Category Archives: Journal of Heterocyclic Chemistry

New energetic 1,2,4‐triazole‐nitrofuroxan hybrids

Posted on 5 March 2024 by

New energetic (1,2,4-triazolyl)furoxans were synthesized and their physicochemical properties were estimated. The obtained results serve as an evidence that an alliance of 1,2,4-triazole and furoxan rings may constitute a suitable platform for the construction of promising energetic materials.

Abstract

New promising energetic materials comprised of 1,2,4-triazole and furoxan rings and bearing explosophoric nitro group were rationally designed and synthesized. All newly prepared compounds were thoroughly characterized and their physicochemical properties were estimated. In the newly synthesized series, (1,2,4-triazolyl)furoxan 4 is completely insensitive to impact and friction and possesses good detonation performance (D = 8.4 km s⁻¹; P = 33 GPa) enabling its further exploration as a promising high-energy material.

Recent developments in synthetic strategies and pharmacological outcomes of synthetic xanthine oxidase inhibitors: A comprehensive review

Posted on 5 March 2024 by

This methodological study highlighted potential xanthine oxidase inhibitors and their therapeutic significance, with an emphasis on those that have the greatest therapeutic efficacy and the fewest side effects.

Abstract

Xanthine oxidase is an important enzyme in purine metabolism that converts hypoxanthine to xanthine and subsequently xanthine to uric acid. Its elevated levels result in an abnormal accumulation of uric acid that results in gout and other pathological conditions, which makes it a prime target for the management of gout. Considering this, numerous reports have been published by the various research groups across the globe focusing on the development of effective xanthine oxidase inhibitors. On that ground, numerous review articles are also available describing the pharmacological outputs of these reports, but a composition highlighting the synthetic strategies used in these research works is still missing. This review will focus on various synthetic strategies adopted by different research groups in developing xanthine oxidase inhibitors with their pharmacological outcomes, along with structure activity relationships. This review will help researchers and pharmaceutical chemists in the design and development of new xanthine oxidase inhibitor leads that are highly efficient and have fewer side effects than existing ones.

Regioselective synthesis of (Z)‐5‐methylene‐containing morpholin‐2‐ones

Posted on 25 February 2024 by

A one-pot, protecting-group-free and regioselective synthesis of enantiomerically pure (Z)-5-methylene-containing morpholin-2-ones, using α-amino acids and 5-bromoenones is presented.

Abstract

An efficient, one-pot, protecting-group-free, and regioselective protocol to obtain enantiomerically pure (Z)-5-methylene-containing morpholin-2-ones, using α-amino acids and 5-bromo-4-methoxy enones as selective starting materials, is reported. The reaction was fully selective in providing the (Z)-regioisomer in all cases, regardless of the α-amino acid used; however, when a secondary amino group was used, only the (E)-isomer was observed. The synthesized compounds were obtained at yields of up to 92%, and their structure was unambiguously assigned by x-ray and 2D-NMR experiments.

Synthesis of benzo[b]pyran, 3,4 dihydropyrano[c]chromene and their new furan derivatives using Cu(II) complex of tetradentate Schiff‐base supported on silica as a nanocatalyst

Posted on 20 February 2024 by nHashem Sharghi, nElahe Mashhadi, nSeyyede Faeze Razavi, nMahdi Aberin

The work investigates the synthesis of benzo[b]pyran, 3,4-dihydropyrano[c]chromene and their new furan derivatives using Cu(II) complex of tetradentate Schiff-base supported on silica in aqueous media. The high yields, recyclable catalyst, environmentally benign milder reaction conditions, without need to column chromatography for purification are the main advantages of this method.

Abstract

Cu(II) Complex of tetradentate Schiff-base supported on silica [Cu(II) Schiff-base@-SiO₂] catalyzed reactions of aryl aldehydes with carbonyl compounds (dimedon/4-hydroxy coumarin/1,3-cyclohexadion) and malononitrile in aqueous media (H₂O:EtOH) to preparation of benzo[b]pyrans and 3,4-dihydropyrano[c]chromanes. Also, using this nanocatalyst, 2-(5-substituted phenyl)furan-2-carboxaldehyde derivatives with carbonyl compounds (dimedon/4-hydroxy coumarin/1,3-cyclohexadion) and malononitrile gave novel tetrahydrobenzo[b]pyran and 3,4-dihydropyrano[c]chromane derivatives in high yields in H₂O:EtOH under reflux conditions. The key advantages of this catalytic systems are the formation of novel products, high yields (78%–93%), short reaction time, broad substrate scope, environmentally friendly reaction conditions and also, without need to column chromatography for purification. Furthermore, the nanocatalyst can be reused six times without losing catalytic activity.

