How are RC's created?

[chainsawkidd]

First Bluelight post, greetings.

I will try to keep this relatively brief.
As I am very interested in drugs of the RC family, what subjects would one need to study in order to learn about how they are created? I understand that it would require years of dedication to reach the end goal, well aware, but we all start somewhere, could anyone please point me towards some helpful links/book PDFs/videos, anything related to the manufacturing of these compounds. Also, any helpful links for beginners of Chemistry, or whatever the exact subject related to my questions is.

Thankyou very much.

 

[someguyontheinternet]

If I understand your question correctly, what you want to learn is medicinal chemistry. It would be helpful to know basic chemistry, organic chemistry, biochemistry, and pharmacology especially pharmacokinetics

Medicinal chemistry is the creation and testing of novel drugs to interact with a specific receptor or protein and it involves the design and modification of new or current ligands at the core

There are others here who are much better versed than me in this particular field, I'm sure they'll pop in here eventually

 

[chainsawkidd]

Yes, thats very helpful information, thankyou kindly. Now off to learn the bare basics of medicinal chem and pharma I go, will be back once I have a laboratory in my bedroom.

 

[Skorpio]

Yes, thats very helpful information, thankyou kindly. Now off to learn the bare basics of medicinal chem and pharma I go, will be back once I have a laboratory in my bedroom.

You are going to want to know organic chemistry, and then some biochemistry to be able to do anything in the medicinal chemistry space. Medicinal chemistry is usually a specialization after the basic undergraduate chem/O-chem/biochem classes have been taken.

Organic chemistry is probably obvious, as this will teach you how to describe and manipulate molecules that you are interested. Biochemistry is important because these molecules are interacting with proteins (usually) in the body, so understanding how proteins function at the molecular level is super important for rational drug design.

Pharmacology is also pretty important for drug design, medicinal chemistry focuses more on the synthesis and optimization of molecules (including managing they r metabolism) while pharmacology focuses on their effects once in a body (and the effects after they have bound to a receptor).

 

[chainsawkidd]

You are going to want to know organic chemistry, and then some biochemistry to be able to do anything in the medicinal chemistry space. Medicinal chemistry is usually a specialization after the basic undergraduate chem/O-chem/biochem classes have been taken.

Organic chemistry is probably obvious, as this will teach you how to describe and manipulate molecules that you are interested. Biochemistry is important because these molecules are interacting with proteins (usually) in the body, so understanding how proteins function at the molecular level is super important for rational drug design.

Pharmacology is also pretty important for drug design, medicinal chemistry focuses more on the synthesis and optimization of molecules (including managing they r metabolism) while pharmacology focuses on their effects once in a body (and the effects after they have bound to a receptor).

Organic chem/bio chem, Pharmacol, med chem. Loosely in that order id imagine since I of course need very entry level fundamentals. Thank you, more valuable info. I often have the habit of getting too ahead of myself, so it helps if I create a loose order like this to follow. Again, if you have any particular source material that you recommend, or ''essential'' books from over the years then do not hesitate to shoot me a message.
Thanks again, Skorpio.

 

[Skorpio]

Organic chem/bio chem, Pharmacol, med chem. Loosely in that order id imagine since I of course need very entry level fundamentals. Thank you, more valuable info. I often have the habit of getting too ahead of myself, so it helps if I create a loose order like this to follow. Again, if you have any particular source material that you recommend, or ''essential'' books from over the years then do not hesitate to shoot me a message.
Thanks again, Skorpio.

It's a cell biology book, but I can't reccomend "Molecular Biology of the Cell" by Alberts. It's extremely clear and covers things from molecular biology, signal transduction, and describes their structure to the level of chemistry.

Ive had non-scientist friends read and enjoy it (they like to read textbooks).

 

[someguyontheinternet]

It's a cell biology book, but I can't reccomend "Molecular Biology of the Cell" by Alberts. It's extremely clear and covers things from molecular biology, signal transduction, and describes their structure to the level of chemistry.

Ive had non-scientist friends read and enjoy it (they like to read textbooks).

