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
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- 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
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- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
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- 235000002906 tartaric acid Nutrition 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
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- SZCZSKMCTGEJKI-UHFFFAOYSA-N tuberin Natural products COC1=CC=C(C=CNC=O)C=C1 SZCZSKMCTGEJKI-UHFFFAOYSA-N 0.000 description 1
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- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical class CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
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- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical class CCCCC(O)=O NQPDZGIKBAWPEJ-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)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Engineering & Computer Science (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)
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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)
| Publication Number | Publication Date |
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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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| JP2016518316A (ja) | 2013-03-15 | 2016-06-23 | セルジーン アビロミクス リサーチ， インコーポレイテッド | Ｍｋ２阻害剤およびそれらの使用 |
| SMT202100311T1 (it) | 2014-09-17 | 2021-07-12 | Celgene Car Llc | Inibitori di mk2 e loro usi |
| 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 |
| US11098057B2 (en) | 2017-03-16 | 2021-08-24 | Celgene Car Llc | 9,10,11,12-tetrahydro-8H-[1,4]diazepino[5′,6′:4,5]thieno[3,2-F]quinolin-8-one compounds and uses thereof |
| US10894796B2 (en) | 2017-03-16 | 2021-01-19 | Celgene Car Llc | MK2 inhibitors, synthesis thereof, and intermediates thereto |
| WO2018170201A1 (en) | 2017-03-16 | 2018-09-20 | Celgene Car Llc | Deuterated analogs of mk2 inhibitors and uses thereof |
| JP7200120B2 (ja) * | 2017-03-16 | 2023-01-06 | セルジーン シーエーアール エルエルシー | Ｍｋ２阻害剤として有用なヘテロアリール化合物 |
| WO2018170199A1 (en) | 2017-03-16 | 2018-09-20 | Celgene Car Llc | Forms and compositions of a mk2 inhibitor |
| 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 |
| US12428415B2 (en) | 2018-10-02 | 2025-09-30 | Disc Medicine, Inc. | Matriptase 2 inhibitors and uses thereof |
| US20220251105A1 (en) * | 2019-05-17 | 2022-08-11 | Celgene Car Llc | Methods of treating a mk2-mediated disorder |
| JP2023513797A (ja) * | 2020-02-14 | 2023-04-03 | ソーク インスティテュート フォー バイオロジカル スタディーズ | Ｕｌｋ１／２阻害剤による単剤療法および併用療法 |
| EP4114411A4 (en) * | 2020-03-02 | 2024-04-24 | Washington University | Compositions and methods for the treatment of pancreatic cancer |
| US20230255979A1 (en) * | 2020-07-24 | 2023-08-17 | Bristol-Myers Squibb Company | Methods of treating acute respiratory disorders |
| WO2022104097A2 (en) * | 2020-11-12 | 2022-05-19 | Akttyva Therapeutics, Inc. | Mk2 activating compounds for use in treating vascular leak and endothelial barrier disorders |
| TW202246282A (zh) * | 2021-02-01 | 2022-12-01 | 美商西建公司 | Ｍｋ２抑制劑、其合成及其中間體 |
| EP4079855A1 (en) * | 2021-04-20 | 2022-10-26 | Eberhard Karls Universität Tübingen Medizinische Fakultät | Compound and method for the prophylaxis and treatment of leukemia |
| TW202328141A (zh) * | 2021-08-27 | 2023-07-16 | 大陸商瑞石生物醫藥有限公司 | 喹啉并呋喃衍生物及其用途 |
| MX2024008704A (es) | 2022-01-14 | 2024-07-22 | Shanghai Hansoh Biomedical Co Ltd | Derivado policiclico que contiene piridina, y metodo de preparacion de este y uso de este. |
| WO2024044731A1 (en) * | 2022-08-26 | 2024-02-29 | Matchpoint Therapeutics Inc. | Diazepino-thieno-quinoxaline compounds and their use in therapy |
| CN120390642A (zh) * | 2022-10-27 | 2025-07-29 | 百时美施贵宝公司 | Mk2抑制剂及其用途 |
| 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 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Family Cites Families (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5015778A (en) | 1989-12-18 | 1991-05-14 | The Dow Chemical Company | Catalytic method to produce hydroxy substituted arylophenones |
| KR100477070B1 (ko) | 1994-03-25 | 2006-04-21 | 이소테크니카 인코포레이티드 | 중수소화작용에의한의약품의효능강화법 |
| US5441946A (en) | 1994-04-14 | 1995-08-15 | Rhone-Poulenc-Rorer Pharmaceuticals, Inc. | Phosphonate derivatives of lipophilic amines |
| GB9828511D0 (en) * | 1998-12-24 | 1999-02-17 | Zeneca Ltd | Chemical compounds |
