Back to Search
Start Over
Piperidine-3,4-diol and piperidine-3-ol derivatives of pyrrolo[2,1-f][1,2,4]triazine as inhibitors of anaplastic lymphoma kinase.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2015 Mar 01; Vol. 25 (5), pp. 1047-52. Date of Electronic Publication: 2015 Jan 17. - Publication Year :
- 2015
-
Abstract
- The diastereoselective synthesis and biological activity of piperidine-3,4-diol and piperidine-3-ol-derived pyrrolotriazine inhibitors of anaplastic lymphoma kinase (ALK) are described. Although piperidine-3,4-diol and piperidine-3-ol derivatives showed comparable in vitro ALK activity, the latter subset of inhibitors demonstrated improved physiochemical and pharmacokinetic properties. Furthermore, the stereochemistry of the C3 and C4 centers had a marked impact on the in vivo inhibition of ALK autophosphorylation. Thus, trans-4-aryl-piperidine-3-ols (22) were more potent than the cis diastereomers (20).<br /> (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Subjects :
- Anaplastic Lymphoma Kinase
Animals
Antineoplastic Agents pharmacokinetics
Cell Line, Tumor
Crystallography, X-Ray
Humans
Lymphoma, Large-Cell, Anaplastic enzymology
Mice, SCID
Models, Molecular
Piperidines chemistry
Piperidines pharmacokinetics
Piperidines therapeutic use
Protein Kinase Inhibitors chemistry
Protein Kinase Inhibitors pharmacokinetics
Protein Kinase Inhibitors therapeutic use
Pyrroles pharmacokinetics
Rats, Sprague-Dawley
Receptor Protein-Tyrosine Kinases metabolism
Triazines pharmacokinetics
Antineoplastic Agents chemistry
Antineoplastic Agents therapeutic use
Lymphoma, Large-Cell, Anaplastic drug therapy
Pyrroles chemistry
Pyrroles therapeutic use
Receptor Protein-Tyrosine Kinases antagonists & inhibitors
Triazines chemistry
Triazines therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 25
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 25655723
- Full Text :
- https://doi.org/10.1016/j.bmcl.2015.01.019