: I find it interesting that the LSD molecule is so sensitive to substitution.
: There aren't many substitutions that will retain activity (just a couple
: of types, as compared with the psychedelic phenethylamine family where you
: can do just tons of stuff). It must be fitting into that receptor pocket
: really nicely. Especially the diethylamine group. I understand just
: about any other substitution pattern there pretty much abolishes activity.
: Hmm. I wonder if you replaced some of the -H's on those two ethyl groups
: with -F's... That would keep the size about the same, but would change the
: charge distribution. Has it been tried? -F for -H is supposed to be a
: fun substitution in bioactive molecules, often modifying activity since
: it's the same size (roughly) as -H, but is a lot harder for enzymes to
: take off. Apparently monofluoroacetic acid is one of the most generally
: toxic substances known (i.e. bad for most life forms) because it gets into
: some important pathway (related to carbon oxidation, Kreb's cycle?) and
: totally fucks it all to hell.

There are other LS amides that _are_ active at dosages less than 20x that of
LSD including ALD-52, d-LS morpholide (20% LSD activity), 1-N-methyl LSD
(40% activity), d-LS dimethylamide (10%), d-LS ethylamide (5%) and
d-(1-N-methyl-LS-pyrrolidide) (7%)
I think research into fluroLSDs has been a bit limited (I certainly
havent seen any in my wandering, and it being a fairly notorious
sheduled drug must put a bit of a damper on human trials..)
It is, however, a good idea..
Does anyone have information on the breakdown path of LSD, I think
it is metabolised by MAO. Certainly MAOIs increase LSD potency.

: Also, -Cl lies somewhere between -H and -CH3 in size (or so I'm told) so
: making of the ethyl groups a 2-chloroethyl group wouldn't be quite as
: bad size-wise as making it a propyl group (which apparently abolishes
: activity). Of course, 2-chloroethyl ethyl amine would polymerize/cyclize
: nicely. Maybe it wouldn't be too easy to work with, so a different

sure looks that way..

: synthesis might be required rather than just using a different amine in
: the amidation step. But I don't really know what I'm talking about, I'm
: just throwing out ideas.