That's a book I've had recommended to me many times. Definitely a good one

https://www.amazon.com/Principles-Pharmacology-Pathophysiologic-Basis-Therapy/dp/1451191006

This is a pretty good one for pharm

 

[chainsawkidd]

Understood, will add to my current list of helpful literature.

 

[AlsoTapered]

As @Skorpio correctly identified, you need a strong grounding in organic chemistry because while in-silico modelling is pretty good at identifying candidate ligands, unless their is a facile synthesis, it's useless.

A lot of people seem to think they can just draw a molecule and assign it a set of attributes. But without that understanding of organic chemistry, that's all it ever will be; an idea with no PROOF.

We occasionally get people who will draw a random chemical, CLAIM to have had it synthesized and have tested them... but at the very least they would receive a GC-MS of the product and any sane researcher would pay the extra for NMR and would post same. But it never happens even if asked.

 

[chainsawkidd]

As @Skorpio correctly identified, you need a strong grounding in organic chemistry because while in-silico modelling is pretty good at identifying candidate ligands, unless their is a facile synthesis, it's useless.

A lot of people seem to think they can just draw a molecule and assign it a set of attributes. But without that understanding of organic chemistry, that's all it ever will be; and idea.

Basic Organic Chemistry is exactly where I have started, also this is somewhat still related as it does involve research but... I found a thread from a short while back where I believe you stated you had access to a large number of papers included in a database? Whether it includes chemistry I cannot remember, but just for the record are the majority of papers ones not able to be found online? And are there any relating to the subject of this thread.... Thankyou.

 

[someguyontheinternet]

There are some good resources in here

⫸STICKY⫷ - Useful neuroscience/pharmacology threads

Neuroanatomy and the Brain Erowid/BlueLight Neuropharmacology Text List of FREE Chemistry Databases BEST Websites to Self-Educate Psycho-Pharmacology?? The Big & Bangin' Miscellaneous Chemistry/Pharmacology Odds N' Ends Thread: Part 3 (see also: v. 1 & v. 2)

bluelight.org

OpenStax | Free Textbooks Online with No Catch

OpenStax offers free college textbooks for all types of students, making education accessible & affordable for everyone. Browse our list of available subjects!

openstax.org

OpenStax | Free Textbooks Online with No Catch

OpenStax offers free college textbooks for all types of students, making education accessible & affordable for everyone. Browse our list of available subjects!

openstax.org

 

[Skorpio]

Basic Organic Chemistry is exactly where I have started, also this is somewhat still related as it does involve research but... I found a thread from a short while back where I believe you stated you had access to a large number of papers included in a database? Whether it includes chemistry I cannot remember, but just for the record are the majority of papers ones not able to be found online? And are there any relating to the subject of this thread.... Thankyou.

If it's not a super new paper scihub is always my first place to look

 

[chainsawkidd]

There are some good resources in here

⫸STICKY⫷ - Useful neuroscience/pharmacology threads

Neuroanatomy and the Brain Erowid/BlueLight Neuropharmacology Text List of FREE Chemistry Databases BEST Websites to Self-Educate Psycho-Pharmacology?? The Big & Bangin' Miscellaneous Chemistry/Pharmacology Odds N' Ends Thread: Part 3 (see also: v. 1 & v. 2)

bluelight.org

OpenStax | Free Textbooks Online with No Catch

OpenStax offers free college textbooks for all types of students, making education accessible & affordable for everyone. Browse our list of available subjects!

openstax.org

OpenStax | Free Textbooks Online with No Catch

OpenStax offers free college textbooks for all types of students, making education accessible & affordable for everyone. Browse our list of available subjects!

openstax.org

Hell yeah. Wisdom is my favourite food. Thanks, pal. I am gonna have a good look around, so much to see, dont know where to start.

 

[chainsawkidd]

If it's not a super new paper scihub is always my first place to look

Another place ive never been. What a great mission statement they have, I've never stuck at anything in life, but im hoping I stick with this, drug design to put it loosely is an end goal, the first step is just finding what basics to learn first, Organic chemistry it seems from the response here.

