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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

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April 20, 2011

Return of the Magic Methyl Group

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Posted by Derek

Well, I've been traveling this week, but have found a bit of time to blog. Today we have something new about SAR, courtesy of the BASF marketing department.

Medicinal chemists are all familiar with the "magic methyl group" effect - the phenomenon of a single methyl sending a compound over the top in terms of activity, selectivity, PK, or what have you. I've seen it several times myself. Usually you starting wondering why you didn't just put the thing in six months before, but that's rarely the way things work out.

Well, we're not the only people who notice such things. Check out this ag-chem ad from BASF for their Kixor herbicide (sent along by an alert reader). Scroll down to the bottom of the page, and you'll find:

Methyl groups serve as "metabolic handles" in crops delivering crop safety and giving you confidence knowing you have made the right choice"

There you have it! Methyl groups add confidence! Now that's worth knowing - and you have to wonder what secrets other functional groups hold. Do carboxylic acids put a spring in your step? Do para-fluoros freshen the breath? Will a sulfonamide help you make the big sale? Someone in the advertising department might believe it - as Dilbert put it, marketing people even believe marketing surveys, so what's the limit?

Comments (18) + TrackBacks (0) | Category: Life in the Drug Labs


COMMENTS

1. Rick on April 21, 2011 3:22 AM writes...

And ethyl groups MUST be twice a good!!! That explains all those warnings about drug-alcohol interactions: it makes the druga twice as good!!! Imagine what could happen if we took our pills with rubbing alcohol!!! P.T. Barnum's observations on the gullibility of consumers and the felonious simple-mindedness of marketing never lose their relevance.

Permalink to Comment

2. A Nonny Mouse on April 21, 2011 3:50 AM writes...

Clearly, you are not aware of the differences between med chem and ag chem.

The objective in ag chem is to allow the compound to degrade to benign materials in a controlled way. Clearly, introduction of the methyl group leads to degradation by soil microbes to a more polar (acid?)group which is inactivated and presumably removed from the environment.

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3. Jal-Frezi on April 21, 2011 3:55 AM writes...

It's interesting the way ag-marketing is going, it always used to be 'never mind what it is, look at what it does in the field'. Increasingly marketing is starting to include quasi-scientific shampoo ad speak. Fairly cringeworthy to the scientists, but the growers and distributors seem to love it.

Permalink to Comment

4. Jal-Frezi on April 21, 2011 4:03 AM writes...

Oh and I think they're talking about selective metabolism of the methyl groups in the crop(s) versus the weeds to give crop safety rather than soil breakdown to prevent persistence.

Permalink to Comment

5. dearieme on April 21, 2011 5:15 AM writes...

There is a "me" in methyl!!

Permalink to Comment

6. El Selectride on April 21, 2011 6:31 AM writes...

It's only magic if they put it on with the fluorosulfonate.

Permalink to Comment

7. Monte Davis on April 21, 2011 7:41 AM writes...

"However, the addition of a branched methyl group as in [4-valine]oxytocin, doubles activity as compared to [Abu4]oxytocin." (PJ Bentley, Endocrine Pahamacology, 1980)

Voila: love handles!

Permalink to Comment

8. Hap on April 21, 2011 7:44 AM writes...

Would the cancer you get from Magic Methyl be magical, too?

Permalink to Comment

9. HelicalZz on April 21, 2011 10:01 AM writes...

Do para-fluoros freshen the breath?

I don't know about that, but butyryl groups sure aren't likely to.

Zz

Permalink to Comment

10. quintus on April 21, 2011 10:45 AM writes...

We had a compound series where a methyl group was a receptor agonist, a CF3 a partial agonist and an ethyl substituent an antagonist. So much for adding a methyl to improve the agonist effects!

Permalink to Comment

11. MoMo on April 21, 2011 1:36 PM writes...

Quintus,

Classic definition of competitive antagonism and E J Ariens would be proud. But the new generation of younger Med chemists are saying "Who"?

You know nothing until you read the classics.

Permalink to Comment

12. GreedyCynicalSelfInterested on April 21, 2011 2:38 PM writes...

I'm starting a company to make a new mouthwash based on organotellurium compounds. I'm looking for some investors.

Permalink to Comment

13. John Waddell on April 21, 2011 10:52 PM writes...

As a 'commercial guy, I loved the Dilbert! So true..

Permalink to Comment

14. cynical1 on April 21, 2011 11:32 PM writes...

Here, let's adapt that ad for Pharma a la Achillion's antibiotic you seemed to like so much....

"Selenophenes serve as "metabolic handles" in drugs delivering drug safety and giving you confidence knowing you have made the right choice."

Yep, I can definitely hear that in a TV add, maybe with someone like Ashton Kutcher as announcer.

Permalink to Comment

15. Ich Dich on April 22, 2011 7:29 AM writes...

May be just me, but does anyone see the acid functionality they refer to as the promoter of translocation? Its an invisible acid, now that's magic.

Permalink to Comment

16. Toad on April 22, 2011 12:17 PM writes...

Ich,

The NH of the acylsulfonylurea moiety is acidic, with a pKa similar to that of the OH in a simple carboxylic acid such as acetic acid.

Acylsulfonamides and acylsufonylureas with appropriate substituent groups are some of the common isosteres (functional replacements) for carboxylic acids in the design of inhibitors for biological targets.

Permalink to Comment

17. lgf on April 22, 2011 4:37 PM writes...

similar to the confidence inspired by Detrol which will enable one to take a leak 12 times a day instead of 13, so you don't have to flee the trolley. You med chem guys are a bit too self agrandizing

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18. Anonymous on April 26, 2011 6:37 PM writes...

@ #12... You might want to contact Westphal or other GSK characters, I'm sure they'd be interested in a "turd like" mouth wash...

Permalink to Comment

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