CCL: W:Computational drug design blues

[Gary Breton <gbreton]"[berry.edu>]

 Sent to CCL by: Gary Breton [gbreton]"[berry.edu]
 Speaking as an organic chemist I can tell you that the answer to your
 question is probably no.  There is no easy way to tell whether a given
 compound is easy or difficult to synthesize other than to give it to a
 medicinal or organic chemist that has experience in and knows synthesis.
 For example, a compound with a nitro group at one position may be very easy
 to synthesize, but move it over one carbon and suddenly you have a very
 difficult system to synthesize.  Any "simple" guidelines would
 probably not
 differentiate between the difficulty in synthesis of these types of isomers.
 While there have been attempts at generating software to aid in
 "deconstructing" molecules towards the goal of making planned
 syntheses
 easier, none of these (at least to my knowledge) is particular robust.  I
 have never heard of an organic chemist...or seen cited in a paper...the use
 of such software to aid in a synthetic route.  While there may be
 exceptions, it certainly isn't the norm.
 ...and I don't say all this just for the sake of job security ;)
 Gary W. Breton
 Associate Professor
 Hard-Working Organic Chemist
 Department of Chemistry
 Berry College
 PO Box 495016
 Mount Berry, GA 30149
 > Sent to CCL by: "Sandeep  Kumar" [kumarsan\a/jhu.edu]
 > Dear CCLers:
 >
 > I need some advice about the drug discovery/design. Using structure based
 > design, one could develope several potential small molecular
 inhibitors/drugs
 > for a given protein target. Many of these compounds may appear very
 attractive
 > as they satisfy all lipinski's rules and your requirements for
 > selectivity/specificity and may even have desirable solubility/ADME
 profiles.
 > These days its possible to incorporate all these features right at the
 > computational design stage. However, the organic synthesis of the compound
 > still remains a bottleneck as it turns out that many of the designed
 compounds
 > are 'hard' to synthesize or may require many steps of synthesis. I was
 > wondering if there are some simple guidelines in the form of literature or
 > 'hands on' experience available which could tell the
 computational/medicinal
 > chemist whether a designed compound would be easy or hard to synthesize
 before
 > he/she talks to the organic chemist.
 >
 > All your responses are greatly appreciated.
 >
 > Yours sincerely
 > Sandeep Kumar, Ph.D.
 > Johns Hopkins University,
 > Dept. of Biology,
 > 106 Mudd Hall,
 > 3400 N. Charles St.
 > Baltimore, MD 21218.
 > Phone: 410-516-8433
 > Email: kumarsan]"[jhu.edu>
 >