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WO1997038664A3 - A method of treating cancer - Google Patents

A method of treating cancer Download PDF

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Publication number
WO1997038664A3
WO1997038664A3 PCT/US1997/006248 US9706248W WO9738664A3 WO 1997038664 A3 WO1997038664 A3 WO 1997038664A3 US 9706248 W US9706248 W US 9706248W WO 9738664 A3 WO9738664 A3 WO 9738664A3
Authority
WO
WIPO (PCT)
Prior art keywords
inhibitor
protein transferase
selective
treating cancer
geranylgeranyl
Prior art date
Application number
PCT/US1997/006248
Other languages
French (fr)
Other versions
WO1997038664A2 (en
Inventor
Jackson B Gibbs
Nancy E Kohl
Allen I Oliff
Original Assignee
Merck & Co Inc
Jackson B Gibbs
Nancy E Kohl
Allen I Oliff
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
Priority claimed from GBGB9611982.1A external-priority patent/GB9611982D0/en
Application filed by Merck & Co Inc, Jackson B Gibbs, Nancy E Kohl, Allen I Oliff filed Critical Merck & Co Inc
Priority to JP09537313A priority Critical patent/JP2000513711A/en
Priority to EP97922313A priority patent/EP0952842A2/en
Priority to AU28022/97A priority patent/AU2802297A/en
Publication of WO1997038664A2 publication Critical patent/WO1997038664A2/en
Publication of WO1997038664A3 publication Critical patent/WO1997038664A3/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
    • C07D295/182—Radicals derived from carboxylic acids
    • C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/005—Enzyme inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/05—Dipeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/06—Tripeptides
    • 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
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/20—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D233/26—Radicals substituted by carbon atoms having three bonds to hetero atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
    • C07D309/30—Oxygen atoms, e.g. delta-lactones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic 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
    • C07D401/02—Heterocyclic 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
    • C07D401/12—Heterocyclic 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
    • 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
    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Steroid Compounds (AREA)

Abstract

The present invention relates to a method of treating cancer which comprises administering to a mammalian patient an effective amount of a combination of geranylgeranyl-protein transferase-type I inhibitor and a farnesyl protein transferase inhibitor. The invention further relates to a method of treating cancer which comprises administering to a mammalian patient an effective amount of a combination of a selective geranylgeranyl-protein transferase-type I inhibitor and a selective farnesyl protein transferase inhibitor. The figure shows the autoradiograph of the immunoprecipates from assay set No. 1 of the in vivo prenylation inhibition by a combination by a selective of FPTase inhibitor and a selective geranylgeranyl-protein transferase-type I inhibitor.
PCT/US1997/006248 1996-04-18 1997-04-15 A method of treating cancer WO1997038664A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP09537313A JP2000513711A (en) 1996-04-18 1997-04-15 Cancer Treatment
EP97922313A EP0952842A2 (en) 1996-04-18 1997-04-15 A method of treating cancer
AU28022/97A AU2802297A (en) 1996-04-18 1997-04-15 A method of treating cancer

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US1558996P 1996-04-18 1996-04-18
US60/015,589 1996-04-18
GBGB9611982.1A GB9611982D0 (en) 1996-06-07 1996-06-07 A method of treating cancer
GB9611982.1 1996-06-07

Publications (2)

Publication Number Publication Date
WO1997038664A2 WO1997038664A2 (en) 1997-10-23
WO1997038664A3 true WO1997038664A3 (en) 1997-11-20

Family

ID=26309466

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1997/006248 WO1997038664A2 (en) 1996-04-18 1997-04-15 A method of treating cancer

Country Status (5)

Country Link
EP (1) EP0952842A2 (en)
JP (1) JP2000513711A (en)
AU (1) AU2802297A (en)
CA (1) CA2251955A1 (en)
WO (1) WO1997038664A2 (en)

Cited By (14)

