CA2439268C - Combination comprising a signal transduction inhibitor and an epothilone derivative - Google Patents
Combination comprising a signal transduction inhibitor and an epothilone derivative Download PDFInfo
- Publication number
- CA2439268C CA2439268C CA002439268A CA2439268A CA2439268C CA 2439268 C CA2439268 C CA 2439268C CA 002439268 A CA002439268 A CA 002439268A CA 2439268 A CA2439268 A CA 2439268A CA 2439268 C CA2439268 C CA 2439268C
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- Prior art keywords
- lower alkyl
- hydrogen
- combination
- proliferative disease
- methyl
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- 150000003883 epothilone derivatives Chemical class 0.000 title claims abstract description 22
- 239000003112 inhibitor Substances 0.000 title claims abstract description 14
- 230000019491 signal transduction Effects 0.000 title claims abstract description 9
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 45
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 44
- 239000001257 hydrogen Substances 0.000 claims abstract description 43
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 40
- 238000011282 treatment Methods 0.000 claims abstract description 33
- 201000010099 disease Diseases 0.000 claims abstract description 32
- 230000000694 effects Effects 0.000 claims abstract description 32
- 230000002062 proliferating effect Effects 0.000 claims abstract description 31
- 239000004480 active ingredient Substances 0.000 claims abstract description 28
- 238000002360 preparation method Methods 0.000 claims abstract description 17
- 229940124617 receptor tyrosine kinase inhibitor Drugs 0.000 claims abstract description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 16
- 230000007423 decrease Effects 0.000 claims abstract description 15
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 claims abstract description 14
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 claims abstract description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 claims abstract description 12
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- 125000004432 carbon atom Chemical group C* 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 150000002431 hydrogen Chemical class 0.000 claims description 14
- 125000004076 pyridyl group Chemical group 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- XRYJULCDUUATMC-CYBMUJFWSA-N 4-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenol Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C=1C=2)=NC=NC=1NC=2C1=CC=C(O)C=C1 XRYJULCDUUATMC-CYBMUJFWSA-N 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 3
- 125000005277 alkyl imino group Chemical group 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical group 0.000 claims description 3
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000004043 oxo group Chemical group O=* 0.000 claims description 3
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 125000001589 carboacyl group Chemical group 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- XGXNTJHZPBRBHJ-UHFFFAOYSA-N n-phenylpyrimidin-2-amine Chemical group N=1C=CC=NC=1NC1=CC=CC=C1 XGXNTJHZPBRBHJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000003386 piperidinyl group Chemical class 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical class 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims 5
- 125000001041 indolyl group Chemical group 0.000 claims 1
- 241001465754 Metazoa Species 0.000 abstract description 11
- 238000000034 method Methods 0.000 abstract description 10
- 229940126062 Compound A Drugs 0.000 abstract description 6
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 abstract description 6
- HESCAJZNRMSMJG-HGYUPSKWSA-N epothilone A Natural products O=C1[C@H](C)[C@H](O)[C@H](C)CCC[C@H]2O[C@H]2C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C HESCAJZNRMSMJG-HGYUPSKWSA-N 0.000 description 17
- QXRSDHAAWVKZLJ-PVYNADRNSA-N epothilone B Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 QXRSDHAAWVKZLJ-PVYNADRNSA-N 0.000 description 17
