Synthesis of some new 3-pyrazolyl-substituted-4(3H)quinazolinones

N-(1-Phenyl-3-methylpyrazol-5-yl)-o-aminobenzamide reacted with orthoesters to yield some new 3-pyrazolyl-substituted-4(3H)quinazolinones (VIIa,b,c,d). An alternative synthesis of Vllb was accomplished by reaction of acetylanthranyl with l-phenyl-3-methyl-5-aminopyrazole.     

Synthesis,crystal structures,and urease inhibition studies of two new Schiff-base copper complexes derived from n-butylamine

Two Schiff-base copper(II) complexes, bis(N-n-butyl-5-chlorosalicylaldiminato) copper(II) (1) and bis(N-n-butyl-4-methoxysalicylaldiminato) copper(II) (2), were synthesized and their solid-state structures were determined by X-ray crystallography. Complex 1 displays a distorted square-planar geometry, while 2 possesses square-planar geometry. Copper(II) complexes 1 and 2 showed strong inhibitory activity against jack bean urease (IC₅₀?=?2.7, 3.5?µmol?L^?1), compared with acetohydroxamic acid (IC₅₀?=?63.00?µmol?L^?1). A molecular modeling study was carried out via the DOCK program to gain understanding of the potent inhibitory activity of these copper species against jack bean urease.     

One pot synthesis of some new N-allyl and N-benzyl quinazolinones and their anti-inflammatory activity

The simple and more reliable one-pot synthesis of some novel compounds of allyl/Benzyl quinazolinone (4aa-4bd) with good yields from readily available derivatives of anthranilic acid and benzoyl chloride was also reported. Interestingly, as compared to Diclofenac sodium, compounds 4ac, 4ad, 4ba, 4bc and 4bd displayed remarkable anti-inflammatory activity (Scheme 1 & Table 2).     

Synthesis and characterization of novel bis-triazolyl quinazolinones

Russian Journal of General Chemistry - A series of 2-methyl-1-[(1-phenyl-1H-1,2,3-triazol-4-yl)methyl]-2-(4-{[(1-phenyl-1H-1,2,3-triazol-4-yl)methyl}amino]phenyl)-2,3-dihydroquinazolin-4(1H)-ones...     

Synthesis and dynamics studies of barbituric acid derivatives as urease inhibitors

Background

Discovery of potent inhibitors of urease (jack bean) enzyme is the first step in the development of drugs against diseases caused by ureolytic enzyme.

Results

Thirty-two derivatives of barbituric acid as zwitterionic adducts of diethyl ammonium salts were synthesized. All synthesized compounds (4a–z and 5a–s) were screened for their in vitro inhibition potential against urease enzyme (jack bean urease). The compounds 4i (IC₅₀ = 17.6 ± 0.23 µM) and 5l (IC₅₀ = 17.2 ± 0.44 µM) were found to be the most active members of the series, and showed several fold more urease inhibition activity than the standard compound thiourea (IC₅₀ = 21.2 ± 1.3 µM). Whereas, compounds 4a–b, 4d–e, 4g–h, 4j–4r, 4x, 4z, 5b, 5e, 5k, 5n–5q having IC₅₀ values in the range of 22.7 ± 0.20 µM–43.8 ± 0.33 µM, were also found as potent urease inhibitors. Furthermore, Molecular Dynamics simulation and molecular docking studies were carried out to analyze the binding mode of barbituric acid derivatives using MOE. During MD simulation enol form is found to be more stable over its keto form due to their coordination with catalytic Nickel ion of Urease. Additionally, structural–activity relationship using automated docking method was applied where the compounds with high biological activity are deeply buried within the binding pocket of urease. As multiple hydrophilic crucial interactions with Ala169, KCX219, Asp362 and Ala366 stabilize the compound within the binding site, thus contributing greater activity.

Conclusions

This research study is useful for the discovery of economically, efficient viable new drug against infectious diseases.

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Graphical abstract: STD. Thiourea (IC₅₀ = 21.2 ± 1.3 µM)

     

Synthesis,characterization and antibacterial studies of some new tellurated azo compounds

