LLY-283, a Potent and Selective Inhibitor of Arginine Methyltransferase 5, PRMT5, with Antitumor Activity was written by Bonday, Zahid Q.;Cortez, Guillermo S.;Grogan, Michael J.;Antonysamy, Stephen;Weichert, Ken;Bocchinfuso, Wayne P.;Li, Fengling;Kennedy, Steven;Li, Binghui;Mader, Mary M.;Arrowsmith, Cheryl H.;Brown, Peter J.;Eram, Mohammad S.;Szewczyk, Magdalena M.;Barsyte-Lovejoy, Dalia;Vedadi, Masoud;Guccione, Ernesto;Campbell, Robert M.. And the article was included in ACS Medicinal Chemistry Letters in 2018.Safety of ((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol The following contents are mentioned in the article:
Protein arginine methyltransferase 5 (PRMT5) is a type II arginine methyltransferase that catalyzes the formation of sym. dimethylarginine in a number of nuclear and cytoplasmic proteins. Although the cellular functions of PRMT5 have not been fully unraveled, it has been implicated in a number of cellular processes like RNA processing, signal transduction and transcriptional regulation. PRMT5 is ubiquitously expressed in most tissues and its expression has been shown to be elevated in several cancers including breast cancer, gastric cancer, glioblastoma and lymphoma. Here we describe the identification and characterization of a novel and selective PRMT5 inhibitor with potent in vitro and in vivo activity. Compound 1 (also called LLY-283) inhibited PRMT5 enzymic activity in vitro and in cells with IC50 of 22 ± 3 nM and 25 ± 1 nM, resp. while its diastereomer, compound 2 (also called LLY-284) was much less active. Compound 1 also showed antitumor activity in mouse xenografts when dosed orally and can serve as an excellent probe mol. for understanding the biol. function of PRMT5 in normal and cancer cells. This study involved multiple reactions and reactants, such as ((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (cas: 158078-04-7Safety of ((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol).
((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (cas: 158078-04-7) belongs to dioxole derivatives. Dioxoles, particularly fluorinated dioxoles, are used as co-monomers to make polymers that find use in forming protective coatings for chemical resistance. 1,3-Benzodioxole can be synthesized from catechol with disubstituted halomethanes.Safety of ((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol
Referemce:
1,3-Benzodioxole – Wikipedia,
Dioxole | C3H4O2 – PubChem