RU2631655C2 - Пирролопиримидиновые соединения для лечения злокачественной опухоли - Google Patents
Пирролопиримидиновые соединения для лечения злокачественной опухоли Download PDFInfo
- Publication number
- RU2631655C2 RU2631655C2 RU2014115847A RU2014115847A RU2631655C2 RU 2631655 C2 RU2631655 C2 RU 2631655C2 RU 2014115847 A RU2014115847 A RU 2014115847A RU 2014115847 A RU2014115847 A RU 2014115847A RU 2631655 C2 RU2631655 C2 RU 2631655C2
- Authority
- RU
- Russia
- Prior art keywords
- alkyl
- group
- mmol
- nrarb
- pyrrolo
- Prior art date
Links
- 201000011510 cancer Diseases 0.000 title claims abstract description 18
- 150000004944 pyrrolopyrimidines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 79
- 150000003839 salts Chemical class 0.000 claims abstract description 36
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 23
- 125000001424 substituent group Chemical group 0.000 claims abstract description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 11
- 125000005647 linker group Chemical group 0.000 claims abstract description 10
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 9
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 6
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 5
- 239000001257 hydrogen Substances 0.000 claims abstract description 5
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- 210000004556 brain Anatomy 0.000 claims abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 3
- 210000001072 colon Anatomy 0.000 claims abstract description 3
- 210000003734 kidney Anatomy 0.000 claims abstract description 3
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- 208000003747 lymphoid leukemia Diseases 0.000 claims abstract description 3
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- 125000005843 halogen group Chemical group 0.000 claims abstract 4
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- 125000000217 alkyl group Chemical group 0.000 claims description 48
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
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- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims 1
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- 125000001188 haloalkyl group Chemical group 0.000 description 6
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- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 3
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- SGNKPJPMWHKOJO-UHFFFAOYSA-N tert-butyl n-[4-(hydroxymethyl)cyclohexyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(CO)CC1 SGNKPJPMWHKOJO-UHFFFAOYSA-N 0.000 description 1
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- OJQMVCWHPJTGRO-UHFFFAOYSA-N tert-butyl-[4-(2-chloro-5-tritylpyrrolo[3,2-d]pyrimidin-7-yl)cyclohex-3-en-1-yl]oxy-dimethylsilane Chemical compound C1C(O[Si](C)(C)C(C)(C)C)CCC(C=2C3=NC(Cl)=NC=C3N(C=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 OJQMVCWHPJTGRO-UHFFFAOYSA-N 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- 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
- C07D487/12—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 three hetero rings
- C07D487/18—Bridged systems
-
- 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
-
- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
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- General Chemical & Material Sciences (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161542392P | 2011-10-03 | 2011-10-03 | |
| US61/542,392 | 2011-10-03 | ||
| US201161547183P | 2011-10-14 | 2011-10-14 | |
| US61/547,183 | 2011-10-14 | ||
| PCT/US2012/058298 WO2013052417A1 (en) | 2011-10-03 | 2012-10-01 | Pyrrolopyrimidine compounds for the treatment of cancer |
Publications (2)
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| RU2014115847A RU2014115847A (ru) | 2015-11-10 |
| RU2631655C2 true RU2631655C2 (ru) | 2017-09-26 |
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| RU2014115847A RU2631655C2 (ru) | 2011-10-03 | 2012-10-01 | Пирролопиримидиновые соединения для лечения злокачественной опухоли |
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| US (3) | US9273056B2 (https=) |
| EP (1) | EP2763988B1 (https=) |
| JP (2) | JP2014532060A (https=) |
| KR (1) | KR102063098B1 (https=) |
| CN (1) | CN103958510B (https=) |
| AU (1) | AU2012318896B2 (https=) |
| BR (1) | BR112014007788A2 (https=) |
| CA (1) | CA2850617A1 (https=) |
| ES (1) | ES2650630T3 (https=) |
| IL (1) | IL231835A0 (https=) |
| MX (1) | MX2014004086A (https=) |
| RU (1) | RU2631655C2 (https=) |
| WO (1) | WO2013052417A1 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| RU2829484C2 (ru) * | 2016-09-16 | 2024-10-30 | ВИТЭ ФАРМАСЬЮТИКАЛЗ, ЭлЭлСи | Ингибиторы взаимодействия менин-mll |
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| WO2011146313A1 (en) | 2010-05-19 | 2011-11-24 | The University Of North Carolina At Chapel Hill | Pyrazolopyrimidine compounds for the treatment of cancer |
