WO2008137630A1 - Utilisation d'inhibiteurs de la hdac pour le traitement des cancers gastro-intestinaux - Google Patents

Utilisation d'inhibiteurs de la hdac pour le traitement des cancers gastro-intestinaux Download PDF

Info

Publication number
WO2008137630A1
WO2008137630A1 PCT/US2008/062341 US2008062341W WO2008137630A1 WO 2008137630 A1 WO2008137630 A1 WO 2008137630A1 US 2008062341 W US2008062341 W US 2008062341W WO 2008137630 A1 WO2008137630 A1 WO 2008137630A1
Authority
WO
WIPO (PCT)
Prior art keywords
aryl
alkyl
heteroaryl
heterocycloalkyl
cycloalkyl
Prior art date
Application number
PCT/US2008/062341
Other languages
English (en)
Inventor
Peter Wisdom Atadja
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=39683987&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2008137630(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority to BRPI0811112-0A2A priority Critical patent/BRPI0811112A2/pt
Priority to US12/594,613 priority patent/US20100137398A1/en
Priority to CN200880014107A priority patent/CN101674825A/zh
Priority to CA002683554A priority patent/CA2683554A1/fr
Priority to MX2009011692A priority patent/MX2009011692A/es
Application filed by Novartis Ag filed Critical Novartis Ag
Priority to EP08747442A priority patent/EP2142190A1/fr
Priority to JP2010507547A priority patent/JP2010526149A/ja
Priority to AU2008247603A priority patent/AU2008247603A1/en
Publication of WO2008137630A1 publication Critical patent/WO2008137630A1/fr
Priority to IL201318A priority patent/IL201318A0/en
Priority to TNP2009000427A priority patent/TN2009000427A1/fr
Priority to MA32315A priority patent/MA31356B1/fr

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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • HDAC inhibitors especially the compounds of formula (I), as defined herein, directly inhibit the proliferation of gastrointestinal cancer, such hepatocellular carcinoma and/or pancreatic cancer.
  • R 3 and R 4 are the same or different and independently selected from H and Ci-C 6 alkyl, or
  • R 10 and R 11 are the same or different and independently selected from H, C r C 4 alkyl and -C(O)-alkyl;
  • R 12 is selected from H, Ci-C ⁇ alkyl, C 4 -C 9 cycloalkyl, C 4 -C 9 heterocycloalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl;
  • Especially useful compounds of formula (Ie), are those wherein R 18 is H, fluoro, chloro, bromo, a C 1 -C 4 BlKyI group, a substituted C 1 -C 4 BlKyI group, a C 3 -C 7 cycloalKyl group, unsubstituted phenyl, phenyl substituted in the para position, or a heteroaryl, e.g., pyridyl, ring.
  • the present invention further relates to the compounds of the formula (If):

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Indole Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

La présente invention concerne l'utilisation d'un inhibiteur de la HDAC pour préparer un médicament destiné au traitement des cancers gastro-intestinaux. L'invention concerne également un procédé de traitement d'un animal à sang chaud, en particulier un être humain, ayant un cancer gastro-intestinal, ledit procédé comprenant l'administration audit animal d'une quantité thérapeutiquement efficace d'un inhibiteur de la HDAC, en particulier un composé de formule (I) tel que défini ici. L'invention concerne en outre une composition pharmaceutique et un emballage commercial.
PCT/US2008/062341 2007-05-04 2008-05-02 Utilisation d'inhibiteurs de la hdac pour le traitement des cancers gastro-intestinaux WO2008137630A1 (fr)

Priority Applications (11)

Application Number Priority Date Filing Date Title
AU2008247603A AU2008247603A1 (en) 2007-05-04 2008-05-02 Use of HDAC inhibitors for the treatment of gastrointestinal cancers
US12/594,613 US20100137398A1 (en) 2007-05-04 2008-05-02 Use of hdac inhibitors for the treatment of gastrointestinal cancers
CN200880014107A CN101674825A (zh) 2007-05-04 2008-05-02 Hdac抑制剂用于治疗胃肠癌的应用
CA002683554A CA2683554A1 (fr) 2007-05-04 2008-05-02 Utilisation d'inhibiteurs de la hdac pour le traitement des cancers gastro-intestinaux
MX2009011692A MX2009011692A (es) 2007-05-04 2008-05-02 Uso de inhibidores de desacetilasa de histona (hdac) para el tratamiento de canceres gastrointestinales.
BRPI0811112-0A2A BRPI0811112A2 (pt) 2007-05-04 2008-05-02 Uso de inibidores de hdac para o tratamento de cânceres gastrointestinais.
EP08747442A EP2142190A1 (fr) 2007-05-04 2008-05-02 Utilisation d'inhibiteurs de la hdac pour le traitement des cancers gastro-intestinaux
JP2010507547A JP2010526149A (ja) 2007-05-04 2008-05-02 消化管がんの処置のためのｈｄａｃ阻害剤の使用
IL201318A IL201318A0 (en) 2007-05-04 2009-10-01 Use of hdac inhibitors for the treatment of gastrointestinal cancers
TNP2009000427A TN2009000427A1 (en) 2007-05-04 2009-10-16 Use of hdac inhibitors for the treatment of gastrointestinal cancers
MA32315A MA31356B1 (fr) 2007-05-04 2009-10-30 Utilisation d'inhibiteurs de la hdac pour le traitement des cancers gastro-intestinaux