| US6861440B2 (en) * | 2001-10-26 | 2005-03-01 | Hoffmann-La Roche Inc. | DPP IV inhibitors |
| TW200413273A (en) | 2002-11-15 | 2004-08-01 | Wako Pure Chem Ind Ltd | Heavy hydrogenation method of heterocyclic rings |
| CN1747949A (zh) | 2002-12-20 | 2006-03-15 | 法马西亚公司 | 无环吡唑化合物 |
| US8362017B2 (en) | 2003-08-29 | 2013-01-29 | Exelixis, Inc. | C-kit modulators and methods of use |
| US20060106020A1 (en) | 2004-04-28 | 2006-05-18 | Rodgers James D | Tetracyclic inhibitors of Janus kinases |
| EP1850681B1 (en) | 2005-02-04 | 2019-12-18 | Firmenich Incorporated | Compounds comprising linked hetero aryl moieties and their use as novel umami flavor modifiers, tastants and taste enhancers for comestible compositions |
| EP1849781A1 (en) | 2006-04-28 | 2007-10-31 | Laboratorios del Dr. Esteve S.A. | Substituted 3-Amino-4-hydroxy pyrrolidines compounds, their preparation and use as medicaments |
| JP2010505961A (ja) | 2006-10-09 | 2010-02-25 | タケダ サン ディエゴ インコーポレイテッド | キナーゼ阻害剤 |
| CA2693904A1 (en) | 2007-07-16 | 2009-01-22 | Novartis Ag | Heterocyclic compounds useful as mk2 inhibitors |
| CA2703203C (en) | 2007-10-22 | 2015-12-15 | Schering Corporation | Bicyclic heterocycle derivatives and methods of use thereof |
| TWI546290B (zh) | 2008-06-27 | 2016-08-21 | 賽基艾維洛米斯研究股份有限公司 | 雜芳基化合物及其用途 |
| US8338439B2 (en) | 2008-06-27 | 2012-12-25 | Celgene Avilomics Research, Inc. | 2,4-disubstituted pyrimidines useful as kinase inhibitors |
| WO2010048149A2 (en) | 2008-10-20 | 2010-04-29 | Kalypsys, Inc. | Heterocyclic modulators of gpr119 for treatment of disease |
| US20110269744A1 (en) * | 2010-03-12 | 2011-11-03 | Astellas Pharma Inc. | Benzazepine Compound |
| EP2508511A1 (en) * | 2011-04-07 | 2012-10-10 | Laboratoire Biodim | Inhibitors of viral replication, their process of preparation and their therapeutical uses |
| EP2511273B8 (en) * | 2011-04-15 | 2019-06-26 | Hivih | Inhibitors of viral replication, their process of preparation and their therapeutical uses |
| JP6396216B2 (ja) | 2012-02-22 | 2018-09-26 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングＭｅｒｃｋ Ｐａｔｅｎｔ Ｇｅｓｅｌｌｓｃｈａｆｔ ｍｉｔ ｂｅｓｃｈｒａｅｎｋｔｅｒ Ｈａｆｔｕｎｇ | 液晶媒体 |
| US9187453B2 (en) * | 2012-03-28 | 2015-11-17 | Takeda Pharmaceutical Company Limited | Heterocyclic compound |
| TW201406758A (zh) * | 2012-06-28 | 2014-02-16 | Daiichi Sankyo Co Ltd | 三環性化合物 |
| AP2015008402A0 (en) * | 2012-09-24 | 2015-04-30 | Claremont Speede | Mobile sender controlled data access and data deletion method and system |
| WO2014050779A1 (ja) * | 2012-09-25 | 2014-04-03 | 第一三共株式会社 | Ｇｓｋ３阻害剤と抗ｄｒ５抗体の組み合わせ |
| WO2014139144A1 (en) | 2013-03-15 | 2014-09-18 | Agios Pharmaceuticals, Inc. | Therapeutic compounds and compositions |
| JP2016518316A (ja) * | 2013-03-15 | 2016-06-23 | セルジーン アビロミクス リサーチ， インコーポレイテッド | Ｍｋ２阻害剤およびそれらの使用 |
| WO2015050957A2 (en) | 2013-10-02 | 2015-04-09 | Treatments For Systemic Lupus Erythematosus | Treatments for systemic lupus erythematosus |
| WO2016032882A1 (en) | 2014-08-25 | 2016-03-03 | Stc.Unm | Inhibition of mk2 in the treatment of cancer |
| SMT202100311T1 (it) | 2014-09-17 | 2021-07-12 | Celgene Car Llc | Inibitori di mk2 e loro usi |
| RU2017128077A (ru) | 2015-01-08 | 2019-02-08 | Мори Матрикс, Инк. | Составы, содержащие пептиды, ингибирующие мк2 |
| JP7200120B2 (ja) | 2017-03-16 | 2023-01-06 | セルジーン シーエーアール エルエルシー | Ｍｋ２阻害剤として有用なヘテロアリール化合物 |
| WO2018170199A1 (en) | 2017-03-16 | 2018-09-20 | Celgene Car Llc | Forms and compositions of a mk2 inhibitor |
| US11098057B2 (en) | 2017-03-16 | 2021-08-24 | Celgene Car Llc | 9,10,11,12-tetrahydro-8H-[1,4]diazepino[5′,6′:4,5]thieno[3,2-F]quinolin-8-one compounds and uses thereof |
| WO2018170201A1 (en) | 2017-03-16 | 2018-09-20 | Celgene Car Llc | Deuterated analogs of mk2 inhibitors and uses thereof |
| US10894796B2 (en) | 2017-03-16 | 2021-01-19 | Celgene Car Llc | MK2 inhibitors, synthesis thereof, and intermediates thereto |
| US20220251105A1 (en) | 2019-05-17 | 2022-08-11 | Celgene Car Llc | Methods of treating a mk2-mediated disorder |
| US20230255979A1 (en) | 2020-07-24 | 2023-08-17 | Bristol-Myers Squibb Company | Methods of treating acute respiratory disorders |
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2015
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- 2015-09-16 EP EP21164056.0A patent/EP3912981A1/en active Pending
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Non-Patent Citations (2)
| Title |
|---|
| Bioorganic & Medicinal Chemistry Letters, 2009, Vol.19, pp.4882-4884. |
| Journal of Medicinal Chemistry, 2012, Vol.55, pp.2035-2047. |
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