Substituted 1,2,3,4-tetrahydroaminonaphthols: antihypertensive agents, calcium channel blockers, and adrenergic receptor blockers with catecholamine-depleting effects

Abstract

Substituted 1,2,3,4-tetrahydroaminonaphthols were found to be calcium channel blockers with antihypertensive properties. These compounds also possessed adrenergic beta-receptor blocking activity. From the structure-activity studies, no clear correlation emerged between the in vitro calcium channel blocking activity and the acute anti-hypertensive activity in cannulated spontaneously hypertensive rats. Extensive pharmacological testing of selected compounds indicated that aminonaphthols are antihypertensive agents with many pharmacological properties. The relative contribution of various pharmacological actions toward the observed antihypertensive activity is unclear. Since the clinically useful calcium channel blocker verapamil is structurally related to these compounds, one of the aminonaphthols, trans-3-[(3,3-diphenylpropyl)amino]-1,2,3,4-tetrahydro-6,7 -dimethoxy-2-naphthalenol (12), was compared with verapamil for calcium channel blocking activity, adrenergic blocking activity, and catecholamine-depleting activity. Both compounds were found to be equipotent in these test systems.

2,6‐Pyridinedicarboxylic Acid (PDCA) Catalyzed Improved Synthetic Approach for 1‐Amidoalkyl Naphthols, Dihydropyrimidin‐2(1H)‐ones and Bis‐indoles

“…The response was well, throughout in the presence of a catalyst. The development of the reaction was observed by TLC and the formation of DHPM was confirmed by IR, 1 H NMR, 13 C NMR and element analysis.…”

“…1-Amidoalkyl-2-naphthol, DHPMs and bis-indole skeletons are present in several pharmaceutical drug intermediates. Amidoalkyl naphthol has gained strong interest by its potent pharmaceutical properties such as adrenoceptor blocking, [13] antihypertensive, [13] and Ca 2 + channel blocking deeds.. [13] (Figure 1) Amidoalkyl naphthol was also used in the synthesis of 1,3-oxazines, which have numerous biological actions including antirheumatic, [14] antibiotic, [15] antitumor, [16] antipsychotic, [17] antihypertensive, [18] analgesic, [19] antianginal, [20] anticonvulsant, [21] antimalarial [22] and antibacterial [21] properties. 1-Amidoalkyl-2-naphthols can be effortlessly transformed into 1-aminoalkyl-2-naphthols derivatives by an amide hydrolysis reaction which exhibits depressor [23] and bradycardia effects in humans.…”

Toxicological Screening of 4-Phenyl-3,4-dihydrobenzo[h]quinolin-2(1H)-one: A New Potential Candidate for Alzheimer’s Treatment

“…The generation of ROS by the metabolism of naphthalene-containing drugs makes it suitable as cancer therapeutics. 3 The naphthalene scaffold possesses various antagonistic activities and used as anticancer agents, 14 antimicrobial, 15 neurodegenerative diseases, 16 anti-inflammatory, 17 antidiabetic, 18 anticonvulsant, 19 antihypertensive, 20 antidepressant, 21 antipsychotic, 22 antitubercular, and antiviral. 23 The introduction of different functional groups on the naphthalene nucleus could provide a promising strategy to achieve various biological activities.…”

Synthesis, Docking Study and Biological Activities Evaluation of 1‐Amidoalkyl‐2‐naphthol Derivatives as Dual Inhibitors of Cholinesterase and α‐Glucosidase

“…The 1‐aminoalkyl‐2‐naphthol derivatives have a variety of biological activities such as depresser, bradycardia effects, antihypertensive and calcium Ca 2+ channel blockers . In addition, molecules with 1,3‐amino oxygen functions have been reported to have a variety of biological and pharmacological properties, including nucleoside antibiotics and HIV protease inhibitors, and are frequently found in biologically active natural products .…”