115378-33-1Relevant articles and documents
Discovery of DS79932728: A Potent, Orally Available G9a/GLP Inhibitor for Treating β-Thalassemia and Sickle Cell Disease
Katayama, Katsushi,Ishii, Ken,Terashima, Hideki,Tsuda, Eisuke,Suzuki, Makoto,Yotsumoto, Keiichi,Hiramoto, Kumiko,Yasumatsu, Isao,Torihata, Munefumi,Ishiyama, Takashi,Muto, Tsuyoshi,Katagiri, Takahiro
, p. 121 - 128 (2021)
Therapeutic reactivation of the γ-globin genes for fetal hemoglobin (HbF) production is an attractive strategy for treating β-thalassemia and sickle cell disease. It was reported that genetic knockdown of the histone lysine methyltransferase EHMT2/1 (G9a/GLP) is sufficient to induce HbF production. The aim of the present work was to acquire a G9a/GLP inhibitor that induces HbF production sufficiently. It was revealed that tetrahydroazepine has versatility as a side chain in various skeletons. We ultimately obtained a promising aminoindole derivative (DS79932728), a potent and orally bioavailable G9a/GLP inhibitor that was found to induce γ-globin production in a phlebotomized cynomolgus monkey model. This work could facilitate the development of effective new approaches for treating β-thalassemia and sickle cell disease.
AMINO SULFONYL COMPOUNDS
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Paragraph 0397-0398, (2018/06/12)
Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.
Synthesis of chiral, enantiopure allylic amines by the Julia olefination of α-amino esters
Benedetti, Fabio,Berti, Federico,Fanfoni, Lidia,Garbo, Michele,Regini, Giorgia,Felluga, Fulvia
, (2016/07/06)
The four-step conversion of a series of N-Boc-protected L-amino acid methyl esters into enantiopure N-Boc allylamines by a modified Julia olefination is described. Key steps include the reaction of a lithiated phenylalkylsulfone with amino esters, giving chiral β-ketosulfones, and the reductive elimination of related α-acetoxysulfones. The overall transformation takes place under mild conditions, with good yields, and without loss of stereochemical integrity, being in this respect superior to the conventional Julia reaction of α-amino aldehydes.