Ketamine salts solubility

[Dresden]

^--Nice.

Here's Another One:

L.L. [LARRY LILAC] BEAN

(Lilacs contain 1,4-dimethoxybenzene, which I conjugated with piperidine and gave a creative name to.)

I'd Try It!!!

I would rather try Disco Crisco, though.

KIMBERLY

AHNOLD, ideal for fighting or race car driving.

DAVID

TINKY WINKY, a Teletubby.

'JWH'-2019



Has this one been thought of lately? Seems like an obvious MXE congener of sorts to me.

MISTER PEABODY

SWEET 16

CRUNK MUFFIN

BLADE RUNNER

And There Ain't No Road Just Like It Anywhere I've Found, Blade Running South On Lake Shore Drive Headed Into Town. And It's 4 AM In The Morning, And All The People Have Gone To Sleep. It's Just You And Your Mind And Lake Shore Drive. And Tomorrow Is Another Day. And The Sun Shines Bright In The Morning Time. And Tomorrow Is Another Day.

RON 'OPIE' HOWARD

AL 'VISHNU' BUNDY

Love Is Blind.

LORD HARLEY 'SO SO DEF' DAVIDSON

The Fear Of The Lord Is The Root Of Righteousness.

ANDREW 'SHIVA' CHRISTIAN

My 'Dance' Keeps Every Universe Going And Is My Duty.

YOU NEED CANDY.



C ANDY

ANDY

GOMER PILE, suspected opiate.

SHAZAAM

CICCONE

HI CHEW

PIKACHU

I would be kind of surprised if these last few did much of anything, but hey, I've been wrong before.

FormerBeagle

Go Ask

ALICE In Wonderland.

Note: I realize pyrylium salts are not usually stable, but ALICE and her congeners are intended to be amine salts.

 

[S.J.B.]

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)

 

[S.J.B.]

Structural Simplification of a Tetrahydroquinoline-Core Peptidomimetic μ-Opioid Receptor (MOR) Agonist/δ-Opioid Receptor (DOR) Antagonist Produces Improved Metabolic Stability
Corresponding author: Henry I. Mosberg (Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, United States)
Journal of Medicinal Chemistry 2019, Volume 62, Issue 8, Pages 4142–4157
Published online March 29th, 2019
https://doi.org/10.1021/acs.jmedchem.9b00219

We have previously reported a series of μ-opioid receptor (MOR) agonist/δ-opioid receptor (DOR) antagonist ligands to serve as potential nonaddictive opioid analgesics. These ligands have been shown to be active in vivo, do not manifest withdrawal syndromes or reward behavior in conditioned-place preference assays in mice, and do not produce dependence. Although these attributes are promising, these analogues exhibit poor metabolic stability in mouse liver microsomes, likely due to the central tetrahydroquinoline scaffold in this series. As such, a structure–activity relationship (SAR) campaign was pursued to improve their metabolic stability. This resulted in a shift from our original bicyclic tetrahydroquinoline core to a monocyclic benzylic-core system. By eliminating one of the rings in this scaffold and exploring the SAR of this new core, two promising analogues were discovered. These analogues (5l and 5m) had potency and efficacy values at MOR better or comparable to morphine, retained their DOR-antagonist properties, and showed a 10-fold improvement in metabolic stability.

5l: R1 = H, R2 = OEt
5m: R1 = H, R2 = OnPr

 

[S.J.B.]

Synthesis and Evaluation of Novel Biased μ-Opioid-Receptor (μOR) Agonists
Corresponding authors: Bohua Zhong and Weiguo Shi (State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology & Toxicology, Beijing, China)
Molecules 2019, Volume 24, Issue 2 Page 259
Published online January 11th, 2019
https://doi.org/10.3390/molecules24020259

‘Biased’ ligands of G protein-coupled receptors (GPCRs) represent a type of promising analgesic with reduced on-target side effects. PZM21, a potent μ-opioid-receptor (μOR)-biased agonist with a new chemical scaffold compared to classic opioids, has been identified as a therapeutic lead molecule for treating pain. In the current study, novel PZM21 analogues were synthesized and evaluated for their in vitro and in vivo efficacy. Novel compound 7a and PZM21 demonstrated undetectable β-arrestin-2 recruitment, however, their analgesic effects need to be further confirmed. Compounds 7b, 7d, and 7g were stronger analgesics than PZM21 in both the mouse formalin injection assay and the writhing test. Compound 7d was the most potent analogue, requiring a dose that was 1/16th to 1/4th of that of PZM21 for its analgesic activity in the two assays, respectively. Therefore, compound 7d could serve as a lead to develop new biased μOR agonists for treating pain.

