16064-23-6Relevant academic research and scientific papers
Acid Catalyzed Multicomponent One-Pot Synthesis of New Quinazolinone based Unsymmetrical C-N Linked Bis Heterocycles
Bhavani, A. K. D.,Kamsani, Supriya,Kandula, Kotaiah,Mudiganti, Sucheta,Myakala, Nagaraju,Rayala, Nagamani,Vodnala, Sumathi
, p. 432 - 436 (2022/01/21)
A novel series of unsymmetrical C-N linked bis heterocycles bearing quinazolinone and acridinedione skeletons have been synthesized in an acid promoted one pot multicomponent reaction. A blend of 6-aminoquinazolin-4-(3H)-one, aromatic aldehydes and cycloh
NEW BRAF INHIBITORS AS PARADOX BREAKERS
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, (2021/06/22)
The invention provides a novel compound having the general formula (I) (I) wherein R1-R3 and X are as defined in the description and in the claims. The compound of formula (I) can be used as a medicament.
Targeting KRAS Mutant Cancers via Combination Treatment: Discovery of a 5-Fluoro-4-(3 H)-quinazolinone Aryl Urea pan-RAF Kinase Inhibitor
Huestis, Malcolm P.,Dela Cruz, Darlene,Dipasquale, Antonio G.,Durk, Matthew R.,Eigenbrot, Charles,Gibbons, Paul,Gobbi, Alberto,Hunsaker, Thomas L.,La, Hank,Leung, Dennis H.,Liu, Wendy,Malek, Shiva,Merchant, Mark,Moffat, John G.,Muli, Christine S.,Orr, Christine J.,Parr, Brendan T.,Shanahan, Frances,Sneeringer, Christopher J.,Wang, Weiru,Yen, Ivana,Yin, Jianping,Siu, Michael,Rudolph, Joachim
, p. 3940 - 3955 (2021/05/04)
Optimization of a series of aryl urea RAF inhibitors led to the identification of type II pan-RAF inhibitor GNE-0749 (7), which features a fluoroquinazolinone hinge-binding motif. By minimizing reliance on common polar hinge contacts, this hinge binder allows for a greater contribution of RAF-specific residue interactions, resulting in exquisite kinase selectivity. Strategic substitution of fluorine at the C5 position efficiently masked the adjacent polar NH functionality and increased solubility by impeding a solid-state conformation associated with stronger crystal packing of the molecule. The resulting improvements in permeability and solubility enabled oral dosing of 7. In vivo evaluation of 7 in combination with the MEK inhibitor cobimetinib demonstrated synergistic pathway inhibition and significant tumor growth inhibition in a KRAS mutant xenograft mouse model.
QUINAZOLIN-4-ONE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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Page/Page column 33, (2008/06/13)
The invention relates to chemical compounds of the formula (I): or pharmaceutically acceptable salts thereof, which possess B-Raf inhibitory activity and are accordingly useful for their anti-cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm-blooded animal such as man.
