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Novartis : Researchers at Novartis Report New Data on Medicinal Chemistry [Discovery of CDZ173 (Leniolisib), Representing a Structurally Novel Class of PI3K...

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10/05/2017 | 05:24pm CEST

Researchers at Novartis Report New Data on Medicinal Chemistry [Discovery of CDZ173 (Leniolisib), Representing a Structurally Novel Class of PI3K Delta-Selective Inhibitors]

By a News Reporter-Staff News Editor at Health & Medicine Week -- Fresh data on Health and Medicine - Medicinal Chemistry are presented in a new report. According to news reporting out of Basel, Switzerland, by NewsRx editors, research stated, "The predominant expression of phosphoinositide 3-kinase d (PI3Kd) in leukocytes and its critical role in B and T cell functions led to the hypothesis that selective inhibitors of this isoform would have potential as therapeutics for the treatment of allergic and inflammatory disease. Targeting specifically PI3Kd should avoid potential side effects associated with the ubiquitously expressed PI3Ka and b isoforms."

Our news journalists obtained a quote from the research from Novartis, "We disclose how morphing the heterocyclic core of previously discovered 4,6-diaryl quinazolines to a significantly less lipophilic 5,6,7,8-tetrahydropyrido[4,3-]pyrimidine, followed by replacement of one of the phenyl groups with a pyrrolidine-3-amine, led to a compound series with an optimal on-target profile and good ADME properties. A final lipophilicity adjustment led to the discovery of CDZ173 (leniolisib), a potent PI3Kd selective inhibitor with suitable properties and efficacy for clinical development as an anti-inflammatory therapeutic. , CDZ173 inhibits a large spectrum of immune cell functions, as demonstrated in B and T cells, neutrophils, monocytes, basophils, plasmocytoid dendritic cells, and mast cells. , CDZ173 inhibits B cell activation in rats and monkeys in a concentration-and time-dependent manner. After prophylactic or therapeutic dosing, CDZ173 potently inhibited antigen-specific antibody production and reduced disease symptoms in a rat collagen-induced arthritis model. Structurally, CDZ173 differs significantly from the first generation of PI3Kd and PI3Kgd-selective clinical compounds. Therefore, CDZ173 could differentiate by a more favorable safety profile."

According to the news editors, the research concluded: "CDZ173 is currently in clinical studies in patients suffering from primary Sj?gren's syndrome and in APDS/PASLI, a disease caused by gain-of-function mutations of PI3Kd."

For more information on this research see: Discovery of CDZ173 (Leniolisib), Representing a Structurally Novel Class of PI3K Delta-Selective Inhibitors. Acs Medicinal Chemistry Letters, 2017;8(9):975-980. (American Chemical Society - www.acs.org; Acs Medicinal Chemistry Letters - www.pubs.acs.org/journal/amclct)

Our news journalists report that additional information may be obtained by contacting K. Hoegenauer, Global Discovery Chemistry, PK Sciences, Chemical Biology and Therapeutics and Autoimmunity, Transplantation and Inflammation, Novartis Institutes for BioMedical Research, Novartis Campus, CH-4002 Basel, Switzerland. Additional authors for this research include N. Soldermann, F. Zecri, R.S. Strang, N. Graveleau, R.M. Wolf, N.G. Cooke, A.B. Smith, G.J. Hollingworth, J. Blanz, S. Gutmann, G. Rummel, A. Littlewood-Evans and C. Burkhart (see also Health and Medicine - Medicinal Chemistry).

The direct object identifier (DOI) for that additional information is: https://doi.org/10.1021/acsmedchemlett.7b00293. This DOI is a link to an online electronic document that is either free or for purchase, and can be your direct source for a journal article and its citation.

Keywords for this news article include: Basel, Europe, Switzerland, Health and Medicine, Medicinal Chemistry.

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2017, NewsRx LLC

(c) 2017 NewsRx LLC, source Health Newsletters

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