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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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May 11, 2011

In Memoriam, Two Chemists

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Posted by Derek

Word reached me yesterday that Corwin Hansch, long of Pomona College, had died. Anyone who's ever done (or thought about) trying to apply mathematical techniques to compound structure-activity relationships has internalized some of his work. (Here's an intro, for those who haven't encountered classical QSAR).

I was quite excited about using such techniques (and their successors) early in my career, but ran into difficulty applying them in the real world. There were several complications - our compounds were (very likely) in several different SAR series, so combining them wasn't doing the analysis any favors; we had gaps in the compound space that would have helped refine the calculations (but were difficult to prepare and not felt to be worth the trouble to make), and, perhaps most importantly, the underlying assay data might not have been as tight as it needed to be to give sensible answers. These problems are not unique.

But that said, Hansch deserves a lot of credit for going after the whole idea of applying linear free-energy relationships to med-chem activity, and for having the fortitude to do so in the computationally deficient early 1960s. It's because of his work (and the many people who followed his lead) that we've come to realize how tricky these problems are. He was indeed a pioneer.

I've also been remiss in not mentioning the unexpected death of David Gin of Illinois and then Sloan-Kettering. Gin was an excellent synthetic chemist who tackled some very difficult problems in carbohydrate chemistry, among other areas - here's just one example, and there are many more. He surely had many more discoveries left to make, and his loss is a loss to the field.

Comments (13) + TrackBacks (0) | Category: Chemical News


COMMENTS

1. Useless Molecule on May 11, 2011 7:36 AM writes...

Gin and Corey ecteinascidin 743 total synthesis is truly a masterpiece.

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2. Jose on May 11, 2011 8:04 AM writes...

"Useless mol" beat me to it: ET-743 is nothing short of staggering, and David will be sadly missed. Too bad it was never made into the full paper it so richly deserved....

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3. Hap on May 11, 2011 10:28 AM writes...

Gin and Myers's synthesis of tunicamycin seemed really cool, as well.

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4. Boghog on May 11, 2011 12:00 PM writes...

While the direct application of Corwin Hansch's QSAR methods turned out to have limited utility in drug discovery, indirectly his methods (especially logP) have had an enormous impact (ala Lipinski and the developability of drugs). Simple but effective. He will be missed.

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5. Boghog on May 11, 2011 12:02 PM writes...

While the direct application of Corwin Hansch's QSAR methods turned out to have limited utility in drug discovery, indirectly his methods (especially logP) have had an enormous impact (ala Lipinski and the developability of drugs). Simple but effective. He will be missed.

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6. chris on May 11, 2011 12:24 PM writes...

I was first introduced to the ideas of Hansch back in the days when I had to use punched cards for input and wait a week to get results. I still think it was when I made the transition from thinking about the properties of new molecules rather than simply in terms of synthetic targets.

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7. AlchemistOrganique on May 11, 2011 12:46 PM writes...

IMHO, the Ugi reaction to couple the complex fragments of ecteinascidin 743 was a really gutsy move. Gin was a great presenter; his brilliance will be missed.

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8. Curious Wavefunction on May 11, 2011 1:37 PM writes...

Corwin Hansch was like Norman Allinger (the molecular mechanics pioneer). He made the field respectable and mainstream even if it has limitations.

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9. Dale DeWitt on May 11, 2011 3:04 PM writes...

"Corwin Hansch Emeritus" http://www.pomona.edu/academics/departments/chemistry/ (05/11/2011)

I think the practice of titling emeritus & deceased '(deceased)' is still alive, though the use of the pure 'deceased' title is a spotty trend often due to the circumstances of the the individual's death. (more commonly as a subheading)

It will be interesting what Pomona College does when they get around to updating their website.

Life is full of interruptions and death is just one of them.

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10. Anonymous on May 11, 2011 8:24 PM writes...

What med chem tools don't have limitations? I can't think of any. The key is knowing the limitations and respecting them.

Corwin helped lay down the foundation for modern medicinal chemistry. When we fail to try and incorporate 2D Hansch analysis into our data analysis we are not doing our jobs as medicinal chemists (PERIOD).

RIP Dr. Hansch

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11. Chemist of Sorts on May 11, 2011 8:35 PM writes...

DYG R.I.P.

A great loss.

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12. in47 on May 18, 2011 9:57 AM writes...

RIP Corwin Hansch.

He didn't teach anymore when I went to Pomona... only had a chance to talk to him once. But he was a great scientist and professor who contributed greatly to society and will be missed.

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13. Dee G on May 19, 2011 8:07 AM writes...

Every time I see an alkyl homologue series, I think "Hansch curve." Rises and falls every time. The optimum values are rarely wrong, the log P's universally helpful...

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