Bluelight

Thread: Ring Constrained Ester Analogs Of Methyl/Ethyl Phenidates.

Results 1 to 23 of 23
  1. Collapse Details
    Ring Constrained Ester Analogs Of Methyl/Ethyl Phenidates. 
    #1
    This is something I've been musing over for a while now. I'd definitely love to gain more concrete information on the possible reality of it.
    So would ring constrained ester analogs of the phenidates be a) possible, b) Have any activity or be inactive, c) how would my proposed changes alter the effects on receptors and subjective effects in vivo/vitro?
    Right now for the the rings I propose:
    Methylenedioxy,
    Ethylenedioxy,
    Furanyl,
    Thiophene.
    I understand that these changes won't give the phenidates magical mdxx properties as they're reuptake inhibitors. Though if they aren't inactive due to steric bulk I also wonder if the ring constraint change would allow for further modification?
    I'm not sure how relevant further modification would be until the initial modification was understood in it's pharmacological profile changes.
    Thank you for your time with this question.

    Psynce.
     

  2. Collapse Details
     
    #2
    The terminology you are using is confusing. Writing "ring constrained ester analogs" sounds like you would tether the ester moiety in a ring. But there are several things that are unclear.
    1. None of the rings you listed contain a constrained ester.
    2. Where else would the ring attach? To the ortho position on the benzene ring?
    Last edited by serotonin2A; 05-10-2016 at 12:46.
     

  3. Collapse Details
     
    #3
    Moderator
    Neuroscience and Pharmacology Discussion
    sekio's Avatar
    Join Date
    Sep 2009
    Location
    streets of simcity
    Posts
    19,044


    like that?
    Guidelines for OD ||| OD Standards ||| OD Directory Read Me First! ||| NPD Rules
    Please read the links above or PM me if I lock your post. Stay Safe. R.I.P. F28
     

  4. Collapse Details
     
    #4
    No sekio I realise I didn't make my question clear enough. My apologies there. My thoughts lay with the ester moiety (I'm pretty rusty on terminology atm so please bare with me) where the ethyl or methyl would be and not with benzene or pipradine rings.
    Would it be possible that the double bond in the ester be opened and then brought round to connect the two oxygens together to form a third ring? That is what I was wishing to convey. In essence forming a tricyclic molecule.
    I'm not expecting anything fantastic from this more just a case of curiosity.
    I hope that's clearer as an explanation.
     

  5. Collapse Details
     
    #5
    Apologies for the double post, on my tablet the edit function deletes my post.
    The thiophene I mentioned isn't what I was thinking of. The idea was if the ester can be formed into a third ring can it be replaced with the ring with sulfur in from your diagram?
     

  6. Collapse Details
     
    #6
    Would it be possible that the double bond in the ester be opened and then brought round to connect the two oxygens together to form a third ring?
    That would not be an ester any more but an acetal of 2-phenyl-2-(piperidin-2-yl)acetaldehyde.
     

  7. Collapse Details
     
    #7
    The active conformation of methylphenidate has a hydrogen bond between the carbonyl and the NH of the piperidine ring, so this may not work well. On the other hand if you replace the ester with a phenyl ring you have desoxypipradrol, so the carbonyl clearly isn't required for potent stimulant activity.
    Last edited by niflheim; 05-10-2016 at 23:24. Reason: Easter is not ester, thanks phone
     

  8. Collapse Details
     
    #8
    Bluelighter Nagelfar's Avatar
    Join Date
    Nov 2007
    Location
    Vancouver, Washington USA
    Posts
    1,909
    OP means the quinolizidines or "restricted rotational analogs" to methylphenidate. And yes, those are active: the link shows their various values

    Quote Originally Posted by psynce of sound View Post
    I understand that these changes won't give the phenidates magical mdxx properties as they're reuptake inhibitors. Though if they aren't inactive due to steric bulk I also wonder if the ring constraint change would allow for further modification?
    Notice the second to bottom one (on the table if you scroll down on my above link to the WP page) is very near phenmetrazine, which is a releaser: so ring-excised and rigidified MPH variants therefore may well have releasers in their midst
    Last edited by Nagelfar; 07-10-2016 at 02:59.
     