A series of tellurated azo compounds [i.e. (4-HOC₆H₄N=N-Ar)TeBr₃ and (4-HOC₆H₄N=N-Ar)₂TeBr₂, where Ar=5-BrC₆H₃, 5-CH₃C₆H₃ and 5-NO₂C₆H₃] were prepared by the reaction of the corresponding 2-(4-hydroxyphenylazo)aryl mercury chloride with tellurium tetrabromide in 1:1 and 2:1?mole ratio, respectively in dry dioxane as a solvent. The reduction of (4-HOC₆H₄N=N-Ar)TeBr₃ by hydrazine hydrate gave the corresponding ditelluride (i.e., (4-HOC₆H₄N=N-Ar)₂Te₂). Treatment of (4-HOC₆H₄N=N-Ar)₂TeBr₂ with hydrazine hydrate afforded the corresponding tellurides, (4-HOC₆H₄N=N-Ar)₂Te), in good yields. The structures of all newly synthesized compounds were assigned on the basis of their elemental and spectroscopic data. The antibacterial activity of tellurated azo compounds along with mercurated azo compounds was tested with agar diffusion method against the bacteria strains Staphylococcus aureus and Escherichia coli. The antibacterial activities of tellurated azo compounds were in some cases equal or better than those of the reference drug. The mercurated azo compounds were found to be the more antibacterial activity of than those of tellurated azo compounds.     

Anti-inflammatory and antibacterial activity study of some novel quinazolinones

Anti-inflammatory and antibacterial activities of some novel quinazolinones were determined. Evaluation of anti-inflammatory activity of test compounds was performed using carrageenan induced paw edema in rats. Oral administration of test compounds 25 mg/kg and 50 mg/kg reduced the paw edema significantly (P < 0.05) in a dose dependent manner compared to carrageenan induced rats. The test compounds were also screened for their antibacterial activity against the strains of Staphylococcus aureus and Escherichia coli at the concentrations of 200 μg/ml and 1 mg/ml. The test compounds showed better activity as that of the standard lincomycin at the tested higher concentration against S. aureus. None of the compounds exhibit comparable activity to that of the standard ceftazidime against E. coli.     

Synthesis and biological studies of some new acrylic acid ethyl esters of quinolinone

Abstract  

A series of new acrylic acid ethyl esters of quinolinones were synthesized from 4-(bromomethyl)quinolinones and screened for in vitro antimicrobial and in vivo analgesic and anti-inflammatory activities. Most of the compounds with chloro substitution at the C-6 or C-7 position in the quinolinone moiety and a methoxy group in the aryloxy moiety showed potent antibacterial and antifungal activities when compared with non-halogenated quinolinones and the quinolinones bearing a CH₃ at the C-8 position. In a pharmacological evaluation, the halogen substitution at the C-6 or C-7 position in quinolinones was found to enhance both analgesic and anti-inflammatory activities of the molecule when compared with a simple unsubstituted (non-halogenated) quinolinone. The structures of all newly synthesized compounds were characterized by elemental analysis, IR, ¹H NMR, ¹³C NMR, and FAB-MS.     

Synthesis and molecular docking studies of some new thiosemicarbazone derivatives as HCV polymeraseinhibitors

Series of new thiosemicarbazones was prepared and molecular studied as inhibitors of HCV 4WTG polymerase. Thus, the thiosemicarbazone derivatives (3a–k) were synthesized by two different ways, from reacting thiosemicarbazides with aldehydes and by one-pot three component reaction using ZnCl₂/SiO₂ as a catalyst under solvent free conditions. Molecular docking analysis of the synthesized products predicted that the thiosemicarbazone derivatives 3c, 3g, and 3k were the most promised as a highly inhibitors for HCV 4WTG polymerase in comparison with Sofosbuvir drug.     

Synthesis,in vitro evaluation,and molecular docking studies of benzofuran based hydrazone a new inhibitors of urease

This work has described the synthesis of novel class (1–25) of benzofuran based hydrazone. The hybrid scaffolds (1–25) of benzofuran based hydrazone were evaluated in vitro, for their urease inhibition. All the newly synthesized analogues (1–25) were found to illustrate moderate to good urease inhibitory profile ranging from 0.20 ± 0.01 to 36.20 ± 0.70 µM. Among the series, compounds 22 (IC₅₀ = 0.20 ± 0.01 µM), 5 (IC₅₀ = 0.90 ± 0.01 µM), 23 (IC₅₀ = 1.10 ± 0.01 µM) and 25 (IC₅₀ = 1.60 ± 0.01 µM) were found to be the many folds more potent than thiourea as standard inhibitor (IC₅₀ = 21.86 ± 0.40 µM). The elevated inhibitory profile of these analogues might be due to presence of dihydroxy and flouro groups at different position of phenyl ring B attached to hydrazone skeleton. These dihydroxy and fluoro groups bearing compounds have shown many folds better inhibitory profile through involvement of oxygen of dihydroxy groups in hydrogen bonding with active site of enzymes. Various types of spectroscopic techniques such as ¹H-, ¹³C- NMR and HREI-MS spectroscopy were used to confirm the structure of all the newly developed compounds. To find SAR, molecular docking studies were performed to understand, the binding mode of potent inhibitors with active site of enzymes and results supported the experimental data.     

