106973-37-9Relevant 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.
N-ACYL CYCLIC AMINE DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
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Page/Page column 91, (2011/10/05)
The present invention provides compounds which show high effectiveness against positive symptoms, negative symptoms and cognitive dysfunction in schizophrenia and reduce conventional side-effect risks as well as have remarkable effects for central neurolo
SYNTHETIC PROCESS
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Page/Page column 29-30, (2008/06/13)
The present invention provides a process for preparing compounds of formula (I) ["insert chemical structure here"](I)or a pharmaceutically acceptable salt thereof. The compounds prepared by the process of the invention inhibit tyrosine kinase activity of growth factor receptors such as HER1, HER2 and HER4 thereby making them useful as antiproliferative agents for the treatment of cancer and other diseases.