How "Heavy Hydrogen" makes Drugs work: Deuterium in Pharmaceuticals, Organic Chemistry & Synthesis
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- Опубліковано 1 чер 2024
- Organic chemistry does not only use abundant forms of atoms but also rare isotopes such as deuterium - the heavy form of hydrogen. Addition of "the D" can completely transform a molecule's reactivity and pharmacokinetic properties. Watch this to find out more about the physical chemistry, biochemistry and organic synthesis associated with Deuterium and more specifically, the discovery route and large-scale process behind the second deuterated drug to be approved by the US FDA, deucravacitinib (Sotyktu).
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00:00 Why you should care about D
01:40 Deuterium's discovery and application in medicinal chemistry (deutetrabenazine)
06:44 Psoriasis landscape, key molecules and mechanisms of action
09:08 Deucravacitinib Tyk 2 deep dive and outlook
12:33 Discovery chemistry route overview
14:54 Process chemistry route deep dive
Main paper: Development of a Commercial Process for Deucravacitinib, a Deuterated API for TYK2 Inhibition; pubs.acs.org/doi/10.1021/acs....
Highly Selective Inhibition of Tyrosine Kinase 2 (TYK2) for the Treatment of Autoimmune Diseases: Discovery of the Allosteric Inhibitor BMS-986165; pubs.acs.org/doi/abs/10.1021/...
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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 UA-cam.
Some recommended books on organic synthesis:
- Clayden, Greeves, Warren; Organic Chemistry (basic organic chemistry knowledge)
- Wyatt, Warren; Organic Synthesis: The Disconnection Approach (excellent introduction to retrosynthesis)
- Kurti, Czako; Strategic Applications of Named Reactions in Organic Synthesis (extensive toolkit of functional group reactions and applications thereof with common conditions)
- Nicolaou et al; Classics in Total Synthesis 1-3 (the ultimate total synthesis trilogy)
- Nicolaou; Molecules That Changed the World (the world's most important molecules and their impact on everyday life)
- Carreira, Kvaerno; Classics in Stereoselective Synthesis (compilation of the groundbreaking methods of stereoselective synthesis and application to synthesis of stereochemically complex structures)
Thumbnail RHS image by aleksandarlittlewolf on Freepik - Наука та технологія
you are, far and away, one of the most effective youtube chemistry channels at teaching.
Wow, thank you!!
I can’t say a huge amount about this due to confidentially but the drug at 12:33 (CTP-543) was a project that I worked on during my time in the pharmaceutical industry. It’s still an active project. Ive since moved on to do a PhD but it was certainly an interesting experience to learn about substituting deuterium into drugs to improve their efficacy.
👀 that's awesome!
Sounds positive!
As someone who went from a more organic chemistry focus to chemical biology, this video and channel is perfection. Keep the total synthesis videos coming! Your explanations of science concepts is direct and understandable, keep up the good work, subscribed.
Thank you!
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Nice video! How about one on the total synthesis of Vit. B12? I know it's rather old but the Woodward/Eschenmoser story and the pure scale of the project could be really interesting...
This synthesis clearly shows that process chemist are the best chemist out there ! 👨🔬
One of the most fascinating of your videos that I have watched so far!
Wow didn't expect this to go into process chemistry! Learning about pharmacokinetics is always interesting.
This type of video is a blessing.
Ist zwar etwas spät, aber: Frohes Neues! :D
Amazing video! Just learned about kinetic isotope effects last semester in Phys Org, interesting to see there are actual uses beyond mechanistic studies.
Omg I was waiting so long for another video!!🔥🔥🔥
very interesting video! loving this medchem/investigational style
Incredibly impressive video I can't say I understood all of it but it's certainly gave me an insight thank you so much
Awesome man, thanks!!
Here from /sci/; keep it up, fren!
Aye bro i really like your channel and how you explain things. One of my favorites!
The way you describe chemistry is exquisitely beautiful....
Thank you for the nice content.
Next time I'll get notified
Love your work! Comenting for the algorithm 🌻
really good video covering many areas of chemistry within a single topic
Thanks 💕
That diazoketone ring forming reaction was cool.
He's back :D
Man, I love some good process chemistry!
İt's really wierd how a bunch of nazi chemists discovered all this basic science in the 1930s yet they all converted to judaism by 1945.
nice video. Keep on growing❤❤
Thank you 💖
The mastery of the morph effect in ppt is impressive 😂
great video and research of the topic... This is so intrereting, and I still lmao about the cylo-proply swag😆
😂😂 thats what I think when I see these molecules which just flex on others
HE'S BACK LETS GO!
Back and here to stay 😎
Beautiful discussion of the organic synthesis; though it did bring me some unpleasant flashbacks of undergrad pchem.
Glad I wasnt the only one 🤣
Very interesting. My company makes d-3 MeI in commercial quantities
01:58 "were carefully prepared using the best purification techniques and temperature controls"... I didn't know Trump was a chemist.
😂 I can imagine him saying "there's no one who's better than me at chemistry" (maybe you know that compliation)
Make organic synthesis great again!
