Ketamine salts solubility

[Doctor Steve Brule]

There are an estimated 10^60th power of chemical compounds. Only 2% of them have been characterized so far.

I focus on dopamine, adrenaline, and serotonin analogs, using Sasha Shulgin's methodology as illustrated in PiHKAL & TiHKAL.

Wouldn't 2% of 10^60 be 2 x 10^58?

 

[Rectify]

Yes, I believe so.

 

[Rectify]

SUPER_DOPER_ROPER
4-(3,4-methylenedioxyphenyl)-4-(1-methyl-3-piperidinyl)-3-oxobutane

DESIGNER_HYATT_WYATT
4-(3,4-methylenedioxyphenyl)-4-(2-piperidinyl)-3-oxobutane

ROLY_POLY
4-(4-methoxyphenyl)-4-(2-piperidinyl)-3-oxobutane

HOLY_MOLY
4-(3,5-dimethoxy-4-methylphenyl)-4-(2-piperidinyl)-3-oxobutane

 

[AlsoTapered]

Wouldn't 2% of 10^60 be 2 x 10^58?

Well, the guy said 'approximately'' and gave a power which represents a HUGE range.

2% is also an approximation of an approximation so simply representing it as a smaller number isn't useful or accurate.

It's possible to DRAW any compound one chooses to but often quite simple compounds have been predicted but haven't been made and we have no way of knowing if they will ever be made - which makes people drawing random molecules a joke. When people began ascribing trivial names and specifying bioactivity... that's like a small child drawing a picture in crayon and naming the picture and imagining a whole back-story.

 

[Rectify]

You're no fun.

WELLBUTRIN
1-(3-chlorophenyl)-1-oxo-N-tert-butylaminopropane

Wolff-Kishner, hydrazine 2HN-NH2, KOH.

BETTERBUTRIN
1-(3-chlorophenyl)-N-tert-butyl-2-aminopropane

 

[Rectify]

THE_REAL_NITTY_GRITTY
(E)-1-(pyridin-3-yl)-2-(1-methyl-2-pyrrolidinyl)ethene

TASTY_WORLD
(Z)-1-(pyridin-3-yl)-2-(1-methyl-2-pyrrolidinyl)-1-carbomethoxyethene

NOBLESSE_OBLIGE
(Z)-1-(pyridin-3-yl)-2-(1-methyl-2-pyrrolidinyl)-1-carbomethoxy-2-methylethene

UNDER_SIEGE
(E)-1-(pyridin-3-yl)-2-(1-methyl-2-pyrrolidinyl)-2-methylethene

TWIGGY
(E)-1-(thiophen-2-yl)-2-(1-methyl-2-pyrrolidinyl)-2-methylethene

BRIDGETTE_BARDO
(E)-1-(thiophen-2-yl)-2-(1-methyl-2-pyrrolidinyl)-2-methyl-1-carbomethoxyethene

AL_CAPONE
(E)-1-phenyl-2-(1-methyl-2-pyrrolidinyl)-2-methyl-1-ethene

OWSLEY
(E)-1-(furan-2-yl)-2-(1-methyl-2-pyrrolidinyl)-2-methyl-1-ethene

MADONNA
(E)-1-(3,4-methylenedioxyphenyl)-2-(1-methyl-2-pyrrolidinyl)-2-methyl-1-ethene

BRITTNEY_SPEARS
(E)-1-(3,4-dichlorophenyl)-2-(1-methyl-2-pyrrolidinyl)-2-methyl-1-ethene

EMINEM
(E)-1-(4-methoxyphenyl)-2-(1-methyl-2-pyrrolidinyl)-2-methyl-1-ethene

 

[MedicinalUser247]

You want to see a funny video I found on Youtube talking about testing LSD on some solders ? I found a video. You might of seen it before.

