Corante

About this Author
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

Chemistry and Drug Data: Drugbank
Emolecules
ChemSpider
Chempedia Lab
Synthetic Pages
Organic Chemistry Portal
PubChem
Not Voodoo
DailyMed
Druglib
Clinicaltrials.gov

Chemistry and Pharma Blogs:
Org Prep Daily
The Haystack
Kilomentor
A New Merck, Reviewed
Liberal Arts Chemistry
Electron Pusher
All Things Metathesis
C&E News Blogs
Chemiotics II
Chemical Space
Noel O'Blog
In Vivo Blog
Terra Sigilatta
BBSRC/Douglas Kell
ChemBark
Realizations in Biostatistics
Chemjobber
Pharmalot
ChemSpider Blog
Pharmagossip
Med-Chemist
Organic Chem - Education & Industry
Pharma Strategy Blog
No Name No Slogan
Practical Fragments
SimBioSys
The Curious Wavefunction
Natural Product Man
Fragment Literature
Chemistry World Blog
Synthetic Nature
Chemistry Blog
Synthesizing Ideas
Business|Bytes|Genes|Molecules
Eye on FDA
Chemical Forums
Depth-First
Symyx Blog
Sceptical Chymist
Lamentations on Chemistry
Computational Organic Chemistry
Mining Drugs
Henry Rzepa


Science Blogs and News:
Bad Science
The Loom
Uncertain Principles
Fierce Biotech
Blogs for Industry
Omics! Omics!
Young Female Scientist
Notional Slurry
Nobel Intent
SciTech Daily
Science Blog
FuturePundit
Aetiology
Gene Expression (I)
Gene Expression (II)
Sciencebase
Pharyngula
Adventures in Ethics and Science
Transterrestrial Musings
Slashdot Science
Cosmic Variance
Biology News Net


Medical Blogs
DB's Medical Rants
Science-Based Medicine
GruntDoc
Respectful Insolence
Diabetes Mine


Economics and Business
Marginal Revolution
The Volokh Conspiracy
Knowledge Problem


Politics / Current Events
Virginia Postrel
Instapundit
Belmont Club
Mickey Kaus


Belles Lettres
Uncouth Reflections
Arts and Letters Daily
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

« The Absolute Bottom of the Publishing Barrel | Main | Huge But Effective »

October 22, 2012

March of the Ugly Tool Compounds

Email This Entry

Posted by Derek

The recent discussions here about ugly tool compounds have prompted an alert reader to send in this example, a putative agonist of the orphan receptor GPR35. Will someone rise to the defense of this one?

Comments (22) + TrackBacks (0) | Category: Chemical News


COMMENTS

1. MoneyShot on October 22, 2012 11:04 AM writes...

My eyes are burning

Permalink to Comment

2. Nixon Nitration Works on October 22, 2012 11:04 AM writes...

We here at the Nixon Nitration Works are in broad support of DC-bi-DNP and other similar compounds! We look forward to the expansion (but not too rapid) of this field.

Permalink to Comment

3. SciChick on October 22, 2012 11:20 AM writes...

Are you sure this is not a lead compound for explosives instead?

Permalink to Comment

4. featherson on October 22, 2012 11:41 AM writes...

At least it has an interpretable 1H NMR.

Permalink to Comment

5. Matt B. on October 22, 2012 11:57 AM writes...

That looks like bad news for any project, be it med chem, synthetic methodology, etc.

Permalink to Comment

6. WCA on October 22, 2012 12:08 PM writes...

Nice Band of Brother's reference, NNW....

Permalink to Comment

7. will on October 22, 2012 12:12 PM writes...

look on the bright side, after you detonate, you no longer have cancer

problem solved

Permalink to Comment

8. partial agonist on October 22, 2012 12:38 PM writes...

Corning Inc. Biochemical Technologies group, Corning NY?

What are these fellows hope to accomplish?

Finding a good dye for a pretty lid for a crock pot or something?

Permalink to Comment

9. gippgig on October 22, 2012 12:39 PM writes...

This looks like it might uncouple oxidative phosphorylation (see Drugs I Shan't Be Taking This Week 1: 2-4,Dinitrophenol on B.R.S.M. (brsmblog.com/?p=1588)). It also reminds me of DDT - try it on bugs.

