Identification of 4-aryl-1H-pyrrole[2,3-b]pyridine derivatives for the development of new B-Raf inhibitors

Chemical Biology & Drug Design
Luca PinziGiulio Rastelli

Abstract

During the last years, a significant interest in the identification of new classes of B-Raf inhibitors has emerged. In this study, which was conceived within an effort that culminated in the recent report of the first dual inhibitors of B-Raf and Hsp90, we describe the identification of four compounds based on 4-aryl-1H-pyrrole[2,3-b]pyridine scaffold as interesting starting points for the development of new B-Raf inhibitors. Structure-activity relationships and predicted binding modes are discussed. Moreover, the novelty of the newly identified structures with respect to currently known B-Raf inhibitors was assessed through a ligand-based dissimilarity assessment. Finally, structural modifications with the potential ability to improve the activity toward B-Raf are put forward.

References

Jun 4, 1999·Progress in Biophysics and Molecular Biology·M H Cobb
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Mar 10, 2001·Recent Progress in Hormone Research·J AvruchX F Zhang
Jun 18, 2002·Nature·Helen DaviesP Andrew Futreal
Nov 26, 2002·Journal of Chemical Information and Computer Sciences·Joseph L DurantJames G Nourse
Feb 5, 2003·Onkologie·R A HilgerD Strumberg
Oct 19, 2004·Cancer Cell·Mathew J Garnett, Richard Marais
Jun 25, 2005·Journal of Medicinal Chemistry·Peter Willett
Jan 6, 2006·Journal of Medicinal Chemistry·Ion Niculescu-DuvazCaroline J Springer
Apr 18, 2008·Journal of Chemical Information and Modeling·Steven W MuchmorePhilip J Hajduk
Aug 18, 2009·ChemMedChem·Miriam Sgobba, Giulio Rastelli
Sep 22, 2009·Journal of Medicinal Chemistry·Adrian L SmithJosette Carnahan
Apr 30, 2010·Journal of Chemical Information and Modeling·David Rogers, Mathew Hahn
Apr 5, 2011·Bioorganic & Medicinal Chemistry·Tony TaldoneGabriela Chiosis
May 27, 2011·Bioorganic & Medicinal Chemistry Letters·Pei-Pei KungRobert Kania
Jun 7, 2011·The New England Journal of Medicine·Paul B ChapmanUNKNOWN BRIM-3 Study Group
Aug 2, 2011·Bioorganic & Medicinal Chemistry Letters·Steve WenglowskyZhaoyang Wen
Sep 29, 2011·Nucleic Acids Research·Anna GaultonJohn P Overington
Feb 22, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kim H T ParaisoKeiran S M Smalley
Nov 12, 2013·Nucleic Acids Research·A Patrícia BentoJohn P Overington
Mar 29, 2014·Bioorganic & Medicinal Chemistry Letters·Steve WenglowskyJoachim Rudolph
Jun 20, 2014·Journal of Medicinal Chemistry·Andrew AnighoroGiulio Rastelli
Oct 16, 2015·Nature·Chao ZhangGideon Bollag

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.