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Pharmacology Learning how chemistry works

This thread contains discussion about a Pharmacology-related topic
polarthedog

polarthedog

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I was wondering, about how much time and research does it take for someone to understand chemistry enough to create new chemicals as opposed to just copying other peoples synthesis recipes? I know that making drugs still is DEFINATELY not as simple as baking a cake even if your following a recipe, but it seems that it would be a whole different level of mastery to be able to make new drugs that have never been made as opposed to making something like meth or heroin.kinda like howmin breaking bad, Walter understood how methamphetamine synthesis worked so well he could just change his recipes around according to his needs, that’s a hell of a lot more impressive than having rote memory of a manufacturing process, both are complicated, but one requires real intrinsic understanding of how molecules interact in general, about how much time would that understanding take to form assuming the person is intellectually capable of doing so?
 
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Well, you’d need an MA in some pharmaceutical science at least to even be anywhere near to “understanding” how drug design works.

To design a drug that someone would actually use? You’re chatting 15 years of work, maybe.

Walter didn’t change anything around really, he just tweaked the cooking process. 😜
 
MsDiz said:
Well, you’d need an MA in some pharmaceutical science at least to even be anywhere near to “understanding” how drug design works.

To design a drug that someone would actually use? You’re chatting 15 years of work, maybe.

Walter didn’t change anything around really, he just tweaked the cooking process. 😜
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Thank you for the good answer, ya I know he didn’t like make a new drug or something, I was trying to give an example of the difference between someone who is able to make meth and someone who understands how the process used to create meth works, or you just any drug.
 
A fairly common PhD subject in medicinal chemistry is something like "synthesis of new analogs of x, etc...".
So I'd say at the very least 7-8 years to come up with a new derivative that may be marginally better than the original molecule, but likely fairly useless in the grand scheme of things, unless you get really lucky.
 
Chemistry starts with protons, neutrons, and electrons.
There are more promising areas of chemistry other than drugs.
The 5 disciplines of chemistry are inorganic, organic, analytical, physical, and biochemistry.
What drugs design falls under mainly is organic synthesis, and then biochemistry.
What you get in high school is the fundamentals. Then onto 4 year college. masters in 2, or right onto Ph.D. as 4-5 years beyond undergrad.
Ph.D.'s typically lead the research for drug design.
But in reality, unless you develop a whole new class of drugs. You're just making analogues.
 
ions said:
Chemistry starts with protons, neutrons, and electrons.
There are more promising areas of chemistry other than drugs.
The 5 disciplines of chemistry are inorganic, organic, analytical, physical, and biochemistry.
What drugs design falls under mainly is organic synthesis, and then biochemistry.
What you get in high school is the fundamentals. Then onto 4 year college. masters in 2, or right onto Ph.D. as 4-5 years beyond undergrad.
Ph.D.'s typically lead the research for drug design.
But in reality, unless you develop a whole new class of drugs. You're just making analogues.
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4meSM said:
A fairly common PhD subject in medicinal chemistry is something like "synthesis of new analogs of x, etc...".
So I'd say at the very least 7-8 years to come up with a new derivative that may be marginally better than the original molecule, but likely fairly useless in the grand scheme of things, unless you get really lucky.
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Thank you, that’s helpful

Ions: I mean it seems like for the most part that’s what people have been doing for a hundred years or however long it’s been since we’ve developed a meaningful understanding of chemistry, it doesn’t seem like whole new classes of drugs are created all that often, the majority of what’s made seems to be analogues of natural drugs. Most of it is just scientists trying shit out and making educated guesses
 
schizopath said:
If you want to make shake n bake. Well theres the internet.

You should have said meth at first and not just "drugs" which implies a capacity to make ANY drug.
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If you really read all my posts, you’ll see I’m using meth manufacturing as an example that the majority of people are hopefully going to get, because meth is a pretty popular drug, and breaking bad was a pretty widely watch tv show.
 
polarthedog said:
If you really read all my posts, you’ll see I’m using meth manufacturing as an example that the majority of people are hopefully going to get, because meth is a pretty popular drug, and breaking bad was a pretty widely watch tv show.
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Sure, I wasnt sure if you were trolling or not on your first post. Meth is the easiest and then comes the modification of opiates and so on. But making a drug from the scratch? Well that takes more than a time, it takes passion for the art/science of chemistry.
 
polarthedog said:
Ions: I mean it seems like for the most part that’s what people have been doing for a hundred years or however long it’s been since we’ve developed a meaningful understanding of chemistry, it doesn’t seem like whole new classes of drugs are created all that often, the majority of what’s made seems to be analogues of natural drugs. Most of it is just scientists trying shit out and making educated guesses
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Look at these recent ones.
There are definitely new drugs being made that don't really look like natural molecules. But it's a very long process that involves bioinformatics, high-throughput screening and lots of people (money).
IMG-2580.jpg
 
MsDiz said:
Well, you’d need an MA in some pharmaceutical science at least to even be anywhere near to “understanding” how drug design works.

To design a drug that someone would actually use? You’re chatting 15 years of work, maybe.

Walter didn’t change anything around really, he just tweaked the cooking process. 😜
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Well I'm 34 years in and all I realize is that their are new things I DON'T know every damned day.