* Cited by examiner, † Cited by third party
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US7407957B2 (en) 2004-08-26 2008-08-05 Maybridge Limited Phthalazinone derivatives
US8691807B2 (en) 2011-06-20 2014-04-08 Incyte Corporation Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as JAK inhibitors
US8933085B2 (en) 2010-11-19 2015-01-13 Incyte Corporation Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as JAK inhibitors
US8933086B2 (en) 2005-12-13 2015-01-13 Incyte Corporation Heteroaryl substituted pyrrolo[2,3-B]pyridines and pyrrolo[2,3-B]pyrimidines as Janus kinase inhibitors
US8987443B2 (en) 2013-03-06 2015-03-24 Incyte Corporation Processes and intermediates for making a JAK inhibitor
US9034884B2 (en) 2010-11-19 2015-05-19 Incyte Corporation Heterocyclic-substituted pyrrolopyridines and pyrrolopyrimidines as JAK inhibitors
US9216984B2 (en) 2009-05-22 2015-12-22 Incyte Corporation 3-[4-(7H-pyrrolo[2,3-D]pyrimidin-4-yl)-1H-pyrazol-1-yl]octane—or heptane-nitrile as JAK inhibitors
US9249145B2 (en) 2009-09-01 2016-02-02 Incyte Holdings Corporation Heterocyclic derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors
US9334274B2 (en) 2009-05-22 2016-05-10 Incyte Holdings Corporation N-(hetero)aryl-pyrrolidine derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines and pyrrol-3-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors
US9359358B2 (en) 2011-08-18 2016-06-07 Incyte Holdings Corporation Cyclohexyl azetidine derivatives as JAK inhibitors
US9464088B2 (en) 2010-03-10 2016-10-11 Incyte Holdings Corporation Piperidin-4-yl azetidine derivatives as JAK1 inhibitors
US9487521B2 (en) 2011-09-07 2016-11-08 Incyte Holdings Corporation Processes and intermediates for making a JAK inhibitor
US9498467B2 (en) 2014-05-30 2016-11-22 Incyte Corporation Treatment of chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) by inhibitors of JAK1
US12440495B2 (en) 2023-10-26 2025-10-14 Incyte Corporation Combination therapy for treatment of myeloproliferative neoplasms

Families Citing this family (34)

