Reported herein is the metal-catalyzed regioselective C–H functionalization of quinoline N-oxides at the 8-position: direct iodination and amidation were developed using rhodium and iridium catalytic systems, respectively. Mechanistic study of the amidation revealed that the unique regioselectivity is achieved through the smooth formation of N-oxide-chelated iridacycle and that an acid additive plays a key role in the rate-determining protodemetalation step. While this approach of remote C–H activation using N-oxide as a directing group could readily be applied to a wide range of heterocyclic substrates under mild conditions with high functional group tolerance, an efficient synthesis of zinquin ester (a fluorescent zinc indicator) was demonstrated.

Regioselective Introduction of Heteroatoms at the C-8 Position of Quinoline N-Oxides: Remote C–H Activation Using N-Oxide as a Stepping Stone

Rhodium(III)-Catalyzed C–C Bond Formation of Quinoline N-Oxides at the C-8 Position under Mild Conditions

Quinoline: a promising antitubercular target

A gold-catalyzed cascade annulation of propargylic silyl ethers with anthranils proceeds through a sequential ring opening/1,2-H-shift/protodeauration/Mukaiyama aldol cyclization. This method offers a regiospecific and modular access to 2-aminoquinolines and other quinoline derivatives under mild conditions and with a broad functional-group tolerance. The conversion is possible on a gram scale, which underlines the synthetic practicability of this methodology. The versatility of the obtained scaffold has been demonstrated by useful postfunctionalization.

Gold-Catalyzed Synthesis of Quinolines from Propargyl Silyl Ethers and Anthranils through the Umpolung of a Gold Carbene Carbon

Introduction: The concept of privileged structures is well known and is often used in the process of drug design and development. Although its assumptions are not clear, its overall usefulness remains high. Various substructures have been identified as privileged and quinoline is a prime example of such a structure.Areas covered: Quinoline drugs that are currently approved or under clinical investigation were reviewed based on a literature search. Their modes of action and outcomes during clinical research are discussed.Expert opinion: Undoubtedly, quinoline-based compounds have a significant impact on anticancer drugs. Although topoisomerase and kinase inhibitors are the only two different classes of agents that are currently approved for anticancer therapy, more than twenty different drug candidates are being tested on humans. The quinoline moiety offers an easily accessible, well-understood scaffold for designing new drugs. It is also a very druggable molecule with the potency for structure opt...

An overview of quinoline as a privileged scaffold in cancer drug discovery

Quinoline (1-azanaphthalene) is a heterocyclic aromatic nitrogen compound characterized by a double-ring structure that contains a benzene ring fused to pyridine at two adjacent carbon atoms. Quinoline compounds are widely used as "parental" compounds to synthesize molecules with medical benefits, especially with anti-malarial and anti-microbial activities. Certain quinoline-based compounds also show effective anticancer activity. This broad spectrum of biological and biochemical activities has been further facilitated by the synthetic versatility of quinoline, which allows the generation of a large number of structurally diverse derivatives. This includes numerous analogues derived from substitution of the quinoline ring system, and derivatization of quinoline ring structure. Quinoline and its analogs have recently been examined for their modes of function in the inhibition of tyrosine kinases, proteasome, tubulin polymerization and DNA repair. In this review, we have summarized our knowledge on quinoline compounds with respect to their anticancer activities, mechanisms of action, structure-activity relationship (SAR), and selective and specific activity against various cancer drug targets. In particular, we focus our review on in vitro and in vivo anticancer activities of quinoline and its analogs in the context of cancer drug development and refinement.

Solomon Vr

Papers

Quinoline as a Privileged Scaffold in Cancer Drug Discovery