07-18-00 23:35
No 30367
Just curious whatall the group opinion would be of this as a target. A guanadine group is a nitrogen, connected to a carbon that is double bonded to a nitrogen and single bonded to another nitrogen. Resonance structures may be drawn.
Proposal:
MDA + bis-Bocthiourea, TEA/HgCl2/DMF 0 C to RT 2H dilute EtOAc, filter celite, rotovap ~45 C. Chromatograph directly with a good layer of sand. Cleave the Boc groups with, say 4 N HCl in dioxane (10-15min), evaporate, take up in water nuet to pH 7 with AmBic, down a MeOH washed then water washed C-18 column, elute with water then water/MeOH if needed, lyophilize appropriate fractions.
Product: Guanadine derive of MDA ta da!!
??? Would this be interesting? Who can speculate on the SAR of this substitution? All around the ring, length of butyl chain, all this is (has been, will be) explored. But what of the amino/methyl amino moiety?
One might also use Monomethyl-bis-Bocthiourea, and get out the methylated guanadino derivative.
Maybe the MD ring has some prob with that strong of cleavage conditions. Hopefully not.
Anywho, what are the thoughts on binding this bugger to the appropriate receptor?
(Hive Bee)
09-14-01 21:34
No 213769
Perhaps if we reduced the guanadine's immine group to it's triamino methane derivative via NaHB4, and then used that in an reductive amination w/ MD-P2P or any other subsituted phenylacteone analog via any of the standard methods, we could obtain a number of ketone derivatives, namely the diamine compound. I believe that the third amine group woulg be able to remain intact due to steric hinderance, and there for have a pair of available electrons to connect with a receptor. Have these di or tri derivatives of phenylacetones been investigated? I think it's worth some thought...
What do you bee's think?Yours in theroy,
Calamus
(Stranger)
09-25-01 10:06
No 217077
Not to put anyones hopes down, but
>MDA + bis-Bocthiourea, TEA/HgCl2/DMF <--- in this case it can be done in a simpler ways.
>??? Would this be interesting? Who can speculate on the SAR of this substitution?
As far as I can predict, this compound should be inactive, unless some enzyme chops
it back to MDA. Why? Because as guanidine it can't and won't move through blood-brain barrier.
Greensnake
(Distinctive Doe)
09-25-01 16:10
No 217172
Here is the way to go if you want to try something like this. Make the pemoline analog of MDA.
Piperonal:
Catechol -->(CI2H2)--> MDBenzene --> (Glycolic Acid)-->
-->MDMandelic Acid --> MDPemoline
See Rhodiums Site for the last one.
I will get references for the glycolic step soon!!
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