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

October 22, 2012

March of the Ugly Tool Compounds

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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


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

My eyes are burning

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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.

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

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

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

At least it has an interpretable 1H NMR.

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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.

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

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

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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

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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?

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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. ( It also reminds me of DDT - try it on bugs.

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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...

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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?

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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!

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

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

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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.

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

Do not shake before using.

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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.

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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".

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

I wonder what color it is?

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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 !!

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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:

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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]

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!

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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!!!"

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