CHEM-X News http://www.chem-x-infinity.com fr 2010-09-03T00:00:00+00:00 daily 1 2010-09-03T00:00:00+00:00 PARTNERSHIP BEETWEEN CHEM-X-INFINITY AND I-STEM INSTITUTE (April 2010) http://www.chem-x-infinity.com/article/article.php/article/i-stem-institute-partnership 2010-09-03T00:00:00+00:00 CHEM-X-INFINITY partnered with I-Stem Institute to identify new treatments for monogenic diseases. Chem-X-Infinity will supply compound libraries, library focusing and early hit-optimization.  

 

CHEM-X-INFINITY is pleased to announce it has signed a partnership with Genopole-based  I-STEM INSTITUTE, a French R&D company dedicated to the development of treatments based on the potential offered by stem cells and applicable to rare diseases of genetic origin. Defined by three key words, “therapeutics”, “monogenic diseases” and “stem cells”, the activity of I-Stem Institute extends from basic biological research and pathological mechanisms up to the transfer of new therapies to clinical research
 
The objective of I-Stem Institute is the development of treatments intended for monogenic diseases, founded on the strong potential of stem cells for substitutive and regenerative therapies. A second original objective of I-Stem Institute is the development of cell models representative of pathologies on the basis of human embryonic stem cell lines each carrying a mutant gene associated with a given disease. These should help elucidate mechanisms of pathogenesis, and consequently, reveal possible therapeutic targets. These models could also be used as a basis for screening compounds libraries in order to discover new potential drugs.

The partnership will be based on the supplying of specific compound libraries, library focusing and early hit-optimization.


]]> CHEM-X-INFINITY WILL ATTEND THE XXIst INTERNATIONAL SYMPOSIUM OF MEDICINAL CHEMISTRY http://www.chem-x-infinity.com/article/article.php/article/21st-ismc-international-symposium-medicinal-chemistry 2010-08-26T00:00:00+00:00 CHEM-X-INFINITY will attend the 21st International Symposium of Medicinal Chemistry on September 5-9th, 2009, in Brussels, Belgium.

 

CHEM-X-INFINITY will attend the 21st International Symposium of Medicinal Chemistry on September 5-9th, 2009, in Brussels, Belgium. The event covers new and common challenges faced during the research and development phases of the drug discovery process, as well as exciting and pertinent success stories. This symposium is recognized worldwide as one of the leading Medicinal Chemistry meetings, as proven by its large international attendance.

The whole program is available at the ISMC website.

Do not hesitate to come to our booth (#24) to meet our Chief Business Officer Bertrand Zemmour and our Chief Scientific Officer Romuald Baudelle, to have a better understanding of our portfolio of libraries, and to receive exclusive information on recent updates.

Bertrand Zemmour - +33-6-087-308-55

]]> CHEM-X-INFINITY AND PROVENCE TECHNOLOGIES RELEASE AN AZAINDOLE LIBRARY http://www.chem-x-infinity.com/article/article.php/article/azaindole-library-kinase-gpcrs-provence-technologies 2010-05-14T00:00:00+00:00 CHEM-X-INFINITY is pleased to announce a new library focused on kinases, DNA processing enzymes and GPCRs. The original azaindole scaffold could be useful for the identification of new potent series. The library was co-designed with Provence Technologies which is a company specialized in the synthesis of azaindoles.

Indole is one of the most ubiquitous privileged structure in the field of medicinal chemistry. Indole derivatives are particularly well represented in natural products, amine GPCR ligands, enzyme inhibitors, DNA and nucleotides interfering compounds. Isosteric replacement of carbon by nitrogen often results in increased activity or selectivity, metabolic stabilization and better pharmacokinetics (increased solubility, oral activity, longer half-life). However, synthetic difficulties have hampered the development of azaindoles, and more specifically, of 4 and 7-azaindoles. In collaboration with Provence Technologies, which has developed new methodologies for the synthesis of functionalized azaindoles (www.azaindole.com), Chem-X-Infinity has delivered a library built upon original 4 and 7-azaindole acidic intermediates.

