A Review of HNS‐32: A Novel Azulene‐l‐Carboxamidine Derivative with Multiple Cardiovascular Protective Actions

Abstract

HNS -32 [N 1 ,N 1 -dimethyl-N 2 -(2-pyridylmethyl)-5-isopropyl-3,8-dimethylazulene-1-carboxamidine] (CAS Registry Number: 186086-10-2) is a newly synthesized azulene derivative. Computer simulation showed that its three dimensional structure is similar to that of the class Ib antiarrhythmic drugs, e.g., lidocaine or mexiletine. HNS-32 potently suppressed ventricular arrhythmias induced by ischemia due to coronary ligation and /or ischemia-reperfusion in dogs and rats. In the isolated dog and guinea pig cardiac tissues, HNS-32 had negative inotropic and chronotropic actions, prolonged atrial-His and Hisventricular conduction time and increased coronary blood flow. In the isolated guinea pig ventricular papillary muscle, HNS-32 decreased maximal rate of action potential upstroke ( & max V ) and shortened action potential duration (APD). These findings suggest that HNS-32 inhibits inward Na + and Ca 2+ channel currents. In the isolated pig coronary and rabbit conduit arteries, HNS-32 inhibited both Ca 2+ channel-dependent and -independent contractions induced by a wide variety of chemical stimuli. HNS-32 is a potent inhibitor of protein kinase C (PKC)-mediated constriction of cerebral arteries. It is likely to block both, Na + and Ca 2+ channels expressed in cardiac and vascular smooth muscles. These multiple ion channel blocking effects are largely responsible for the antiarrhythmic and vasorelaxant actions of HNS-32. This drug may represent a novel approach to the treatment of arrhythmias.

Homogeneous and Heterogeneous Gold Catalysis for Materials Science

“…Their electronic structure combined with their unique photophysical properties render azulenes as interesting materials for organic electronics. Applications for substituted azulenes can also be found in MOFs (metal–organic framework) for hydrogen storage, as photosensitizers, , or in medicinal chemistry. − The first total synthesis of azulene was established by Pfau and Plattern in 1936 . This multistep synthesis starting from 1,6-cyclodecation over an aldol reaction, reduction, and following dehydration and dehydratization furnished azulenes in low yields.…”

Azulenesulfonium Salts: Accessible, Stable, and Versatile Reagents for Cross‐Coupling

“…Azulene ( 1 ) is a non‐alternant aromatic hydrocarbon which has fascinated chemists for many years owing to its blue color and high dipole moment . Substituted azulenes have been employed in diverse contexts, including medicinal chemistry (as antiulcer, antidiabetic, anticancer, antiarrhythmic, and anti‐erectile‐dysfunction agents, and as TXA 2 τ receptor antagonists), solar cells, metal–organic frameworks for hydrogen storage, and organic electronics, among others. Uses of azulenes in stimuli‐responsive systems have also been disclosed, most commonly in halochromic materials, but also in probes for soft metal cations, fluoride, other anions, and biomolecule analytes .…”

Facile One-pot Synthesis of A Novel Propargyl-Azulene Hybrid Derivative: Cycloaddition Reaction and Some Spectroscopic Properties

“…Therefore, substituted azulene reported in the literature relates to the positions, which are the most reactive in SEAr reactions. With their unique chemical and electronic properties, the substituted azulenes have diverse applications in medicinal chemistry (as antiulcer (Yanagisawa et al, 1988), antidiabetic (Imamura et al, 2012), anticancer (Asato et al, 1993), antiarrhythmic (Tanaka and Shigenobu, 2001) and anti-erectiledysfunction (Shoji et al, 2020) agents, and as TXA2 receptor antagonists (Tomiyama et al, 1993)), in photosensitizers (Ghasimi et al, 2016), multistate switches (Vlasceanu et al, 2016), as metal-organic frameworks for hydrogen storage (Barman et al, 2010), chromophores (Wang et al, 1999;.…”