Journal of medicinal chemistry, 2017-01, Vol.60 (2), p.767-786
2017
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Design and Synthesis of a Pan-Janus Kinase Inhibitor Clinical Candidate (PF-06263276) Suitable for Inhaled and Topical Delivery for the Treatment of Inflammatory Diseases of the Lungs and Skin
- Ist Teil von
- Journal of medicinal chemistry, 2017-01, Vol.60 (2), p.767-786
- Ort / Verlag
- United States: American Chemical Society
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- By use of a structure-based computational method for identification of structurally novel Janus kinase (JAK) inhibitors predicted to bind beyond the ATP binding site, a potent series of indazoles was identified as selective pan-JAK inhibitors with a type 1.5 binding mode. Optimization of the series for potency and increased duration of action commensurate with inhaled or topical delivery resulted in potent pan-JAK inhibitor 2 (PF-06263276), which was advanced into clinical studies.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0022-2623eISSN: 1520-4804DOI: 10.1021/acs.jmedchem.6b01634Titel-ID: cdi_proquest_miscellaneous_1852692706
- Format
- –
- Schlagworte
- Administration, Cutaneous, Administration, Inhalation, Animals, Anti-Inflammatory Agents - administration & dosage, Anti-Inflammatory Agents - chemical synthesis, Anti-Inflammatory Agents - pharmacology, Anti-Inflammatory Agents - toxicity, Binding Sites, Crystallography, X-Ray, Dogs, Drug Design, Hepatocytes - metabolism, Heterocyclic Compounds, 2-Ring - administration & dosage, Heterocyclic Compounds, 2-Ring - chemical synthesis, Heterocyclic Compounds, 2-Ring - pharmacology, Heterocyclic Compounds, 2-Ring - toxicity, Humans, Indazoles - administration & dosage, Indazoles - chemical synthesis, Indazoles - pharmacology, Indazoles - toxicity, Janus Kinase 1 - antagonists & inhibitors, Janus Kinase 2 - antagonists & inhibitors, Janus Kinase 3 - antagonists & inhibitors, Janus Kinases - antagonists & inhibitors, Lung Diseases - drug therapy, Mice, Inbred BALB C, Microsomes, Liver - metabolism, Phosphorylation, Protein Kinase Inhibitors - administration & dosage, Protein Kinase Inhibitors - chemical synthesis, Protein Kinase Inhibitors - pharmacology, Protein Kinase Inhibitors - toxicity, Rats, Skin Diseases - drug therapy, Solubility