PZM21:

7d:

 

[S.J.B.]

Synthesis and Structure–Affinity Relationships of Spirocyclic Benzopyrans with Exocyclic Amino Moiety
Corresponding author: Bernhard Wünsch (Institut für Pharmazeutische und Medizinische Chemie, Universität Münster, Münster, Germany)
Journal of Medicinal Chemistry 2019, Volume 62, Issue 8, Pages 4204–4217
Published online April 2nd, 2019
https://doi.org/10.1021/acs.jmedchem.9b00449

σ1 and/or σ2 receptors play a crucial role in pathological conditions such as pain, neurodegenerative disorders, and cancer. A set of spirocyclic cyclohexanes with diverse O-heterocycles and amino moieties (general structure III) was prepared and pharmacologically evaluated. In structure–activity relationships studies, the σ1 receptor affinity and σ1:σ2 selectivity were correlated with the stereochemistry, the kind and substitution pattern of the O-heterocycle, and the substituents at the exocyclic amino moiety. cis-configured 2-benzopyran cis-11b bearing a methoxy group and a tertiary cyclohexylmethylamino moiety showed the highest σ1 affinity (Ki = 1.9 nM) of this series of compounds. In a Ca2+ influx assay, cis-11b behaved as a σ1 antagonist. cis-11b reveals high selectivity over σ2 and opioid receptors. The interactions of the novel σ1ligands were analyzed on the molecular level using the recently reported X-ray crystal structure of the σ1 receptor protein. The protonated amino moiety forms a persistent salt bridge with E172. The spiro[benzopyran-1,1′-cyclohexane] scaffold and the cyclohexylmethyl moiety occupy two hydrophobic pockets. Exchange of the N-cyclohexylmethyl moiety by a benzyl group led unexpectedly to potent and selective μ-opioid receptor ligands.

 

[sekio]

 

[sekio]

help me I need 50 cc's of Texas carbon to finish this synthesis

[jumping on couch] FUCK YO VALENCES, BUY SOME MORE ORBITALS YA RICH MOTHERFUCKA

but what happens when you draw a methylenedioxy ring on it?????

yeah I want some of whatever venus drug the authors were on when they drew this shit

(ref)
(apparently starfleet still uses hydroxyzine and propoxyphene... who said the future was in fentanyl chemistry???)

 

[S.J.B.]

(ref)
(apparently starfleet still uses hydroxyzine and propoxyphene... who said the future was in fentanyl chemistry???)

I liked their Vulcan "tri-ox compound"... I guess the authors weren't aware of ozone.

 

[sekio]

'Rytaline' also made me laugh. Gene Roddenberry apparently abused methylphenidate so it seems somewhat appropriate. For sone reason, space-ritalin is actually some sort of demethylpenicillin hydrazide. Again, with texas carbon.

Also, you're supposed to administer 500 cc of, ahem, "tri-ox", in a dose? All at once? If that were liquid ozone you'd probably explode. In fact even 500 cc of gas would be thoroughly destructive to anything coming close to organic material. I wonder if potassium superoxide sublingual tablets are also availiable.

 

[Dresden]

HNO3 + H2SO4

VITRIOL

MONEY MAKER

SAINT PETER

a PEP PILL, probably not that strong though

4-METHYL-FOCALIN (wouldn't mind trying this one)

SASS

Not 100% sure sass is even psychoactive; don't particularly care. It was fun to name and draw. :/

DOPAMINE (DA)

IVAN

ETHYLHEXEDRINE

suspected NOOTROPE inspired by bethanechol

N-METHYL-INTERESTING because interesting was interesting

BACKSTREET ATL

{because I am creative}

FLAKKITA (a-pvp lite)

FANI (smacky)

MARTA

is

SMARTA

I dreamed about MARTA (which I forgot I had already named DISCO CRISCO iirc) & SMARTA while I slept for 20 hours last night. Very sedating. Appear to be super strong fentanyl type opiates, which are not my cup of tea. Will stick with INTERESTING (their N-methyl or N-ethyl deshomologue and bare phenyl analogue) for now if at all; it is safe to say it is in fact a stimulant, I would say. :/ Still prefer amphetamine for my ADHD, but dexmethylphenidate and interesting are fun and effective too and more complex structurally and pharmacologically than simple amphetamine. It could be said that interesting is a 'logical stimulant,' with a 1-oxy substituent. You know, 1 representing the Sun and Leo and all. I predict that N-methyl interesting will be an opiate, which doesn't particularly interest me, though I wouldn't say no to it at a reasonable dose and an appropriate time and place. Enjoy. Yours truly, The Mad Scientist.