That very cool i never imagine deterium hydrogen isotope besides potential cancer uses (maybe) for making new drugs. I thought it was only used in nuclear reactors and nuclear bombs.
Thanks for watching!
I'd like to see some work done on Sanguinarine. If possible.
>Obamium
Subscribed!
🤣
Duterated DMT for stroke victims, duterated specific spots to help protect it from mono amines oxidase enzymes allowing the drug to have a slightly longer action allowing more time for oxygen to return to the brain helping to prevent long term trauma
There's also research for DMT being used in the recovery process for stroke
What are the differences between deuterium and tritium in chemical reactions?
Reacts like H or D, but is heavier (one more neutron) and radioactive (beta decay). More used in nuclear physics than organic chemistry except for labeling
@@totalsynthesis but does it change the reaction rate? Ive done chemistry with tritium but never measured reaction rates
@@puo2123 yes, increased isotope effect due to even higher mass
Please put the morphine D³ in my I.V.
Got a bad habit and I hope the potency doesn't kill me.
I'm not good at math but H is 1 and D is 2 so 1 cubed would equal 1 but 2 cubed would equal 8.
Also i think you were saying something or mean to say something about morphine hydrochloride. But instead morphine deuterium chloride.
@@garrysekelli6776 Deuterium chloride or hydrogen chloride is in this case irrelevant.
What might be more effective though could be the N-trideuteromethyl analogue, but I'd have to look up the metabolic pathway... .
As a sidenote, as codeine is a prodrug for m., I'd expect codeine's O-trimethyl congener to be a less effective analgesic.
Amide. With an e. Not amid, like the American scientists pronounce.
hi
Hello friend
Deuterium instead of Protium (the ordinary hydrogen isotope) in your body... Do we know how that works out, e.g. in your mitochondria? Nope, we don't 👐🏻
Not in my body!🙅🏻
If you consider that Deuterium is occuring in nature in 1 out of 6500 normal hydrogens, and your body is processing billions upon billions of molecules... we are probably fine with having some hundred milligrams of drugs with deuterium in us :)
@@totalsynthesis Well, I don't like the drugs that interfere with processes in our body, and often only mask symptoms. Now follows a bit too long rant..
I don't like the fact that most pharmaceutical companies have a financial model that prospers when customers (me, "the patient") are life long prescribed their "medicines". Examples are plenty: statins, blockers, NSAID, antacids and e.g. stuff that helps you with athlete's food. Chemotherapy, Fentanyl, Oxycodone.
But also the 'innocent' Acetaminophen is dangerous, due to its interaction with other drugs. They usually don't cure but "manage" your disease process.
I don't believe that we'll be honestly informed about threats that Deuterium may form for us.
I see more in healthier living, staying away from packaged food, all the sugars and refined carbs, and not to forget the vegetable oils. These cause the metabolic diseases that make the pharmaceutical companies flourish, up to trillions of dollars per year.
Perhaps it's interesting to see the wheels behind our modern society.. You know them probably. The big investors and their owned big three (pharma, food, media).
A lot of writing that goes way beyond Deuterium, I admit.
I see more in food, minerals, vitamins. And yes, when really necessary may use "allopathic" drugs.
@@rredding I understand your sentiment, and also agree the value of healthier lifestyle is underappreciated - however, unfortunately there are people who try their best and still get for example cancer or inflammatory disease. Maybe we will get them at some point in our life despite our best efforts to prevent them? I'm certain I would be happy about having something that gives me the chance for disease remission. Are drugs perfect? No - but are they of value? Absolutely. That includes drugs that manage symptoms/ progression as well as drugs that have a high likelihood of actually curing the disease - they do exist, and they are priced even higher.
Whether those prices are fair, and if it's ok for the pharmaceutical industry to have one of the highest margins across industries - that's another point...
@@rredding All drugs interfere with the processes in your body. That's how they work. They are for when processes in your body aren't doing what is good for you, like with autoimmune diseases.
And also we do know what deuterium drugs do in your body -- as we do with every drug that is released to the public. According to studies you can replace as much as 20% of your daily water intake with heavy water (en.m.wikipedia.org/wiki/Heavy_water#Toxicity_in_humans), with nothing happening to you. That's way past what most drugs will kill you at. Additionally the deuterium in drugs is often attached to a C rather than an O preventing proton exchange with ambient water in your body (it stays in the drug).
Putting the D into Drugs got me laughing af what is wrong with me...
😂😂😂 fine sense of humor
@@totalsynthesis ❤️♿️❤️
/sci/ bro
deuturmom
Nile red is a horrible example of chemist or something close
:(
Hola TS, you speak of neutrons but I posit to you that no such thing exists. Your so-called neutron will very shortly turn into a proton and an electron. It would be stupid to assume that this electron and proton were created in some kind of atomic fissioning event, instead it would be prudent to assume that the proton and electron were in some intimately paired situation. In fact when you assume that one of the electrons has moved to the interior of the atomic structure then you can do away with one of your fundamental forces and simply assume protons are held together because of this inner electron. Less fundamental forces equals a more believable model of reality. I don't know if you'll get anything from this text, most people can barely function within their current paradigms let alone envision another. Don't hate, just relate.