  9. Collapse Details
     
    #9
    I think he rather meant 2-((1,3-dioxan-2-yl)(phenyl)methyl)piperidine (sorry, I'm too tired to upload this, believe it or not) by this:

    Would it be possible that the double bond in the ester be opened and then brought round to connect the two oxygens together to form a third ring? That is what I was wishing to convey. In essence forming a tricyclic molecule.
     

  10. Collapse Details
     
    #10
    Quote Originally Posted by adder View Post
    I think he rather meant 2-((1,3-dioxan-2-yl)(phenyl)methyl)piperidine (sorry, I'm too tired to upload this, believe it or not) by this:
    That is what I thought too.
     

  11. Collapse Details
     
    #11
    Bluelighter Nagelfar's Avatar
    Join Date
    Nov 2007
    Location
    Vancouver, Washington USA
    Posts
    1,909
    OP, did you mean the tentative: 2-((1,3-dioxan-2-yl)(phenyl)methyl)piperidine (someone draw me a picture, literally)

    or quinolizidine MPH analogs?
     

  12. Collapse Details
     
    #12
    2-((1,3-dioxan-2-yl)(phenyl)methyl)piperidine is what I was referring to if my reading of that is correct. Though your quinolizidine analogs proposal is definitely interesting and something I'm interested in looking into.
     

  13. Collapse Details
     
    #13
    Bluelighter Nagelfar's Avatar
    Join Date
    Nov 2007
    Location
    Vancouver, Washington USA
    Posts
    1,909
    Quote Originally Posted by psynce of sound View Post
    2-((1,3-dioxan-2-yl)(phenyl)methyl)piperidine is what I was referring to if my reading of that is correct. Though your quinolizidine analogs proposal is definitely interesting and something I'm interested in looking into.
    Anybody got the 2D skeletal of that one? For it's one for which I am unaware, I made the MPH analog page on WP and would like to include that class.

    Like sekio drew? Like non-benzene space-filling of the (methyl)napthylidate?
    Last edited by Nagelfar; 12-10-2016 at 22:51.
     

  14. Collapse Details
     
    #14
    Bluelighter Nagelfar's Avatar
    Join Date
    Nov 2007
    Location
    Vancouver, Washington USA
    Posts
    1,909
    Quote Originally Posted by psynce of sound View Post
    I understand that these changes won't give the phenidates magical mdxx properties as they're reuptake inhibitors. Though if they aren't inactive due to steric bulk I also wonder if the ring constraint change would allow for further modification?
    Quote Originally Posted by sekio View Post


    like that?
    OK, if as the above, then they may be like methylnaphthylidate, and have increased serotonin affinity as a reuptake inhibitor. If as the above and like my restricted rotational though, then they might be serotonin releasers as the ring contracted restricted rotational variants come close to phenmetrazine.
     

  15. Collapse Details
     
    #15
    Quote Originally Posted by Nagelfar View Post
    Anybody got the 2D skeletal of that one? For it's one for which I am unaware, I made the MPH analog page on WP and would like to include that class.

    Like sekio drew? Like non-benzene space-filling of the (methyl)napthylidate?
    The compound being discussed appears to be theoretical. Hence, it is probably a bit premature to put it on wikipedia.
     

  16. Collapse Details
     
    #16
    Bluelighter Nagelfar's Avatar
    Join Date
    Nov 2007
    Location
    Vancouver, Washington USA
    Posts
    1,909
    Quote Originally Posted by serotonin2A View Post
    The compound being discussed appears to be theoretical. Hence, it is probably a bit premature to put it on wikipedia.
    I could mention it as to "not be confused with" such a class, I put a mention of the theoretical above on its talk page; to test the water, as it were, to see if one has been made in the literature.

    By the way, as with the 1-, & 2-, naphthalene analogs, I think the proper name would be something along the lines of a 2-benzene (para-meta linked) ring. "Constrained" makes me think of "restricted rotation" of the overall molecule, not of the para or meta additions in and of themselves or what they *could be* if not linked, which not even existing yet I think 'constrained' is a bit of a confusing nomenclature to use in this instance.
     

