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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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August 19, 2008

Fighting Boredom, Profitably

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Posted by Derek

I wanted to recommend this post by Milkshake over at Org Prep Daily (and not just because he liked the recent column I wrote for Chemistry World). I was writing about the limited number of reactions that some med-chem labs get locked into, and the effect of this both on the compounds that get made, and on the motivation of the chemists. Milkshake has a good set of recommendations on how to avoid the boredom trap, and I recommend checking them out. He ends with the following:

You should care about the chemistry methodology and do things not just to crank out the final compounds to fill up the testing queue. Your boss (has) perhaps lost all his chemistry interest already and maybe he is unnerved about the project progress and pushes people hard - but while you try not to get fired you don’t necessarily want to think like your boss (and end up wretched). If you continue to look at your research project with curiosity and do things also for the sake of your chemistry interest you are likely to be more original because thinking about the methodology will suggest new directions in your medchem project. You may get accused of playing with chemistry and going off-tangent but you will likely remain more content and productive. . .

And this is all true. Most projects need some oddball compounds thrown into them, to keep things interesting (and honest), and it’s the people who are keeping up with the literature who will probably make them. I went through a period some years ago when I didn’t stay current with the journals very well, and if I’d let that continue to slide, it would have had a bad effect. (RSS was one of the things that saved me!)

But there’s another very good reason to stay sharp and run the unusual reactions, though: the boring reactions are increasingly going to be shipped to someone else, someone who probably works in a very different time zone. Yep, this is my “give ‘em something they can’t get in Shanghai” talk again. The outsourcing shops are there to pound out molecules as quickly as possible, and they’re going to use well-established chemistry as much as they can. Now, that’s the same pressure that operates in most med-chem projects, but I strongly recommend differentiating yourself if possible.

Be the person who runs the new stuff, who reads the literature and adopts things quickly, and who makes compounds that aren’t like all the stuff that’s already in the screening deck. You don’t have to go completely crazy, you know. There are plenty of good, reasonable structures that no one else is making at your company – have no doubt – and if you’re the person who makes them and who introduces new chemistry into the department, you have something with which to justify your salary (or a higher one!) On the other hand, if you’re the person who cranks out the sulfonamide libraries, well. . .they can get that cheaper somewhere else, you know.

Comments (7) + TrackBacks (0) | Category: Life in the Drug Labs


1. Petros on August 19, 2008 8:19 AM writes...

Some interesting points that the pair of you make. I'd totally agree with you that there is a need to think (at least) slightly laterally or even outside of the box. If something works it might be valuable when working in hot areas where there is a lot of potentially overlapping IP.

I think Milkshake's point about not abandoning scanning the chemical literature is also valid. In the days when I was working as a med chemist when our library switched to taking journals on mcirofiche rather than hard copy, it severely hindered scanning the literature and certainly made me less inclidned to do so becuase of the incovenience of the format for such a purpose. Modern electronic versions are betetr, although not (I feel) as good as the old hard copies.

It also begs the question as to which synthetic journals to scan? A topic you have addressed before.

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2. NH_chem on August 19, 2008 8:43 AM writes...

The problem is that the boss has to answer to people above him who don't understand chemistry thus want to know why X number of compounds have not been made and tested.

Staying ahead of that game is critical for employment in a larger company. In a smaller one, you can be more "academic" in thoughts but ultimately they are driven by VCs who want results.

It is a fine line to walk, that is for sure. Nice comments made.

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3. Anonymously Pfired on August 19, 2008 9:36 AM writes...

Indeed there is a balance that must be struck between chemical curiosity and bottom line productivity. If you look around you, I'm sure you can point out those handful of people that always seem to be at the forefront of innovation. These people often distinguish themselves in more than one way, ie: chemistry, technology, novel medchem experiment design, etc. These are the people that drive projects, not through some coronation of leadership, but by example, with actions and ideas. They are excited and exciting.

I'll end with my philosophy and attitude toward all things: Live your life like an exclamation, not an explanation.

Good luck to us all!

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4. milkshake on August 19, 2008 3:08 PM writes...

Derek thank you for the plug - I noticed that the stats were going off the charts...

The reason I wrote that post was that very recently I got transferred to another research project (and to a more human boss) within our medicinal chemistry. My difficulties with the previous boss and project were all related to things that you mentioned in the Chem World column.

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5. BCP on August 19, 2008 6:57 PM writes...

I think that the pair of you make a great point, that should also be translated into med chem thinking as well. I see many teams that end up stifled by their own dogma, or worse, myopic with their expectations of what minor tweaks they can/can't make to their series, while intellectually discarding vast swathes of SAR. True creative thinking in our med chem labs is something that is surprisingly rare IMHO.

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6. Anders on August 20, 2008 2:06 AM writes...

Come on over to the scale-up business, we never get bored!

Frustrated yes, bored no...

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7. kumar on August 20, 2008 2:24 AM writes...

Now days any body can make anything. Chemistry evolved irrespective of the time zones.

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