947249-41-4Relevant articles and documents
A Conformational Restriction Strategy for the Identification of a Highly Selective Pyrimido-pyrrolo-oxazine mTOR Inhibitor
Borsari, Chiara,Rageot, Denise,Dall'Asen, Alix,Bohnacker, Thomas,Melone, Anna,Sele, Alexander M.,Jackson, Eileen,Langlois, Jean-Baptiste,Beaufils, Florent,Hebeisen, Paul,Fabbro, Doriano,Hillmann, Petra,Wymann, Matthias P.
, p. 8609 - 8630 (2019/10/16)
The mechanistic target of rapamycin (mTOR) plays a pivotal role in growth and tumor progression and is an attractive target for cancer treatment. ATP-competitive mTOR kinase inhibitors (TORKi) have the potential to overcome limitations of rapamycin derivatives in a wide range of malignancies. Herein, we exploit a conformational restriction approach to explore a novel chemical space for the generation of TORKi. Structure-activity relationship (SAR) studies led to the identification of compound 12b with a ~450-fold selectivity for mTOR over class I PI3K isoforms. Pharmacokinetic studies in male Sprague Dawley rats highlighted a good exposure after oral dosing and a minimum brain penetration. CYP450 reactive phenotyping pointed out the high metabolic stability of 12b. These results identify the tricyclic pyrimido-pyrrolo-oxazine moiety as a novel scaffold for the development of highly selective mTOR inhibitors for cancer treatment.
Efficient synthesis of pyrazine boronic esters via palladium-catalyzed Miyaura borylation
Lu, Hongtao,Wang, Shengqiang,Li, Jingya,Zou, Dapeng,Wu, Yusheng,Wu, Yangjie
supporting information, p. 839 - 842 (2017/02/10)
A facile and efficient protocol for palladium-catalyzed Miyaura borylation reaction of chloropyrazines with B2pin2has been developed. A certain range of difficult-to-access pyrazine boronic esters can be easily prepared from the corresponding chloropyrazines in moderate to good yields.
Synthesis and in vitro and in vivo evaluation of phosphoinositide-3-kinase inhibitors
Burger, Matthew T.,Knapp, Mark,Wagman, Allan,Ni, Zhi-Jie,Hendrickson, Thomas,Atallah, Gordana,Zhang, Yanchen,Frazier, Kelly,Verhagen, Joelle,Pfister, Keith,Ng, Simon,Smith, Aaron,Bartulis, Sarah,Merrit, Hanne,Weismann, Marion,Xin, Xiaohua,Haznedar, Joshua,Voliva, Charles F.,Iwanowicz, Ed,Pecchi, Sabina
supporting information; experimental part, p. 34 - 38 (2011/04/22)
Phospoinositide-3-kinases (PI3K) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. A series of 2-morpholino, 4-substituted, 6-(3-hydroxyphenyl) pyrimidines have been reported as potent inh