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I Like to Draw Pictures of Random Molecules

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^ the fluorine on the cyclohexyl ring? metabolic blockade to increase T1/2? Is P450 hydroxylation of the ring main first pass metabolism? I would expect hydrolysis of the tertiary amide to be responsible for shorter half-life. yes?
 
1-carbomethoxy-1-(2-piperidinyl)-1-(2,5-dimethoxy-4-chlorophenyl)methane.png


DOC-MPH
 
U-47700

330px-U-47700_fixedstructure.svg.png


NSFW:

U-47700 is an opioid analgesic drug developed by a team at Upjohn in the 1970s[1] that acts as a selective agonist of the µ-opioid receptor with a Kd value of 5.3 nM compared to 910 nM for the κ-opioid receptor[2][3] and has around 7.5 x the potency of morphine in animal models.

U-47700 is a structural isomer of the earlier opioid AH-7921 and the result of a great deal of work elucidating the quantitative structure–activity relationship of the scaffold. Upjohn looked for the key moieties which gave the greatest activity[8] and posted over a dozen patents on related compounds, each optimizing one moiety[9][10][11][12][13][14][15][16] until they discovered that U-47700 was the most active.[17]

U-47700 became the lead compound of selective kappa-opioid receptor ligands such as U-50488, U-51754 (containing a single methylene spacer difference) and U-69,593, which share very similar structures.[18][2] Although not used medically, the selective kappa ligands are used in research.

U-47700 has never been studied on humans, but would be expected to produce effects similar to those of other potent opioid agonists, including strong analgesia, sedation, euphoria, constipation, itching and respiratory depression which could be harmful or fatal. Tolerance and dependence would be expected to develop.[28]

Combined consumption of U-47700 and fentanyl caused one fatality in Belgium. 17 opioid overdoses and several deaths in the USA had initially been associated with U-47700 in April 2016,[31] as of September 2016 at least 15 fatalities were confirmed.

Legal status

Following its sale as a designer drug, U-47700 was made illegal in Sweden on 26 January 2016.

U-47700 was emergency scheduled in Ohio on 3 May 2016 by executive order of Governor John Kasich.

The United States Drug Enforcement Administration (DEA) proposed a temporary placement of U-47700 into Schedule I of the Controlled Substances Act on 7 September 2016


It apparently feels oxycodone-like to some people, so I take it it is a little more uplifting and stimulating than say morphine... the feeling is popular but it has a short-lived effect and has done terrible things for people like addictions worse than heroin.

I like opioids, or I should say liked because I don't allow myself to indulge anymore in general, but even if I did this one scared me too much - I've heard real horror stories from a BL-er I was sorta close to / heard from and of.

You should probably think twice before getting involved with U-47700.

I've tried AH-7921 though a while back and though it was very peculiar and while it may be effective as an analgesic, it's not a strong drug if you just using it for quelling shitty feelings like a junkie of sorts.
 
Had been meaning to give, I THINK it was that one, some similar looking open chain dichlorophenyl-based thing like that at any rate.

Like oxycodone? meaning meh and no rush to speak of then or am I missing something there. HOW short acting is this drug?
 
https://psychonautwiki.org/wiki/U-47700 read your heart out.. maybe it was the AH-7921 that I mentioned you are thinking of, it's indeed very close to this one: the N-desmethyl analogue.

I have not taken U-47700 so I can't pitch it to you nor do the opposite beyond the warning I gave earlier... enough people like it, but then again plenty of people like oxycodone while you don't apparently... and not diamorphine a whole lot either I think so maybe this one isn't really for you anyway.

Do tell me about the ergot if you please, that should be damn interesting. The boletes I talked about earlier were mostly Edulis (ceps), Badius and L. Scabrum...
 
imho U4x pretty much like highly potent Tramadol: mu Opioid + SNDRI and possibly releaser as well. Not surprising that it is extremely addictive:).. basically speed-ball: massive Dopamine release + mu activation. But the 3,4-dichlorophenyl pattern generally gives more SERT selectivity (kind of like 3,4 dichloropheny MPH analog). Though I don't think anybody has tested that but the structure looks too close to that of Tramadol and other SNDRIs not to have dopaminergic/serotonergic.. but who knows?

Now..even more potent opioid:
tst1_zpssjqmgxth.png

(at least as good as fenta. 10x more than U-477 or 100x morphine at least!! since adding phenolic OH (like with tramadol M1) jack up mu Opioiod affinity dramatically> 1000x in the case of tramadol.

OH substitution also increase Dopaminergic as well (relative to H) and decrease serotonergic and tend to give DNRI DNRAs selectively. SERT transporter doesnt like hydrophilic groups (cautiously generalizing what is known about SAR of OP and SNDRI/R.. but who knows?

