Structure-based design of isoindoline-1,3-diones and 2,3-dihydrophthalazine-1,4-diones as novel B-Raf inhibitors

Xiaolun Wang; Edward J Salaski; Dan M Berger; Dennis Powell; Yongbo Hu; Donald Wojciechowicz; Karen Collins; Eileen Frommer

doi:10.1016/j.bmcl.2011.10.012

Structure-based design of isoindoline-1,3-diones and 2,3-dihydrophthalazine-1,4-diones as novel B-Raf inhibitors

Bioorg Med Chem Lett. 2011 Dec 1;21(23):6941-4. doi: 10.1016/j.bmcl.2011.10.012. Epub 2011 Oct 12.

Authors

Xiaolun Wang¹, Edward J Salaski, Dan M Berger, Dennis Powell, Yongbo Hu, Donald Wojciechowicz, Karen Collins, Eileen Frommer

Affiliation

¹ Pfizer Worldwide Research and Development, Pearl River, NY 10965, USA. xxw104@gmail.com

PMID: 22024030
DOI: 10.1016/j.bmcl.2011.10.012

Abstract

Structure-guided design led to the discovery of novel chemical scaffolds for B-Raf inhibitors. Both type I and type II kinase inhibitors have been explored and lead compounds with good potency and excellent selectivity have been identified.

MeSH terms

Benzenesulfonates / chemistry
Benzenesulfonates / pharmacology
Drug Design*
Enzyme Activation / drug effects
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Imidazoles / chemistry
Imidazoles / pharmacology
Isoindoles / chemical synthesis*
Isoindoles / chemistry
Isoindoles / pharmacology
Models, Molecular
Molecular Structure
Niacinamide / analogs & derivatives
Phenylurea Compounds
Phthalazines / chemical synthesis*
Phthalazines / chemistry
Phthalazines / pharmacology
Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
Pyridines / chemistry
Pyridines / pharmacology
Sorafenib
Structure-Activity Relationship

Substances

Benzenesulfonates
Enzyme Inhibitors
Imidazoles
Isoindoles
Phenylurea Compounds
Phthalazines
Pyridines
SB-590885
Niacinamide
Sorafenib
Proto-Oncogene Proteins B-raf