Design, Synthesis, and Biological Evaluation of Novel Potent and Selective αvβ3/αvβ5 Integrin Dual Inhibitors with Improved Bioavailability. Selection of the Molecular Core was written by Marugan, Juan Jose;Manthey, Carl;Anaclerio, Beth;Lafrance, Lou;Lu, Tianbao;Markotan, Tom;Leonard, Kristi A.;Crysler, Carl;Eisennagel, Stephen;Dasgupta, Malini;Tomczuk, Bruce. And the article was included in Journal of Medicinal Chemistry in 2005.Application of 205676-84-2 This article mentions the following:
A novel series of potent and selective αvβ3/αvβ5 dual inhibitors was designed, synthesized, and evaluated against several integrins. These compounds were synthesized through a Mitsunobu reaction between the guanidinium mimetics and the corresponding central templates. Guanidinium mimetics with enhanced rigidity [i.e., [(2-pyridinyl)amino]propoxy vs. the 2-(6-methylamino-2-pyridinyl)ethoxy] led to improved activity toward αvβ3. Exemplary oral bioavailability in mice was achieved using the indole central scaffold. Although, oral bioavailability was maintained when the indole mol. core was replaced with the bioisosteric benzofuran or benzothiophene ring systems, it was found to not significantly impact the integrin activity or selectivity. However, the indole series displayed the best in vivo pharmacokinetic properties. Thus, the indole series was selected for further structure-activity relationships to obtain more potent αvβ3/αvβ5 dual antagonist with improved oral bioavailability. The compounds thus prepared and studied included 5-[3-(2-pyridinylamino)propoxy]-1H-indole-1-propanoic acid (I), 5-[2-[6-(methylamino)-2-pyridinyl]ethoxy]-1H-indole-1-propanoic acid, 6-[2-[6-(methylamino)-2-pyridinyl]ethoxy]benzo[b]thiophene-3-propanoic acid (II), and 6-[2-[6-(methylamino)-2-pyridinyl]ethoxy]-3-benzofuranpropanoic acid (III). In the experiment, the researchers used many compounds, for example, tert-Butyl methyl(6-methylpyridin-2-yl)carbamate (cas: 205676-84-2Application of 205676-84-2).
tert-Butyl methyl(6-methylpyridin-2-yl)carbamate (cas: 205676-84-2) belongs to pyridine derivatives. Pyridine has a conjugated system of six π electrons that are delocalized over the ring. The molecule is planar and, thus, follows the Hückel criteria for aromatic systems. Several pyridine derivatives play important roles in biological systems. While its biosynthesis is not fully understood, nicotinic acid (vitamin B3) occurs in some bacteria, fungi, and mammals.Application of 205676-84-2