- QXRSDHAAWVKZLJ-OXZHEXMSSA-N Epothilone B Natural products O=C1[C@H](C)[C@H](O)[C@@H](C)CCC[C@@]2(C)O[C@H]2C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C QXRSDHAAWVKZLJ-OXZHEXMSSA-N 0.000 description 16
- 229960002411 imatinib Drugs 0.000 description 12
- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 12
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- 238000012360 testing method Methods 0.000 description 6
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- 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
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- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Cosmetics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0104840.4A GB0104840D0 (en) | 2001-02-27 | 2001-02-27 | Use of organic compounds |
| GB0104840.4 | 2001-02-27 | ||
| US33904001P | 2001-10-30 | 2001-10-30 | |
| US60/339,040 | 2001-10-30 | ||
| PCT/EP2002/002049 WO2002067941A2 (en) | 2001-02-27 | 2002-02-26 | Combination comprising a signal transduction inhibitor and an epothilone derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2439268A1 CA2439268A1 (en) | 2002-09-06 |
| CA2439268C true CA2439268C (en) | 2010-01-19 |
Family
ID=26245767
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002439268A Expired - Fee Related CA2439268C (en) | 2001-02-27 | 2002-02-26 | Combination comprising a signal transduction inhibitor and an epothilone derivative |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US7723339B2 (https=) |
| EP (1) | EP1385522B1 (https=) |
| JP (1) | JP4499359B2 (https=) |
| KR (1) | KR100848197B1 (https=) |
| CN (1) | CN1511036B (https=) |
| AT (1) | ATE434438T1 (https=) |
| AU (1) | AU2002308218B2 (https=) |
| BR (1) | BR0207649A (https=) |
| CA (1) | CA2439268C (https=) |
| CY (1) | CY1109347T1 (https=) |
| DE (1) | DE60232719D1 (https=) |
| DK (1) | DK1385522T3 (https=) |
| ES (1) | ES2326264T3 (https=) |
| IL (2) | IL157466A0 (https=) |
| MX (1) | MXPA03007729A (https=) |
| NO (1) | NO325416B1 (https=) |
| NZ (1) | NZ527764A (https=) |
| PL (1) | PL207197B1 (https=) |
| PT (1) | PT1385522E (https=) |
| RU (1) | RU2313345C2 (https=) |
| SK (1) | SK287489B6 (https=) |
| WO (1) | WO2002067941A2 (https=) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999001124A1 (en) | 1996-12-03 | 1999-01-14 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
| US6204388B1 (en) | 1996-12-03 | 2001-03-20 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| WO2002072085A1 (en) | 2001-03-14 | 2002-09-19 | Bristol-Myers Squibb Company | Combination of epothilone analogs and chemotherapeutic agents for the treatment of proliferative diseases |
| PT1392313E (pt) * | 2001-05-16 | 2007-07-17 | Novartis Ag | Combinação que compreende n - ( 5- [ 4- ( metil-piperazinomrtil ) - benxoilamido ] - 2 -metilfenil ) - 4 -( 3 - piridil ) - 2 - pirimidina-amina e um agente quimioterapêutico |
| EP1704863A3 (en) * | 2001-05-16 | 2010-11-24 | Novartis AG | Combination comprising N-5-4-(4-Methyl-Piperazino-Methyl-)Benzoyla Mido]-2-Methylphenyl -4-(3-Pyridyl)-2Phyrimidine-amine and a chemotherapeutic agent |
| EP1441736A2 (en) * | 2001-10-29 | 2004-08-04 | Novartis AG | Use of 7h-pyrrolo[2,3-d]pyrimidine derivatives in the treatment of solid tumor diseases |
| US6921769B2 (en) | 2002-08-23 | 2005-07-26 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| US7649006B2 (en) | 2002-08-23 | 2010-01-19 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| DE60330407D1 (de) | 2002-08-23 | 2010-01-14 | Sloan Kettering Inst Cancer | Synthese von Epothilonen, Zwischenprodukte davon, Analoga und ihre Verwendung |
| US20050171167A1 (en) * | 2003-11-04 | 2005-08-04 | Haby Thomas A. | Process and formulation containing epothilones and analogs thereof |
| US20060121511A1 (en) | 2004-11-30 | 2006-06-08 | Hyerim Lee | Biomarkers and methods for determining sensitivity to microtubule-stabilizing agents |
| JO2596B1 (en) * | 2004-11-30 | 2011-02-27 | نوفارتيس ايه جي | Compositions include epothelones and tyrosine protein kinase inhibitors and their pharmaceutical uses |