 

[vecktor]

@nuke was indeed a she and smart as hell too. She is in a ton of the early threads in PD talking about all RCs that were first hitting the market in the old days, all of the classic Tryps and Phens that laid the groundwork for what the scene became down the road. Havent seen her on here in many years.

to paraphrase:
O, what may (wo)man within (them) hide,
Though angel on the outward side!
Measure for Measure (William Shakespeare, 1604 or something)

 

[AlsoTapered]

Library Genesis

libgen.pm

Above is a hotlink to the paper that discusses Spiridone (R-4066) and it's derivatives.
From the lext:

A comparison of the potency ratios (Table 11), computed relative to methadone, shows that the racemic mixtures of compounds lb and IC are half as potent (ratio = 106) as compound la (ratio = 212) which possesses to chiral center. This may indicate the existence of only one activeste sreoisomer as has been shown in the methadone-methadol-acetylmethadol series[8]. The relative potencies were la > lb = Ic
So it's x212 more potent than methadone and it's duration of action is over three times that of methadone.

Library Genesis

libgen.pm

[8] Above is the link that discusses how the ketone, hydroxyl or ester moiety interacts with the amine function present within the 3,3-diphenyl heptanone (methadone) class of opioid.

Now, it one overlays despropanyl bezitramide (bezitramide is a prodrug), you instantly see that the 3 aromatic rings overlay, the basic amine overlays and the nitrile overlays the ketone function so while the two classes of opioid appear unrelated, in truth when viewed in 3D in their minimum-energy conformation, they overlay.

It also suggests that their is a despropanyl bezitramide derivative that is much MORE potent than the parent compound.

 

[MedicinalUser247]

Wow ! This is a ton of valuable information.

 

[someguyontheinternet]

If you're interested in learning neuropharm I would highly recommend learning basic neuroscience first, including major brain regions and structures to understand the flow of information inputs as well as how behaviors are produced and what regions are involved in higher order processing, memory, and attentional awareness. Then learn pharmacology with the perspective of thinking about neuronal circuits

 

[MedicinalUser247]

See that's the thing... I've studied a little bit about Pharmacology, but not so much about chemistry and neuroscience.

 

[someguyontheinternet]

Having chemistry knowledge does help with pharmacology but its more necessary in medicinal chemistry. In medicinal chemistry usually you already have a protein target you're trying to drug and designing a chemical to do that. Neuropharm is more about finding the target in the first place

 

[AlsoTapered]

Having chemistry knowledge does help with pharmacology but its more necessary in medicinal chemistry. In medicinal chemistry usually you already have a protein target you're trying to drug and designing a chemical to do that. Neuropharm is more about finding the target in the first place

I studied medicinal chemistry for 8 years and practiced that learning for decades. When I studied, neuropharmacology didn't really exist as a separate subject.

I'm happy for people to give me targets and then going on to design ligands. Often it's training-sets that discover targets.

 

[someguyontheinternet]

What do you mean by training sets?

What I mean by discover targets is to elucidate the underlying mechanism of a signaling pathway or neuronal circuit, I didn't think that medicinal chemists were involved in that part

 

[AlsoTapered]

I have posted a link to papers that use training-sets in this thread. I was used to find the key moieties and their spatial relationships for MOP, DOP and KOP ligands. Now those appear to use the minimum-energy conformation but new software allows for near-minimum conformations.

 

[someguyontheinternet]

Ah you're referring to ligands as targets, I'm using target to refer to a protein/receptor. Maybe I need to find the correct terminology

 

[AlsoTapered]

Ah you're referring to ligands as targets, I'm using target to refer to a protein/receptor. Maybe I need to find the correct terminology

No - a ligand is a chemical which has affinity for a receptor. I'm not sure if the term 'target' and 'receptor' refer to quite the same thing. I'm GUESSING that 'target' more generally refers to a domain - but when I studied, we targeted receptors using ligands to produce agonism, partial-agonism, silent agonism, inverse agonism or antagonism. But language changes and can mean different things in different disciplines.

 

[someguyontheinternet]

How do you find which receptor/protein to target?

 

[AlsoTapered]

Well, historically it was the study of naturally occurring ligands but over time rational design and high-throughput screening have taken over. More recently people began to use in-silico models and in the last few months... sigh... AI.

But if you pulled those papers, you can see how we first classified an 'opiate receptor' and then discovered MOR, DOR and KOR were subtypes and most recently NOP has been identified. Now some researchers theorize that their are several more subtypes but it's that theorizing isn't what I deal with,