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US91599607P 2007-05-04 2007-05-04
US60/915,996 2007-05-04

Publications (1)

Publication Number Publication Date
WO2008137630A1 true WO2008137630A1 (fr) 2008-11-13

Family

ID=39683987

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2008/062341 WO2008137630A1 (fr) 2007-05-04 2008-05-02 Utilisation d'inhibiteurs de la hdac pour le traitement des cancers gastro-intestinaux

Country Status (16)

Country Link
EP (1) EP2142190A1 (fr)
JP (1) JP2010526149A (fr)
KR (1) KR20100016171A (fr)
CN (1) CN101674825A (fr)
AU (1) AU2008247603A1 (fr)
BR (1) BRPI0811112A2 (fr)
CA (1) CA2683554A1 (fr)
CL (1) CL2008001269A1 (fr)
IL (1) IL201318A0 (fr)
MA (1) MA31356B1 (fr)
MX (1) MX2009011692A (fr)
RU (1) RU2009144842A (fr)
TN (1) TN2009000427A1 (fr)
TW (1) TW200908964A (fr)
WO (1) WO2008137630A1 (fr)
ZA (1) ZA200906739B (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002022577A2 (fr) * 2000-09-01 2002-03-21 Novartis Ag Inhibiteurs de desacetylase
WO2005040101A1 (fr) * 2003-10-27 2005-05-06 S*Bio Pte Ltd Hydroxamates connectes a l'acyluree et a la sulfonyluree
WO2005040161A1 (fr) * 2003-10-27 2005-05-06 S*Bio Pte Ltd Hydroxamates lies au biaryle: preparation et applications pharmaceutiques
WO2006075165A1 (fr) * 2005-01-13 2006-07-20 Btg International Limited Combinaison de virus oncolytiques a des inhibiteurs d'angiogenese

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002022577A2 (fr) * 2000-09-01 2002-03-21 Novartis Ag Inhibiteurs de desacetylase
WO2005040101A1 (fr) * 2003-10-27 2005-05-06 S*Bio Pte Ltd Hydroxamates connectes a l'acyluree et a la sulfonyluree
WO2005040161A1 (fr) * 2003-10-27 2005-05-06 S*Bio Pte Ltd Hydroxamates lies au biaryle: preparation et applications pharmaceutiques
WO2006075165A1 (fr) * 2005-01-13 2006-07-20 Btg International Limited Combinaison de virus oncolytiques a des inhibiteurs d'angiogenese