Synthesis and spectroscopic studies of some quinolylmethylphosphonates

Monoethyl esters of 2-quinolylmethylphosphonic acid ( 3 ) and 8-quinolylmethylphosphonic acid ( 6 ) have been prepared. The corresponding diethyl esters 1 and 4 , and sodium salts of monoesters 2 and 5 , respectively, have also been isolated. The properties of the monoethyl esters of 8- and 2-quinolylmethylphosphonic acid are very different. While the former was isolated as the hydrochloride, the latter did not form such a salt. Molecular weight determination indicated a dimeric structure of the monoester 3 , and spectroscopic measurements confirmed the association presumably owing to the hydrogen bonding between the P?O and P-OH groups.     

Reissert compound studies. XXX. Synthesis and alkylation of some new reissert compounds

The synthesis of several new isoquinoline Reissert compounds is described. Alkylation reactions of the anions of these new Reissert compounds and a rearrangement reaction are reported.     

Synthesis of some new arylindoles

New indole derivatives — 2-ethoxycarbonyl-5(p-acetylphenyl)indole andpara-substituted 2-diphenylindoles —key compounds for synthesis of new bisindoles, were synthesized from 4-acetyl-4-nitrodiphenyl.I. Dzhavakhishvili Tbilisi State University, Tbilisi 380028. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1351–1354, October, 1994. Original article submitted September 15, 1994.     

Synthesis of some new indolizines

The reaction between 4‐dimethylaminopyridine (DMAP) and 2‐bromoacetophenone(s) readily gives 1‐ [2‐(4‐substitutedphenyl)‐2‐oxoethyl]‐4‐(dimethylamino)pyridinium bromide ( 1–14 ). Action of aqueous NaOH on 1–8 generates the corresponding pyridinium ylide ( 15–22 ), which is isolated as a colored stable crystalline solid. Addition of 15–22 to dimethylacetylene dicarboxylate (DMAD) gives dimethyl 3‐(substitutedbenzoyl)‐7‐(dimethylamino)indolizine‐1,2‐dicarboxylate ( 23–30 ) in 46–62% yield.     

New cocrystals of heterocyclic drugs: structural,antileishmanial, larvicidal and urease inhibition studies

Many heterocycles have been developed as drugs due to their capacity to interact productively with biological systems. The present study aimed to synthesize cocrystals of the heterocyclic antitubercular agent pyrazinamide ( PYZ , 1 , BCS III) and the commercially available anticonvulsant drug carbamazepine ( CBZ , 2 , BCS class II) to study the effect of cocrystallization on the stability and biological activities of these drugs. Two new cocrystals, namely, pyrazinamide–homophthalic acid (1/1) ( PYZ:HMA , 3 ) and carbamazepine–5-chlorosalicylic acid (1/1) ( CBZ:5-SA , 4 ), were synthesized. The single-crystal X-ray diffraction-based structure of carbamazepine–trans-cinnamic acid (1/1) ( CBZ:TCA , 5 ) was also studied for the first time, along with the known cocrystal carbamazepine–nicotinamide (1/1) ( CBZ:NA , 6 ). From a combination drug perspective, these are interesting pharmaceutical cocrystals to overcome the known side effects of PYZ ( 1 ) therapy, and the poor biopharmaceutical properties of CBZ ( 2 ). The purity and homogeneity of all the synthesized cocrystals were confirmed by single-crystal X-ray diffraction, powder X-ray diffraction and FT–IR analysis, followed by thermal stability studies based on differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Detailed intermolecular interactions and the role of hydrogen bonding towards crystal stability were evaluated quantitatively via Hirshfeld surface analysis. The solubility of CBZ at pH 6.8 and 7.4 in 0.1 N HCl and H₂O were compared with the values of cocrystal CBZ:5-SA ( 4 ). The solubility of CBZ:5-SA was found to be significantly improved at pH 6.8 and 7.4 in H₂O. All the synthesized cocrystals 3 – 6 exhibited a potent urease inhibition (IC₅₀ values range from 17.32 ± 0.89 to 12.3 ± 0.8 µM), several times more potent than standard acetohydroxamic acid (IC₅₀ = 20.34 ± 0.43 µM). PYZ:HMA ( 3 ) also exhibited potent larvicidal activity against Aedes aegypti. Among the synthesized cocrystals, PYZ:HMA ( 3 ) and CBZ:TCA ( 5 ) were found to possess antileishmanial activity against the miltefosine-induced resistant strain of Leishmania major, with IC₅₀ values of 111.98 ± 0.99 and 111.90 ± 1.44 µM, respectively, in comparison with miltefosine (IC₅₀ = 169.55 ± 0.20 µM).