Synthesis of 1‐(4‐hydroxybutyl)‐2‐benzoyl indoles from 2‐pyrrolidine benzaldehydes and α‐bromoacetophenones in deep eutectic solvent

Posted on 20 February 2024 by

In the absence of organic solvents, catalysts, and other additives, 1-(4-hydroxybutyl)-2-benzoyl indoles were synthesized from 2-pyrrolidine benzaldehydes and α-bromoacetophenones in deep eutectic solvents, underwent cyclization and ring opening processes.

Abstract

A novel and highly efficient method for the synthesis of 1-(4-hydroxybutyl)-2-benzoyl indoles from 2-pyrrolidine benzaldehyde and α-bromoacetophenone in a choline chloride (ChCl)/ZnCl₂ eutectic mixture was developed. This method, which does not require any catalyst, additive, or alkali, is useful for realizing tandem cyclization reactions. Several indoles were produced after cyclization and ring opening processes. Not all the compounds obtained are reported in the literature. This synthetic strategy proves that deep eutectic solvents can replace catalysts and organic solvents. Consequently, this is an environmentally friendly strategy that has significant potential in the development of green and sustainable chemistry.

Synthesis and biological evaluation of 3‐hydroxypyrazoles as aquaporin 9 inhibitors

Posted on 15 February 2024 by

A series of 3-hydroxypyrazole derivatives were synthesized and one of them, chosen based on in silico results, effectively inhibited aquaporin 9 (AQP9) in vitro.

Abstract

A series of 3-hydroxypyrazole derivatives have been synthesized by a base-promoted reaction of nitro-substituted donor–acceptor cyclopropanes with hydrazines. The synthesized compounds have been investigated for their ability to inhibit aquaporin 9 (AQP9) in rat Leydig cells (LC-540). The protein data bank structure for AQP9 was predicted using homology modeling; and the protein–ligand interaction for the synthesized hydroxyl pyrazole derivatives were analyzed using molecular modeling and docking studies. The results of in silico analyses showed that compound 5b had a higher binding affinity with AQP9 than other compounds. Further, in vitro studies conducted in LC-540 cells confirmed that compound 5b effectively inhibits AQP9. Hence, compound 5b may be used as an inhibitor in enhancing our understanding of AQP9 function, and in the treatment of several diseases.

Synthesis of tricyclic pyrazolopyrimidine arylidene ester derivatives and their cytotoxic and molecular docking evaluations

Posted on 14 February 2024 by nTong Lu, nLifei Nie, nDan Tang, nKhurshed Bozorov, nJiangyu Zhao, nHaji Akber Aisan

Research basis and work of this paper.

Abstract

Our research team has synthesized 33 tricyclic pyrazolopyrimidine arylidene ester derivatives using the lead compound CAM551 as a starting point. This was achieved by a designed five-step synthesis strategy. The synthesized compounds' inhibitory activities against HT-116 human colorectal adenocarcinoma cell line and HGC27 human gastric cancer cells were assessed through traditional MTT assays. The designed and synthesized compounds demonstrated superior inhibition against both types of cancer cells. Additionally, compound 7b, which contains a long-chain substituent, exhibited improved inhibition against hepatocellular carcinoma cells and a greater safety profile. These findings indicate that compound 7b has the potential as an antitumor lead compound for future research.

Novel oxadiazole functionalized pyridopyrimidine derivatives; their anticancer activity and molecular docking studies

Posted on 13 February 2024 by nRaghu Dasari, nSrinivas Gali, nRajashekar Korra, nNamratha Vaddirajun

A series of novel oxadiazole functionalized pyridopyrimidine derivatives prepared. All the final compounds 7a-l evaluated for anti cancer activity against four human cancer cell lines and promising compounds 7d and 7k have been identified and evaluated for molecular docking interactions

