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Explore This Drug Synthesis is Literally Breathtaking | Medicinal Chemistry & Organic Synthesis with 60,308 views, 1,816 likes, and 62 comments. Experience the impact of this video content that has captured audience attention.

This molecule might look like any other 'flat drug' - but there's a mystery hidden behind its synthesis! Coupled with the fact that it showed promise in asthma due to its novel mechanism, you could say that it's breath-taking (actually more like breath-giving, but I figured no one will understand this). Watch this video to learn more about organic synthesis, drug development and more! https://total-synthesis.com/organic-chemistry-practice-problems/ 🧑‍🎓➡️ Free organic chemistry practice problems https://www.instagram.com/totalsynthesis_official/ 👉 Follow me on Instagram for updates on random research, mechanism quizzes and interesting news! https://www.total-synthesis.com 00:00 A breath-taking synthesis 00:23 Structure of our target molecule 01:37 Intro to PI3K enzymes and inhibitor drugs 03:41 Levels of chemistry sophistication 05:09 Retrosynthesis of AZD8154 and overview 05:57 Forward synthesis # 1 07:26 What was the problem? 08:19 Forward synthesis # 2 11:10 How legit is the solution? 12:03 FDA stance on PI3K inhibitors, and conclusion Disclaimer - This channel does not provide medical advice! No information on this channel is intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of information on Youtube. Key references: - Discovery of AZD8154, a Dual PI3Kγδ Inhibitor for the Treatment of Asthma | J. Med. Chem. 2021, 64, 8053 - Class I Phosphoinositide 3-Kinase PIK3CA/p110α and PIK3CB/p110β Isoforms in Endometrial Cancer | Int. J. Mol. Sci. 2018, 19, 3931 - The Pathogenic Role of PI3K/AKT Pathway in Cancer Onset and Drug Resistance: An Updated Review | Cancers 2021, 13, 3949 - Discovery of Highly Isoform Selective Orally Bioavailable Phosphoinositide 3-Kinase (PI3K)-γ Inhibitors | J. Med. Chem. 2018, 61, 5435 - An Intramolecular Diels–Alder Approach to the Isoindolinone Core of AZD8154 | doi.org/10.1021/acs.oprd.3c00507 - Selection and Development of the Manufacturing Route for EP1 Antagonist GSK269984B | Org. Process Res. Dev. 2010, 14, 820 - Characterisation of pharmacokinetics, safety and tolerability in a first-in-human study for AZD8154, a novel inhaled selective PI3Kγδ dual inhibitor targeting airway inflammatory disease | Br J Clin Pharmacol. 2022, 88, 260 - Copanlisib for treatment of B-cell malignancies: the development of a PI3K inhibitor with considerable differences to idelalisib | Drug Des Devel Ther 2018, 12, 2577 Recommended organic chemistry books: - Winter; Organic Chemistry I For Dummies (start here if you are absolutely friggin clueless) | https://amzn.to/4fmF97q - Clayden, Greeves, Warren; Organic Chemistry (basic organic chemistry knowledge) | https://amzn.to/4ul57ft - Wyatt, Warren; Organic Synthesis: The Disconnection Approach (excellent introduction to retrosynthesis) | https://amzn.to/4fmF97q | https://amzn.to/3Q529xn - Kurti, Czako; Strategic Applications of Named Reactions in Organic Synthesis (extensive toolkit of functional group reactions and applications thereof with common conditions) | https://amzn.to/43cbzKH - Grossmann; The Art of Writing Reasonable Organic Reaction Mechanisms (building intuition for intermediate and advanced reaction mechanisms) | https://amzn.to/4dOiIXA - Nicolaou; Classics in Total Synthesis 1-4 (simply legendary series) | https://amzn.to/4o986pz | https://amzn.to/3ROsRLp | https://amzn.to/3S4vCYV | https://amzn.to/4dPI9YL - Nicolaou; Molecules That Changed the World (the world's most important molecules and their impact on everyday life) | https://amzn.to/4odZwWW - Carreira, Kvaerno; Classics in Stereoselective Synthesis (compilation of the groundbreaking methods of stereoselective synthesis and application to synthesis of stereochemically complex structures) | https://amzn.to/4dZk9kH - Anslyn; Modern Physical Organic Chemistry (almost anything you will need for (organic) physical chemistry) | https://amzn.to/4gwOZUL

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