Lim, Ji Woong published the artcileIdentification of crizotinib derivatives as potent SHIP2 inhibitors for the treatment of Alzheimer’s disease, COA of Formula: C8H6ClN, the publication is European Journal of Medicinal Chemistry (2018), 405-422, database is CAplus and MEDLINE.
SH2 domain-containing inositol 5′-phosphatase 2 (SHIP2) is a lipid phosphatase that produces phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) from phosphatidylinositol 3,4,5-triphosphate (PI(3,4,5)P3), and is involved in many diseases such as neurodegenerative diseases. A recent report demonstrating that SHIP2 inhibition decreased tau hyperphosphorylation induced by amyloid β and rescued memory impairment in a transgenic Alzheimer’s disease mouse model indicates SHIP2 can be a promising therapeutic target for Alzheimer’s disease. In the present study, the authors have developed novel, potent SHIP2 inhibitors by extensive structural elaboration of crizotinib discovered from a high-throughput screening. The authors’ representative compound 43 ((R)-5-(5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)pyrimidin-2-amine) potently inhibited SHIP2 activity as well as GSK3β activation in HT22 neuronal cells. It was also shown that 43 has favorable physicochem. properties, especially high brain penetration. Considering SHIP2 is one of key signal mediators for tau hyperphosphorylation, the authors’ potent SHIP2 inhibitor 43 may function as a promising lead compound for the treatment of Alzheimer’s disease.
European Journal of Medicinal Chemistry published new progress about 612-13-5. 612-13-5 belongs to nitriles-buliding-blocks, auxiliary class Organic Pigment, name is 2-(Chloromethyl)benzonitrile, and the molecular formula is C8H6ClN, COA of Formula: C8H6ClN.
Referemce:
https://en.wikipedia.org/wiki/Nitrile,
Nitriles – Chemistry LibreTexts