N&PD Moderators: Skorpio
Pharmacology In the Pipeline
This thread contains discussion about a Pharmacology-related topic
4DQSAR
Bluelighter
https://www.science.org/blogs/pipeline
Derek Lowe, genuine genius, gentleman and gentle man... also hilarous.
IF you REALLY wish to become a medicinal chemist, follow this person. The HTMA story alone is worth it.
tuppingtoncity
Bluelighter
Second this, Derek lowe is wonderful
Smyth2
Bluelighter
1-(1,3-Benzothiazol-5-yl)propan-2-amine
https://pubchem.ncbi.nlm.nih.gov/compound/82491118
Alan C. Gibbs, et al. WO2024148267 (to Empathbio Inc).
4DQSAR
Bluelighter
Markush structures - could be thousands of things. This annoys me and as a rule-of-thumb, the more structures you cram into one patent, the weaker the legal protections around a specific member of that HUGE groups.
Empathbio is wholly owned by ATAI Life Sciences., itself now owned by AltiBeckley. Is it a patent zombie? Well, hard to fathom the inner workings but we ALL know that the Don AOKed entactogens and psychedelics for treatment of mental health so if nothing else, the stock price will go up as we WILL see a bubble. Hacking down who has what is a nightmare.
Derek Lowe comment on Nitazenes:
and the original paper:
A µ-opioid receptor superagonist analgesic with minimal adverse effects - Nature
N-desethyl-fluornitrazene is a µ-opioid receptor agonist derived from nitazenes that has supramaximal intrinsic efficacy that produces analgesia with minimal adverse effects in rodent models.
www.nature.com
Enjoy!
4DQSAR
Bluelighter
@charlz - I think someone posted the actual papers a few weeks ago and it certainly is interesting. I keep wondering if this could also be explained as a demonstration of a duelist as no mention is made of the NOP receptors which being very similar to the MOR receptor, was only accidentally discovered by Janssen in the 1960s who could not explain the analgesia of a ligand that by rights should not have been as good as it appeared to be. Of course, he then went on record as saying that the scaffold and those related to it were so synthetically challanging that a decision was made to focus on the phenylpiperidine class i.e. phenoperidine --> fentanyl --> carfentanil/alfentanil/remifentanyl i.e. focus on medications for the 'head of the table' i.e. anesthetists.
It wasn't pure pragmatism but the 3,3-diphenylheptanones were still yielding new medicines BUT it ended up with Janssen's new medicines only competition was other Jannsen medicines.
If you look at the code numbers you can at once see just how deeply he mined both scaffolds but equally note how those numbers thin out. If you wish to, you can draw a graph to see just how thinned out it all became.
He was only pipped at the post as greatest Belgian in history because the poll was a Flemish (regional) TV programme. But being runner-up to a saint is possibly a division between faith and science. Only post mortem was he was awarded Most Important Belgian Scientist. I contest he did more good but that's just one opinion.
I suspect his incredible productivity was in pipelining the development i.e. rational design, Dreiding molecular models, intuition, serendipity and as with all things, sheer hard work. Design, hand off to team, test, iterate, repeat. IF you do that at speed you CAN go quite fast. I don't think any faster would have been safe, and from the little I know of the man, he did consider the end user; rare.
I’ve read this blog daily since 2012. Honestly has helped me catch papers beyond the journals I focused on.
Derek is amazing at writing about science in a way that is easily digestible by lay folk, but also avoids the lies to children a lot of science communicators fall into.
I read the quick one about heart cells and cancer. I like how simply he explains things. The stuff he writes about sounds like important stuff, if only I knew more of the terms.
His posts “things I wouldn’t work with” are a great exploration of some wild chemistry.
I also thought this article is quite interesting regarding how cells make sure that cell death inducing proteins can function even in the face of catastrophic cellular damage.
