AU2005281299B2 - Novel phenylaminopyrimidine derivatives as inhibitors of BCR-ABL kinase - Google Patents
Novel phenylaminopyrimidine derivatives as inhibitors of BCR-ABL kinase Download PDFInfo
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- AU2005281299B2 AU2005281299B2 AU2005281299A AU2005281299A AU2005281299B2 AU 2005281299 B2 AU2005281299 B2 AU 2005281299B2 AU 2005281299 A AU2005281299 A AU 2005281299A AU 2005281299 A AU2005281299 A AU 2005281299A AU 2005281299 B2 AU2005281299 B2 AU 2005281299B2
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- Australia
- Prior art keywords
- formula
- methyl
- trifluoromethyl
- phenyl
- compound
- Prior art date
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- 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 title claims description 15
- XGXNTJHZPBRBHJ-UHFFFAOYSA-N n-phenylpyrimidin-2-amine Chemical class N=1C=CC=NC=1NC1=CC=CC=C1 XGXNTJHZPBRBHJ-UHFFFAOYSA-N 0.000 title abstract description 10
- 108091000080 Phosphotransferase Proteins 0.000 title description 7
- 102000020233 phosphotransferase Human genes 0.000 title description 7
- 239000003112 inhibitor Substances 0.000 title description 3
- -1 Phenyl pyrimidine amine Chemical class 0.000 claims abstract description 124
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- 238000000034 method Methods 0.000 claims abstract description 62
- 230000008569 process Effects 0.000 claims abstract description 53
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 24
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- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims abstract description 20
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims abstract description 20
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 142
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 70
- 235000002639 sodium chloride Nutrition 0.000 claims description 58
- 150000003839 salts Chemical class 0.000 claims description 52
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 42
- 229910052757 nitrogen Inorganic materials 0.000 claims description 41
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 36
- 239000000203 mixture Substances 0.000 claims description 34
- SIMLOQFADCPLAT-UHFFFAOYSA-N 4-phenylpyrido[3,2-d]pyrimidin-2-amine Chemical compound C=12N=CC=CC2=NC(N)=NC=1C1=CC=CC=C1 SIMLOQFADCPLAT-UHFFFAOYSA-N 0.000 claims description 25
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
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- 125000003118 aryl group Chemical group 0.000 claims description 10
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- GDIIPKWHAQGCJF-UHFFFAOYSA-N 4-Amino-2-nitrotoluene Chemical compound CC1=CC=C(N)C=C1[N+]([O-])=O GDIIPKWHAQGCJF-UHFFFAOYSA-N 0.000 claims description 9
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- KMIOJWCYOHBUJS-HAKPAVFJSA-N vorolanib Chemical compound C1N(C(=O)N(C)C)CC[C@@H]1NC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C KMIOJWCYOHBUJS-HAKPAVFJSA-N 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- NLIVDORGVGAOOJ-MAHBNPEESA-M xylene cyanol Chemical compound [Na+].C1=C(C)C(NCC)=CC=C1C(\C=1C(=CC(OS([O-])=O)=CC=1)OS([O-])=O)=C\1C=C(C)\C(=[NH+]/CC)\C=C/1 NLIVDORGVGAOOJ-MAHBNPEESA-M 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
- 229940057977 zinc stearate Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/66—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/18—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
-
- 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
- C07D213/82—Amides; Imides in position 3
-
- 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