 

[Rectify]

WATCH:

TINO
1-(1-thia-indene-5-yl)-2-methylaminopropane

 

[chainsawkidd]

WATCH:

TINO
1-(1-thia-indene-5-yl)-2-methylaminopropane

Synthetic Methamphetamine analogue? Also im not sure what the ''WATCH:'' part related to, thought maybe you forgot to add some sort of link...
IF you have any helpful information feel free to reply or DM.

 

[AlsoTapered]

WATCH:

TINO
1-(1-thia-indene-5-yl)-2-methylaminopropane

[1-(1-Benzothiophen-5-yl)propan-2-yl](methyl)amine

[1-(1-Benzothiophen-5-yl)propan-2-yl](methyl)amine | C12H15NS | CID 165889699 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.

pubchem.ncbi.nlm.nih.gov

I think the person who designed, synthesized, patented, obtained a CAS number and even lectures on this compound is the one who get's to name it.

Entactogens, MDMA, and Bringing New Love Drugs To Market | Matthew Baggott

This episode will explore entactogens, which are drugs like MDMA, 2C-B, and Methalone. Our guest is Matthew Baggott.

www.jameswjesso.com

In a way it's a good think that people like Shulgin & Nichols made thousands of compounds, recorded the syntheses and activity and DIDN'T patent them is a good thing because it's severely limited what these new startups CAN obtain patents for.

Psychedelics are evidently on the roadmap to become a highly profitable industry.

 

[Rectify]

Or they could bite the bullet and let the patent holder(s) get their cut. But with Markush structures being recognized by patent law, things get dicey.

 

[AlsoTapered]

You cannot synthesize what you cannot make. Patents use Markush structures just so simplify the description of what they are patenting. So their synthesis, while I'm certain is workable, almost certainly isn't an optimal synthesis.

I've noted that their are well over 200 patents that simply cover improvements to the synthesis of sertraline (for example). Not a new compound, an improved route. Then I noted that this is true for all popular (read profitable) medicines.

We ALL know the game where a new chiral medicine is introduced as the raecemate so 16 years on, behold, they can 'discover' that the enantiopure medicine has an improved safety profile, is more active... whatever they need to patent the chiral compound and voila, another 20 years of patent protection.

Citalopram --> Escitalopram
Ketamine --> Esketamine
Zopiclone --> Eszopiclone
Salbutamol --> Levosalbutamol

With the ring-substituted amphetamines and tryptamines where both isomers are known and explored, patents on specific ratios of the two enantiomers has become a loophole to gain a patent.

In fact, the entire field of identifying optimized routes to the resolution of raecemic medicines is such a potentially profitable arena for third party developers to patent methods to resolve isomers even BEFORE any decision has been made to go on to produce the enantiopure medicine. Tramadol is the trans-pair and lo and behold in 1997 a third party patented a very simple method (using tartaric acid) to resolve (1S,2S) tramadol, the isomer with opiate activity. I presume they did so because tramadol is SO cheap that a chiral synthesis would still cost more to produce a given amount of (1S,2S).

 

[snmfmy]

It was my probably naive understanding that a lot of the research chemicals are developed with a cookie cutter positional substitution of functional groups or halogens.

This is further filtered by known reactions to allow the substitutions to open or close the ring, etc.

There's a known road map for increased potency and decreased potency that are mostly the rule but sometimes aren't. For example, the beta key tone analogs of MDXX empathogens are significantly less potent. MDMA is more potent than βK-MDMA, βκ-2-CB Is much less potent than 2cb yet astoundingly has been reported to have a much longer duration of action.

And then you have the substitution at positions around the benzene ring, halogenation using chlorine fluorine and bromine and iodine.

So I think during a good portion of the RC explosion it was cookie cutter exercise, now it's probably a lot more medicinal organic chemistry applied to finding new novel substances with easy to execute synthesis pathways with reasonable yields that agonize or antagonize particular targets of the brain.

To explain a little bit more clearly, you have the 2-MMC, 3-MMC, 4-MMC, Then you have the CMC series. Then you have the FMC series. And it was sort of like throw spaghetti at the wall and see if it sticks.