| Structural highlights
Publication Abstract from PubMed
Optimization of lead compound 1, through extensive use of structure-based design and a focus on PI3Kdelta potency, isoform selectivity, and inhaled PK properties, led to the discovery of clinical candidates 2 (GSK2269557) and 3 (GSK2292767) for the treatment of respiratory indications via inhalation. Compounds 2 and 3 are both highly selective for PI3Kdelta over the closely related isoforms and are active in a disease relevant brown Norway rat acute OVA model of Th2-driven lung inflammation.
Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3-Kinase delta for the Treatment of Respiratory Disease.,Down K, Amour A, Baldwin IR, Cooper AW, Deakin AM, Felton LM, Guntrip SB, Hardy C, Harrison ZA, Jones KL, Jones P, Keeling SE, Le J, Livia S, Lucas F, Lunniss CJ, Parr NJ, Robinson E, Rowland P, Smith S, Thomas DA, Vitulli G, Washio Y, Hamblin JN J Med Chem. 2015 Sep 24;58(18):7381-99. doi: 10.1021/acs.jmedchem.5b00767. Epub, 2015 Sep 3. PMID:26301626[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Down K, Amour A, Baldwin IR, Cooper AW, Deakin AM, Felton LM, Guntrip SB, Hardy C, Harrison ZA, Jones KL, Jones P, Keeling SE, Le J, Livia S, Lucas F, Lunniss CJ, Parr NJ, Robinson E, Rowland P, Smith S, Thomas DA, Vitulli G, Washio Y, Hamblin JN. Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3-Kinase delta for the Treatment of Respiratory Disease. J Med Chem. 2015 Sep 24;58(18):7381-99. doi: 10.1021/acs.jmedchem.5b00767. Epub, 2015 Sep 3. PMID:26301626 doi:http://dx.doi.org/10.1021/acs.jmedchem.5b00767
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