Efficient Synthesis of Some New 1,3,4‐Thiadiazoles and 1,2,4‐Triazoles Linked to Pyrazolylcoumarin Ring System as Potent 5α‐Reductase Inhibitors

Abstract

in Wiley Online Library (wileyonlinelibrary.com).The current study in this article concerned with construction of five-membered heterocycles with multiple heteroatoms as nitrogen and sulfur from readily available starting materials and reagents. Treatment of 1-(2oxo-2H-chromene-3-carbonyl)-3-phenyl-1H-pyrazol-5(4H)-one with each of phenylisothiocyanate in alcoholic potassium hydroxide and carbon disulfide in basic medium gave rise to a thioanilide and methylthio derivatives, respectively. Treatment of the latter compounds with a variety of hydrazonoyl halides resulted in construction of thiadiazole moiety linked to pyrazole ring. Furthermore, triazole derivatives were synthesized from the thioanilide derivative through its reaction with methyl iodide followed by reaction with hydrazonoyl halides. 5α-Reductase inhibition activity for the prepared compounds was investigated against the reference drug anastrozole, and the results showed that the inhibition activity of compounds 5g and 11g is more potent than anastrozole. Also compounds bearing triazole moiety is more potent than compounds bearing thiadiazole one. Moreover, the anti-prostate cancer screening anti-androgenic bioassay in human prostate cancer cells for the tested compounds was evaluated, and the results showed great inhibition growth and potential antiandrogens.

<p>3,6-Disubstituted 1,2,4-Triazolo[3,4-<em>b</em>]Thiadiazoles with Anticancer Activity Targeting Topoisomerase II Alpha</p>

“…Both classes of heterocycles are known for processing a wide spectrum of biological activities like anti-microbial, anti-inflammatory, anti-convulsant, antioxidant, anti-leishmanial, anti-viral, anti-hypertensive and anti-depressant. [14][15][16] Of great interest is the potent anticancer activity which is attributable to reaction sites that both heterocyclic compounds carry including the toxophoric N-C-S moiety and the acidic proton at C-2 in the thiadiazole and triazole rings, respectively. Moreover, modifications at different positions of heterocyclic compounds as well as the fusion of the two core structures of triazoles and thiadiazoles rings they all constitute alternative synthetic possibilities capable of leading to novel chemical entities.…”

Synthesis, Spectroscopic Studies and Keto-Enol Tautomerism of Novel 1,3,4-Thiadiazole Derivative Containing 3-Mercaptobutan-2-one and Quinazolin-4-one Moieties

“…The role of this biological effective character arises from their properties related to drugs for the treatment of many different diseases. The β-keto-enol derivatives containing the 1,3,4-thiadiazole group with 2,4-hydroxyphenyl function [ 20 ] show many biological effects including antitumor [ 28 ], antifungal [ 29 ], antibacterial [ 29 ], anti-immflammatory [ 30 , 31 ], anticonvulsant [ 32 ], antiviral [ 33 ], antituberculosis [ 34 ], antihypertensive [ 35 ], antidepressant activity [ 36 ], and anti-androgens [ 37 ]. Therefore, a deep understanding of the tautomeric mechanism is very significant for medicinal chemistry perspective.…”

Catalytic Preparation of 1-Aryl-Substituted 1,2,4-Triazolium Salts

“…16−20 N -Aryl-substituted 1,2,4-triazoles are also frequent building blocks in organic compounds with biological activity. 21−23 Although less common than imidazolium or 1,2,3-triazolium salts, 1,2,4-triazolium salts have been successfully used as ionic liquids for dissolving cellulose. 24…”