CA2855446C - Thienopyrimidine inhibitors of atypical protein kinase c - Google Patents
Thienopyrimidine inhibitors of atypical protein kinase c Download PDFInfo
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- CA2855446C CA2855446C CA2855446A CA2855446A CA2855446C CA 2855446 C CA2855446 C CA 2855446C CA 2855446 A CA2855446 A CA 2855446A CA 2855446 A CA2855446 A CA 2855446A CA 2855446 C CA2855446 C CA 2855446C
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- 239000003112 inhibitor Substances 0.000 title description 3
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- 125000006584 (C3-C10) heterocycloalkyl group Chemical group 0.000 claims description 118
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 102
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- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- MFTKMJCLNKMCEL-UHFFFAOYSA-N phosphinan-1-ium 1-oxide Chemical compound O=[P+]1CCCCC1 MFTKMJCLNKMCEL-UHFFFAOYSA-N 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000000865 phosphorylative effect Effects 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
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- 125000005936 piperidyl group Chemical group 0.000 description 1
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- 238000010837 poor prognosis Methods 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
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- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
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- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
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- 230000035755 proliferation Effects 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical group CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
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- 210000002307 prostate Anatomy 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000002577 pseudohalo group Chemical group 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000006513 pyridinyl methyl group Chemical group 0.000 description 1
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- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000002594 sorbent Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
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- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 1
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- 229940095064 tartrate Drugs 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- AOCSUUGBCMTKJH-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCN AOCSUUGBCMTKJH-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 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
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- OVRJVKCZJCNSOW-UHFFFAOYSA-N thian-4-one Chemical compound O=C1CCSCC1 OVRJVKCZJCNSOW-UHFFFAOYSA-N 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
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- 238000000844 transformation Methods 0.000 description 1
- 238000012301 transgenic model Methods 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/20—Spiro-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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
- C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| US201161563310P | 2011-11-23 | 2011-11-23 | |
| US61/563,310 | 2011-11-23 | ||
| PCT/US2012/065831 WO2013078126A1 (en) | 2011-11-23 | 2012-11-19 | Thienopyrimidine inhibitors of atypical protein kinase c |
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| CA2855446A1 CA2855446A1 (en) | 2013-05-30 |
| CA2855446C true CA2855446C (en) | 2021-04-20 |
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| US (3) | US9604994B2 (en:Method) |
| EP (2) | EP2782917B1 (en:Method) |
| JP (1) | JP6206926B2 (en:Method) |
| CN (1) | CN104053661B (en:Method) |
| AU (2) | AU2012340869B2 (en:Method) |
| CA (1) | CA2855446C (en:Method) |
| ES (1) | ES2575143T3 (en:Method) |
| IL (1) | IL232559B (en:Method) |
| IN (1) | IN2014CN04558A (en:Method) |
| MX (1) | MX355088B (en:Method) |
| WO (1) | WO2013078126A1 (en:Method) |
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| EP2802330A4 (en) * | 2012-01-10 | 2015-10-21 | Nimbus Iris Inc | IRAQ INHIBITORS AND USES THEREOF |
| US9085586B2 (en) | 2012-07-11 | 2015-07-21 | Nimbus Iris, Inc. | IRAK inhibitors and uses thereof |
| HK1210732A1 (en) | 2012-07-11 | 2016-05-06 | Nimbus Iris, Inc. | Irak inhibitors and uses thereof |
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| US9518065B2 (en) | 2013-09-27 | 2016-12-13 | Nimbus Iris, Inc. | IRAK inhibitors and uses thereof |
| TWI675836B (zh) | 2014-03-25 | 2019-11-01 | 美商伊格尼塔公司 | 非典型蛋白質激酶ｃ之氮雜喹唑啉抑制劑 |
| EP3394056B1 (en) * | 2015-12-22 | 2021-04-14 | Shy Therapeutics LLC | Compounds for the treatment of cancer and inflammatory disease |
| TW201813963A (zh) | 2016-09-23 | 2018-04-16 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
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| TW201815787A (zh) | 2016-09-23 | 2018-05-01 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
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| EP3642209B1 (en) * | 2017-06-21 | 2023-11-29 | Shy Therapeutics LLC | Compounds that interact with the ras superfamily for the treatment of cancers, inflammatory diseases, rasopathies, and fibrotic disease |
| WO2019119206A1 (en) | 2017-12-18 | 2019-06-27 | Merck Sharp & Dohme Corp. | Purine inhibitors of human phosphatidylinositol 3-kinase delta |
| CN108658999B (zh) * | 2018-04-24 | 2021-02-05 | 温州大学 | 2-苯基杂环并[2,3-d]嘧啶-4(3H)-酮类化合物的合成方法 |
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| US12246009B2 (en) * | 2018-11-20 | 2025-03-11 | Georgetown University | Compositions and methods for treating neurodegenerative, myodegenerative, and lysosomal storage disorders |
| WO2020132071A1 (en) | 2018-12-19 | 2020-06-25 | Shy Therapeutics. Llc | Compounds that interact with the ras superfamily for the treatment of cancers, inflammatory diseases, rasopathies, and f1brotic disease |
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| CN116410205B (zh) * | 2021-12-29 | 2024-07-05 | 上海皓元生物医药科技有限公司 | 一种3-取代-9-甲基-噻吩并三唑并噁嗪类化合物的制备方法 |
| CN116925098A (zh) * | 2022-04-09 | 2023-10-24 | 深圳湾实验室 | 靶向泛素特异性蛋白酶1(usp1)的小分子抑制剂及其应用 |
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| WO2004111057A1 (en) | 2003-06-11 | 2004-12-23 | Xention Discovery Limited | Thienopyrimidine derivatives as potassium channel inhibitors |
| US20050239806A1 (en) | 2004-01-13 | 2005-10-27 | Ambit Biosciences Corporation | Pyrrolopyrimidine derivatives and analogs and their use in the treatment and prevention of diseases |
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| EP2782917A1 (en) | 2014-10-01 |
| CN104053661A (zh) | 2014-09-17 |
| EP2782917B1 (en) | 2016-03-02 |
| AU2017203725A1 (en) | 2017-06-22 |
| US10954251B2 (en) | 2021-03-23 |
| MX355088B (es) | 2018-04-04 |
| US9604994B2 (en) | 2017-03-28 |
| IL232559B (en) | 2018-04-30 |
| IL232559A0 (en) | 2014-06-30 |
| JP6206926B2 (ja) | 2017-10-04 |
| CN104053661B (zh) | 2018-06-19 |
| US20140323435A1 (en) | 2014-10-30 |
| US20190106433A1 (en) | 2019-04-11 |
| JP2014533728A (ja) | 2014-12-15 |
| CA2855446A1 (en) | 2013-05-30 |
| AU2017203725B2 (en) | 2019-02-28 |
| IN2014CN04558A (en:Method) | 2015-09-18 |
| ES2575143T3 (es) | 2016-06-24 |
| AU2012340869B2 (en) | 2017-03-02 |
| NZ625447A (en) | 2015-09-25 |
| AU2012340869A1 (en) | 2014-06-19 |
| EP3048106B1 (en) | 2019-11-06 |
| US20170158706A1 (en) | 2017-06-08 |
| HK1202529A1 (zh) | 2015-10-02 |
| MX2014006233A (es) | 2014-10-17 |
| WO2013078126A1 (en) | 2013-05-30 |
| US10183950B2 (en) | 2019-01-22 |
| EP3048106A1 (en) | 2016-07-27 |
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