No medicinal chemist knows how every class of medicine works, all you pick up is how to LEARN efficiently. I can usually pick up the pharmacore of a new class in about a day BUT then one has to learn about the ADME and other dull but required aspects. It's 99% dull.
 
polarthedog said:
Thank you for the good answer, ya I know he didn’t like make a new drug or something, I was trying to give an example of the difference between someone who is able to make meth and someone who understands how the process used to create meth works, or you just any drug.
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AFAIK, to be able to understand and create organic chemistry synthesis, set up a lab etc, you need about 6 years in Uni.
That would be just to know enough to be able to synth though, then you'd need a longer course of study to be able to research new potential psychoactives.
 
I'm going to come in with a totally different perspective.

Chemistry is a lot like cooking. Most chemistry is following existing recipes that have been done before, or making slight changes to them (changing starting material for a similar looking one, scaling up or down, etc). That kind of chemistry can be done by basically anyone if they are careful to follow instructions and have the neccesary equipment.

Certainly any experience helps, but by no means do you need to spend years in school to do chemistry. In fact, in a bygone time, chemistry was treated more like a trade than a university course.

Necessary skills include: being able to follow directions, having good research skills, planning ahead, patience, being able to keep a clean workspace, being able to measure various quantities (temperature, weight, time, volume) accurately, being able to take good notes and records, knowing about appropriate safety equipment and using it, being able to pour/handle/measure various substances, etc.

A properly equipped lab can cost millions but you can also get a basic set of glassware for under $200. Especially if you stick to used/surplus equipment.

Now the thing with discovering totally new drugs, is it's actually two problems:
1. You need to figure out where the drug binds and its efficacy (the biology half)
2. You need to figure out how to make that drug in significant quantity (the chemistry half).

Traditionally new drugs have been discovered by a rather brute force method of making analogues of existing drugs (or even totally novel structures) and screening them against targets (formerly live animals, today cell culture) then making further adjustments and repeating, etc. - but with the advent of high resolution structures of many target receptors, drugs can also be designed a little more rationally, to fit into exactly where they need to go.

However, none of this is done by single people any more. Drug development is very much a team effort. Otherwise prepare to dedicate yourself to making hundreds or thousands of compounds of similar structure and test them one by one in cell culture (or whatever).

And all that is just to develop a "lead compound", don't get me started about actually developing commercially saleable drugs.
 
While it IS possible for one person to do it all - I think methylphenidate was more or less Leandro Panizzon, we have found that specialization is now key. One person will now collect every reference to compounds with an affinity to a given receptor and quite possible run a training set to find the key moieties. Then a few candidates will be designed and passed on to the lab. The lab will then generally have someone who finds at least 2 facile routes and pass that on to organic chemists to produce a stock of said candidates and with a stock of candidates to hand, pass it on. Then another team will carry out all of the required tests to check that the candidates aren't mutagenic and so on and proceed to animal models. That done, further animal models will test efficacy and safety (like TI). Then someone else will proceed to pilot scale which is more of a chemical engineering matter and human trials take place.

When all THAT looks OK, someone will have to scale further so back to the chemical engineer and we go into proper stage 1a trials which are generally 1% of the expected active dose. The dose is run up to check for side-effects and generally the safety profile. That done stage 1b trials check that the candidate's side-effect profile is consistent. Then stage 2 trials will seek to check that the candidate actually does the job it was designed to do (all the time watching for minority side-effects) and then onto stage 3 where a decent number of people WITH the condition the candidate is designed to treat all the while carefully checking for problems.

With that, one is faced with 2 books (they are quite literally HUGE spiral bound books) that require someone to fill in all of the details on testing, results and and confirming that all requirements are met. This is part of the licencing process and takes YEARS to complete.

Finally a licence is granted (or not) and then it's back to the chemical engineers once again to scale the whole process so that the production cost of the drug is kept as low as is humanly possible.

Even then, stage 4 is termed 'clinical pharmacovigilance' which requires the licence-holder to read, assess and act on feedback from those prescribing the drug.

So lovely as it is to home produce a known compound, it's very much the SAFETY that is the key element in drug development. Not that the makers personally feel bad if a medicine harms someone - it's the fact that they might have to adjust the product from black-box warnings to ultimately pulling the drug. NOT because the maker essentially cares, but because class action legal actions cost billions.

Reaching stage 2 isn't too difficult although you can expect to expend tens of millions of pounds, it's the fact that 75% of candidates fail at stage 2 and so possibly 3 years are wasted.

As it is, it takes on average 13 years from someone identifying the need for a new medicine to it actually being prescribable.

I hasten to add that pipelining is a big deal. The researchers do their work (maybe a year) and move on to something else. The lab team will spend maybe a year and move on to something else. The vast majority of term is in licencing. I'm forever impressed by the exploits of organic chemists but having known people who worked at Upjohn's drug discovery lab, they spent just a few months working on a candidate. They would continue to develop the scaffold but often it would be in vain because medicines rely on people BUYING them and so more often than not, even improvements don't actually reach the market.

A good example would be ketamine. A couple of years after ketamine was discovered, the 2-chloro-5-methoxy homologue was discovered to be far better BUT because ketamine was such a success, their was no need for an improved version.

So anyone expecting perfection, forget it. You don't get the time to keep on developing because if, 1 year later you find something better, it doesn't matter, if something is good enough, it's good enough. I can point to so many examples of this happening.

In short - the person whose name is on the patent's ISN'T the one who did the bench-scale chemistry (at least since the 1980s). I know this from bitter experience BUT I DID learn who does and it's the person(s) who designed the candidate.
 
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