RU2594742C2 - Макроциклические соединения в качестве ингибиторов киназы trk - Google Patents
Макроциклические соединения в качестве ингибиторов киназы trk Download PDFInfo
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- RU2594742C2 RU2594742C2 RU2012155278/04A RU2012155278A RU2594742C2 RU 2594742 C2 RU2594742 C2 RU 2594742C2 RU 2012155278/04 A RU2012155278/04 A RU 2012155278/04A RU 2012155278 A RU2012155278 A RU 2012155278A RU 2594742 C2 RU2594742 C2 RU 2594742C2
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- Prior art keywords
- fluoro
- compound
- ring
- alkyl
- heptaen
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- AHZBPDSFCYDTDR-HXUWFJFHSA-N tert-butyl n-[3-[4-fluoro-2-[(2r)-1-[3-(hydroxymethyl)pyrazolo[1,5-a]pyrimidin-5-yl]pyrrolidin-2-yl]phenoxy]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCOC1=CC=C(F)C=C1[C@@H]1N(C2=NC3=C(CO)C=NN3C=C2)CCC1 AHZBPDSFCYDTDR-HXUWFJFHSA-N 0.000 description 1
- AMWSEGBTTPQUKW-UHFFFAOYSA-N tert-butyl n-but-3-yn-2-ylcarbamate Chemical compound C#CC(C)NC(=O)OC(C)(C)C AMWSEGBTTPQUKW-UHFFFAOYSA-N 0.000 description 1
- DSPYCWLYGXGJNJ-UHFFFAOYSA-N tert-butyl n-prop-2-ynylcarbamate Chemical compound CC(C)(C)OC(=O)NCC#C DSPYCWLYGXGJNJ-UHFFFAOYSA-N 0.000 description 1
- GXSUQMVJYXMTTC-UQKHFXBCSA-N tert-butyl-[(5r)-5-(5-fluoro-2-methoxyphenyl)pyrrolidin-3-yl]oxy-dimethylsilane;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.COC1=CC=C(F)C=C1[C@@H]1NCC(O[Si](C)(C)C(C)(C)C)C1 GXSUQMVJYXMTTC-UQKHFXBCSA-N 0.000 description 1
- MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 1
- NYBWUHOMYZZKOR-UHFFFAOYSA-N tes-adt Chemical class C1=C2C(C#C[Si](CC)(CC)CC)=C(C=C3C(SC=C3)=C3)C3=C(C#C[Si](CC)(CC)CC)C2=CC2=C1SC=C2 NYBWUHOMYZZKOR-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
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- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
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- 238000012546 transfer Methods 0.000 description 1
- 239000003558 transferase inhibitor Substances 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- KCQKQIRSYUCNMP-QGZVFWFLSA-N triazolo[4,5-b]pyridin-3-yl 5-[(2r)-2-(5-fluoro-2-methoxypyridin-3-yl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidine-3-carboxylate Chemical compound COC1=NC=C(F)C=C1[C@@H]1N(C2=NC3=C(C(=O)ON4C5=NC=CC=C5N=N4)C=NN3C=C2)CCC1 KCQKQIRSYUCNMP-QGZVFWFLSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 102000015533 trkA Receptor Human genes 0.000 description 1
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- 231100000397 ulcer Toxicity 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
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Classifications
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- 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
- C07D487/22—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 four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed systems contains four or more hetero rings
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- 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
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
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- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
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| US201061426716P | 2010-12-23 | 2010-12-23 | |
| US61/426,716 | 2010-12-23 | ||
| PCT/US2011/036452 WO2011146336A1 (en) | 2010-05-20 | 2011-05-13 | Macrocyclic compounds as trk kinase inhibitors |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2708674C2 (ru) * | 2014-12-15 | 2019-12-11 | СиЭмДжи ФАРМАСЬЮТИКАЛ КО., ЛТД. | Конденсированные кольцевые гетероарильные соединения и их применение в качестве ингибиторов trk |
| RU2778294C2 (ru) * | 2018-03-28 | 2022-08-17 | Фочон Байосайенсис, Лтд. | Макроциклические соединения как ингибиторы киназ trk |
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| EP2350075B1 (en) | 2008-09-22 | 2014-03-05 | Array Biopharma, Inc. | Substituted imidazo[1,2b]pyridazine compounds as trk kinase inhibitors |
| KR101853026B1 (ko) | 2008-10-22 | 2018-04-27 | 어레이 바이오파마 인크. | ＴＲＫ 키나아제 억제제로서 치환된 피라졸로［１,５ａ］ 피리미딘 화합물 |
| AR077468A1 (es) | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
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| ES2621220T3 (es) * | 2012-03-06 | 2017-07-03 | Pfizer Inc. | Derivados macrocíclicos para el tratamiento de enfermedades proliferativas |
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