Abstract

A series of novel oxadiazole functionalized pyridopyrimidine derivatives prepared starting from 6-methyl/ethyl-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridine-3-carbonitrile 1. This compound 1 on reaction with sulfuric acid obtained compound 2, further compound 2 on reaction with chloroacetamide followed by reaction with ethoxy methylene malonic diethyl ester coupling and further cyclization to obtain compound 5. Compound 5 on reaction with hydrazide hydrate obtained hydrazide derivatives 6. Compound 6 on reaction with diverse substituted aromatic acids to get oxadiazole derivatives 7a–l. All the final compounds 7a–l evaluated for anticancer activity against four human cancer cell lines such as HeLa—cervical cancer (CCL-2); COLO 205—colon cancer (CCL-222); HepG2—liver cancer (HB-8065); and MCF7—breast cancer (HTB-22) and promising compounds 7d and 7k have been identified and evaluated for molecular docking interactions.

New quinoxaline‐piperazine‐oxazole conjugates: Synthesis, in vitro anticancer, in silico ADMET, and molecular docking studies

Posted on 5 February 2024 by

Herein, we described the synthesis of some new phthalazine piperazine-pyrazole conjugates(6a-n) and their in vitro anticancer activity against four human cancer cell lines such as PC-3, MCF-7, DU-145, and A-549. The anticancer activity results reveals that the four compounds 6c, 6h, 6i, and 6n shown promising activity than the standard drug Erlotinib. Furthermore, the in silico studies of compounds 6c, 6h, 6i, and 6n supports the in vitro anticancer results. In addition, ADMET analyses were carried out on four potent compounds and results accordant with the in vitro anticancer and in vitro EGFR tyrosine kinase inhibition data.

Abstract

In this paper, we describe the synthesis of some new quinoxaline-piperazine-oxazole amide conjugates 6a-n from 3-chloroquinoxaline-2-carbonitrile using well-known reaction sequences. The synthesized compounds were characterized by ¹H NMR,¹³C NMR, and mass spectral analysis. The compounds were tested for their in vitro antiproliferative activity toward four different cancer cell lines such as PC-3, MCF-7, DU-145, and A-549 by MTT method. The compounds, 6c, 6h, 6i, and 6n were found to be more potent than the standard Erlotinib. In vitro tyrosine kinase EGFR inhibition studies using four potent compounds revealed that 6n has double inhibiting tendency with value IC₅₀ of 0.22 μM and 6h with value of IC₅₀ 0.27 μM compared to reference compound. Molecular docking studies of active compounds, 6c, 6h, 6i, and 6n on EGFR receptor suggested that all the compounds have more binding energies than that of Erlotinib. Furthermore, the in silico pharmacokinetic profile was accomplished for the active compounds, 6c, 6h, 6i, and 6n using SWISS/ADME and pk CSM, whereas compounds, 6h, 6i, and 6c followed Lipinski rule, Veber rule, Egan rule and Muegge rule. The remaining compound 6n did not follow Lipinski rule, Ghose rule because one common violation, that is, because of high molecular weight (MW > 350).

Design, synthesis, and pesticidal activities of novel pyrimidin‐4‐amine derivatives containing trifluoroethyl sulfide moiety

Posted on 2 February 2024 by

By connecting the key intermediate trifluoroethyl sulfide with pyrimidinamine, we obtained T4 with LC₅₀ was 0.19 mg/L against T. urticae and T15 with EC₅₀ was 1.32 mg/L against P. sorghi after active testing and structural optimization.

Abstract

In order to overcome the problem of pesticide resistance, it is necessary to discover novel pesticides with new mechanisms of action. Herein, a series of novel pyrimidin-4-amine derivatives containing trifluoroethyl sulfide moiety were designed and synthesized. Bioassays indicated that the title compounds synthesized possessed excellent acaricidal activity against Tetranychus urticae and fungicidal activity against Erysiphe graminis and Puccinia sorghi. Especially, the acaricidal activity of 5-chloro-6-(difluoromethyl)-N-(2-(2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)phenoxy)ethyl)pyrimidin-4-amine (compound T4, LC₅₀ = 0.19 mg/L) against T. urticae was close to commercial acaricide cyenopyrafen, and the fungicidal activity of 5-chloro-6-(difluoromethyl)-2-methyl-N-(2-(3-((2,2,2-trifluoroethyl)thio)phenoxy)ethyl)pyrimidin-4-amine (compound T15, EC₅₀ = 1.32 mg/L) against P. sorghi. was superior to commercial fungicide tebuconazole. The synthesis and characterization of these compounds were given and the structure–activity relationships were discussed.