36847-11-7Relevant articles and documents
AMINE-SUBSTITUTED ARYL OR HETEROARYL COMPOUNDS AS EHMT1 AND EHMT2 INHIBITORS
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Paragraph 01122-01124, (2017/11/10)
The present disclosure relates to amine-substituted aryl or heteroaryl compounds. The present disclosure also relates to pharmaceutical compositions containing these compounds and methods of treating a disorder (e.g., sickle cell anemia) via inhibition of a methyltransferase enzyme selected from EHMT1 and EHMT2, by administering an amine-substituted aryl or heteroaryl compound disclosed herein or a pharmaceutical composition thereof to subjects in need thereof. The present disclosure also relates to the use of such compounds for research or other non-therapeutic purposes.
Identification of NVP-BKM120 as a potent, selective, orally bioavailable class i PI3 kinase inhibitor for treating cancer
Burger, Matthew T.,Pecchi, Sabina,Wagman, Allan,Ni, Zhi-Jie,Knapp, Mark,Hendrickson, Thomas,Atallah, Gordana,Pfister, Keith,Zhang, Yanchen,Bartulis, Sarah,Frazier, Kelly,Ng, Simon,Smith, Aaron,Verhagen, Joelle,Haznedar, Joshua,Huh, Kay,Iwanowicz, Ed,Xin, Xiaohua,Menezes, Daniel,Merritt, Hanne,Lee, Isabelle,Wiesmann, Marion,Kaufman, Susan,Crawford, Kenneth,Chin, Michael,Bussiere, Dirksen,Shoemaker, Kevin,Zaror, Isabel,Maira, Sauveur-Michel,Voliva, Charles F.
supporting information; experimental part, p. 774 - 779 (2011/12/03)
Phosphoinositide-3-kinases (PI3Ks) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein we describe the structure guided optimization of a series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines where the pharmacokinetic properties were improved by modulating the electronics of the 6-position heterocycle, and the overall druglike properties were fine-tuned further by modification of the 4-position substituent. The resulting 2,4-bismorpholino 6-heterocyclic pyrimidines are potent class I PI3K inhibitors showing mechanism modulation in PI3K dependent cell lines and in vivo efficacy in tumor xenograft models with PI3K pathway deregulation (A2780 ovarian and U87MG glioma). These efforts culminated in the discovery of 15 (NVP-BKM120), currently in Phase II clinical trials for the treatment of cancer.
Total synthesis of (-)-7-epicylindrospermopsin, a toxic metabolite of the freshwater cyanobacterium Aphanizomenon ovalisporum, and assignment of its absolute configuration
White, James D.,Hansen, Joshua D.
, p. 1963 - 1977 (2007/10/03)
(Chemical Equation Presented) The Z and E nitrones 38 and 39 from condensation of aldehyde 20 with hydroxylamine 36 underwent intramolecular dipolar cycloaddition to give the substituted 1-aza-7-oxobicyclo[2.2.1] heptanes 40 and 41 in a ratio of 2:1, respectively. Reductive N-O bond cleavage of 40 followed by carbonylation gave cyclic urea 47 in which inversion of the secondary alcohol was effected via an oxidation-reduction sequence. After conversion of the p-bromobenzyl ether 50 to azide 54, activation of the cyclic urea as its O-methylisourea and reduction of the azide led to spontaneous cyclization to afford the tricyclic nucleus 59 of cylindrospermopsin. Global deprotection, including hydrolysis of the 2,4-dimethyoxypyrimidine appendage to a uracil, and then monosulfation of the resultant diol 60 afforded a substance identical with natural (-)-7-epicylindrospermopsin (1). The asymmetric synthesis of (-)-7-epicylindrospermopsin defines its absolute configuration as 7S,8R,10S,12S,13R,14S.
