80144-46-3

Upstream product

• 80144-43-0 5-amino-3-(4-methoxy-phenyl)-1H-pyrazole-4-carbonitrile 
• 77287-34-4 formamide 
• 940-00-1 (4-methoxyphenyl)trimethylstannane 
• 83255-86-1 3-bromo-4-aminopyrazolo<3,4-d>pyrimidine 
• 2380-63-4 4-Aminopyrazolo<3,4-d>pyrimidin 
• 5720-07-0 4-methoxyphenylboronic acid 
• 151266-23-8 4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidine 
• 111509-93-4 2-Cyano-3-(4-methoxyphenyl)-3-morpholinoacrylonitrile 
• 6392-01-4 N-(4-methoxy-thiobenzoyl)-morpholine 

Downstream Products

• 1300584-73-9 2-(1-(4-amino-3-(4-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-3-(3-fluorophenyl)-4H-chromen-4-one 

Relevant academic research and scientific papers

Discovery of (S)-2-(1-(4-Amino-3-(3-fluoro-4-methoxyphenyl)-1 H-pyrazolo[3,4- d]pyrimidin-1-yl)propyl)-3-cyclopropyl-5-fluoroquinazolin-4(3 H)-one (IHMT-PI3Kδ-372) as a Potent and Selective PI3KδInhibitor for the Treatment of Chronic Obstructive Pulmonary Disease

Accumulated pieces of evidence have shown that PI3Kδplays a critical role in chronic obstructive pulmonary disease (COPD). Using a fragment-hybrid approach, we discovered a potent and selective PI3Kδinhibitor (S)-18. In the biochemical assay, (S)-18 inhibits PI3Kδ(IC50 = 14 nM) with high selectivity over other class I PI3Ks (56～83 fold). (S)-18 also achieves good selectivity over other protein kinases in the kinome (S-score (35) = 0.015). In the cell, (S)-18 selectively and potently inhibits the PI3Kδ-mediated phosphorylation of AKT T308 but not other class I PI3K-mediated signaling. Additionally, (S)-18 exhibits no apparent inhibitory effect on CYP isoforms except for a moderate effect on CYP2C9. Furthermore, it shows no apparent inhibitory activity against hERG (IC50 > 10 μM). In vivo, (S)-18 displays favorable PK properties for inhaled delivery and improves lung function in a rodent model of pulmonary inflammation. These results suggest that (S)-18 might be a new potential therapeutic candidate for COPD.

1,2-DITHIOLANE COMPOUNDS USEFUL IN NEUROPROTECTION, AUTOIMMUNE AND CANCER DISEASES AND CONDITIONS

This invention provides confounds of the formula (I): wherein Y1, Y2 Z, X1, X2, and W are defined in the specification. These compounds are useful in the treatment of tyrosine kinases, MAPK signaling pathway kinases and Ρ13K/ΑΚΤ/mTor signaling pathway kinases-mediated diseases; or conditions, such as neurodegeneration, neuroprotection, cancer, autoimmune as well as other diseases and conditions associated with the modulation of tyrosine kinases selected from FYN, FYN Y531F, FLT3, FLT3 -ITD, BRK, ITK, FRK, BTK, BMX, SRC, FGR, YES1, LCK, HCK, RET, CSK, LYN, and ROSI; MAPK pathway kinases selected from ARAF, BRAE CRAP, ERK1 /2, MEK1, MEK2, MEK3, MEK4, MEK5. MEK6, and MEK7; and P13K/AKT/mTor pathway kinases: selected from mTor, P13K a, Ρ13Κ β, P13Kγ, and P13K δ.

With the biological activity of the pyrazolo [3, 4 - d] pyrimidines reagent synthesis process (by machine translation)

The invention relates to a novel pyrazole and having biological activity [3, 4 - d] pyrimidines reagent synthesis process, comprising the following steps: step a, first the compound (1) with the brominating reaction, forming compound (2), then in the presence of a catalyst under the condition of R - SnMe with3 Reaction, to obtain compound (3); the second step, the compound (3) with compound (4) in the toluene solvent in heating to carry out the reaction, to obtain compound (5); step three, the compound (5) is dissolved in DMF, temperature, then adding potassium carbonate, different uncle butyl-bromide and organic acid salt, can be. The present invention provides a process for synthesizing a last step in the introduction of a branch chain alkanes in the yield of 82% above, improves the 4 - amino substituent of the existence of the pyrazolo (3, 4 - d) pyrimidine introduction efficiency of the branched alkane, is applied to the new pyrazolo (3, 4 - d) pyrimidine derivatives of the large-scale synthesis. (by machine translation)

NOVEL KINASE MODULATORS

The present invention provides PI3K protein kinase modulators, methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and/or amelioration of kinase mediated diseases or disorders with them.

Polarized Ethylenes. IV. Synthesis of Polarized Ethylenes Using Thioamides and Methyl Dithiocarboxylates and their Application to Syntheses of Pyrazoles, Pyrimidines, Pyrazolopyrimidines, and 5-Azacyclazines

Polarized ethylenes having both electron-donating (an amino or a methylthio group) and electron-accepting (cyano, carbamoyl, methyl ester) groups on the adjacent two olefinic carbon atoms were prepared by the condensation of S-alkylthioamidinium salts or