at room temperature for at least 15 minutes after SA-APC detection mix addition.
  • the reaction plates are then read on an Envision plate reader (Perkin-Elmer) with 605nm excitation 615 nM and 640nm emission wavelengths. 2
  • a negative control i.e. a readout in which the kinases are not inhibited
  • the assay is run without any test compound added.
  • Staurosporine a general kinase inhibitor, is used as a positive control.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

La présente invention porte sur au moins un composé de Formule I ou un sel pharmaceutiquement acceptable de celui-ci. La présente invention porte également sur des compositions pharmaceutiques comprenant au moins un composé de Formule I ou un sel pharmaceutiquement acceptable et un ou plusieurs véhicules pharmaceutiquement acceptables choisis parmi les supports, les adjuvants et les excipients. L'invention porte sur des procédés de traitement de patients souffrant de certaines maladies et certains troubles sensibles à la modulation de kinases angiogéniques, qui consistent à administrer à de tels patients une quantité d'au moins un composé de Formule I ou d'un sel pharmaceutiquement acceptable efficace pour réduire les signes ou symptômes de la maladie ou du trouble. Ces maladies comprennent un cancer, dont une néoplasie du sein, le cancer de l'endomètre, le cancer du côlon et l'épithéliuma malpighien spinocellulaire du cou. Les procédés de traitement consistent à administrer au moins un tel composé de Formule I ou un sel pharmaceutiquement acceptable comme unique principe actif ou à administrer au moins un composé de Formule I ou un sel pharmaceutiquement acceptable en association avec un ou plusieurs autres agents thérapeutiques. L'invention porte également sur un procédé permettant de déterminer la présence ou l'absence d'une kinase angiogénique dans un échantillon consistant à mettre en contact l'échantillon avec au moins un composé de Formule I ou un sel pharmaceutiquement acceptable dans des conditions qui permettent la détection d'activité de la kinase angiogénique, détecter un niveau de l'activité de la kinase angiogénique et à partir de celui-ci déterminer la présence ou l'absence de la kinase angiogénique dans l'échantillon.
PCT/US2010/052420 2009-10-15 2010-10-13 Certaines urées substituées comme modulateurs de l'activité de kinases Ceased WO2011046991A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US25198009P 2009-10-15 2009-10-15
US61/251,980 2009-10-15

Publications (2)

Publication Number Publication Date
WO2011046991A2 true WO2011046991A2 (fr) 2011-04-21
WO2011046991A3 WO2011046991A3 (fr) 2011-08-18

Family

ID=43876837

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2010/052420 Ceased WO2011046991A2 (fr) 2009-10-15 2010-10-13 Certaines urées substituées comme modulateurs de l'activité de kinases

Country Status (1)

Country Link
WO (1) WO2011046991A2 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103214479A (zh) * 2012-01-18 2013-07-24 武汉东宇生物医药科技有限公司 吡唑类萘脲类酪氨酸激酶抑制剂及其应用
WO2013120896A1 (fr) * 2012-02-13 2013-08-22 Harmonic Pharma Composé destiné à être utilisé dans la prévention et/ou le traitement d'une maladie neurodégénérative ou d'une maladie comprenant une activation de la phosphodiestérase-4 (pde4)
WO2015043342A1 (fr) * 2013-09-29 2015-04-02 镇江蓝德特药业科技有限公司 Nouveau dérivé d'a-naphtylurée et son application médicale
WO2015051149A1 (fr) * 2013-10-04 2015-04-09 The Trustees Of Columbia University In The City Of New York Analogues de sorafenib et leurs utilisations
CN104788366A (zh) * 2014-01-21 2015-07-22 王若文 Raf激酶抑制剂五氟化硫基芳基脲及其制备方法和应用
WO2018035346A1 (fr) * 2016-08-17 2018-02-22 Ichan School Of Medicine At Mount Sinal Composés inhibiteurs de kinase, compositions et méthodes de traitement du cancer
CN108117551A (zh) * 2016-11-29 2018-06-05 华东理工大学 取代(1H-吡唑[3,4-b]吡啶)脲类化合物及其抗肿瘤用途

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0104153D0 (en) * 2001-02-20 2001-04-11 Reckitt Benckiser Inc Improvements in or relating to organic compositions
CA2666005C (fr) * 2002-03-01 2016-01-19 Dyax Corp. Peptides liant des recepteurs kdr et vegf/kdr et leurs utilisations en diagnostic et therapie
US7932044B2 (en) * 2005-07-01 2011-04-26 Cell Signaling Technology, Inc. Identification of non-small cell lung carcinoma (NSCLC) tumors expressing PDGFR-α
US7910595B2 (en) * 2005-12-21 2011-03-22 Abbott Laboratories Anti-viral compounds

