Cinnoline Scaffold—A Molecular Heart of Medicinal Chemistry?

Abstract

The cinnoline nucleus is a very important bicyclic heterocycle that is used as the structural subunit of many compounds with interesting pharmaceutical properties. Cinnoline derivatives exhibit broad spectrum of pharmacological activities such as antibacterial, antifungal, antimalarial, anti-inflammatory, analgesic, anxiolytic and antitumor activities. Some of them are under evaluation in clinical trials. In the present review, we have compiled studies focused on the biological properties of cinnoline derivatives conducted by many research groups worldwide between 2005 and 2019. Comprehensive and target oriented information clearly indicate that the development of cinnoline based molecules constitute a significant contribution to the identification of lead compounds with optimized pharmacodynamic and pharmacokinetic properties.

Heterocycles in Medicinal Chemistry

“…The complexity and wideness of this issue are documented by two review articles. The first is a comprehensive up-to-date review focused on cinnoline derivatives exhibiting a broad spectrum of pharmacological activities such as antibacterial, antifungal, antimalarial, anti-inflammatory, analgesic, anxiolytic, and antitumor [1], and the second one deals with the research and applications of nucleotide analogues, especially the second-generation bridged nucleic acids [2].…”

1H-Benzo[de]cinnolines: an interesting class of heterocycles

“…Dorofeenko et al demonstrated using 1 H NMR in CF3CO2H that 6-methoxy-1H-benzo[de]cinnoline 13 and its N-methyl derivative protonate on C7. 21 © ARKAT USA, Inc (10) with methyl and propyl iodides as well as with benzyl chloride in alkaline medium leads to the formation of the corresponding both N-substituted (11, 39, 40) and 9-substituted cinnoline derivatives (41,42) and also to the dimerization product (43) of the initial compound that corresponds to the formation of a N1-C9 bond (Scheme 3). 22 IR and 1 H NMR spectra were used to establish the structures; remember that protonation takes place at C7 while the alkylation occurs at C9.…”

Understanding the aqueous chemistry of quinoline and the diazanaphthalenes: insight from DFT study

“…A mono doping of naphthalene with N at position 1 yields a quinolone molecule [ 19 , 20 ]. While cinnoline, quinazoline and quinoxaline are derived via di-doping of naphthalene with N atoms at positions 1 and 2, 1 and 3, and 1 and 4, respectively [ 21 , 22 , 23 , 24 ]. The inclusion of N atoms in the backbone of naphthalene chemically alters the electronic make-up, hence the emergence of new properties of interest.…”