PHREEX ('Dave')
N-methyl-3-oxo-hexahydromorphinan
Should be a potent opiate.

SHINY HINY
N-methyl-3,4-methylenedioxymorphinan
Bon apetit! (literally, 'good ape tit')

This Is What I Want Next Month:

PARIS HILTON

So Elegant.

* * *

LUCIFER

JUCIFER

REVELATIONS

OMAR

MAHMOUD

ULYSSES
1,2,3,11,12,13,14,15-octahydro-N,N-diethyllysergamide

The lone double bond is neccessary for the in vivo embedded piperidinyl pharmacophore aromatization to the N-methyl pyridinium species, which is most responsible for activity.

ODYSSEUS
N,N-diethyl-1,2,3,13,14,15,16-heptahydro-12-oxolysergamide

DOCTOR SEUSS, possible 5-HT2a & CB2 agonist
4-oxo-1-pentyl-N,N-diethyl-1,2,3,12,13,14,15,16-octahydrolysergamide

JABBERWOCKY
N,N-diethyl-12-oxo-1-pentyl-4-oxo-1,2,3,13,14,15,16-heptahydrolysergamide

HIPPIE FLIP
N,N-diethyl-12,13-methylenedioxylysergamide

THE MIND BENDER
1-(3-methoxyphenyl)-1-(N-(1-oxopropyl)-N-phenylamino)-4-methyl-4-azacyclohexane

SVELTE
2,6-dimethyl-4-oxa-3,5-diphenyl-piperidine
so simple it hurts

2-amino-1-phenylpropane

"Ah, Clean Burning Propane!!!"--King Of The Hill (cartoon series) quote.

CHLORTYLENOL

But seriously,

ETHEREAL

'Some People Lose Their Faith In Heaven Because It Shows Them Too Little. But How Many People Lose Their Faith In Heaven Because It Shows Them Too Much?"

CIRRUS

ASPIRINAMINE (AA)
-inspired by methyl salicylate and
4-oxypiperidine
-I'm posting this because I'm bored
-I highly doubt AA is a good drug

OTOH, This One Might Be A (short acting) Blockbuster:

SENSATION

REVERSE ESTER SENSATION

CAKE

CHRISTOPHER

Some Scientists, Lyricists, Popping Guinesses

COLUMBUS

ELAINE

 

[S.J.B.]

Monoamine receptor interaction profiles of 4-aryl-substituted 2,5-dimethoxyphenethylamines (2C-BI derivatives)
Corresponding author: Matthias E. Liechti (Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, University of Basel, Basel, Switzerland)
European Journal of Pharmacology 2019, Volume 855, Pages 103-111
Published online May 4th, 2019
https://doi.org/10.1016/j.ejphar.2019.05.014

Many ring-substituted phenethylamines exert psychedelic effects that are thought to be primarily mediated by interactions with serotonergic 5-hydroxytryptamine 2 (5-HT2A) receptors. The 2,5-dimethoxyphenethylamine (2C derivative) core structure with small lipophilic substituents at the 4-position seems to be particularly favorable for psychedelic effects. In contrast, 2C derivatives with bulky lipophilic substituents at the 4-position of the phenyl ring tend to display antagonist behavior at serotonin 5-HT2 receptor sites. To gain a better understanding of agonist and antagonist behavior of substituted phenethylamines, binding affinities and functional activation and inhibition of a series of 4′-aryl substituted 2,5-dimethoxyphenethylamine (2C-BI derivatives) at various monoamine receptors were determined. In addition, the interactions of the compounds with monoamine transporters were assessed. Various 2C-BI derivatives potently bound to human serotonergic and adrenergic receptors and to rat and mouse trace amine-associated receptor 1. Additionally, 2C-BI-8 and 2C-BI-12 activated serotonin 5-HT2A and 5-HT2B receptors at submicromolar concentrations. 2C-BI-1 and 2C-BI-7 were the only 2C-BI derivatives to activate human trace amine-associated receptor 1. 2C-BI-3 and 2C-BI-4 interacted with monoamine transporters but with low overall potency. In conclusion, the tested 2C-BI derivatives displayed diverse pharmacological profiles. The relatively high affinities of various 2C-BI derivatives at the serotonin 5-HT2A receptor indicate a high steric tolerance of the binding pocket. Potent partial activation of the serotonin 5-HT2A receptor by 2C-BI-8 and 2C-BI-12 suggests that these substances may potentially exert psychedelic effects similar to other compounds of the 2C family.

