1-(2-Aminoethyl)-6-aryl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepines with diuretic and natriuretic activity

Abstract

A series of 1-(2-amino-1-phenylethyl)-6-phenyl-4H- [1,2,4]triazolo[4,3-a][1,4]benzodiazepines was prepared and evaluated for diuretic activity. These compounds have diuretic and natriuretic activity but no kaliuretic activity when evaluated by oral administration to the conscious rat. The structure requirements for this activity are discussed. In particular it was found that the 2-aminoethyl side chain at C-1 with hydrogen or methyl substituents on the amino group was required for diuretic activity. A substituent at C-8 was also required; soft substituents such as methylthio and iodo at this position favored activity. Compounds with both phenyl and 2-pyridyl substituents at C-6 were active; substituents on the C-6 phenyl, however, reduced or eliminated the activity. Substituents other than phenyl at the 1-position of the 2-aminoethyl side chain were detrimental to activity; phenyl substitution at this position was required for activity when the substituent at C-8 was chloro but not when it was bromo.

Studies on synthesis and evaluation of quantitative structure–activity relationship of 10-methyl-6-oxo-5-arylazo-6,7-dihydro-5H-[1,3]azaphospholo[1,5-d][1,4]benzodiazepin-2-phospha-3-ethoxycarbonyl-1-phosphorus dichlorides

“…Reagents and conditions: (i) 1,4-di-oxan, ClCH 2 COCl, 3 N NaOH, CH 2 Cl 2 , 30 min; (ii) NH 3 /CH 3 OH; (iii) RC 6 H 4 NH 2 , NaNO 2 / HCl, 0-5°C; (iv) ClCH 2 COOC 2 H 5 ,THF, 36 h. reference drugs, respectively. The screening results reveal that reported compounds showed a remarkable effect on the bactericidal potency.…”

“…[1][2][3][4][5] Interest in the chemistry, synthesis and biology of this pharmacophore continues to be fuelled by their activity against a variety of CNS disorders as well as due to wide biological properties such as antianxiety, anticonvulsant, sedative/hypnotic, muscle relaxing and tranquilizing. [6][7][8] Many drugs incorporating BDZ core nucleus which extensively binds to plasma and tissue proteins have been developed over the past two decades and they became the most commonly prescribed group of psychotherapeutic drugs worldwide. 9,10 After the discovery of benzodiazepine receptors in the CNS and peripheral tissues 11,12 many attempts have also been made to correlate the molecular structure with the biological activity of these compounds.…”

Synthesis, Characterization and Biological Evaluation of a Novel Series of 1,2,4‐Triazolo‐[3,4‐b]‐1,3,4‐thiadiazines Containing an Amide Linkage

“…Synthesis of nitrogen containing heterocyclic systems has been attracting increasing interest over the past decades because of their utility in various applications. Over the years, a special attention has been given to N ‐bridged heterocyclic systems derived from 1,2,4‐triazoles owing to their promising biological activities such as antihypertensive, antimicrobial, anticonvulsant, antidepressant, analgesic, antitumor , and so forth. Many pyrazole derivatives make up the core structure of numerous biologically active molecules.…”

Synthesis, Structural Study and Biological Activity of Bridgehead Nitrogen Containing Triazolo-thiadiazine Derivatives

“…1,2,4-Triazoles fused with 1,3,4-thiadiazines are found to possess diverse applications in the field of medicine 5,6 . Triazolo-thiadiazines are reported to show a broad spectrum of pharmacologicallly important properties like antifungal 7 , antibacterial 8 , antiviral 9 , anthelmentic 10 , antitumor 11 , anti-inflammatory 12 , antituberculor 13 , diuretics 14 , anticancer 15 and hypoglycaemic agents 16 . These two fused systems are reported to possess significant CNS depressant, herbicidal, anthelmintic activities and have been widely used in pharmaceutical and agrochemical industry 17 .…”