| BR112014007788A2 (pt) | 2011-10-03 | 2017-04-18 | Univ North Carolina Chapel Hill | compostos de pirrolopirimidina para tratamento do câncer |
| CN104302627A (zh) | 2012-05-22 | 2015-01-21 | 北卡罗来纳大学教堂山分校 | 用于治疗癌症的嘧啶化合物 |
| CA2879542A1 (en) | 2012-07-25 | 2014-01-30 | Salk Institute For Biological Studies | Regulating the interaction between tam ligands and lipid membranes with exposed phosphatidylserine |
| WO2014062774A1 (en) | 2012-10-17 | 2014-04-24 | The University Of North Carolina At Chapel Hill | Pyrazolopyrimidine compounds for the treatment of cancer |
| US9771330B2 (en) | 2012-11-27 | 2017-09-26 | The University Of North Carolina At Chapel Hill | Pyrimidine compounds for the treatment of cancer |
| US20150291606A1 (en) | 2014-04-11 | 2015-10-15 | The University Of North Carolina At Chapel Hill | Mertk-specific pyrrolopyrimidine compounds |
| CN106188060A (zh) * | 2015-04-29 | 2016-12-07 | 厦门大学 | 嘧啶并吡咯类化合物、其制备方法、药用组合物及其应用 |
| US9840503B2 (en) | 2015-05-11 | 2017-12-12 | Incyte Corporation | Heterocyclic compounds and uses thereof |
| WO2017027717A1 (en) * | 2015-08-12 | 2017-02-16 | Incyte Corporation | Bicyclic fused pyrimidine compounds as tam inhibitors |
| US10053465B2 (en) | 2015-08-26 | 2018-08-21 | Incyte Corporation | Pyrrolopyrimidine derivatives as TAM inhibitors |
| WO2017062797A1 (en) * | 2015-10-07 | 2017-04-13 | The University Of North Carolina At Chapel Hill | The methods for treatment of tumors |
| US10709708B2 (en) | 2016-03-17 | 2020-07-14 | The University Of North Carolina At Chapel Hill | Method of treating cancer with a combination of MER tyrosine kinase inhibitor and an epidermal growth factor receptor (EGFR) inhibitor |
| MD3436461T2 (ro) | 2016-03-28 | 2024-05-31 | Incyte Corp | Compuși pirolotriazină ca inhibitori TAM |
| US10899758B2 (en) * | 2016-09-16 | 2021-01-26 | Vitae Pharmaceuticals, Llc | Inhibitors of the menin-MLL interaction |
| JP2020502062A (ja) | 2016-11-17 | 2020-01-23 | ザ ユニバーシティ オブ ノース カロライナ アット チャペル ヒル | アルキルピロロピリミジン類似体、及びその製造方法と使用方法 |
| SI3687996T1 (sl) | 2017-09-27 | 2022-04-29 | Incyte Corporation | Soli pirolotriazinskih derivatov, ki so uporabne kot zaviralci TAM |
| US11247990B1 (en) | 2017-12-07 | 2022-02-15 | Array Biopharma Inc | Bicyclic fused pyridine compounds as inhibitors of TAM kinases |
| AU2018397483A1 (en) * | 2017-12-28 | 2020-08-13 | Development Center For Biotechnology | Heterocycle compounds as Tyro3, Axl and Mertk (TAM) family of receptor tyrosine kinase inhibitors |
| MD3813800T2 (ro) | 2018-06-29 | 2025-10-31 | Incyte Corp | Formulări de inhibitor al AXL/MER |
| KR102163494B1 (ko) * | 2018-10-26 | 2020-10-08 | 한국과학기술연구원 | 단백질 키나아제 저해제인 헤테로방향족 매크로시클릭 유도체 |
| CA3146343A1 (en) * | 2019-04-02 | 2020-10-08 | Meryx, Inc. | Polymorphs of a kinase inhibitor, pharmaceutical compositions containing such a compound, preparation methods, and applications |
| EP4114401A1 (en) | 2020-03-06 | 2023-01-11 | Incyte Corporation | Combination therapy comprising axl/mer and pd-1/pd-l1 inhibitors |
| CN112043710A (zh) * | 2020-09-28 | 2020-12-08 | 广州智睿医药科技有限公司 | 一种治疗或预防与lrrk2激酶或异常lrrk2突变激酶活性相关疾病的药物 |
| CN115073469B (zh) * | 2021-03-15 | 2023-12-22 | 药雅科技(上海)有限公司 | 吡咯并嘧啶类化合物作为激酶抑制剂的制备及其应用 |
| WO2025170773A1 (en) * | 2024-01-26 | 2025-08-14 | The University Of North Carolina At Chapel Hill | Tam-family degraders and uses thereof |
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- 2012-10-01 ES ES12839069.7T patent/ES2650630T3/es active Active
- 2012-10-01 KR KR1020147010156A patent/KR102063098B1/ko active Active
- 2012-10-01 WO PCT/US2012/058298 patent/WO2013052417A1/en not_active Ceased
- 2012-10-01 CA CA2850617A patent/CA2850617A1/en not_active Abandoned
- 2012-10-01 MX MX2014004086A patent/MX2014004086A/es unknown
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- 2012-10-01 US US14/348,805 patent/US9273056B2/en active Active
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| RU2829484C2 (ru) * | 2016-09-16 | 2024-10-30 | ВИТЭ ФАРМАСЬЮТИКАЛЗ, ЭлЭлСи | Ингибиторы взаимодействия менин-mll |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103958510A (zh) | 2014-07-30 |
| EP2763988B1 (en) | 2017-09-20 |
| WO2013052417A1 (en) | 2013-04-11 |
| AU2012318896B2 (en) | 2017-03-02 |
| KR102063098B1 (ko) | 2020-01-08 |
| ES2650630T3 (es) | 2018-01-19 |
| AU2012318896A1 (en) | 2014-05-22 |
| US10179133B2 (en) | 2019-01-15 |
| RU2014115847A (ru) | 2015-11-10 |
| JP2017101043A (ja) | 2017-06-08 |
| US20160151372A1 (en) | 2016-06-02 |
| JP2014532060A (ja) | 2014-12-04 |
| US9795606B2 (en) | 2017-10-24 |
| KR20140095471A (ko) | 2014-08-01 |
| HK1201256A1 (en) | 2015-08-28 |
| US20140243315A1 (en) | 2014-08-28 |
| JP6316925B2 (ja) | 2018-04-25 |
| EP2763988A4 (en) | 2015-06-03 |
| IL231835A0 (en) | 2014-05-28 |
| US20180104247A1 (en) | 2018-04-19 |
| MX2014004086A (es) | 2014-09-22 |
| BR112014007788A2 (pt) | 2017-04-18 |
| CA2850617A1 (en) | 2013-04-11 |
| EP2763988A1 (en) | 2014-08-13 |
| US9273056B2 (en) | 2016-03-01 |
| CN103958510B (zh) | 2016-10-19 |
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