Hey Bwiti!
I searched an hour in my closet of articles for you
, I think you might find this interesting
. Here are analgesic activity data for prodine analogs. You have a low melting beta (trans) and a high melting alpha (cis) analog of prodine. In prodine, the 3-piperidine substituent is methyl. Now, I have this article where they made some analogs of prodine, with other substituents on the 3 position than methyl.
R (in 3 position) Analgesic activity
alpha -CH3 1
beta -CH3 7
alpha -CH2-CH3 1.1
beta -CH2-CH3 1.25
alpha -CH2-CH=CH2 11
beta -CH2-CH=CH2 3
alpha -CH2-CH=CH-CH3 0.03
beta -CH2-CH=CH-CH3 0.04
For the analgesic activity, they take morphine as a standard (with an analgesic activity value of 1)
I made no typing error: with the allyl, the alpha isomer is the most potent.
Now, concerning the ref. ...
... The article is called "Piperidine derivatives. IV. 1,3-disubstituted-4-aryl-4-acyloyl piperidines", the authors are: A. Zieging, Alex Motchane and John Lee. It is published in november 1957, the volume is 22 and the pages are 1521 - 1528. However, I must have been in a hurry when I copied the article, since I completly forgot to write down from which journal it is. I think it is JOC, but it can equally good be J. Chem. Soc. ... or even JACS. Well, sorry about that.
Oh, and do I need to say that these analogs can equally good can be made like in the above patent?
I've heard a lot about the production of 1-methyl-4-phenyl-4-acetoxypiperidine from a-methylstyrene, but what about synthing an active analgesic from 2-methyl-1-butene instead? With 2-methyl-1-butene, you 'd get a prodine compound where the phenyl on the 4-position of the piperidine ring is replaced by a methyl. Now, since the phenyl on the 4-position is quite essential for analgesic activity, I don't think using 2-methyl-1-butene would be a good idea. And certainly not with the acetoxy, as a general rule, it is always less potent thant the propionoxy ester.
Cheers