A review of HNS-32: a novel azulene-1-carboxamidine derivative with multiple cardiovascular protective actions.

  title={A review of HNS-32: a novel azulene-1-carboxamidine derivative with multiple cardiovascular protective actions.},
  author={Y. Tanaka and Koki Shigenobu},
  journal={Cardiovascular drug reviews},
  volume={19 4},
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… 
7 Citations
Synthesis and biological evaluation of C-glucosides with azulene rings as selective SGLT2 inhibitors for the treatment of type 2 diabetes mellitus: discovery of YM543.
Here, a series of C-glucosides with azulene rings in the aglycon moiety was synthesized and the inhibitory activities toward hSGLT1 and hSGLT2 were evaluated. Starting from the azulene derivative 7
Direct synthesis of 2-arylazulenes by [8+2] cycloaddition of 2H-cyclohepta[b]furan-2-ones with silyl enol ethers.
The 2-phenylazulene derivatives obtained by this study showed noticeable fluorescence in acidic media, which was confirmed by single-crystal X-ray analysis.
C4-aldehyde of guaiazulene: synthesis and derivatisation.
An approach for the selective functionalisation of guaiazulene which takes advantage of the acidity of the protons on the gua Diazulene C4 methyl group to produce an aldehyde which constitutes a building block for the construction of azulenes substituted on the seven-membered ring.
Azulenesulfonium Salts: Accessible, Stable, and Versatile Reagents for Cross‐Coupling
These azulene sulfonium salts are bench‐stable species that may be employed as pseudohalides for cross‐coupling in Suzuki–Miyaura reactions with a diverse selection of coupling partners.
Gold-Catalyzed Direct Alkynylation of Azulenes.
A novel catalytic method for the direct C-H alkynylation of azulenes is developed using hypervalent iodonium reagent TIPS-EBX under mild reaction conditions.
Azulenes with aryl substituents bearing pentafluorosulfanyl groups: synthesis, spectroscopic and halochromic properties
Azulenes with SF5-containing substituents gave significantly different spectroscopic responses to protonation depending on the regioisomer in question.


Cardiovascular and antiarrhythmic effects of the azulene-1-carboxamidine derivative N1,N1-dimethyl-N2-(2-pyridylmethyl)-5-isopropyl-3, 8-dimethylazulene-1-carboxamidine.
HNS-32 possesses multiple cardiac direct effects which are unique compared with well-established antiarrhythmic drugs, it may become a leading compound in the search for novel antiarrHythmic agents.
HNS-32, a novel azulene-1-carboxamidine derivative, inhibits nifedipine-sensitive and -insensitive contraction of the isolated rabbit aorta
Investigation of the vasorelaxant profile of a novel azulene-1-carboxamidine derivative of HNS-32 indicates that it inhibits both L-type Ca2+ channel-dependent and -independent vascular contraction.
Relaxant Action of Azulene‐1‐carboxamidine Derivative N1, N1‐dimethyl‐N2‐(2‐pyridylmethyl)‐5‐isopropyl‐3,8‐dimethylazulene‐1‐carboxamidine (HNS‐32) in Pig Coronary Artery
Although inhibitions of L-type Ca2+ channels and protein kinase C may be partly responsible for H NS-32 action, some direct action on the contractile systems seems to be involved in the coronary relaxation by HNS-32.
Cerebral artery selective inhibition of protein kinase c-mediated contraction by hns-32, a novel azulene-1-carboxamidine derivative.
Findings indicate that HNS-32 selectively suppresses cerebral artery contraction mediated via an activation of protein kinase C.
Effects of isoquinoline derivatives, HA1077 and H-7, on cytosolic Ca2+ level and contraction in vascular smooth muscle.
The results suggest that the inhibitory effects of isoquinoline derivatives, HA1077 and H-7, are due to a decrease in [Ca2+]i and in the Ca2+ sensitivity of contractile elements in vascular smooth muscle.
Effects of HNS-32, a Novel Antiarrhythmic Agent, on Guinea-Pig Myocardium
Results suggest that NHS-32 has V<sub>max</sub> reducing activity on myocardial tissue, which may be responsible for antiarrhythmic effect and the drug may also have additional effect on the Ca<sup>2+</sup> channel at higher concentrations.
Pharmacologic Properties of KT2–962 (6‐Isopropyl‐3‐[4‐(p‐Chlorobenzenesulfonylamino)‐Butyl]‐ Azulene‐1‐Sulfonic Acid Sodium Salt); a New TXA2/Prostaglandin Endoperoxide Receptor Antagonist
Results indicate that KT is a new nonpros-tanoid type TXA2/PGH2 receptor antagonist that is orally effective and long acting.
Assessment in pig coronary artery of long-lasting and potent calcium antagonistic actions of the novel dihydropyridine derivative mepirodipine hydrochloride.
The specific binding of [3H]nitrendipine to the membrane of pig coronary artery was inhibited by YM-09730-5, thereby indicating that [3 H]nitrenderipine and Ym- 09730- 5 compete for the similar receptor sites of dihydropyridine-sensitive Ca channels.
Synthesis and pharmacological study of the thiophene analogue of taclamine, QM-7184, a new neuroleptic drug with potent alpha-adrenoceptor blocking activity.
This new drug shows a neuroleptic profile in rodents and a high affinity for alpha-noradrenergic receptors, both in the cortex and in the striatum, which is about 20 and 90 times higher than those of haloperidol and butaclamol, respectively.
Antitumor activity of a novel antitumor antibiotic, quinocarmycin citrate (KW2152).
A novel antitumor antibiotic, 2a,3,4,5,6,6a,7,11b-octahydro-11-methoxy-12-methyl-3,6-imino-1H-2-oxa-11 c- azanaphth(1,2,3-cd)azulene-5-carboxylic acid monocitrate (quinocarmycin citrate; KW2152) was