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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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January 7, 2013

Bioisosteres

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Posted by Derek

A couple of years ago, I referred to a journal article summarizing many recent examples of bioisosteres in medicinal chemistry. I've been meaning to mention a book that came out late last year, Bioisosteres in Medicinal Chemistry. It looks to be a compendium of all the latest information on functional group substitutions and their effects on solubility, pharmacokinetics, metabolism and the like. Worth a look if this is one of your interests - you can look over the table of contents at that Amazon link.

Comments (8) + TrackBacks (0) | Category: Book Recommendations


COMMENTS

1. Galen on January 7, 2013 5:37 PM writes...

Any one have an idea for a bioisostere for aryl or het-aryl trifluoromethoxy? Bonus points for added solubility.

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2. Galen on January 7, 2013 6:35 PM writes...

^besides halogens.

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3. mmm on January 7, 2013 6:49 PM writes...

how about bioisosteres for isoquinoline

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4. Insilicoconsulting on January 7, 2013 10:35 PM writes...

I frequently mine biosteres from bioactivity/bioassay data at pubchem and chembl , other than ones mentioned in literature .

A very useful site is http://swissbioisostere.ch/ .

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5. chris on January 8, 2013 2:15 AM writes...

@1
Cyclopropyl?

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6. Pete on January 8, 2013 8:49 AM writes...

Understanding the conformational preferences of what you're trying to replace usually represents a good start to bioisostere design.

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7. istvan on January 9, 2013 3:55 PM writes...

Searching BIOSTER for "trifluoromethoxy" retrieved
1) the obvious "trifluoromethylthio" group:
McEvoy F J et al, J Med Chem, 11: 1248 (1968)
Ducray P et al, Bioorg Med Chem Lett, 18: 2935 (2008)
2) "cyclopentyloxy":
Lowe J A III et al, Bioorg Med Chem Lett, 20: 907 (2010)
3) an interesting replacement is based on a benzhydryl-to-trifluoromethoxybenzyl was also found:
Taylor S J et al, Bioorg Med Chem Lett, 19: 5864 (2009)

Good luck ;-)

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8. istvan on January 9, 2013 4:08 PM writes...

SORRY for multiple uploads...

For mmm on isoquinolines, here are some examples from BIOSTER:

furopyridine, phenylpyridine, indazole, isoquinolinone, pyridopyridazine, N,N-dimethylaniline, pyrazolotriazine, dihydroisoquinoline, iminochromene, chromanone, quinazoline, phthalazine, cinnamonitrile, benzimidazole, o-dichlorobenzene, benzamide, naphthyridine, phenyl ketone, and vinylpyridine (vinyl replaceing the 'benzene' ring system).

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