Examples of active azaindole compounds include many kinase inhibitors and GPCR antagonists. The scaffold is so small that it could be useful in any research domain and could be considered as a good surrogate for indole to improve pharmacokinetic properties or to insure patentability. It is noticeable that more than 44 % of the compounds are predicted to be CNS by our model developed with CIPF.

Details and scientific references can be found in the azaindole library brochure.

Feel free to request a login password to have access to the structures.

]]> CHEM-X-INFINITY RELEASES A PEPTIDE SURROGATE LIBRARY http://www.chem-x-infinity.com/article/article.php/article/protease-alkylamide-aminoamide-pepdisomimetic-surrogate-library 2010-02-17T00:00:00+00:00 CHEM-X-INFINITY is pleased to announce a new library focused on proteases. Two versatile linkers have been used to synthesize compounds able to interact with serine and cysteine residues of proteins. The compounds could also have applications in GPCRs and antibiotics.

Peptides have the capability to adopt several positions in the binding sites. This flexibility is a real advantage for first intention screenings when few information about the active site is available. But due to their poor metabolic stability, peptides have to be modified to become interesting leads.

In a strategy related to the design of our dialkylaminoamide library, we focused this library around alkylonitrile and aminoamides compounds. Several examples of alkylonitrile compounds were described as cathepsin and dipeptidyl peptidase inhibitors. The main challenge of those series is to achieve selectivity by finely tuning the substituants close to the nitrile. We designed eight original scaffolds to address this problem.

The ethylenediamine linker is often used to design pro-drugs. Numerous bio-active compounds contain this linkage, including some antihistaminics. Our objective was to introduce a substitution on the link to improve its stability towards proteases.

Details and scientific references can be found in the peptide surrogate library brochure.

Feel free to request a login password to have access to the structures.
 

]]> CHEM-X-INFINITY PRESENTS TWO PEPTIDOMIMETIC LIBRARIES http://www.chem-x-infinity.com/article/article.php/article/peptidomimetic-dialkylaminoamide-protein-interation-enzyme-gpcr-ion-channel-library 2010-01-06T00:00:00+00:00 CHEM-X-INFINITY released a new focused library centered on the linker dialkylaminoamide. This versatile linker can be found in various active molecules targeting enzymes, ion channels and GPCRs. A selection of potent peptidomimetic structures is also presented.
 

Finding new small molecules able to disrupt protein-protein interactions is challenging. Starting from natural ligands is a good solution if the problem of their instability in biological media is controlled. Several strategies were used to design these libraries of peptidomimetic compounds.

Unnatural amino acids can be synthesized using the Petasis reaction, a multiple component reaction involving an amine, an acid and a boronic acid. Starting from secondary amines and glyoxylic acid, original diakylaminoamides can be efficiently obtained. These small acids can fool the proteases recognition sites to stabilize the molecule in vivo. Related active compounds can be found in enzyme inhibitors, ion channels regulators, GPCR antagonists and some antibacterials.

Our selection of peptidomimetics was based on scaffolds that mimic beta-turns: spiropyrrolidinones, tetrahydrocarbolines, hexahydro-pyrazinopyrimidinediones, hexahydro-thiazolopyridinones, original benzodiazepines, spirohydantoines and spirothiazolidines. Original dihydrooxadiazolines were added since this heterocycle is a good isostere of a peptide linking. A selection of focused fragments and of molecules containing at least two peptidic bounds was also selected to optimize the diversity of the library.
   
Details and scientific references can be found in the dialkylaminoamide library brochure and in the peptidomimetic selection brochure.

Feel free to request a login password to have access to the structures.