- C07D401/14—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 three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicinal Preparation (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| IN908/CHE/2004 | 2004-09-09 | ||
| IN908CH2004 | 2004-09-09 | ||
| PCT/IN2005/000243 WO2006027795A1 (en) | 2004-09-09 | 2005-07-19 | Novel phenylaminopyrimidine derivatives as inhibitors of bcr-abl kinase |
Publications (2)
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| AU2005281299A1 AU2005281299A1 (en) | 2006-03-16 |
| AU2005281299B2 true AU2005281299B2 (en) | 2012-03-15 |
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| EP (2) | EP1786799B1 (https=) |
| JP (1) | JP5184887B2 (https=) |
| KR (1) | KR100948453B1 (https=) |
| CN (1) | CN101068805B (https=) |
| AP (1) | AP2470A (https=) |
| AU (1) | AU2005281299B2 (https=) |
| BR (1) | BRPI0515081B8 (https=) |
| CA (1) | CA2591321C (https=) |
| CY (1) | CY1113617T1 (https=) |
| DK (1) | DK1786799T3 (https=) |
| EA (1) | EA013328B1 (https=) |
| ES (1) | ES2390227T3 (https=) |
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| MA (1) | MA28922B1 (https=) |
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| NO (1) | NO337598B1 (https=) |
| NZ (1) | NZ554361A (https=) |
| PL (1) | PL1786799T3 (https=) |
| PT (1) | PT1786799E (https=) |
| SI (1) | SI1786799T1 (https=) |
| UA (1) | UA94570C2 (https=) |
| WO (1) | WO2006027795A1 (https=) |
| ZA (2) | ZA200701942B (https=) |
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| US6667300B2 (en) * | 2000-04-25 | 2003-12-23 | Icos Corporation | Inhibitors of human phosphatidylinositol 3-kinase delta |
| WO2005113556A1 (en) | 2004-05-13 | 2005-12-01 | Icos Corporation | Quinazolinones as inhibitors of human phosphatidylinositol 3-kinase delta |
| AP2470A (en) | 2004-09-09 | 2012-09-17 | Natco Pharma Ltd | Novel phenylaminopyrimidine derivatives as inhibitors of BCR-ABL kinase |
| US8735415B2 (en) | 2004-09-09 | 2014-05-27 | Natco Pharma Limited | Acid addition salts of (3,5-Bis trifluoromethyl)-N-[4-methyl-3-(4-pyridin-3yl-pyrimidin-2ylamino)-phenyl]-benzamide |
| US20110190328A1 (en) * | 2004-09-09 | 2011-08-04 | Natco Pharma Limited | Acid addition salts of (3,5-bis trifluoromethyl)-n-[4-methyl-3-(4-pyridin-3yl-pyrimidin-2ylamino)-phenyl]-benzamide |
| US7939541B2 (en) * | 2004-09-09 | 2011-05-10 | Natco Pharma Limited | Intermediates and a process employing the intermediates for the preparation of (3-trifluoromethylsulfonyl)-N-[4-methyl-3-(4-pyridin-3yl-pyrimidin-2ylamino)-phenyl]-benzamide |
| WO2008031534A1 (en) * | 2006-09-11 | 2008-03-20 | Syngenta Participations Ag | Insecticidal compounds |
| BRPI0718677A2 (pt) * | 2006-11-03 | 2013-11-26 | Irm Llc | Compostos e composições como inibidores de quinases proteicas |
| EA200900779A1 (ru) * | 2006-12-14 | 2010-02-26 | Байер Шеринг Фарма Акциенгезельшафт | Производные дигидропиридина, полезные как ингибиторы протеинкиназы |
| EA019524B1 (ru) * | 2007-05-04 | 2014-04-30 | Айрм Ллк | СОЕДИНЕНИЯ И КОМПОЗИЦИИ КАК ИНГИБИТОРЫ КИНАЗЫ с-kit И PDGFR |
| KR101122481B1 (ko) * | 2007-05-04 | 2012-02-29 | 아이알엠 엘엘씨 | Ｃ-ｋｉｔ 및 ｐｄｇｆｒ 키나제 억제제로서의 피리미딘 유도체 및 조성물 |
| US8293757B2 (en) | 2007-08-22 | 2012-10-23 | Irm Llc | 5-(4-(haloalkoxy)phenyl) pyrimidine-2-amine compounds and compositions as kinase inhibitors |
| MX2010002005A (es) | 2007-08-22 | 2010-03-11 | Irm Llc | Derivados de 2-heteroaril-amino-pirimidina como inhibidores de cinasa. |
| AP2651A (en) * | 2008-03-04 | 2013-04-25 | Natco Pharma Ltd | Crystal form of phenylamino pyrimidine derivatives |
