CHEM-X News http://www.chem-x-infinity.com fr 2011-09-27T00:00:00+00:00 daily 1 2011-09-27T00:00:00+00:00 PARTNERSHIP BETWEEN CHEM-X-INFINITY AND XANCHEM http://www.chem-x-infinity.com/article/article.php/article/xanchem-collaboration-chemhit-tetrahydropyridoindole-pyrrolopyridine-naphtyridines-benzothiepinone 2011-09-27T00:00:00+00:00 CHEM-X-INFINITY partnered with XANCHEM to produce libraries around original scaffolds. The compounds will be of particular interest in the oncology field.  

Xanchem is a chemical company specializing in radical chemistry, gold chemistry and multi-component reactions. Xanchem designs, develops and manufactures original heterocyclic, aromatic, and heteroaromatic derivatives, which are particularly suitable as synthons and scaffolds for the early stages of drug discovery programs. Its expertise includes original tetrahydropyridoindoles, pyrrolopyridines, naphtyridines and benzothiepinones.

CHEM-X-INFINITY is pleased to announce it has signed a partnership with XANCHEM for the design of new original libraries. The libraries will explore the diversity space around XANCHEM’s original scaffolds. Based on our property predictions, the selected molecules could have applications in the kinases, ion channels and proteases fields. The molecules are designed to fully respect the Lipinski rules to offer ideal compounds for first intention screenings.

The partnership is a long term commitment with the objective to develop several thematic libraries. The first library having applications in the oncology field will be released in October, 2011.

]]> PARTNERSHIP BETWEEN CHEM-X-INFINITY AND ORIBASE PHARMA http://www.chem-x-infinity.com/article/article.php/article/oribase-collaboration-chemhit-pyrazolopyrimidine-thienopyridine-pyrrolopyrimidine-imidazopyrimidine 2011-07-20T00:00:00+00:00 CHEM-X-INFINITY partnered with ORIBASE PHARMA to offer kinase focused libraries. The compounds are built around several small aza-heterocycles underused in combinatorial libraries and will have applications in the oncology field.  

ORIBASE PHARMA is a French Contract Research Organization dedicated to the design and synthesis of kinase inhibitors. ORIBASE PHARMA developed a unique technology platform for efficient drug discovery consisting in chemoinformatics and organic chemistry processes. ORIBASE PHARMA has currently a portfolio of five kinase inhibitors in pre-clinical development. During its research programs, ORIBASE PHARMA developed ways to obtain efficiently hard-to-synthesize aza-heterocycles.

CHEM-X-INFINITY is pleased to announce it has signed a partnership with ORIBASE PHARMA for the design of original libraries focused on kinase inhibition. The libraries will explore the diversity space around ORIBASE PHARMA’s original scaffolds. The molecules are poorly described in the literature and are free of patentability. They are designed to fully respect the Lipinski rules to offer ideal compounds for first intention screenings.

The partnership is a long term commitment with the objective to develop several thematic libraries focused on kinases. The first library having applications in the oncology field will be released in December, 2011.

]]> CHEM-X-INFINITY WILL ATTEND THE 18TH MOLECULAR MEDICINE TRI-CONFERENCE http://www.chem-x-infinity.com/article/article.php/article/18th-molecular-medicine-tri-conference-2011 2011-01-11T00:00:00+00:00 CHEM-X-INFINITY will attend the 18th Molecular Medicine Tri-Conference on February 23rd-25th, 2011 in San Francisco, CA.

CHEM-X-INFINITY is delighted to participate to the 18th edition of this international event dedicated to many aspects of health research. Please do not hesitate to come and visit us at Booth #333 or to contact our business developer to know more about our new products!

contact@chem-x-infinity.com

]]> REPORT OF THE SCT ANNUAL WORKSHOP IN MEDICINAL CHEMISTRY http://www.chem-x-infinity.com/article/article.php/article/sct-gfpp-annual-workshop-medicinal-chemistry 2010-12-10T00:00:00+00:00 The SCT Annual Workshop in Medicinal Chemistry was held the 7th of December in Paris at the Faculté de Médecine Cochin Port-Royal in collaboration with GFPP. Please read in this news our feeling about the event.

