CN109963844B - 一类抑制并降解酪氨酸蛋白激酶alk的化合物 - Google Patents
一类抑制并降解酪氨酸蛋白激酶alk的化合物 Download PDFInfo
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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
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- QAHVHSLSRLSVGS-UHFFFAOYSA-N sulfamoyl chloride Chemical compound NS(Cl)(=O)=O QAHVHSLSRLSVGS-UHFFFAOYSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229940088801 thalidomide 100 mg Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- UAEJRRZPRZCUBE-UHFFFAOYSA-N trimethoxyalumane Chemical compound [Al+3].[O-]C.[O-]C.[O-]C UAEJRRZPRZCUBE-UHFFFAOYSA-N 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- 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
-
- 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
- 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
Abstract
Description
化合物编号 | 抑制率 | 化合物编号 | 抑制率 |
3 | 98% | 14 | 89% |
7 | 97% | 15 | 95% |
10 | 99% | 45 | 98% |
13 | 69% |
化合物编号 | 抑制率(%) | 化合物编号 | 抑制率(%) |
3 | 72 | 15 | 100 |
7 | 98 | 45 | 97 |
14 | 99 |
Claims (4)
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CN2017107830670 | 2017-09-03 | ||
CN201710783067.0A CN109422733A (zh) | 2017-09-03 | 2017-09-03 | 一类抑制并降解酪氨酸蛋白激酶alk的化合物 |
PCT/CN2018/103709 WO2019042444A1 (zh) | 2017-09-03 | 2018-09-02 | 一类抑制并降解酪氨酸蛋白激酶alk的化合物 |
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CN109963844A CN109963844A (zh) | 2019-07-02 |
CN109963844B true CN109963844B (zh) | 2022-08-12 |
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CN201880004044.8A Active CN109963844B (zh) | 2017-09-03 | 2018-09-02 | 一类抑制并降解酪氨酸蛋白激酶alk的化合物 |
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US (1) | US11485726B2 (zh) |
CN (2) | CN109422733A (zh) |
WO (1) | WO2019042444A1 (zh) |
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US11458123B2 (en) | 2016-11-01 | 2022-10-04 | Arvinas Operations, Inc. | Tau-protein targeting PROTACs and associated methods of use |
JP2021521192A (ja) * | 2018-04-13 | 2021-08-26 | アルビナス・オペレーションズ・インコーポレイテッドArvinas Operations, Inc. | セレブロンリガンドおよび同リガンドを含む二機能性化合物 |
CN110684015A (zh) * | 2018-07-06 | 2020-01-14 | 四川大学 | 靶向alk的protac及其应用 |
JP7297053B2 (ja) | 2018-08-20 | 2023-06-23 | アルビナス・オペレーションズ・インコーポレイテッド | 神経変性疾患を治療するためのe3ユビキチンリガーゼ結合活性を有するキメラ(protac)化合物を標的とし、アルファ-シヌクレインタンパク質を標的とするタンパク質分解 |
WO2020249048A1 (zh) * | 2019-06-12 | 2020-12-17 | 上海科技大学 | Alk蛋白调节剂及其抗肿瘤应用 |
JP2022546375A (ja) * | 2019-08-23 | 2022-11-04 | 北京泰徳製薬股▲フン▼有限公司 | Egfrおよびalkを阻害してそれらの分解を阻害する化合物 |
US20230265116A1 (en) * | 2020-07-16 | 2023-08-24 | Beigene, Ltd. | Degradation of (egfr) by conjugation of egfr inhibitors with e3 ligase ligand and methods of use |
CN111892578B (zh) * | 2020-08-03 | 2023-10-20 | 沈阳药科大学 | 一种靶向降解黏着斑激酶的化合物及应用 |
CN114478532A (zh) * | 2020-10-26 | 2022-05-13 | 上海美志医药科技有限公司 | 靶向降解Btk的化合物及其抗肿瘤用途 |
WO2022171123A1 (en) * | 2021-02-10 | 2022-08-18 | Beigene, Ltd. | Egfr degraders and methods of use |
CN116940581A (zh) * | 2021-05-19 | 2023-10-24 | 和径医药科技(上海)有限公司 | 一类新型蛋白降解剂及其应用 |
IL309528A (en) * | 2021-06-21 | 2024-02-01 | Beigene Switzerland Gmbh | (R)-glutrimide CRBN ligands and methods of use |
CN117203216A (zh) | 2021-06-25 | 2023-12-08 | 和径医药科技(上海)有限公司 | 蛋白抑制剂或降解剂、包含其的药物组合物及医药上的用途 |
CN113735828B (zh) * | 2021-09-07 | 2022-10-28 | 南方医科大学 | 一种靶向降解egfr的化合物及其制备方法和应用 |
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US11485726B2 (en) | 2022-11-01 |
WO2019042444A1 (zh) | 2019-03-07 |
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CN109963844A (zh) | 2019-07-02 |
US20200199106A1 (en) | 2020-06-25 |
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