Permalink to Comment

10. processchemist on October 22, 2012 12:42 PM writes...

Not so impressive, if you're old enough to remember amine isolation through picrate crystallization :)...
The chloromethylene touch is really soul-stirring...

Permalink to Comment

11. MTK on October 22, 2012 12:55 PM writes...

Don't laugh, partial agonist.

After all, the entire drug industry can trace its roots to the dye industry, right?

Permalink to Comment

12. Tomsky on October 22, 2012 4:02 PM writes...

According to PubMed these guys from Corning have published more than 8 papers describing different GPR35 agonists in the last 18 months. It all looks like the junk that has fallen out of an HTS. Some people have no shame!

Permalink to Comment

13. Stud studulous on October 22, 2012 4:50 PM writes...

Compounds like this is why medicinal chemistry is being cut everywhere.

Permalink to Comment

14. Secondaire on October 22, 2012 6:22 PM writes...

Oh dear Heavens.

The 1,1,-dichloroalkene I can *kind* of see; it does show up in some legitimate med chem non-tool compound efforts (I believe Silverman published some GABA-AT inhibitors with that particular moiety, if I recall correctly). It doesn't make it great, but there are much worse.

But the ridiculous stack of nitro groups? No. Dude, just no. I'm surprised this compound doesn't blow up when hit with a hammer.

Permalink to Comment

15. gippgig on October 22, 2012 8:18 PM writes...

Do not shake before using.

Permalink to Comment

16. Morten G on October 23, 2012 5:59 AM writes...

Heptares uses radio-agonists/antagonists/inverse-agonists/etc to screen for point mutations that stabilise GPCRs in which ever conformation. They use the mutants for structural biology and SBDD.
Of course synthesizing radioactive explosives may give you a few OH&S issues.

Maybe GPR35 is a bi-nitrophenol receptor? Then it makes perfect sense.

Permalink to Comment

17. Vader on October 23, 2012 10:58 AM writes...

My first thought was that it looked like a pesticide.

My second thought was "high explosive".

Permalink to Comment

18. myma on October 23, 2012 12:25 PM writes...

I wonder what color it is?

Permalink to Comment

19. anonymous on October 23, 2012 6:17 PM writes...

OMG !!! I'll give back my Ph.D. if that molecule isn't a mitochondrial uncoupler WITH GUSTO !!

Permalink to Comment

20. Mfernflower on January 13, 2014 10:37 AM writes...

Nitro DDT! Hooray! We can kill bugs, Blow stuff up and fry mitochondria in one single molecule! (Just dont let Rachel Carson's followers find out) This tops the list of "Death-on-a-stick" molecules along with this gem: http://pubs.acs.org/doi/ipdf/10.1021/ja409801p

Permalink to Comment

21. Mfernflower on January 13, 2014 4:09 PM writes...

@16 , It would appear so. A quick google search caused this list of agonists to show up:

5-nitro-2-(3-phenylpropylamino) benzoic acid[2]
Kynurenic acid[2][3]
Lysophosphatidic acid[2]
Pamoic acid[2]
Zaprinast[2][4]


It would seem like they were trying to mess with how 5-nitro-2-(3-phenylpropylamino) benzoic acid works and somehow got the structure of DDT merged into there candidate's structure!

Permalink to Comment

22. Mfernflower on January 14, 2014 9:11 PM writes...

Here is what whent past my mind when I saw this:

Topmost portion of the molecule: "A dichloroalkene, This is either going to be really good or really f*cking bad"

Middle alkane linker section: "This is starting to look a bit like DDT. This is probably going to end up horribly"

Bottom potion of the molecule: "HOLY SH1T! What the f*ck were they thinking??!?!! It looks like someone took 2,4-DNP and DDT and blended there structures together! I think I am going to vomit! Even someone like myself could not make a more horrifying structure if I tried!!!"

Permalink to Comment

POST A COMMENT




Remember Me?



EMAIL THIS ENTRY TO A FRIEND

Email this entry to:

Your email address:

Message (optional):




RELATED ENTRIES
Why Not Bromine?
Fragonomics, Eh?
Amicus Fights Its Way Through in Fabry's
Did Pfizer Cut Back Some of Its Best Compounds?
Don't Optimize Your Plasma Protein Binding
Fluorinated Fingerprinting
One of Those Days
ChemDraw Days