| EP2634252B1 (en) | 2005-02-11 | 2018-12-19 | University of Southern California | Method of expressing proteins with disulfide bridges |
| US8008256B2 (en) * | 2006-05-01 | 2011-08-30 | University Of Southern California | Combination therapy for treatment of cancer |
| WO2010056901A2 (en) | 2008-11-13 | 2010-05-20 | University Of Southern California | Method of expressing proteins with disulfide bridges with enhanced yields and activity |
| WO2010108503A1 (en) | 2009-03-24 | 2010-09-30 | Life & Brain Gmbh | Promotion of neuronal integration in neural stem cell grafts |
| AU2011255647A1 (en) | 2010-05-18 | 2012-11-15 | Cerulean Pharma Inc. | Compositions and methods for treatment of autoimmune and other diseases |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1989006692A1 (en) * | 1988-01-12 | 1989-07-27 | Genentech, Inc. | Method of treating tumor cells by inhibiting growth factor receptor function |
| DE4138042C2 (de) | 1991-11-19 | 1993-10-14 | Biotechnolog Forschung Gmbh | Epothilone, deren Herstellungsverfahren sowie diese Verbindungen enthaltende Mittel |
| TW225528B (https=) | 1992-04-03 | 1994-06-21 | Ciba Geigy Ag | |
| US5679683A (en) * | 1994-01-25 | 1997-10-21 | Warner-Lambert Company | Tricyclic compounds capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family |
| MX9800215A (es) * | 1995-07-06 | 1998-03-31 | Novartis Ag | Pirrolopirimidas y procesos para su preparacion. |
| DK1367057T3 (da) | 1996-11-18 | 2009-01-19 | Biotechnolog Forschung Gmbh | Epothiloner E og F |
| CO4940418A1 (es) * | 1997-07-18 | 2000-07-24 | Novartis Ag | Modificacion de cristal de un derivado de n-fenil-2- pirimidinamina, procesos para su fabricacion y su uso |
| US6302838B1 (en) * | 1998-02-25 | 2001-10-16 | Novartis Ag | Cancer treatment with epothilones |
| WO2000000485A1 (de) * | 1998-06-30 | 2000-01-06 | Schering Aktiengesellschaft | Epothilon-derivate, verfahren zu deren herstellung, zwischenprodukte und ihre pharmazeutische verwendung |
| IL144370A0 (en) * | 1999-02-11 | 2002-05-23 | Schering Ag | Epothilon derivatives, method for the production and the use thereof as pharmaceuticals |
| DE19908760A1 (de) * | 1999-02-18 | 2000-08-24 | Schering Ag | Neue Epothilon-Derivate, Verfahren zu deren Herstellung und ihre pharmazeutische Verwendung |
-
2002
- 2002-02-26 AU AU2002308218A patent/AU2002308218B2/en not_active Ceased
- 2002-02-26 JP JP2002567308A patent/JP4499359B2/ja not_active Expired - Fee Related
- 2002-02-26 AT AT02744903T patent/ATE434438T1/de active
- 2002-02-26 KR KR1020037011205A patent/KR100848197B1/ko not_active Expired - Fee Related
- 2002-02-26 MX MXPA03007729A patent/MXPA03007729A/es active IP Right Grant
- 2002-02-26 CN CN028056086A patent/CN1511036B/zh not_active Expired - Fee Related
- 2002-02-26 PT PT02744903T patent/PT1385522E/pt unknown
- 2002-02-26 DK DK02744903T patent/DK1385522T3/da active
- 2002-02-26 BR BR0207649-7A patent/BR0207649A/pt not_active Application Discontinuation
- 2002-02-26 ES ES02744903T patent/ES2326264T3/es not_active Expired - Lifetime
- 2002-02-26 IL IL15746602A patent/IL157466A0/xx unknown
- 2002-02-26 WO PCT/EP2002/002049 patent/WO2002067941A2/en not_active Ceased
- 2002-02-26 NZ NZ527764A patent/NZ527764A/en not_active IP Right Cessation
- 2002-02-26 US US10/469,367 patent/US7723339B2/en not_active Expired - Fee Related
- 2002-02-26 SK SK1071-2003A patent/SK287489B6/sk not_active IP Right Cessation
- 2002-02-26 CA CA002439268A patent/CA2439268C/en not_active Expired - Fee Related
- 2002-02-26 EP EP02744903A patent/EP1385522B1/en not_active Expired - Lifetime
- 2002-02-26 RU RU2003127392/15A patent/RU2313345C2/ru not_active IP Right Cessation
- 2002-02-26 DE DE60232719T patent/DE60232719D1/de not_active Expired - Lifetime
- 2002-02-26 PL PL363288A patent/PL207197B1/pl not_active IP Right Cessation
-
2003
- 2003-08-18 IL IL157466A patent/IL157466A/en not_active IP Right Cessation
- 2003-08-25 NO NO20033769A patent/NO325416B1/no not_active IP Right Cessation
-
2009
- 2009-08-28 CY CY20091100900T patent/CY1109347T1/el unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20150226 |