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
DATABASE EMBASE [online] ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL; September 2006 (2006-09-01), ROBERTS L R ET AL: "Emerging drugs for hepatocellular carcinoma", XP002492695, Database accession no. EMB-2006450357 *
DI FAZIO P. ET AL: "The novel HDAC-inhibitor Panobinostat inhibits growth of human hepatocellular carcinoma xenografts in nude mice", 2008 AACR ANNUAL MEETING ABSTRACT # 734, 13 April 2008 (2008-04-13), XP002492694 *
EXPERT OPINION ON EMERGING DRUGS 200609 GB, vol. 11, no. 3, September 2006 (2006-09-01), pages 469 - 487, ISSN: 1472-8214 *
FANG JING YUAN: "Histone deacetylase inhibitors, anticancerous mechanism and therapy for gastrointestinal cancers", JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, vol. 20, no. 7, July 2005 (2005-07-01), pages 988 - 994, XP002492690, ISSN: 0815-9319 *
LABONTE M. ET AL: "The effects of histone deacetylase inhibitors on epidermal growth factor receptor expression in colon cancer cell lines: implications for combination therapy.", 98TH AACR ANNUAL MEETING, ABSTRACT # 683, 15 April 2007 (2007-04-15), Los Angeles, CA, USA, XP002492691, Retrieved from the Internet <URL:http://www.aacrmeetingabstracts.org/cgi/content/meeting_abstract/2007/1_Annual_Meeting/683?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=1&andorexacttitle=and&andorexacttitleabs=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT> [retrieved on 20080919] *
REMISZEWSKI S W ET AL: "N-Hydroxy-3-phenyl-2-propenamides as novel inhibitors of human histone deacetylase with in vivo antitumor activity: Discovery of (2E)-N-hydroxy-3-[4-[[2-hydroxyethyl)[2-(1H-indol-3-yl)ethyl]amino]me thyl]phenyl]-2-propenamide (NVP-LAQ824)", JOURNAL OF MEDICINAL CHEMISTRY, US AMERICAN CHEMICAL SOCIETY. WASHINGTON, vol. 46, 1 January 2003 (2003-01-01), pages 4609 - 4624, XP002414496, ISSN: 0022-2623 *
WIEDMANN M. ET AL: "Treatment of pancreatic cancer with two novel histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589.", 2007 ASCO ANNUAL MEETING PROCEEDINGS ABSTRACT 4624, June 2007 (2007-06-01), XP002492693, Retrieved from the Internet <URL:http://www.asco.org/ASCO/Abstracts+%26+Virtual+Meeting/Abstracts?&vmview=abst_detail_view&confID=47&abstractID=31358> [retrieved on 20080806] *
WIEDMANN M. ET AL: "Two novel histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589 are active against biliary tract cancer and potentiate the efficacy of gemcitabine.", 2006 ASCO ANNUAL MEETING PROCEEDINGS ABSTRACT 4149, June 2006 (2006-06-01), XP002492692, Retrieved from the Internet <URL:http://www.asco.org/ASCO/Abstracts+%26+Virtual+Meeting/Abstracts?&vmview=abst_detail_view&confID=40&abstractID=30467> [retrieved on 20080806] *

Also Published As

Publication number Publication date
MX2009011692A (es) 2009-11-10
IL201318A0 (en) 2010-05-31
KR20100016171A (ko) 2010-02-12
AU2008247603A1 (en) 2008-11-13
BRPI0811112A2 (pt) 2014-12-23
RU2009144842A (ru) 2011-06-10
CN101674825A (zh) 2010-03-17
CA2683554A1 (fr) 2008-11-13
ZA200906739B (en) 2010-06-30
TW200908964A (en) 2009-03-01
JP2010526149A (ja) 2010-07-29
MA31356B1 (fr) 2010-05-03
EP2142190A1 (fr) 2010-01-13
CL2008001269A1 (es) 2008-12-19
TN2009000427A1 (en) 2011-03-31

Similar Documents

Publication Publication Date Title
AU2007328281B2 (en) Combination of an HDAC inhibitor and an antimetabolite
US20100137398A1 (en) Use of hdac inhibitors for the treatment of gastrointestinal cancers
JP5876435B2 (ja) 骨髄腫の処置のためのｈｄａｃ阻害剤の使用
WO2008137630A1 (fr) Utilisation d&#39;inhibiteurs de la hdac pour le traitement des cancers gastro-intestinaux
WO2008150782A1 (fr) Utilisation d&#39;inhibiteurs de hdac pour le traitement de la destruction osseuse
AU2008204928B2 (en) Formulations of deacetylase inhibitors
EP2155193A1 (fr) Utilisation d&#39;inhibiteurs hdac pour le traitement du mélanome
WO2008002634A1 (fr) Utilisation d&#39;inhibiteurs de la hdac pour le traitement des lymphomes
AU2006306240A1 (en) Combination of histone deacetylase inhibitors and radiation

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 200880014107.4

Country of ref document: CN

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

Ref document number: 08747442

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 579955

Country of ref document: NZ

Ref document number: 2008247603

Country of ref document: AU

Ref document number: 2008747442

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 201318

Country of ref document: IL

WWE Wipo information: entry into national phase

Ref document number: 12594613

Country of ref document: US

WWE Wipo information: entry into national phase

Ref document number: 2683554

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 12009501972

Country of ref document: PH

ENP Entry into the national phase

Ref document number: 2008247603

Country of ref document: AU

Date of ref document: 20080502

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: MX/A/2009/011692

Country of ref document: MX

ENP Entry into the national phase

Ref document number: 20097022965

Country of ref document: KR

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 2009111620

Country of ref document: EG

WWE Wipo information: entry into national phase

Ref document number: 2010507547

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: DZP2009000701

Country of ref document: DZ

WWE Wipo information: entry into national phase

Ref document number: 2009144842

Country of ref document: RU

ENP Entry into the national phase

Ref document number: PI0811112

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20091103