761446-44-0Relevant academic research and scientific papers
Efficient salt-induced kinase inhibitor and preparation method thereof
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Paragraph 0184-0186, (2021/09/04)
The invention discloses an efficient salt-induced kinase inhibitor and a preparation method thereof, and the efficient salt-induced kinase inhibitor is characterized by comprising substances of a chemical formula in the invention. The salt-induced kinase inhibitor with excellent performance has high inhibitory activity for in-vitro experiments and also has high cell inhibitory activity.
AMINOPYRAZINE COMPOUNDS AS HPK1 INHIBITOR AND THE USE THEREOF
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Page/Page column 94, (2021/02/26)
Disclosed herein is an aminopyrazine compound of Formula (I), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and pharmaceutical compositions comprising thereof. Also disclosed is a method of treating HPK1 related disorders or diseases by using the compound disclosed herein.
IMPROVED METHOD FOR THE MANUFACTURE OF 3-[(1S)-1-IMIDAZO[1,2-A]PYRIDIN-6-YLETHYL]-5-(1-METHYLPYRAZOL-4-YL)TRIAZOLO[4,5-B]PYRAZINE AND POLYMORPHIC FORMS THEREOF
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Page/Page column 28-29, (2020/05/07)
This specification generally relates to an improved method for the manufacture of 3-[(lS)-l -imidazo[ 1,2-a]pyridin-6-ylethyl]-5-(l-methylpyrazol-4-yl)triazolo[4,5- bjpyrazine (I), or pharmaceutically acceptable salts thereof; polymorphic forms thereof; and intermediates useful in the manufacture of such compounds and salts thereof. Formula (I).
C-H Borylation Catalysts that Distinguish between Similarly Sized Substituents like Fluorine and Hydrogen
Miller, Susanne L.,Chotana, Ghayoor A.,Fritz, Jonathan A.,Chattopadhyay, Buddhadeb,Maleczka, Robert E.,Smith, Milton R.
supporting information, p. 6388 - 6392 (2019/08/26)
By modifying ligand steric and electronic profiles it is possible to C-H borylate ortho or meta to substituents in aromatic and heteroaromatic compounds, where steric differences between accessible C-H sites are small. Dramatic effects on selectivities between reactions using B2pin2 or 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (HBpin) are described for the first time. Judicious ligand and borane combinations give highly regioselective C-H borylations on substrates where typical borylation protocols afford poor selectivities.
Discovery of Potent and Orally Effective Dual Janus Kinase 2/FLT3 Inhibitors for the Treatment of Acute Myelogenous Leukemia and Myeloproliferative Neoplasms
Yang, Tao,Hu, Mengshi,Qi, Wenyan,Yang, Zhuang,Tang, Minghai,He, Jun,Chen, Yong,Bai, Peng,Yuan, Xue,Zhang, Chufeng,Liu, Kongjun,Lu, Yulin,Xiang, Mingli,Chen, Lijuan
, p. 10305 - 10320 (2019/11/19)
Herein, we describe the design, synthesis, and structure-activity relationships of a series of unique 4-(1H-pyrazol-4-yl)-pyrimidin-2-amine derivatives that selectively inhibit Janus kinase 2 (JAK2) and FLT3 kinases. These screening cascades revealed that 18e was a preferred compound, with IC50 values of 0.7 and 4 nM for JAK2 and FLT3, respectively. Moreover, 18e was a potent JAK2 inhibitor with 37-fold and 56-fold selectivity over JAK1 and JAK3, respectively, and possessed an excellent selectivity profile over the other 100 representative kinases. In a series of cytokine-stimulated cell-based assays, 18e exhibited a higher JAK2 selectivity over other JAK isoforms. The oral administration of 60 mg/kg of 18e could significantly inhibit tumor growth, with a tumor growth inhibition rate of 93 and 85% in MV4-11 and SET-2 xenograft models, respectively. Additionally, 18e showed an excellent bioavailability (F = 58%), a suitable half-life time (T1/2 = 4.1 h), a satisfactory metabolic stability, and a weak CYP3A4 inhibitory activity, suggesting that 18e might be a potential drug candidate for JAK2-driven myeloproliferative neoplasms and FLT3-internal tandem duplication-driven acute myelogenous leukemia.
