1146159-35-4

Upstream product

• 1885-29-6 anthranilic acid nitrile 
• 108240-11-5 4-chloro-2-(2-methoxyphenyl)quinazoline 
• 21615-34-9 2-Methoxybenzoyl chloride 
• 1028-96-2 2-(2-methoxyphenyl)quinazolin-4-ol 
• 708289-25-2 C₁₅H₁₂N₂O₂ 

Downstream Products

• 1146159-36-5 2-[4-((R)-piperidin-3-ylamino)quinazolin-2-yl]phenol 

Relevant academic research and scientific papers

Structure-based design of potent and selective 2-(quinazolin-2-yl)phenol inhibitors of checkpoint kinase 2

Structure-based design was applied to the optimization of a series of 2-(quinazolin-2-yl)phenols to generate potent and selective ATP-competitive inhibitors of the DNA damage response signaling enzyme checkpoint kinase 2 (CHK2). Structure-activity relationships for multiple substituent positions were optimized separately and in combination leading to the 2-(quinazolin-2-yl) phenol 46 (IC50 3 nM) with good selectivity for CHK2 against CHK1 and a wider panel of kinases and with promising in vitro ADMET properties. Off-target activity at hERG ion channels shown by the core scaffold was successfully reduced by the addition of peripheral polar substitution. In addition to showing mechanistic inhibition of CHK2 in HT29 human colon cancer cells, a concentration dependent radioprotective effect in mouse thymocytes was demonstrated for the potent inhibitor 46 (CCT241533).

THERAPEUTIC OXY-PHENYL-ARYL COMPOUNDS AND THEIR USE

The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain oxy phenyl aryl compounds (referred to herein as OPA compounds), as described herein, which, inter alia, inhibit Checkpoint Kinase 2 (CHK2) kinase function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK2 kinase function, and in the treatment of diseases and conditions that are mediated by CHK2, that are ameliorated by the inhibition of CHK2 kinase function, etc., including proliferative conditions such as cancer, etc., optionally in combination with another agent, for example, (a) a DNA topoisomerase I or II inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or TS inhibitor; (d) a microtubule targeted agent; and (e) ionising radiation.