A Conformational Restriction Strategy for the Identification of a Highly Selective Pyrimido-pyrrolo-oxazine mTOR Inhibitor was written by 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.. And the article was included in Journal of Medicinal Chemistry in 2019.Name: 4-Dimethoxymethylpyrimidin-2-ylamine This article mentions the following:
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 chem. 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 min. 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. In the experiment, the researchers used many compounds, for example, 4-Dimethoxymethylpyrimidin-2-ylamine (cas: 165807-05-6Name: 4-Dimethoxymethylpyrimidin-2-ylamine).
4-Dimethoxymethylpyrimidin-2-ylamine (cas: 165807-05-6) belongs to pyrimidine derivatives. The aromatic compound pyrimidine, and its derivatives, are ubiquitous in nature. They are found in nucleic acids, vitamins, amino acids, antibiotics, alkaloids, and a variety of toxins. For example, the neurotoxin tetrodotoxin is a pyrimidine derivative. It is found in a number of species including the Japanese puffer fish, the blue-ringed octopus, and the orange-bellied newt. Tetrodotoxin prevents the transmission of nerve signals and can result in paralysis and death.Name: 4-Dimethoxymethylpyrimidin-2-ylamine
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia