The speakers for the morning of June 8th were Bob Grubbs and Magid Abou-Gharbia. As usual, Bobby Grubbs’ talk was concerned with the latest wonders of olefin metathesis. We saw ATM’s of molecular Cheerios. Pretty cool, actually. Grubbs got the trip to Stockholm for a reason and the work of his group continues to produce molecular wonders. He was able to demonstrate the production of rings with degrees of polymerization in excess of 5000. Using NMR and a carefully chosen ring monomer, they could sort out linear polymers from cyclic polymers. Linear polymers will thread a crown ether while the cyclic form will not. By attaching a crown ether (24-crown-8 ??) to polystyrene beads, they could collect and physically separate the linear from the cyclic forms. They were also producing brush polymers.
Prof. Magid Abou-Gharbia, Temple University, gave a talk with lots of fascinating insights into some current thinking on industrial drug discovery. At least from the point of view of a former Wyeth guy. I have been away from the pharma-related work for a number of years now and haven’t really missed it. But his talk has revived enthusiasms in me that have been in a long slumber.
Anyway, he described the development of the anti-depressant Effexor and their efforts to keep the molecule simple and free of excessive stereocenters. Studies of the metabolism of Effexor lead to the discovery of the des-methyl analog, now called Pristiq.
Concerning High Throughput Synthesis (HTS)-
“… you’re going to get a lot of decorated molecules, but they are not going to be biopharmaceutically useful.”
Abou-Gharbia lamented the languishing of natural products chemistry. He gave some examples of Rapamycin work, which according to his presentation, was originally isolated from a soil sample from Easter Island. Much productive work apparently has been derived from the modification of this macrocycle. It’s all in the literature.
One of the main take-away lessons from Abou-Gharbia is that workers shouldn’t get too focused on SAR. His advice was that structure-property relationships need an early examination as well. Dual optimization. If the bioavailability is low, then the in vivo activity will not match the in vitro activity- an expensive and time consuming realization.
Lamentations on Chemistry 
“you’re going to get a lot of decorated molecules, but they are not going to be biopharmaceutically useful.””
Sounds like the last 15 years were a waste! Glad I stuck to needlepoint!
Golly. That was awkward. But, moving on …
Gharbia also lamented the demise of chemistry in the UK. Evidently the Brits as a whole are terrified of chemicals. This has lead to some universities to shut down chemistry departments. It would be interesting to learn more about this.
No matter how sophisticated the engineering analysis, something wonderfully new requires somebody (not a committee) to be clever and original (insubordinate). SAR and HTS had their days, produced useful products, and grew exhausted. The most fanatic Edisonian effort cannot find a lost silver dollar under a corner street light if it was dropped in the dark center of the block.
Discovery then also requires poorly managed basic research staffed by Severely and Profoundly Gifted folk who deeply offend and outright frighten Personnel (Human Resources, Human Factors Engineering, Frat Initiation). Google does it just that way and Google is unstoppable. The superior human brain cannot tolerate silence. Bore it and it creates something interesting.
Test evolution by breeding lab mice for 50 generations, but what will obtain from a uniform genome? Do it with wild field mice, e.g., Chernobl, and discover Official Truth about chronic radiation exposure is explicitly empirically deficient.
Nicely put. I’m in line with you there.