CCL: Lead optimization

Hi Vincent,

Thanks for your reply. Basically I work in an academic lab and we would like to purchase some interesting analogues of compounds that we have found. So far, we have no structure and no SAR information.
I am currently just using a substructure/similarity search to identify compounds. I was wondering if there was anything else out there that might be useful in searching. One thought I had was searching using Bioisosterism, where a chemical group or fragment is replaced by an equivalent group.
What I have found so far is Similarity in BioIsosteric Space (SiBIS) from http://www.moltop.com/, and Brood from OpenEye
The Quantum Isostere Database also looks very interesting

Ideally I would like to find a resource that would explain reasons for making particular chemical substitutions or an automatic way of suggesting them

Cheers

Iain

On Tue, Dec 2, 2008 at 11:34 AM, Vincent Leroux vincent.leroux ~~ loria.fr <owner-chemistry:ccl.net> wrote:

Sent to CCL by: Vincent Leroux [vincent.leroux|*|loria.fr]
Hi Iain,

Depends of what you have at this stage. Crystal / NMR structures of complexes, or model structures, or none? Were mutagenesis experiments performed? If there is a target structural model involved, was its conformational space explored, with normal modes analysis / molecular dynamics? You might have biological activity measurements already, but on how much compounds? Are the assays reliable? Were SAR studies done? Were trials of any kind conducted? etc.

There are numerous lead optimization strategies to choose from, answering the above questions could determine which ones are available to you mostly by eliminating the ones that are not. You might also want to check what amount of effort / manwork you can investigate, what tools are available to you, and in which fields that can be involved in the drug design process (biology, lab chemistry, theoretical chemistry, computer science...).

You should specify this somewhat so that the related specialists here will be able to help you.

VL


Iain Wallace iain.m.wallace _ gmail.com a écrit :

Hi all,

I was wondering if anybody could give me some basic pointers on lead optimizations.
First of all,  is there any (free) software that will propose interesting analogues to make/buy, and give a rationalization for proposing them
And also, does any one know of any reviews or books that explains the lead optimization process? I would really like to find something with worked examples

Thanks a million,

Cheers

Iain



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