| US8067422B2 (en) | 2008-03-04 | 2011-11-29 | Natco Pharma Limited | Crystal form of phenylamino pyrimidine derivatives |
| WO2012004801A1 (en) * | 2010-07-07 | 2012-01-12 | Hetero Research Foundation | Process for imatinib mesylate |
| GB2488788B (en) * | 2011-03-07 | 2013-07-10 | Natco Pharma Ltd | Oral formulation of phenylaminopyrymidine compound with enhanced bioavailability and pharmacological response |
| EP2751104B1 (en) | 2011-09-01 | 2019-09-25 | Novartis AG | Compounds and compositions as c-kit kinase inhibitors |
| US9061028B2 (en) | 2012-02-15 | 2015-06-23 | Natco Pharma Limited | Process for the preparation of Nilotinib |
| CA2876539A1 (en) * | 2012-06-15 | 2013-12-19 | Basf Se | Multicomponent crystals comprising dasatinib and selected co-crystal formers |
| GEAP202014833A (en) | 2015-12-18 | 2020-06-25 | Natco Pharma Ltd | Pharmaceutical compositions comprising phenylaminopyrimidine derivative |
| WO2017156350A1 (en) | 2016-03-09 | 2017-09-14 | K-Gen, Inc. | Methods of cancer treatment |
| WO2022016021A1 (en) | 2020-07-15 | 2022-01-20 | Third Harmonic Bio, Inc. | Crystalline forms of a selective c-kit kinase inhibitor |
| EP4247368A4 (en) | 2020-11-19 | 2024-10-23 | Third Harmonic Bio, Inc. | PHARMACEUTICAL COMPOSITIONS OF A SELECTIVE C-KIT KINASE INHIBITOR AND METHODS FOR THE PREPARATION AND USE THEREOF |
| CN113125689B (zh) * | 2021-03-29 | 2022-02-22 | 创芯国际生物科技(广州)有限公司 | 一种新型mtt细胞活力检测试剂盒及其应用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO1999015164A1 (en) * | 1997-09-23 | 1999-04-01 | Zeneca Limited | Amide derivatives for the treatment of diseases mediated by cytokines |
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| TW225528B (https=) | 1992-04-03 | 1994-06-21 | Ciba Geigy Ag | |
| US5516775A (en) | 1992-08-31 | 1996-05-14 | Ciba-Geigy Corporation | Further use of pyrimidine derivatives |
| WO1995009851A1 (en) | 1993-10-01 | 1995-04-13 | Ciba-Geigy Ag | Pharmacologically active pyrimidineamine derivatives and processes for the preparation thereof |
| PT672041E (pt) | 1993-10-01 | 2002-04-29 | Novartis Ag | Derivados da piridina farmacologicamente activos e processos para a sua preparacao |
| WO1995009847A1 (en) | 1993-10-01 | 1995-04-13 | Ciba-Geigy Ag | Pyrimidineamine derivatives and processes for the preparation thereof |
| 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 |
| WO2000007991A1 (en) * | 1998-08-04 | 2000-02-17 | Astrazeneca Ab | Amide derivatives useful as inhibitors of the production of cytokines |
| GB0022438D0 (en) | 2000-09-13 | 2000-11-01 | Novartis Ag | Organic Compounds |
| ES2337995T3 (es) * | 2002-06-28 | 2010-05-03 | Nippon Shinyaku Co., Ltd. | Derivado de amida. |
| GB0222514D0 (en) * | 2002-09-27 | 2002-11-06 | Novartis Ag | Organic compounds |
| AU2003242988A1 (en) * | 2003-06-06 | 2005-01-04 | Adibhatla Kali Sathya Bhujanga Rao | Process for the preparation of the anti-cancer drug imatinib and its analogues |
| ATE454152T1 (de) * | 2003-06-13 | 2010-01-15 | Novartis Pharma Gmbh | 2-aminopyrimidin-derivate als raf-kinase-hemmer |
| AP2470A (en) | 2004-09-09 | 2012-09-17 | Natco Pharma Ltd | Novel phenylaminopyrimidine derivatives as inhibitors of BCR-ABL kinase |
| BRPI0718677A2 (pt) * | 2006-11-03 | 2013-11-26 | Irm Llc | Compostos e composições como inibidores de quinases proteicas |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999015164A1 (en) * | 1997-09-23 | 1999-04-01 | Zeneca Limited | Amide derivatives for the treatment of diseases mediated by cytokines |
Non-Patent Citations (1)
| Title |
|---|
| OGATA M. et aI, Journal of Medicinal Chemistry, vol. 29, no. 3, March 1986, pp 417-423. * |
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