science Tuesday, October 16, 2012. Post by Lednicer
Friend of the SciScoop Blog Dan Lednicer is a retired organic chemist with a penchant for pastels. He reminisces about how serendipity doesn’t always lead to success and how ego surfing can sometimes reveal more about other people and their drug habits than about the ego doing the surfing!
Back in the early 1970s when I was at the bench as a chemist at the now-defunct Upjohn Company, in Kalamazoo, Michigan, I almost accidentally backed into a novel class of centrally acting analgesics. My assignment at the time involved the synthesis of compounds that would be of potential use for treating cardiovascular diseases. When the specific series of compounds failed to show any worthwhile activity the project was terminated and remaining target substances were submitted for general screening.
Through an intricate set of circumstances a newly hired pharmacologist also tested compounds from my lab for analgesic activity in mice. One of those agents very unexpectedly showed activity in that new screen. The potency of that first agent, active at ten times the dose of codeine was nothing to write home about. The finding was however most unexpected since the structure of the agent had very few features in common with that of known opiates. My lab then set aside its assigned goal and concentrated on exploring this finding by synthesizing a large number of structurally related compounds in order to study the structure activity relations (SAR).
After a year or so, we had gained some insight into SAR of the series. We then synthesized, almost as a stunt, a compound that incorporated all the structural features that seemed to enhance potency. The resulting compound was an effective analgesic in mice at about 7 micrograms per kilogram body weight. This calculates to approximately 12,000 times the potency of morphine. A report of this finding appeared in 1977 the Journal of Medicinal Chemistry. Patents on that series issued not much later. The article did point out that the structure would overlay that of the opioid fentanyl. This seemed to be the end of the story since Upjohn showed little interest in the series.
The most potent compound of the series was resurrected sometime in the mid-2000s. In the interim the world saw the proliferation of personal computers, the Internet and then search engines. Google, which soon followed became an indispensable research tool for composing my post-retirement books.
In slack periods I occasionally Googled my last name. One of the early hits “Who Is Daniel Lednicer?” really caught my eye. This turned out to be a discussion site, called “Bluelight” composed of individuals interested in recreational drugs. My name came up because they had discovered the papers and patents on the potent analgesics. They were especially intrigued by the fact that these agents were “legal” since they escaped the US Drug Enforcement Agency (DEA) edicts on drugs related to opioids and structurally related drugs The structures series has not yet been deemed “related” probably because it has not yet come to the attention of the DEA. Somewhere along the line the most potent compound of the series was dubbed “Bromadol”. This drug name has now gone almost viral and features its own Wiki page. It was astonishing to find a recent account of an individual who had actually ingested Bromadol, 4-(4-bromophenyl)-4-(dimethylamino)-1-(2-phenylethyl)cyclohexanol.
Serendipity doesn’t always bring success for organic chemists, but it seems that decades later their discoveries can turn up in the strangest of places. I just hope the DEA calls before they come to arrest me because my apartment management just repainted the doors.
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