Keylor, Mitchell H.; Gulati, Anmol; Kattar, Solomon D.; Johnson, Rebecca E.; Chau, Ryan W.; Margrey, Kaila A.; Ardolino, Michael J.; Zarate, Cayetana; Poremba, Kelsey E.; Simov, Vladimir; Morriello, Gregori J.; Acton, John J.; Pio, Barbara; Yan, Xin; Palte, Rachel L.; McMinn, Spencer E.; Nogle, Lisa; Lesburg, Charles A.; Adpressa, Donovon; Lin, Shishi; Neelamkavil, Santhosh; Liu, Ping; Su, Jing; Hegde, Laxminarayan G.; Woodhouse, Janice D.; Faltus, Robert; Xiong, Tina; Ciaccio, Paul J.; Piesvaux, Jennifer; Otte, Karin M.; Wood, Harold B.; Kennedy, Matthew E.; Bennett, David Jonathan; DiMauro, Erin F.; Fell, Matthew J.; Fuller, Peter H. published an article in 2022. The article was titled 《Structure-Guided Discovery of Aminoquinazolines as Brain-Penetrant and Selective LRRK2 Inhibitors》, and you may find the article in Journal of Medicinal Chemistry.Formula: C10H18INO2 The information in the text is summarized as follows:
The leucine-rich repeat kinase 2 (LRRK2) protein has been genetically and functionally linked to Parkinson′s disease (PD), a disabling and progressive neurodegenerative disorder whose current therapies are limited in scope and efficacy. In this report, we describe a rigorous hit-to-lead optimization campaign supported by structural enablement, which culminated in the discovery of brain-penetrant, candidate-quality mols. as represented by compounds 22 and 24. These compounds exhibit remarkable selectivity against the kinome and offer good oral bioavailability and low projected human doses. Furthermore, they showcase the implementation of stereochem. design elements that serve to enable a potency- and selectivity-enhancing increase in polarity and hydrogen bond donor (HBD) count while maintaining a central nervous system-friendly profile typified by low levels of transporter-mediated efflux and encouraging brain penetration in preclin. models. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-iodopiperidine-1-carboxylate(cas: 301673-14-3Formula: C10H18INO2)
tert-Butyl 4-iodopiperidine-1-carboxylate(cas: 301673-14-3) is one of organic iodides. Organic iodides are used in veterinary products (Organic Iodide Powder) as a nutritional source of iodine. In the chemical industry, alkyl iodides serve as excellent alkylating agents and, specifically, methyl iodide is used as a methylating agent in the synthesis of various pharmaceutical drugs. Oceanic alkyl iodides are believed to be the principal source of atmospheric iodine.Formula: C10H18INO2
Referemce:
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com