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103214479A (zh) * 2012-01-18 2013-07-24 武汉东宇生物医药科技有限公司 吡唑类萘脲类酪氨酸激酶抑制剂及其应用
WO2013120896A1 (fr) * 2012-02-13 2013-08-22 Harmonic Pharma Composé destiné à être utilisé dans la prévention et/ou le traitement d'une maladie neurodégénérative ou d'une maladie comprenant une activation de la phosphodiestérase-4 (pde4)
WO2015043342A1 (fr) * 2013-09-29 2015-04-02 镇江蓝德特药业科技有限公司 Nouveau dérivé d'a-naphtylurée et son application médicale
US9469639B2 (en) 2013-09-29 2016-10-18 Radiant Pharma & Tech. Co., Ltd. Naphthylurea derivatives and medical applications thereof
WO2015051149A1 (fr) * 2013-10-04 2015-04-09 The Trustees Of Columbia University In The City Of New York Analogues de sorafenib et leurs utilisations
CN104788366A (zh) * 2014-01-21 2015-07-22 王若文 Raf激酶抑制剂五氟化硫基芳基脲及其制备方法和应用
WO2018035346A1 (fr) * 2016-08-17 2018-02-22 Ichan School Of Medicine At Mount Sinal Composés inhibiteurs de kinase, compositions et méthodes de traitement du cancer
CN110072526A (zh) * 2016-08-17 2019-07-30 西奈山伊坎医学院 治疗癌症的激酶抑制剂化合物、组合物和方法
JP2019528279A (ja) * 2016-08-17 2019-10-10 アイカーン スクール オブ メディシン アット マウント サイナイ キナーゼ阻害物質化合物、組成物、及びがんの治療方法
US10519113B2 (en) 2016-08-17 2019-12-31 Icahn School Of Medicine At Mount Sinai Kinase inhibitor compounds, compositions, and methods of treating cancer
US11066370B2 (en) 2016-08-17 2021-07-20 Icahn School Of Medicine At Mount Sinai Kinase inhibitor compounds, compositions, and methods of treating cancer
CN108117551A (zh) * 2016-11-29 2018-06-05 华东理工大学 取代(1H-吡唑[3,4-b]吡啶)脲类化合物及其抗肿瘤用途
CN108117551B (zh) * 2016-11-29 2020-03-27 华东理工大学 取代(1H-吡唑[3,4-b]吡啶)脲类化合物及其抗肿瘤用途

Also Published As

Publication number Publication date
WO2011046991A3 (fr) 2011-08-18

Similar Documents

Publication Publication Date Title
US7625931B2 (en) Certain substituted diphenyl ureas, as modulators of kinase activity
US8222421B2 (en) Certain substituted ureas, as modulators of kinase activity
Mahmoud et al. Novel 2-indolinone thiazole hybrids as sunitinib analogues: Design, synthesis, and potent VEGFR-2 inhibition with potential anti-renal cancer activity
TWI398439B (zh) 特定經取代醯胺、其製法及其用途
JP2013028628A (ja) キナーゼ活性モジュレーターとしての１，３−ジアリール置換尿素
WO2011046991A2 (fr) Certaines urées substituées comme modulateurs de l'activité de kinases
CN114057771B (zh) 大环化合物及其制备方法和应用
US20090176809A1 (en) Raf inhibitor compounds and methods
WO2004072081A1 (fr) 8-heteroaryle-6-phenyle-imidazo[1,2-a]pyrazines comme modulateurs de l'activite kinase
CN117720554A (zh) 一种pan-KRAS抑制剂化合物及其制备方法和用途
EP1189899B1 (fr) Inhibiteurs de thrombine a base de pyrazinone
RS51616B (sr) Derivati heteroaril uree korisni za inhibiciju chk1
CN107501279B (zh) 呋喃并喹啉二酮类化合物及其医药用途
CN115583938A (zh) 靶向BCL9/β-连环蛋白互相作用的小分子化合物
CN101163691A (zh) 作为激酶活性调节剂的1,3-二芳基取代的脲
CN120309588B (zh) 一种具有雄激素受体和组蛋白去乙酰化酶6双重抑制作用的乙内酰硫脲类化合物及其用途
CN118772141A (zh) 用于治疗癌症的DNA聚合酶Theta抑制剂
CN116836161A (zh) Parp1抑制剂
HK1114392A (en) 1,3-diaryl substituted ureas as modulators of kinase activity
HK40049062A (en) Tetrahydroquinolino derivatives for the treatment of metastatic and chemoresistant cancers

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 10823984

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase in:

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 10823984

Country of ref document: EP

Kind code of ref document: A2