Khirsariya, Prashant published the artcileSynthesis and Profiling of Highly Selective Inhibitors of Methyltransferase DOT1L Based on Carbocyclic C-Nucleosides, Safety of 1-(3-((((2R,3S,4R,5R)-5-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)(isopropyl)amino)propyl)-3-(4-(tert-butyl)phenyl)urea, the publication is Journal of Medicinal Chemistry (2022), 65(7), 5701-5723, database is CAplus and MEDLINE.
Histone methyltransferase DOT1L is an attractive therapeutic target for the treatment of hematol. malignancies. Here, we report the design, synthesis, and profiling of new DOT1L inhibitors based on nonroutine carbocyclic C-nucleoside scaffolds. The exptl. observed SAR was found to be nontrivial as seemingly minor changes of individual substituents resulted in significant changes in the affinity to DOT1L. Mol. modeling suggested that these trends could be related to significant conformational changes of the protein upon interaction with the inhibitors. The compounds 22 and (-)-53 (MU1656), carbocyclic C-nucleoside analogs of the natural nucleoside derivative EPZ004777, and the clin. candidate EPZ5676 (pinometostat) potently and selectively inhibit DOT1L in vitro as well as in the cell. The most potent compound MU1656 was found to be more metabolically stable and significantly less toxic in vivo than pinometostat itself.
Journal of Medicinal Chemistry published new progress about 1338466-77-5. 1338466-77-5 belongs to tetrahydrofurans, auxiliary class Epigenetics,Histone Methyltransferase, name is 1-(3-((((2R,3S,4R,5R)-5-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)(isopropyl)amino)propyl)-3-(4-(tert-butyl)phenyl)urea, and the molecular formula is C28H41N7O4, Safety of 1-(3-((((2R,3S,4R,5R)-5-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)(isopropyl)amino)propyl)-3-(4-(tert-butyl)phenyl)urea.
Referemce:
https://en.wikipedia.org/wiki/Tetrahydrofuran,
Tetrahydrofuran | (CH2)3CH2O – PubChem