Recent advances of pyrrolopyridines derivatives: a patent and literature review

ABSTRACT

Introduction: Several pyrrolopyridines or azaindoles have been reported in the literature as biologically-active molecules. Most of them are anticancer agents, and few possess other therapeutic effects.

Areas covered: The most recent biologically-active pyrrolopyridine derivatives have been reviewed from the patents and research articles published from 2010 to the mid of 2016. Their structural and biological features have been explained. In general, the pyrrolopyridine scaffold mimics the purine ring of the ATP molecule. So the well-designed pyrrolopyridine analogues can successfully act as kinase inhibitors for treatment of cancer and/or other diseases. The most successful pyrrolopyridine derivative that is currently used in the market is vemurafenib, which is used for treatment of melanoma. Its chemical and biological features have been reviewed and explained.

Expert opinion: The heterocyclic pyrrolopyridine nucleus mimics the purine ring of ATP. So they can work as inhibitors of the kinase at hinge region. Due to the structural similarity with ATP, these pyrrolopyridine derivatives are estimated to be non-selective kinase inhibitors. The selectivity is conferred mainly from the different substituents attached to the azaindole nucleus. More details are presented in the ‘Expert Opinion’ section at the end of this article. This section covers the chemistry and the biological properties of therapeutically-efficient pyrrolopyridine-possessing compounds.

KEYWORDS:

• Pyrrolopyridine
• azaindole
• anticancer
• kinase inhibitors
• vemurafenib

Article highlights

• The recently reported biologically active pyrrolopyridines have been reviewed.

• Most of them are kinase inhibitors due to the structural similarity between the pyrrolopyridine nucleus and ATP purine ring system.

• Most of them are anticancer, and few possess other therapeutic effects such as antiviral, muscarinic antagonist, antiparkinson’s, etc.

• The most successful and marketed pyrrolopyridine compound is Vemurafenib, a selective inhibitor of V600E mutated B-RAF kinase used for treatment of melanoma.

• The binding modes to the receptor sites, the SAR, and the most important biological properties of the most potent pyrrolopyridine compounds have been reviewed.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.