CA2644841C - Use of c-src inhibitors in combination with a pyrimidylaminobenzamide compound for the treatment of leukemia - Google Patents
Use of c-src inhibitors in combination with a pyrimidylaminobenzamide compound for the treatment of leukemia Download PDFInfo
- Publication number
- CA2644841C CA2644841C CA2644841A CA2644841A CA2644841C CA 2644841 C CA2644841 C CA 2644841C CA 2644841 A CA2644841 A CA 2644841A CA 2644841 A CA2644841 A CA 2644841A CA 2644841 C CA2644841 C CA 2644841C
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- Prior art keywords
- lower alkyl
- leukemia
- combination
- mono
- compound
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 96
- 208000032839 leukemia Diseases 0.000 title claims abstract description 50
- 102000001332 SRC Human genes 0.000 title abstract description 29
- 108060006706 SRC Proteins 0.000 title abstract description 29
- 239000003112 inhibitor Substances 0.000 title description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims abstract description 9
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims abstract description 8
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims abstract description 8
- HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 claims abstract 2
- 125000000217 alkyl group Chemical group 0.000 claims description 73
- -1 benzcycloalkyl Chemical group 0.000 claims description 69
- 150000003839 salts Chemical group 0.000 claims description 29
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- 125000002950 monocyclic group Chemical group 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
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- 239000003937 drug carrier Substances 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 125000003373 pyrazinyl group Chemical class 0.000 claims description 9
- 125000000714 pyrimidinyl group Chemical class 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 7
- 125000004434 sulfur atom Chemical group 0.000 claims description 7
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
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- 230000000694 effects Effects 0.000 abstract description 45
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- 125000003282 alkyl amino group Chemical group 0.000 description 15
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- 150000003254 radicals Chemical class 0.000 description 7
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 6
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- 239000011737 fluorine Substances 0.000 description 4
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- 150000003230 pyrimidines Chemical class 0.000 description 4
- 238000009097 single-agent therapy Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
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- ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 125000004414 alkyl thio group Chemical group 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229960002448 dasatinib Drugs 0.000 description 3
- 125000002883 imidazolyl group Chemical group 0.000 description 3
- 125000001041 indolyl group Chemical group 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000000561 purinyl group Chemical class N1=C(N=C2N=CNC2=C1)* 0.000 description 3
- 125000000168 pyrrolyl group Chemical group 0.000 description 3
- 125000000335 thiazolyl group Chemical group 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- RXYPXQSKLGGKOL-UHFFFAOYSA-N 1,4-dimethylpiperazine Chemical compound CN1CCN(C)CC1 RXYPXQSKLGGKOL-UHFFFAOYSA-N 0.000 description 2
- 125000004173 1-benzimidazolyl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N1* 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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Classifications
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- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- 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
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (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)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US79043706P | 2006-04-07 | 2006-04-07 | |
| US60/790,437 | 2006-04-07 | ||
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| NZ556673A (en) | 2005-02-03 | 2010-03-26 | Gen Hospital Corp | Method for treating gefitinib and/or erlotinib resistant cancer with an EGFR inhibitor |
