cas 1000578-10-8, methyl 4-oxo-3,4-dihydroquinazoline-8-carboxylate | Articles data ｜lookchem

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1000578-10-8

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Identification of Clinical Candidate M2698, a Dual p70S6K and Akt Inhibitor, for Treatment of PAM Pathway-Altered Cancers
Herein, we report the discovery of a novel class of quinazoline carboxamides as dual p70S6k/Akt inhibitors for the treatment of tumors driven by alterations to the PI3K/Akt/mTOR (PAM) pathway. Through the screening of in-house proprietary kinase library, 4-benzylamino-quinazoline-8-carboxylic acid amide 1 stood out, with sub-micromolar p70S6k biochemical activity, as the starting point for a structurally enabled p70S6K/Akt dual inhibitor program that led to the discovery of M2698, a dual p70S6k/Akt inhibitor. M2698 is kinase selective, possesses favorable physical, chemical, and DMPK profiles, is orally available and well tolerated, and displayed tumor control in multiple in vivo studies of PAM pathway-driven tumors.
Chen, Xiaoling,Clark, Anderson,Crowley, Lindsey,Deselm, Lizbeth,Georgi, Katrin,Goutopoulos, Andreas,Haxell, Thomas,Heasley, Brian H.,Huck, Bayard,Jackson, Jennifer,Johnson, Theresa,Jones, Reinaldo,Lan, Ruoxi,Lin, Jing,Machl, Andreas,Mochalkin, Igor,Moore, Joseph,Neagu, Constantin,Potnick, Justin,Richardson, Thomas E.,Rohdich, Felix,Sherer, Brian,Sutton, Amanda,Tian, Hui,Wilker, Erik,Xiao, Yufang
p. 14603 - 14619
(2021/10/20)

QUINAZOLINE CARBOXAMIDE AZETIDINES
The invention provides novel quinazoline carboxamide azetidine compounds according to Formula (I) and use for the treatment of hyperproliferative diseases, such as cancer.
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(2012/06/15)

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Chemical Properties

Appearance/Colour :White crystalline powder
Boiling Point: 450.9 °C at 760 mmHg
Flash Point:226.5 °C
Density: 1.39g/cm³
PKA: 0.43±0.20(Predicted)
PSA: 72.05000
LogP: 0.70970

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