Method for preparing aryl boronate at room temperature
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Paragraph 0020-0022; 0049-0051; 0081-0083, (2019/05/11)
The invention discloses a method for preparing aryl boronate represented by a formula I at a room temperature. The method comprises: carrying out a reaction on a diboron compound represented by a formula II and an aryl halide in an organic solvent for 0.5-8 h at a room temperature under the actions of an alkali, a chloro(2-dicyclohexylphosphino-2',4',6'-tri-isopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium (II) catalyst and a 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl ligand, and carrying out post-treatment to obtain the corresponding aryl boronate. According to the present invention, the method has characteristics of mild reaction conditions, simple operation, wide application range, good compatibility with various functional groups on aryl, high efficiency and economy, can achieve high yield of aryl borate under normal pressure and normal pressure conditions, and is suitable for large-scale preparation of aryl borate. The formulas I and II are defined in the specification, wherein R' represents any one selected from phenyl with substituent, pyridyl, thienyl, indyl, pyrazolyl and naphthyl.
Preparation method of pyrazol compound
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Paragraph 0037-0043; 0046-0051; 0053-0058; 0080-0086, (2019/01/14)
The invention belongs to the technical field of organic synthesis, particularly relates to a preparation method of a pyrazol compound, in more particular to a preparation method of 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxapentaborane-2-yl)-1H-pyrazol. The preparation method of the 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxapentaborane-2-yl)-1H-pyrazol comprises the following steps of by taking tetrahydrofuran and 1-methyl-4-bromo-pyrazol as raw materials, and performing reaction with triisopropyl borate and pinacol to prepare the 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxapentaborane-2-yl)-1H-pyrazol. The preparation method is liable in operation of the whole reaction process, available in raw material, low in cost and high in purity and yield of products.
SUBSTITUTED BICYCLE HETEROCYCLIC DERIVATIVES USEFUL AS ROMK CHANNEL INHIBITORS
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Page/Page column 189, (2018/06/06)
Disclosed are compounds of Formula (I) or a salt thereof, wherein R1 is (II) or (III); each W is independently NR1b or O; Z is a bond or CHR1d; and R1, R2, Rd, R3, L1, L2, R1a, R1b, R1c, and n are define herein. Also disclosed are methods of using such compounds as inhibitors of ROMK, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating cardiovascular diseases.
Preparation and application of novel purine analogue JAK (janus kinase) inhibitor
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Paragraph 0155; 0156; 0157; 0159, (2018/09/21)
The invention provides medicine for preventing, treating and/or relieving autoimmunity diseases such as Psoriasis, rheumatoid arthritis, inflammatory enteritis diseases, sjogren's syndrome, behcet's diseases, multiple sclerosis and systemic lupus erythematosus. The medicine has excellent JAK inhibitory activity. The invention also provides a medically acceptable composition containing the compoundand a method for preparing the compound.
Room-temperature borylation and one-pot two-step borylation/Suzuki-Miyaura cross-coupling reaction of aryl chlorides
Ji, Hong,Wu, Li-Yang,Cai, Jiang-Hong,Li, Guo-Rong,Gan, Na-Na,Wang, Zhao-Hua
, p. 13643 - 13648 (2018/04/24)
A highly efficient room-temperature borylation strategy of aryl chlorides is described. Utilizing Buchwald's second-generation preformed catalyst, boronate esters were obtained for a wide range of substrates in high yield. The method was also applied to Suzuki-Miyaura cross-coupling reaction in a one-pot two-step sequential manner, providing a facile and convenient access to the direct synthesis of biaryl compounds from aryl chlorides.