]]> CHEM-X-INFINITY RECEIVED THE FRENCH RESEARCH TAX CREDIT ACCREDITATION http://www.chem-x-infinity.com/article/article.php/article/credit-impot-recherche-french-tax-credit-r-d-chem-x-infinity 2009-12-07T00:00:00+00:00 CHEM-X-INFINITY is pleased to announce that it has received the accreditation for the French R&D tax credit for years 2009 to 2012. The system allows French companies to have a tax credit for R&D services outsourced in approved companies.

On the 2nd of December, 2009, the French Ministry of Education and Research granted CHEM-X-INFINITY the accreditation for the French R&D tax credit (“Crédit d’Impôt Recherche”) for years 2009 to 2012. The accreditation was based on a research document showing that Chem-X-Infinity has expertise and resources to conduct R&D projects in parallel synthesis and in molecular modeling.

The system allows French companies to have a tax credit for R&D services outsourced in approved companies. More information is available on the site of the French Ministry of Research.

]]> CHEM-X-INFINITY RELEASES A PYRAZOLE PROPIONAMIDE LIBRARY http://www.chem-x-infinity.com/article/article.php/article/pyrazole-propionamide-gpcr-nsaid-antiinflammatory-library 2009-12-02T00:00:00+00:00 CHEM-X-INFINITY released a new focused library centered on the pyrazole propionamide scaffold. Many strategies for the synthesis of pyrazoles are described in the literature. We used an original cyclisation to obtain pyrazole propionamides that could have applications in the GPCR field and for the discovery of new NSAIDs.

Our first pyrazole library was centered on 1-aryl-5-aminopyrazoles for DNA and RNA intercalating agents. Intercalating agents are often planar molecules that disrupt base stacking. The objective of this new library was to substitute the pyrazole with a flexible side chain to obtain molecules able to adapt an enzyme site. Systematic variations around the intermediates allow a quick SAR establishment.
   
Many applications can be considered for this collection of compounds, particularly amine and peptide GPCR inhibition and the identification of new series of non-steroidal anti-inflammatory drugs. Other themes are described in the brochure of the library.

Feel free to request a login password to have access to the structures.

]]> CHEM-X-INFINITY RELEASES A QUINOLINE CARBOXAMIDE LIBRARY http://www.chem-x-infinity.com/article/article.php/article/quinoline-carboxamide-gpcr-protein-enzyme-ion-channel-library 2009-10-16T00:00:00+00:00 CHEM-X-INFINITY is pleased to present a new diverse library centered around the quinoline carboxamide scaffold. This small and versatile heterocycle offers many interaction possibilities with diverse receptors as peptide and amine GPCRs or ion channels. The library is a good collection for first intention screenings.

In our internal database of drugs and active compounds of more than 2,500 molecules, 63 entries have a quinoline in their substructure. This may seem poor, but if you compare with the 79 compounds having a naphtyl substructure and the 56 compounds with a biphenyl, you realize that quinolines remain an important feature for active molecules. Moreover the substructure was listed in the most common atomic frameworks in drugs (G. W. Bemis and M. A. Murcko, “The Properties of Known Drugs. 1. Molecular Frameworks”, J. Med. Chem., 1996, 39, 2887-2893).

Quinolines are conveniently synthesized in one step from isatin and an acetophenone. This method is suitable for parallel synthesis since the final compounds all have an active carboxylic acid in the 4-position. The diversity of acetophenones is limited but we were able to select 16 starting materials and 80 diverse partners to explore an optimal space around the quinoline-4-carboxamide scaffold.

Many applications can be considered for this collection of compounds within the Lipinski’s rules, as diverse as amine and peptide GPCR inhibition, ion channels modulators and enzyme inhibitors. Former active molecules sharing the quinoline carboxamide substructure are detailed and discussed in the brochure of the library.

Feel free to request a login password to have access to the structures.

