KR102457848B1 - Mk2 억제제 및 이의 용도 - Google Patents
Mk2 억제제 및 이의 용도 Download PDFInfo
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- KR102457848B1 KR102457848B1 KR1020177010439A KR20177010439A KR102457848B1 KR 102457848 B1 KR102457848 B1 KR 102457848B1 KR 1020177010439 A KR1020177010439 A KR 1020177010439A KR 20177010439 A KR20177010439 A KR 20177010439A KR 102457848 B1 KR102457848 B1 KR 102457848B1
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- AHRQYOSAXZQCIG-UHFFFAOYSA-N pyrimidine-5-carbonitrile Chemical compound N#CC1=C=NC=N[CH]1 AHRQYOSAXZQCIG-UHFFFAOYSA-N 0.000 description 1
- IIVUJUOJERNGQX-UHFFFAOYSA-N pyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=CN=CN=C1 IIVUJUOJERNGQX-UHFFFAOYSA-N 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 238000000163 radioactive labelling Methods 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 229940100618 rectal suppository Drugs 0.000 description 1
- 239000006215 rectal suppository Substances 0.000 description 1
- 230000025053 regulation of cell proliferation Effects 0.000 description 1
- 230000014493 regulation of gene expression Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 239000013037 reversible inhibitor Substances 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000019491 signal transduction Effects 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
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 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
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- LYPGDCWPTHTUDO-UHFFFAOYSA-M sodium;methanesulfinate Chemical compound [Na+].CS([O-])=O LYPGDCWPTHTUDO-UHFFFAOYSA-M 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000003206 sterilizing agent Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
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- PDAFIZPRSXHMCO-ZCFIWIBFSA-N tert-butyl n-[(2r)-1-hydroxypropan-2-yl]carbamate Chemical compound OC[C@@H](C)NC(=O)OC(C)(C)C PDAFIZPRSXHMCO-ZCFIWIBFSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000005308 thiazepinyl group Chemical group S1N=C(C=CC=C1)* 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- DBAKEZYZWPGPHH-UHFFFAOYSA-N thieno[3,2-f]quinoline Chemical compound C1=CC=C2C(C=CS3)=C3C=CC2=N1 DBAKEZYZWPGPHH-UHFFFAOYSA-N 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 208000030901 thyroid gland follicular carcinoma Diseases 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
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- 238000002054 transplantation Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
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- 229910052722 tritium Inorganic materials 0.000 description 1
- SZCZSKMCTGEJKI-UHFFFAOYSA-N tuberin Natural products COC1=CC=C(C=CNC=O)C=C1 SZCZSKMCTGEJKI-UHFFFAOYSA-N 0.000 description 1
- 230000006433 tumor necrosis factor production Effects 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical class CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
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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
- C07D495/12—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
-
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Epidemiology (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)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (5)
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|---|---|---|---|
| US201462051788P | 2014-09-17 | 2014-09-17 | |
| US62/051,788 | 2014-09-17 | ||
| US201562199927P | 2015-07-31 | 2015-07-31 | |
| US62/199,927 | 2015-07-31 | ||
| PCT/US2015/050495 WO2016044463A2 (en) | 2014-09-17 | 2015-09-16 | Mk2 inhibitors and uses thereof |
Publications (2)
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| KR20170063734A KR20170063734A (ko) | 2017-06-08 |
| KR102457848B1 true KR102457848B1 (ko) | 2022-10-25 |
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| KR1020177010439A Active KR102457848B1 (ko) | 2014-09-17 | 2015-09-16 | Mk2 억제제 및 이의 용도 |