Now to get less Opioid and more cocaine-like (or may be more MDMA-like?? more serotonergic??
tst2_zpsh51j8nlm.png


PS: the original U4x patent doesn't cover much SAR .. would be nice to see some more U4x on the RC market!
 
What do you base the notion that U-47700 is an SNDRI on? Many opioids like oxycodone appear to have some serotonergic action (it's definitely not only tramadol that can get involved in serotonin syndrome etc) but it's another thing to compare to tramadol which is a rather significant SRI and also dangerous to mess with. If U-47700 was like that and tolerance to the opioidergic effects would be affected a lot leading to increased doses, you'd expect issues (people have been known to take a lot of it once they get going, also I've known a person to abuse it who also took a lot of other things like stimulants and I never heard of any serotonergic crisis); issues because the SRI effect wouldn't necessarily see the same tolerance development?
It's worth noting that the manner in which oxycodone influences serotonin levels or has interactions with other drugs is very poorly understood.

The phenol does seem like a good idea though, has it been tested?
 
I kind of like that. It made me think of this, which I'm not sure will exist.

2,3-methylenedioxy-4-(2-aminopropyl)furan.png
 
Trifluoromescaline-3,5-dragonfly

(8-(Trifluoromethoxy)furo%5B2%2C3-f%5D%20%5B3%5Dbenzofuran-4-yl)ethan-2-amine.png


(8-(Trifluoromethoxy)furo[2,3-f] [3]benzofuran-4-yl)ethan-2-amine

I don't know what's ambiguous about this formula?, polycyclic nomenclature is NOT my forte

1-((3%2C4-methylenedioxy)thiophen-5-yl)-2-methylaminopropane.png


The 2,3-methylenedioxy seems more analogous to MDMA but I don't know that the rings are stable... at least the 3,4 connected backbone has been made.

1-((2%2C3%2C4-trimethoxy)thiophen-5-yl)-ethan-2-amine.png


Strikeaposamine? Surely if you make a molecule that dabs it means it gets you very high?

2-(methylethylamino)2%2C3-dihydro%5B1%2C4%5Doxazino%5B2%2C3%2C4-hi%5Dindole.png
 
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a lot of oxygen in last few posts … stable?

the 2,3-MDIO looks kinda sexy if it will stay put
 
I think so for most but not sure.. kinda foresee problems with Dresdens entry, and don't know if the thiophene counterpart was made but that is why I chose the other methylenedioxy thiophene orientation. I don't know about the significance of the sulfur position in methiopropamine.

Damn, inspired by MDAI and above ideas I wanted to make something freaky, and figured out the nomenclature by myself, no copy pasta. :)

4%2C5-methylenedioxy-2-thiabicyclo%5B1.2.5%5Ddec-3%2C5(1)-dien-8-ylamine.png


4,5-methylenedioxy-2-thiabicyclo[1.2.5]dec-3,5(1)-dien-8-ylamine

I can make the linkage to the amine 2-carbon for you instead of 3-carbon if you like.. but I like this one because it looks like a lab mouse growing sulfur on its back.. ;p
Unfortunately now that I see it I think maybe it's too constrained?

Also: the ambiguity in opsin was just that I didn't explicitly say that the ethanamine connects at position 1 although it is implicit from the fact that the formula says the amine is on the 2-position... a normal chemist correctly infers that this only happens because it refers to something that must be happening at the other one where the counting started.
 
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Not bad and in theme :D .. question about it: if thiophene is bioisosteric to benzene does that make that benzothiophene like naphthalene and the above molecule probably PAL-287 like?
And if sulfur is in the same group as oxygen, then why isn't furan similarly bioisosteric?
I think benzofuran analogues of indoles may suffer from the problem that the 1-position nitrogen proton is missing for essential bonding interactions rather than something else, wonder if a sulfurane would solve that but those are pretty exotic..
 
Solipsis said:
Not bad and in theme :D .. question about it: if thiophene is bioisosteric to benzene does that make that benzothiophene like naphthalene and the above molecule probably PAL-287 like?
And if sulfur is in the same group as oxygen, then why isn't furan similarly bioisosteric?
I think benzofuran analogues of indoles may suffer from the problem that the 1-position nitrogen proton is missing for essential bonding interactions rather than something else, wonder if a sulfurane would solve that but those are pretty exotic..
Click to expand...

I guess it largely depends on the molecule and its target whether 2-furanyl substitutes for a phenyl or an ortho-substituted phenyl. In case of amphetamine and MPA I suppose the 2-furanyl analogue may have a too small aromatic ring along with inappropriate electronics. After all furan is less aromatic than thiophene which is directly related to charge delocalization, obviously sulfur is better at it.
 
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