 

[FormerBeagle]

Any thoughts about this compound? I just noticed that 2,6-diisopropylphenol is available fairly inexpensively. The phenol itself has pretty problematic hurdles to recreational use, between the formulation issues, the difficulty in titrating a dose without full loss of consciousness, the necessity of IV administration, and the specter of death. So how about the carbamate? Works for other alcohols to give compounds with increased activity. Would be interesting to see if it was a prodrug only, or active as such. Also perhaps this would allow oral or intranasal, or vaporization as routes of admin. I think I've got some phosgene around here somewhere...

 

[nuttynutskin]

Isn't that what killed Michael Jackson?

 

[FormerBeagle]

Yes, propofol did kill him. But my live-in anesthesiologist is more vigilant than his was.

 

[nuttynutskin]

Yes, propofol did kill him. But my live-in anesthesiologist is more vigilant than his was.

 

[sekio]

7-Hydroxymitragynine Is an Active Metabolite of Mitragynine and a Key Mediator of Its Analgesic Effects
Andrew C. Kruegel, Rajendra Uprety, Steven G. Grinnell, Cory Langreck, Elizabeth A. Pekarskaya, Valerie Le Rouzic, Michael Ansonoff, Madalee M. Gassaway, John E. Pintar, Gavril W. Pasternak, Jonathan A. Javitch, Susruta Majumdar, Dalibor Sames

https://pubs.acs.org/doi/10.1021/acscentsci.9b00141

... Here we report evidence that an active metabolite plays an important role in mediating the analgesic effects of mitragynine. We find that mitragynine is converted in vitro in both mouse and human liver preparations to the much more potent mu-opioid receptor agonist 7-hydroxymitragynine and that this conversion is mediated by cytochrome P450 3A isoforms. Further, we show that 7-hydroxymitragynine is formed from mitragynine in mice and that brain concentrations of this metabolite are sufficient to explain most or all of the opioid-receptor-mediated analgesic activity of mitragynine. At the same time, mitragynine is found in the brains of mice at very high concentrations relative to its opioid receptor binding affinity, suggesting that it does not directly activate opioid receptors. The results presented here provide a metabolism-dependent mechanism for the analgesic effects of mitragynine and clarify the importance of route of administration for determining the activity of this compound.

very cool

i wonder if cyp3a4 inducers would make kratom more effective...

 

[Skorpio]

Wouldn't phosgene make a dicarbonate, or would the steric hindrance from the ortho Ips prevent that? If you can quench with ammonia quick enough it would probably fly, assuming that the phosgene could attack the alcohol at all.

Propofol and a shit ton of midazolam and other benzos and sleep meds killed mj. That being said hope your live in cardiologist knows cpr.

 

[FormerBeagle]

Wouldn't phosgene make a dicarbonate, or would the steric hindrance from the ortho Ips prevent that? If you can quench with ammonia quick enough it would probably fly, assuming that the phosgene could attack the alcohol at all.

Phosgene is kind of the reagent to beat for this general reaction. I'm pretty sure it would attack the phenol, even with the steric hindrance. Might take some persuading though. Yes, ammonia would be step 2. There are probably better ways to get the carbamate in there these days, but what can I say? I'm a fan of the classics.

That being said hope your live in cardiologist knows cpr.

Are you kidding? He graduated from the top of his class at Hollywood Upstairs Medical College.

 

[Skorpio]

I guess the other question is whether the carbamate would cleave in an appreciable amount to release an active dose, or if it would be active on it's own.

There is conflicting ish data on whether propofol binds the transmembrane helices as solvent anesthetics or closer to the pores as barbiturates do. If it binds at the transmembrane helices it may be less amenable to adding bulk than the barb region.

 

[Skorpio]

Another thing to look into would be the kinetics of fospropofol, could be enlightening.