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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: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

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October 25, 2007

Looking Backwards

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Posted by Derek

A colleague reminded me the other day of a project that he and I had worked on back at the Wonder Drug Factory seven years ago. "Seven years ago", I thought. . .I was the project leader on that one, trying to keep things alive as weird toxicology kept torpedoing everything. In the end, we held it together long enough to get four compounds into two-week tox testing, whereupon every one of them wiped out for yet another set of ugly reasons. Ah, yes. No one's going to have to work on that stuff again, that's for sure.

Hmm, I thought. What was I doing seven years before that? Well, I was back at my first drug industry job in New Jersey. The company had just moved into a new building the year before, and the old site was on its way to becoming a Home Depot. I was spending my days cranking out molecules hand over fist. Boy, did I run a lot of reductive aminations. It's safe to say that during those years I ran the majority of all the reductive aminations that I'll ever run in my life, unless something rather unforeseen crops up. We made thousands of compounds on that project, and I remember pointing out in a talk that nobody makes that many compounds if they really understand what they're doing. This was not a popular line of reasoning, but it's hard to refute, unless saying how much you don't like something counts as a refutation.

And seven years before that? Still in the lab. I was midway through grad school, wrestling with the middle of what turned into twenty-seven linear steps by the time I pulled the plug. (At this point, I began to reflect that I've been doing chemistry for quite some time now). In 1986 I didn't know that I wasn't going to end up finishing the molecule, and I was still hauling buckets of intermediates up the mountainside, only to find them alwyas mysteriously lighter and smaller by the time I got to the top. My response, naturally enough, was to start with larger buckets - what else was there to do?

And seven years before that? That finally takes me over the chemistry horizon, back to my senior year of high school in Arkansas, and to what might as well be a different planet entirely. Although I was interested in chemistry - as I was in most all the sciences, something I've never lost - I'd never heard of a Grignard reagent, and I didn't know what a nucleophile was. Counting up, I see that some time next year will mark the point at which I will have spent a slim majority of my lifetime doing organic chemistry, which is an odd thought. And it makes me wonder what I'll be up to seven years from now. . .

Comments (11) + TrackBacks (0) | Category: Graduate School | Life in the Drug Labs


COMMENTS

1. milkshake on October 25, 2007 11:01 PM writes...

Looking back can be like staring into an abyss.
"What does not kill me just makes me more depressed."

Permalink to Comment

2. Sleepless in SSF on October 25, 2007 11:18 PM writes...

I figure Derek's message will spawn a spate of reminiscences, so what the heck:
0x7yr: proteomic mass spec at a biotech in South San Francisco (14 compounds in the clinic since I started six years ago) and adjunct faculty in chemistry at local JC; hoping my stock options are in the money before they expire in 4 years
-1x7yr: getting pretty fed up with faculty life at the Moo U campus of the University of California; decide that universities are the most bureaucratic of all organizations -- and I spent years in goverment lab before this
-2x7yr: senior scientist in a government lab specializing in environmental analysis of PCDD/F (dioxins and furans); eventually can't, in good conscience, continue to contribute to false public hysteria over dioxin
-3x7yr: two years into PhD at University of Toronto; wrote up MSc project as a fall back in case the PhD thing doesn't work out
-4x7yr: freshman at Canada's premier cow college; win a Rubber Bible (60th Edition!) for getting best grade in General Chem

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3. Anonymous BMS Researcher on October 26, 2007 2:19 PM writes...


Hmmm, let's see:

Seven years ago I was already working at BMS -- though at the nadir of the Plavix debacle it looked for a while I might soon be leaving BMS. Seven years before that, I was at Yale. Seven years before that, I was in grad school. Seven years before that, I was an undergrad. Seven years before that I was in SEVENTH grade. Seven years before that I was in kindergarten. And Seven years before that my parents were engaged.

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4. CMC guy on October 26, 2007 2:34 PM writes...

Track back is an interesting perspective but the Blog before this one (Come On...) makes me wonder where we'll be 7 years in the future.

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5. Dana H. on October 26, 2007 6:30 PM writes...

This is fun!

Seven years ago, I was writing formulation modeling software in C++. Seven years before that, I was writing polymer modeling software in C. Seven years before that, I was writing my Ph.D. thesis on simulations of argon clusters that I did with software written in Fortran. Seven years before that, I had just started college with a double major in chemistry and physics because I couldn't decide which I liked more. (I took Organic 101 over the summer, during which I used BASIC to draw molecules on a PET personal computer for fun.) Seven years before that, I was in fifth grade.

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6. SP on October 26, 2007 7:01 PM writes...

Y'all are so old.
-7- second year of grad school, just dumping my 1st year project and starting the project that became my thesis.
-14- 10th grade chemistry. Our final project, which I want to go back and take another crack at with better math and equipment, was to mix 20 or so clock reaction components at different concentrations at the start of the 1812 overture and have one change color at each cannon blast.

Permalink to Comment

7. kirsten on October 27, 2007 8:55 AM writes...

On a different topic entirely, I remember the heady days of gabapentin and what a useful drug it was going to be, not just for seizures, but for neurogenic pain as well. I have seen patients taking huge doses of this stuff.

Now I have heard from a physician that the response to this drug isn't dose-related at all, but that the response curve to pregabalin is, and therefore it is a much better drug? HUH? Is gabapentin just some amytriptyline-type dirty drug or what gives?

I'd appreciate a chemist's opinion on this, as I don't know that much about GABA receptors.

Thanks in advance.

Permalink to Comment

8. Daniel Newby on October 27, 2007 7:07 PM writes...

IIRC, the lion's share of gabapentin uptake is through a saturable transporter. Once you reach a dose that saturates the transporter, further increases in therapeutic effect require massive dose increases.

On the upside, it's almost overdose proof.

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9. Dustin James on October 29, 2007 12:44 PM writes...

I'll join in:

7 years ago (2000) I was nearing the end of my employment at a microelectronics service company, having learned to design and pilot water treatment solutions for semiconductor wastewater streams, about as far from the organic synthesis of my graduate school days as you could get.
7 years before that (1993) I was working and living in Wichita, KS, at a specialty chemical company (now closed) that had just changed from a centralized R&D department to a decentralized one. I stayed but many coworkers were let go or left. Our major products were hydrocarbon functional fluids, with no heteroatoms. We dealt with one reaction (Fridel Krafts aromatic alkylation and transalkylation) and distillation for every product we made.
7 years before that (1986) I was 1.5 years into my process development work at a pharmaceutical company in upstate New York. It had been taken over by a consumer products company that was trying to make its way in the pharmaceutical world. That company exited pharmaceuticals discovery a year or two ago.
7 years before that (1979) I was in my senior year of college, married three years and just pledged a fraternity. Looking forward to graduation and had just decided to go to graduate school after spending the summer in an NSF URP program at The University of Texas at Austin.

No, I never imagined I would be where I am today. You do what you have to do, and (I believe) go where God leads you.

Dustin

Permalink to Comment

10. totally process on October 31, 2007 8:37 AM writes...

As I finish up work on yet another p38 inhibitor, I remember that 7 years ago I was in the throes of a campaign for a p38 inhibitor at another company. We almost killed ourselves making that compound because "the competition was already in the clinic"..supposedly phase II. Soemtimes the lack of progress the human race can have towards one single kinase is mind-numbing.

7 years before that I was blissfully unaware of the seemingly innocent letter/number combination p38.

Permalink to Comment

11. milkshake on October 31, 2007 10:33 AM writes...

A p38 project is like mother in law - one can remember it fondly when all is over.

(It is frustrating when medicinal chemists advance over-decorated structures that are hard to make and putify)

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