CHEM-X-INFINITY attended the 21st International Symposium of Medicinal Chemistry on September 5th-9th, 2010. The bis-annual event gathered more than 1 100 persons at the fully renovated Square Meeting Center in Brussels, covering all aspects of modern medicinal chemistry, with about 30 sessions of scientific talks and more than 500 posters.

Many state-of-the-art optimization programs were presented in several therapeutic areas. In the “Hot Topics in CNS Diseases” session, James Mills (Pfizer) disclosed series of trisubstituted triazoles as vasopressin 1b (V1b) antagonists for mood control. Thomas J. Woltering (Hoffman-La Roche) discussed the inhibition of metabotropic glutamate receptor 2/3 (mGlu2/3) by series of dihydro-benzodiazepinones for the same application. Anette Graven Sams (Lundbeck) showed promising piperidine series displaying selectivity against the GPCR muscarinic M1 receptor over the M2 to M5 subtypes as antipsychotic agents. For the last talk, Eric Jnoff (UCB) identified series of dihydro-oxazol-2-ylamines as alpha2c adrenergic receptor agonist to treat neuropathic pain.

 “Successful Strategies in Drug Discovery” began with two examples from Hoffmann-La Roche presented by Torsten Hoffman: the discovery of the first glycine transporter 1 (GlyT1) receptor inhibitor which is in Phase III to treat schizophrenia and aleglitazar, a peroxisome proliferator-activated receptor (PPAR) agonist also in Phase III for type II diabete. Beat Ernst (University of Basel) showed how a fragment based approach and click chemistry provided high affinity ligands of selectins. Christophe Biot (University of Lille 1) discussed the potency of bioorganometallic chemistry to introduce new classes of active molecules, like ferroquine which is in Phase II as an antimalarial. Nicholas K. Terrett (Ensemble Discovery) presented a new technology able to synthesize thousands of macrocyclic peptidomimetics that could be useful in the protein-protein interaction field.

Mark Wittman (Bristol-Myers Squibb) presented the first “Oncology Case Study" with an inhibitor of the kinase IGF-1R. Lutz Weber (NexusPharma) showed how multiple component reactions could provide new scaffolds able to disrupt protein-protein interaction, like the dihydroquinazolinone inhibitor of the MDM2-p53 interaction. Stefan Peukert discussed how a HTS against the smoothened receptor (Smo) led to two promising series of inhibitors: aminopyridazines and diaminopyridines.

In the “Recently Disclosed New Medicines” session, William Washburn (BMS) explained the discovery of dapagliflozin, a sodium dependant glucose co-transporter (SGLT2) inhibitor in Phase III for type 2 diabete developed in partnership with Astra Zeneca. Timothy Guzi (Schering-Plough) described the identification of pyrazolopyrimidines as selective CHK1 inhibitors for cancer applications. Pierre Raboisson (Tibotec) told how the analoging of ciluprevir led to TMC435, a quinoline-based hepatitis C virus (HCV) protease inhibitor currently in Phase II. Paul Coleman (Merck) finally discussed the discovery of MK-4305, a potent dual orexin receptor antagonist for sleep disorders.

Some new chemical entities were disclosed for the first time like the direct renin inhibitor currently in early phase clinical development for hypertension and presented by David A. Claremon (Vitae). Yves P. Auberson (Novartis) explained the discovery of BGG492, a competitive AMPA/kainite antagonist for the treatment of migraine and epilepsy. Paul Whittamore (Astra Zeneca) showed a series of thio-alkoxynicotinamide optimized for the inhibition of acidic 11 beta hydroxysteroid dehydrogenase type 1 (11beta-HSD1) for the treatment of obesity. Craig Johnstone (Astra Zeneca) disclosed the structure of a glucokinase activator, an aminopyrazole based molecule with the potential to improve glucose regulation in type 2 diabetes.

The meeting ended with a stunning lecture by G. Verdine (Harvard University) explaining that biologics and small molecules are currently addressing only 20 % of the potential targets and that the next challenges of chemistry should be to find new technologies to address the remaining 80 %. One proposed solution is the synthesis of stapled or stitched peptides using macrocyclic metathesis and an application for the transcription factor ICN/CSL-dnMAML complex was presented.

Globally the 21st International Symposium of Medicinal Chemistry held its promises with a good organization, high quality presentations and respect of the schedule. It is always a pity in this type of event to have to choose between the sessions and to miss some talks you’re interested in. A solution to avoid this frustration would be to give a copy of the presentation to all the attendees.

We would like to thank all the participants who stopped to our booth. It was a great pleasure to have a talk with you. We apologize to all the speakers we did not mention in this news. If you find any mistake in the structures presented here or in the comments don’t hesitate to contact us for a rectification.