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| KR20150133172A (ko) | 2013-03-15 | 2015-11-27 | 셀진 아빌로믹스 리서치, 인코포레이티드 | Mk2 억제제 및 이의 용도 |
| SG10201902326XA (en) | 2014-09-17 | 2019-04-29 | Celgene Car Llc | Mk2 inhibitors and uses thereof |
| CN106632077B (zh) * | 2016-10-10 | 2019-01-22 | 上海再启生物技术有限公司 | 一种2-氨基-4-溴嘧啶的制备方法 |
| JP2020511468A (ja) * | 2017-03-16 | 2020-04-16 | セルジーン シーエーアール エルエルシー | Ｍｋ２阻害剤の重水素化アナログおよびその使用 |
| US11124525B2 (en) | 2017-03-16 | 2021-09-21 | Celgene Car Llc | Heteroaryl compounds useful as MK2 inhibitors |
| CA3054826A1 (en) | 2017-03-16 | 2018-09-20 | Celgene Car Llc | Mk2 inhibitors, synthesis thereof, and intermediates thereto |
| CN110678178B (zh) * | 2017-03-16 | 2023-10-03 | 百时美施贵宝公司 | Mk2抑制剂的形式和组合物 |
| JP2020514361A (ja) * | 2017-03-16 | 2020-05-21 | セルジーン シーエーアール エルエルシー | ９，１０，１１，１２−テトラヒドロ−８ｈ−［１，４］ジアゼピノ［５’，６’：４，５］チエノ［３，２−ｆ］キノリン−８−オン化合物およびその使用 |
| CN107058259A (zh) * | 2017-05-18 | 2017-08-18 | 南京中医药大学 | 分子标志物mk2基因及其应用 |
| AU2019351912B2 (en) * | 2018-10-02 | 2025-07-31 | Disc Medicine, Inc. | Matriptase 2 inhibitors and uses thereof |
| WO2020236636A1 (en) * | 2019-05-17 | 2020-11-26 | Celgene Car Llc | Methods of treating a mk2-mediated disorder |
| WO2021163633A1 (en) * | 2020-02-14 | 2021-08-19 | Salk Institute For Biological Studies | Mono and combination therapies with ulk1/2 inhibitors |
| EP4114411A4 (en) * | 2020-03-02 | 2024-04-24 | Washington University | Compositions and methods for the treatment of pancreatic cancer |
| KR20230044446A (ko) * | 2020-07-24 | 2023-04-04 | 브리스톨-마이어스 스큅 컴퍼니 | 급성 호흡기 장애의 치료 방법 |
| CA3201774A1 (en) * | 2020-11-12 | 2022-05-19 | Akttyva Therapeutics, Inc. | Mk2 activating compounds for use in treating vascular leak and endothelial barrier disorders |
| EP4284805A1 (en) * | 2021-02-01 | 2023-12-06 | Celgene Corporation | Mk2 inhibitors, the synthesis thereof, and intermediates thereto |
| EP4079855A1 (en) * | 2021-04-20 | 2022-10-26 | Eberhard Karls Universität Tübingen Medizinische Fakultät | Compound and method for the prophylaxis and treatment of leukemia |
| CN117940433A (zh) * | 2021-08-27 | 2024-04-26 | 瑞石生物医药有限公司 | 喹啉并呋喃衍生物及其用途 |
| AU2023207395A1 (en) | 2022-01-14 | 2024-07-11 | Jiangsu Hansoh Pharmaceutical Group Co., Ltd. | Pyridine-containing polycyclic derivative, and preparation method therefor and use thereof |
| WO2024044731A1 (en) * | 2022-08-26 | 2024-02-29 | Matchpoint Therapeutics Inc. | Diazepino-thieno-quinoxaline compounds and their use in therapy |
| EP4608401A2 (en) * | 2022-10-27 | 2025-09-03 | Bristol-Myers Squibb Company | Mk2 inhibitors and uses thereof |
| EP4661875A1 (en) * | 2023-02-07 | 2025-12-17 | Celgene Corporation | Compounds and compositions useful as degraders of mk2 kinase |
| WO2024229401A2 (en) * | 2023-05-04 | 2024-11-07 | Matchpoint Therapeutics Inc. | Diazepino-thieno-quinoxaline compounds and their use in therapy |
| WO2025002076A1 (zh) * | 2023-06-26 | 2025-01-02 | 深圳信立泰药业股份有限公司 | 一种mk2抑制剂在制备预防和/或治疗疾病药物中的应用 |
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| JP2020514361A (ja) | 2017-03-16 | 2020-05-21 | セルジーン シーエーアール エルエルシー | ９，１０，１１，１２−テトラヒドロ−８ｈ−［１，４］ジアゼピノ［５’，６’：４，５］チエノ［３，２−ｆ］キノリン−８−オン化合物およびその使用 |
| WO2020236636A1 (en) | 2019-05-17 | 2020-11-26 | Celgene Car Llc | Methods of treating a mk2-mediated disorder |
| KR20230044446A (ko) | 2020-07-24 | 2023-04-04 | 브리스톨-마이어스 스큅 컴퍼니 | 급성 호흡기 장애의 치료 방법 |
-
2015
- 2015-09-16 SG SG10201902326XA patent/SG10201902326XA/en unknown
- 2015-09-16 CN CN201580058026.4A patent/CN106998692B/zh active Active
- 2015-09-16 SI SI201531617T patent/SI3193611T1/sl unknown
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| US20130137708A1 (en) | 2010-06-04 | 2013-05-30 | The Regents Of The University Of California | Methods and compositions for kinase inhibition |
| US20140018343A1 (en) | 2012-07-11 | 2014-01-16 | Nimbus Iris, Inc. | Irak inhibitors and uses thereof |
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