]]> CHEM-X-INFINITY ATTENDED THE 5TH DRUG DESIGN AND LEAD DISCOVERY SUMMIT http://www.chem-x-infinity.com/article/article.php/article/drug-design-lead-discovery-chemical-compound-library 2009-10-01T00:00:00+00:00 CHEM-X-INFINITY attended the 5th Drug Design and Lead Discovery Summit on October 14-16th, 2009, in San Diego, CA. The event covered new and common challenges faced during the research phase of the drug discovery process, as well as exciting and pertinent success stories. The conference had a focus on ligand-based drug design strategies that highlight the alternates, value, applicability, efficacy and effectiveness of pharmacophore-based strategies for lead finding and optimization.  

The 5th Annual Modern Drug Discovery & Development summit was held in San Diego the 14th to the 16th of October, 2009. It was a good place to meet important project leaders involved in modern medicinal chemistry. More than 140 talks were organized into seven tracks to cover all the strategies for drug discovery and development.


“Biological Therapeutics” presented new achievements in antibody-based therapies, vaccine developments, protein applications and biologics delivery. “Advances in Stem Cell Discoveries” covered the status and future of stem cell research while the US government changed this year its policy concerning human embryonic stem cells. “Partnering, Licensing & Outsourcing” gave precious information about the ways to select the best partners for a good collaboration. “Toxicity & Drug Safety” was dedicated to PK / PD / TD markers and new techniques to assess toxicity. “Translational Medicine” was a diverse program to discover a selection of all the themes of the summit.


Among others, in the “Drug Desing & Lead Discovery” track, new dopamine transporter inhibitors identified using pharmacophore based design were presented by Istvan J. Enyedy from Biogen Idec. Andreas Kuglstatter, from Roche Palo Alto, described five strategies based on fragments to design new kinase inhibitors. Dramane Lainé discussed the COPD program of GlaxoSmithKline where quinuclidine series were identified as new long acting muscarinic antagonists. George Keresu from Gedeon Richter introduced the concept of “lead obesity” and the way to improve optimization using ligand efficacy and lipophylic efficacy. Finally a very chemical talk from Jie Jack Li described the generation of new potent MMP-13 inhibitors for the treatment of osteoarthritis at Bristol Myers Squibb.


Metalloproteases have also applications in cancer therapy like the MMP-14 new inhibitor series presented by Lili Huang from Dyax during the “Cancer Targets & Therapeutics” track. A first session was dedicated to novel oncology biomarkers. In session II, interesting chemical series were described like the new aminopyrrolidines Akt inhibitors from Pfizer discussed by Kevin Freeman-Cook and the thiazole urea AZD7762 from Astra Zeneca, presented by Susan Ashwell, an inhibitor of checkpoint kinase which is now in phase I clinical trials. The last session explored the possibilities to use RNA technologies for cancer therapy.


]]> CHEM-X-INFINITY PRESENTS A DIHYDROQUINAZOLINONE LIBRARY http://www.chem-x-infinity.com/article/article.php/article/dihydroquinazolinone-antibiotic-diuretic-analgesic-library 2009-09-18T00:00:00+00:00 CHEM-X-INFINITY released a new focused library centered around the dihydroquinazolinone scaffold. Using a well-known two steps connecting chemistry and diverse sets of amines and aldehydes, the compounds could be useful for the research of new diuretics, analgesics, antibiotics and anti-tumoral compounds.

Parallel synthesis is fond of connecting chemistries that can rapidly create a scaffold able to dispose the diversity elements in 3D positions. Dihydroquinazolinones belong to this family. Starting from isatoic anhydride or analogs, the heterocycle is produced in two steps using amines and aldehydes, two of the most diverse families of building blocks. Since the diversity elements are in a short connectivity distance in a rigid cycle, the final molecules adopt a 3D structure able to interact with complex active sites.

It is not surprising to see many applications for this scaffold. In the Pubchem database, for the 414 dihydroquinazolinones having been tested in at least one assay, 329 hits are described in screenings against receptors as diverse as proteases, kinases, GPCRs or protein-protein interaction. Molecules on the market sharing the structure belong to the thiazide diuretic family. Other applications are described in the literature and are discussed in the brochure of the library.

Feel free to request a login password to have access to the structures.

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