  17. Collapse Details
     
    #17
    Moderator
    Neuroscience and Pharmacology Discussion
    sekio's Avatar
    Join Date
    Sep 2009
    Location
    streets of simcity
    Posts
    19,044
    like this?


    On paper it'd be stable at least for a little bit, but I'd expect it to hydrolise to ritalinal (? aldehyde form of ritalinic acid) pretty quick, faster than a methyl ester would.

    Pharmcology wise I think it'd be close to MPH.
    Guidelines for OD ||| OD Standards ||| OD Directory Read Me First! ||| NPD Rules
    Please read the links above or PM me if I lock your post. Stay Safe. R.I.P. F28
     

  18. Collapse Details
     
    #18
    Quote Originally Posted by Nagelfar View Post
    I could mention it as to "not be confused with" such a class,
    That doesn't make any sense to me as a rationale. How exactly would someone be confused if the wikipedia page shows a picture of the actual structure? I don't think that is appropriate -- ie, you are using a subterfuge to introduce something theoretical into wikipedia.
     

  19. Collapse Details
     
    #19
    Bluelighter Nagelfar's Avatar
    Join Date
    Nov 2007
    Location
    Vancouver, Washington USA
    Posts
    1,909
    Quote Originally Posted by serotonin2A View Post
    That doesn't make any sense to me as a rationale. How exactly would someone be confused if the wikipedia page shows a picture of the actual structure? I don't think that is appropriate -- ie, you are using a subterfuge to introduce something theoretical into wikipedia.
    Huh? it can't add the picture of what is mentioned here *because of the fact* that what is spoken of here is theoretical, it must be the formulaic name that it would be distinguished from; and clarification if this were mentioned again would be good w/o image clarified immed. here, as I was confused.
     

  20. Collapse Details
     
    #20
    Quote Originally Posted by Nagelfar View Post
    Huh? it can't add the picture of what is mentioned here *because of the fact* that what is spoken of here is theoretical, it must be the formulaic name that it would be distinguished from; and clarification if this were mentioned again would be good w/o image clarified immed. here, as I was confused.
    My point is that no one is going to go to that wikipedia page, look at the picture, and think it is referring to the theoretical compound discussed here. That couldn't happen because there is a structural diagram on the wikipedia page.

    The fact that you were confused by this post on bluelight has no bearing on whether someone could possibly be confused by the wikipedia page.
     

  21. Collapse Details
     
    #21
    Quote Originally Posted by sekio View Post
    like this?


    On paper it'd be stable at least for a little bit, but I'd expect it to hydrolise to ritalinal (? aldehyde form of ritalinic acid) pretty quick, faster than a methyl ester would.

    Pharmcology wise I think it'd be close to MPH.
    Things like this have been tested. Swapping the piperidine for a morpholine was the best example. The 2,6 dioxine can be e benzene (or p-Me benzene) so you can get serotonin action without the v.long T1/2. Illegal in UK, not sure about elsewhere.
     

  22. Collapse Details
     
    #22
    Bluelighter Nagelfar's Avatar
    Join Date
    Nov 2007
    Location
    Vancouver, Washington USA
    Posts
    1,909
    Quote Originally Posted by serotonin2A View Post
    The fact that you were confused by this post on bluelight has no bearing on whether someone could possibly be confused by the wikipedia page.
    That such an issue could come up elsewhere, It's a list, it's for completeness, so the mention is in the talk page that the terminology used for something that could lead one to the WP page is disambiguated lightly in context, is what I mean. Regardless, too much said about a simple clarification which has already been done.
     

  23. Collapse Details
     
    #23
    Bluelight Crew Solipsis's Avatar
    Join Date
    Mar 2007
    Location
    NL
    Posts
    15,270
    Quote Originally Posted by clubcard View Post
    Things like this have been tested. Swapping the piperidine for a morpholine was the best example. The 2,6 dioxine can be e benzene (or p-Me benzene) so you can get serotonin action without the v.long T1/2. Illegal in UK, not sure about elsewhere.
    The 2,5-dioxine would be much more stable than the 2,6 just like morpholines aren't as unstable as hemiaminals?
     

Posting Permissions

  • You may not post new threads
  • You may not post replies
  • You may not post attachments
  • You may not edit your posts
  •