| EP3488866A1 (en) | 2005-11-04 | 2019-05-29 | Wyeth LLC | Antineoplastic combinations with mtor inhibitor, herceptin, and/or hki-272 |
| US8022216B2 (en) | 2007-10-17 | 2011-09-20 | Wyeth Llc | Maleate salts of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide and crystalline forms thereof |
| ES2531322T3 (es) | 2008-06-17 | 2015-03-13 | Wyeth Llc | Combinaciones antineoplásicas que contienen HKI-272 y vinorelbina |
| EP3175853B1 (en) * | 2008-08-04 | 2023-11-01 | Wyeth LLC | Antineoplastic combinations of neratinib and capecitabine |
| MX380504B (es) | 2010-06-03 | 2025-03-12 | Pharmacyclics Llc | El uso de inhibidores de la tirosina quinasa de bruton (btk). |
| HK1206073A1 (en) | 2012-07-24 | 2015-12-31 | 药品循环有限责任公司 | Mutations associated with resistance to inhibitors of bruton's tyrosine kinase (btk) |
| CN103113355B (zh) * | 2013-02-27 | 2014-08-13 | 无锡爱内特生物科技有限公司 | 一种Bcr/Abl酪氨酸激酶抑制剂及其制备方法和在治疗慢性粒细胞白血病中的应用 |
| US20170114323A1 (en) | 2014-06-19 | 2017-04-27 | Whitehead Institute For Biomedical Research | Uses of kinase inhibitors for inducing and maintaining pluripotency |
| US12371667B2 (en) | 2021-05-13 | 2025-07-29 | Washington University | Enhanced methods for inducing and maintaining naive human pluripotent stem cells |
| CN116178358B (zh) * | 2022-11-04 | 2024-04-19 | 济南大学 | 一种靶向c-Src激酶SH3结构域的化合物及其应用 |
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| CH690773A5 (de) * | 1996-02-01 | 2001-01-15 | Novartis Ag | Pyrrolo(2,3-d)pyrimide und ihre Verwendung. |
| US7238525B2 (en) * | 2000-06-30 | 2007-07-03 | The Regents Of The University Of California | Strategy for leukemia therapy |
| WO2002062334A2 (en) * | 2001-02-05 | 2002-08-15 | Pezzuto John M | Cancer chemopreventative compounds and compositions and methods of treating cancers |
| ATE431417T1 (de) * | 2001-06-14 | 2009-05-15 | Univ California | Mutationen in der mit der resistenz gegenüber sti-571 assoziierten bcr-abl-tyrosinkinase |
| EP2258371A1 (en) * | 2001-08-10 | 2010-12-08 | Novartis AG | Use of c-Src inhibitors alone or in combination with STI571 for the treatment of leukaemia |
| EP1473043A1 (en) * | 2003-04-29 | 2004-11-03 | Boehringer Ingelheim Pharma GmbH & Co.KG | Pharmaceutical combination for the treatment of diseases involving cell proliferation, migration or apotosis of myeloma cells, or angiogenesis |
| AU2003291245A1 (en) * | 2003-11-06 | 2004-06-06 | Wyeth | 4-anilino-3-quinolinecarbonitriles for the treatment of chronic myelogenous leukemia (cml) |
| US20060069101A1 (en) * | 2004-09-27 | 2006-03-30 | Kim Kyoung S | Prodrugs of protein tyrosine kinase inhibitors |
| US20060235006A1 (en) * | 2005-04-13 | 2006-10-19 | Lee Francis Y | Combinations, methods and compositions for treating cancer |
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2007
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- 2007-04-05 CN CNA2007800120868A patent/CN101415426A/zh active Pending
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- 2007-04-05 RU RU2008143703/15A patent/RU2008143703A/ru unknown
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- 2007-04-05 BR BRPI0710675-0A patent/BRPI0710675A2/pt not_active IP Right Cessation
- 2007-04-05 EP EP07727867A patent/EP2010182A2/en not_active Withdrawn
- 2007-04-05 WO PCT/EP2007/053399 patent/WO2007116025A2/en not_active Ceased
- 2007-04-05 KR KR1020117016784A patent/KR101292508B1/ko not_active Expired - Fee Related
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2012
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- 2012-11-08 RU RU2012147511/15A patent/RU2012147511A/ru not_active Application Discontinuation
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2013
- 2013-01-31 JP JP2013016980A patent/JP2013136596A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CA2644841A1 (en) | 2007-10-18 |
| RU2008143703A (ru) | 2010-05-20 |
| WO2007116025A2 (en) | 2007-10-18 |
| JP2013136596A (ja) | 2013-07-11 |
| JP2009532438A (ja) | 2009-09-10 |
| KR20110097966A (ko) | 2011-08-31 |
| KR20090031855A (ko) | 2009-03-30 |
| RU2012147511A (ru) | 2014-05-20 |
| WO2007116025A3 (en) | 2007-12-13 |
| AU2007235976A1 (en) | 2007-10-18 |
| US20130040972A1 (en) | 2013-02-14 |
| EP2010182A2 (en) | 2009-01-07 |
| US20100152198A1 (en) | 2010-06-17 |
| MX2008012903A (es) | 2008-10-13 |
| KR101292508B1 (ko) | 2013-08-01 |
| BRPI0710675A2 (pt) | 2011-08-23 |
| CN101415426A (zh) | 2009-04-22 |
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