Toxic Extract Used in Poison Arrows Could Be The Future of Male Contraception (Science Alert)
PETER DOCKRILL
18 JAN 2018
There's no shortage of scientific research trying to find an effective, safe version of the pill for men, but we doubt any existing drug candidates have a history as deadly and fearsome as this new discovery.
Scientists have identified a chemical that could be suitable for a male contraceptive pill in a plant extract that African warriors and hunters traditionally used as a heart-stopping poison on their arrows.
A team of researchers from the University of Minnesota and the University of Kansas say ouabain, a toxic substance derived from two kinds of African plants – and also produced in mammals in lower amounts – could serve as the basis for a working male pill.
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Fast-forward a couple thousand years, and European scientists in the 18th century discovered the extract acted as a cardiac glycoside – a compound that can increase the force of heartbeats while decreasing their rate of contractions.
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Now, the research team has used experiments with male rats to demonstrate that, after tampering with the molecular arrangement of the extract, a modified ouabain analogue can still curb the animals' fertility while being non-toxic, leaving the heart and other bodily systems alone.
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more: https://www.sciencealert.com/toxic-extract-poison-arrows-male-pill-ouabain-contraceptive?perpetual=yes&limitstart=1
ouabain: 
= new reply since forum marked as read
abiraterone, the successful prostate cancer drug, because I happened to be looking at the structure of abiraterone today and because both molecules have a heterocyclic substituent at the 17 position of the steriod nucleus.
The original J. Med Chem Paper is apparently open sourced. It's Blanco, J. Med. Chem., Article ASAP
The most potent analogues were not, in fact, glycosides:
I love #10 and #17, leaving the protecting groups in place and finding activity, but I'm not entirely sure that's going to be great pharmacokinetically.
Here's the scheme for the synthethic steps for an analogue.
If you're a simplistic guy like me, you look at a carboxylic function, here masked as a lactone and you immediately say "tetrazole!" but here we have a triazol doing the same job.
Cool.
Over the years I forgot about how cool medicinal chemistry can be, and, since the days of the organic medicinal chemist are nowhere near what they used to be, it fills me with a kind of nostalgia for more beautiful days, the days when you could look at a toxin and use it to make a drug.
It would be a nice medication to have, very much so, an oral male contraceptive.
Thanks for the memories!