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US6524832B1 (en) 1994-02-04 2003-02-25 Arch Development Corporation DNA damaging agents in combination with tyrosine kinase inhibitors
US6117641A (en) 1996-04-11 2000-09-12 Mitotix, Inc. Assays and reagents for identifying anti-fungal agents and uses related thereto
WO1997038293A2 (en) 1996-04-11 1997-10-16 Mitotix, Inc. Assays and reagents for identifying anti-fungal agents, and uses related thereto
US6727082B1 (en) 1996-04-11 2004-04-27 Gpc Biotech Inc. Assays and reagents for identifying anti-fungal agents, and uses related thereto
CA2301880A1 (en) * 1997-08-27 1999-03-04 Merck & Co., Inc. A method of treating cancer
US6103487A (en) * 1997-08-27 2000-08-15 Merck & Co., Inc. Method of treating cancer
CZ298511B6 (en) * 1997-12-22 2007-10-24 Schering Corporation Use of benzocycloheptapyridine compounds in combination with antineoplastic medicaments for preparing a compound medicament intended for treating proliferative diseases
US6096757A (en) 1998-12-21 2000-08-01 Schering Corporation Method for treating proliferative diseases
FR2780892B1 (en) * 1998-07-08 2001-08-17 Sod Conseils Rech Applic USE OF PRENYLTRANSFERASE INHIBITORS FOR THE PREPARATION OF A MEDICINAL PRODUCT FOR TREATING CONDITIONS RESULTING FROM MEMBRANE FIXATION OF HETEROTRIMERIC PROTEIN
HRP990246A2 (en) 1998-08-07 2000-06-30 Du Pont Pharm Co Succinoylamino benzodiazepines as inhibitors of a beta protein production
NZ525513A (en) 1998-08-07 2004-09-24 Pont Pharmaceuticals Du Succinoylamino lactams as inhibitors of Abeta protein production
EP1313426A2 (en) 1998-12-24 2003-05-28 Bristol-Myers Squibb Pharma Company Succinoylamino benzodiazepines as inhibitors of a-beta protein production
US6316462B1 (en) 1999-04-09 2001-11-13 Schering Corporation Methods of inducing cancer cell death and tumor regression
US6503902B2 (en) 1999-09-13 2003-01-07 Bristol-Myers Squibb Pharma Company Hydroxyalkanoylaminolactams and related structures as inhibitors of a β protein production
US6960576B2 (en) 1999-09-13 2005-11-01 Bristol-Myers Squibb Pharma Company Hydroxyalkanoylaminolactams and related structures as inhibitors of Aβ protein production
CA2387493A1 (en) 1999-10-08 2001-04-19 Lorin Andrew Thompson Amino lactam sulfonamides as inhibitors of a.beta. protein production
CA2395862A1 (en) 2000-02-17 2001-08-23 Hong Liu Succinoylamino carbocycles and heterocycles as inhibitors of a.beta. protein production
US6495540B2 (en) 2000-03-28 2002-12-17 Bristol - Myers Squibb Pharma Company Lactams as inhibitors of A-β protein production
MXPA02009729A (en) 2000-04-03 2003-03-27 Bristol Myers Squibb Pharma Co CYCLIC LACTAMS AS INHIBITORS OF A beta PROTEIN PRODUCTION.
MXPA02009755A (en) 2000-04-03 2003-03-27 Bristol Myers Squibb Pharma Co CYCLIC LACTAMS AS INHIBITORS OF Abeta PROTEIN PRODUCTION.
AU2001257006A1 (en) 2000-04-11 2001-10-23 Du Pont Pharmaceuticals Company Substituted lactams as inhibitors of abeta protein production
BR0106717A (en) 2000-06-01 2002-04-16 Bristol Myers Squibb Pharma Co Compounds, pharmaceutical composition and uses of innovative lactam compounds
BRPI0707537A2 (en) 2006-02-07 2011-05-03 Wyeth Corp 11-beta hsd1 inhibitors
UY30639A1 (en) 2006-10-17 2008-05-31 Kudos Pharm Ltd SUBSTITUTED DERIVATIVES OF 2H-FTALAZIN-1-ONA, ITS CRYSTAL FORMS, PREPARATION PROCESS AND APPLICATIONS
ES2903444T3 (en) 2007-06-13 2022-04-01 Incyte Holdings Corp Use of Janus(R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile kinase inhibitor salts
CN102238945B (en) 2008-10-07 2014-10-29 阿斯利康(英国)有限公司 Pharmaceutical formulation 514
UA111588C2 (en) 2010-05-21 2016-05-25 Інсайт Холдінгс Корпорейшн JAK INHIBITOR COMPOSITION FOR LOCAL APPLICATION
WO2013173720A1 (en) 2012-05-18 2013-11-21 Incyte Corporation Piperidinylcyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as jak inhibitors
ES2880814T3 (en) 2012-11-15 2021-11-25 Incyte Holdings Corp Ruxolitinib Sustained Release Dosage Forms
KR20160045081A (en) 2013-08-07 2016-04-26 인사이트 코포레이션 Sustained release dosage forms for a jak1 inhibitor
WO2019113487A1 (en) 2017-12-08 2019-06-13 Incyte Corporation Low dose combination therapy for treatment of myeloproliferative neoplasms
AU2019213665B2 (en) 2018-01-30 2024-06-13 Incyte Corporation Processes for preparing (1 -(3-fluoro-2-(trifluoromethyl)isonicotinyl)piperidine-4-one)
SG11202009441PA (en) 2018-03-30 2020-10-29 Incyte Corp Treatment of hidradenitis suppurativa using jak inhibitors
US11833155B2 (en) 2020-06-03 2023-12-05 Incyte Corporation Combination therapy for treatment of myeloproliferative neoplasms

