Abstract
Tyrosine kinases are implicated in a wide array of cellular physiological processes,
including cell signaling. The discovery of the BCR-ABL tyrosine kinase inhibitor
imatinib and its FDA approval in 2001 paved the way for the development of small molecule
chemical entities of diverse structural backgrounds as tyrosine kinase inhibitors for
the treatment of various ailments. Two of the most prominent tyrosine kinases as drug targets
are the epidermal growth factor receptor (EGFR) and the vascular endothelial growth
factor receptor (VEGFR), as evidenced by the clinical success of their many inhibitors in
the drug market. Among several other physiological roles, EGFR regulates epithelial tissue
development and homeostasis, while VEGFR regulates tumor-induced angiogenesis.
The pyrrolo[2,3-d]pyrimidine nucleus represents a deaza-isostere of adenine, the nitrogenous
base of ATP. The recent introduction of many pyrrolo[2,3-d]pyrimidines to the drug
market as tyrosine kinase inhibitors makes them a hot topic in the medicinal chemistry research
area at the present time. This review article comprehensively sheds light on the
structure-activity relationship (SAR) of pyrrolo[2,3-d]pyrimidines as EGFR and VEGFR
tyrosine kinase inhibitors, aiming to provide help medicinal chemists in the design of future
pyrrolopyrimidine kinase inhibitors.
Keywords:
Pyrrolo[2, 3-d]pyrimidines, tyrosine kinases, EGFR, VEGFR, SAR, kinase inhibitors.
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