The Société de Chimie Thérapeutique (SCT - Therapeutical Chemistry Society) presented its Annual Workshop in Medicinal Chemistry the 7th of December in Paris at the Faculté de Médecine Cochin Port-Royal in collaboration with the Groupe Français des Peptides et de Protéines (GFPP – French Group of Peptides and Proteins). The main focus was “Peptidic and Peptidomimetic drugs”.

Despite a snowing day in Paris, about 250 attendees came to hear about several success stories of peptide developments. Pierre Rivière (Ferring Pharmaceuticals, the company is celebrating its 60th anniversary) gave a global analysis of the peptidic pipeline, with the conclusion that for one registered compound, only 4.2 peptides entered in clinical phases, compared to 9.1 for small molecules.

Jean-Alain Fehrentz (Institut des Biomolécules Max Mousseron) discussed the development of macimorelin (JMV 1843), a ghrelin-mimetic growth hormone secretagogue in Phase III for adult growth hormone deficiency (AGHD) and JMV 2959, its heterocyclic analogue having also properties to cure alcohol and cocaine addiction. Daniel Obrecht (Polyphor) presented the protein epitope mimetics (PEM) strategy and its applications for the discovery of POL6326, a CXCR4 inhibitor in Phase IIa for stem cell transplantation and certain leukemias, and the antibacterial POL7080.

Anders Dyhr Toft (Novo Nordisk) explained the discovery of liraglutide, a glucagon-like peptide-1 (GLP-1) analog used for type 2 diabete. Jorgen Wittendorf (Ferring) discussed the strategy to find the appropriate formulation of abarelix, a gonadotropin-releasing hormone (GnRH) receptor blocker launched in 2008 for prostate cancer.

 

Eric Zanelli (Peptimmune) gave clues to understand the mechanism of action of glatiramer acetate (copaxone), a random polymer of four aminoacids currently used to treat multiple sclerosis, and PI 2301, an analog synthesized on solid support displaying a better stability and reducing the number of injection from 1 per day to 1 per week. He also announced the creation of the company Declion, dedicated to the development of new polymers on solid support for novel vaccines and antibodies.

Finally, Bruno Pfeiffer (Servier) awarded the Prix de la Vocation en Chimie Thérapeutique (Servier dotation) to Morgane Petit (Université Paris Descartes) for her work on the development of photoactive probes to deliver glutamate, and to Claude Szalata (Université de Reims) for the synthesis of cyclopropyltryptamines as 5-HT6 inhibitors.

In conclusion, we thank all the organizers for this high quality meeting which demonstrated that the future of peptides and peptidomimetics is very promising.

]]> PARTNERSHIP BETWEEN CHEM-X-INFINITY AND DIVERCHIM http://www.chem-x-infinity.com/article/article.php/article/diverchim-chem-x-infinity-partnership 2010-11-19T00:00:00+00:00 CHEM-X-INFINITY partnered with DIVERCHIM to design and produce original libraries from synthetic analogues of natural compounds. The compounds will be of particular interest in the oncology field.

 In less than 10 years, DIVERCHIM has become the first French CRO in chemistry for life science. Their teams conduct pharmaceutical research in collaboration with many pharmaceutical and biotechnology companies. DIVERCHIM has expertise in comprehensive medicinal chemistry and molecular modelling. Those activities are fully complementary with CHEM-X-INFINITY’s expertise in high throughput automated library synthesis.

CHEM-X-INFINITY is pleased to announce it has signed a partnership with DIVERCHIM for the design of new original libraries. Using DIVERCHIM’s synthetic expertise, several projects were selected based on analogues of natural compounds. The companies will work together to design the best molecules around those new promising scaffolds to offer collections of innovative compounds for first intention screenings.

The partnership is a long term commitment with the objective to co-develop several thematic libraries. The first library having applications in the oncology field should be released in the first semester of 2011.

]]> CHEM-X-INFINITY ATTENDED THE XXIst INTERNATIONAL SYMPOSIUM OF MEDICINAL CHEMISTRY http://www.chem-x-infinity.com/article/article.php/article/21st-ismc-international-symposium-medicinal-chemistry 2010-09-22T00:00:00+00:00 CHEM-X-INFINITY attended the 21st International Symposium of Medicinal Chemistry on September 5th-9th, 2010, in Brussels, Belgium. Please read in this news our feeling about the event.

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.

]]> PARTNERSHIP BETWEEN 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 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.


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