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5420245A (en) * 1990-04-18 1995-05-30 Board Of Regents, The University Of Texas Tetrapeptide-based inhibitors of farnesyl transferase
US5470832A (en) * 1994-01-31 1995-11-28 Merck & Co., Inc. Inhibitors of geranylgeranyl-protein transferase

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5420245A (en) * 1990-04-18 1995-05-30 Board Of Regents, The University Of Texas Tetrapeptide-based inhibitors of farnesyl transferase
US5470832A (en) * 1994-01-31 1995-11-28 Merck & Co., Inc. Inhibitors of geranylgeranyl-protein transferase

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7407957B2 (en) 2004-08-26 2008-08-05 Maybridge Limited Phthalazinone derivatives
US9206187B2 (en) 2005-12-13 2015-12-08 Incyte Holdings Corporation Heteroaryl substituted pyrrolo[2,3-B] pyridines and pyrrolo[2,3-B] pyrimidines as Janus kinase
US8933086B2 (en) 2005-12-13 2015-01-13 Incyte Corporation Heteroaryl substituted pyrrolo[2,3-B]pyridines and pyrrolo[2,3-B]pyrimidines as Janus kinase inhibitors
US8946245B2 (en) 2005-12-13 2015-02-03 Incyte Corporation Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as Janus kinase inhibitors
US9216984B2 (en) 2009-05-22 2015-12-22 Incyte Corporation 3-[4-(7H-pyrrolo[2,3-D]pyrimidin-4-yl)-1H-pyrazol-1-yl]octane—or heptane-nitrile as JAK inhibitors
US9334274B2 (en) 2009-05-22 2016-05-10 Incyte Holdings Corporation N-(hetero)aryl-pyrrolidine derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines and pyrrol-3-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors
US9249145B2 (en) 2009-09-01 2016-02-02 Incyte Holdings Corporation Heterocyclic derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors
US9464088B2 (en) 2010-03-10 2016-10-11 Incyte Holdings Corporation Piperidin-4-yl azetidine derivatives as JAK1 inhibitors
US9034884B2 (en) 2010-11-19 2015-05-19 Incyte Corporation Heterocyclic-substituted pyrrolopyridines and pyrrolopyrimidines as JAK inhibitors
US8933085B2 (en) 2010-11-19 2015-01-13 Incyte Corporation Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as JAK inhibitors
US9023840B2 (en) 2011-06-20 2015-05-05 Incyte Corporation Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as JAK inhibitors
US8691807B2 (en) 2011-06-20 2014-04-08 Incyte Corporation Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as JAK inhibitors
US9359358B2 (en) 2011-08-18 2016-06-07 Incyte Holdings Corporation Cyclohexyl azetidine derivatives as JAK inhibitors
US9487521B2 (en) 2011-09-07 2016-11-08 Incyte Holdings Corporation Processes and intermediates for making a JAK inhibitor
US9221845B2 (en) 2013-03-06 2015-12-29 Incyte Holdings Corporation Processes and intermediates for making a JAK inhibitor
US8987443B2 (en) 2013-03-06 2015-03-24 Incyte Corporation Processes and intermediates for making a JAK inhibitor
US9498467B2 (en) 2014-05-30 2016-11-22 Incyte Corporation Treatment of chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) by inhibitors of JAK1
US12440495B2 (en) 2023-10-26 2025-10-14 Incyte Corporation Combination therapy for treatment of myeloproliferative neoplasms

Also Published As

Publication number Publication date
JP2000513711A (en) 2000-10-17
WO1997038664A2 (en) 1997-10-23
EP0952842A2 (en) 1999-11-03
AU2802297A (en) 1997-11-07
CA2251955A1 (en) 1997-10-23

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