cas 959237-34-4, 2,4-Dichloro-7-iodoquinazoline | Articles data ｜lookchem

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959237-34-4

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Design and synthesis of novel diaminoquinazolines with in vivo efficacy for β-catenin/t-cell transcriptional factor 4 pathway inhibition
We are introducing a novel series of 2,4-diaminoquinazolines as β-catenin/Tcf4 inhibitors which were identified by ligand-based design. Here we elucidate the SAR of this series and explain how we were able to improve key molecular properties such as solubility and cLogP leading to compound 9. Analogue 9 exhibited better biological activity and improved physical and pharmacological properties relative to the HTS hit 49. Furthermore, 9 demonstrated good cell growth inhibition against several human colorectal cancer lines such as LoVo and HT29. In addition, treatment with compound 9 led to gene expression changes that overlapped significantly with the transcriptional profile resulting from the pathway inhibition by siRNA knockdown of β-catenin or Tcf4. Subsequently, 9 was tested for efficacy in a β-catenin/RKE-mouse xenograft, where it led to more then 50% decrease in tumor volume. 2009 American Chemical Society.
Dehnhardt, Christoph M.,Venkatesan, Aranapakam M.,Chen, Zecheng,Ayral-Kaloustian, Semiramis,Dos Santos, Osvaldo Dos,Delos Santos, Efren,Curran, Kevin,Follettie, Max T.,Diesl, Veronica,Lucas, Judy,Geng, Yi,DeJoy, Susan Quinn,Petersen, Rosanne,Chaudhary, Inder,Brooijmans, Natasja,Mansour, Tarek S.,Arndt, Kim,Chen, Lei
experimental part
p. 897 - 910
(2010/07/05)

AMINO-SUBSTITUTED QUINAZOLINE DERIVATIVES AS INHIBITORS OF β-CANTENIN/TCF-4 PATHWAY AND CANCER TREATMENT AGENTS
The present invention relates to amino-substituted quinazoline derivatives as inhibitors of β-catenin/tcf-4 pathway, which can be useful in the treatment of cancer; to processes for their preparation; to pharmaceutical compositions comprising them; and to methods of using them.
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(2008/12/07)

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Chemical Properties

Boiling Point: 279.2 °C at 760 mmHg
Flash Point:122.7 °C
Density: 2.083 g/cm³
Storage Temp.:under inert gas (nitrogen or Argon) at 2–8 °C
Vapor Pressure: 0.00689mmHg at 25°C
Refractive Index: 1.741
PSA: 25.78000
LogP: 3.54120

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