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An Overview of Helminthiasis
Published in Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay, Medicinal Chemistry of Neglected and Tropical Diseases, 2019
Leyla Yurttaș, Betül Kaya Çavușoğlu, Derya Osmaniye, Ulviye Acar Çevik
Praziquantel (7) is a highly effective broad-spectrum agent which is used for the control of schistosomiasis and some species of cestodes and trematodes. Praziquantel is the drug of choice in the therapy of Shistosoma mansoni, S. haematobium, S. japonicum, S. intercalatum, S. mecongi and Taenia solium. The antihelminth action of praziquantel has not been fully elucidated yet, however considerable research assumes that its activity is due to the disruption of calcium homeostasis. As a result, increasing permeability of the helminth membrane to monovalent and bivalent cations, mainly Ca2+, causes contractions and spastic paralysis of the worm. The side effects include abdominal pain, bloody diarrhoea, dizziness, nausea, headache, pruritus, lassitude and drowsiness. Praziquantel is a pregnancy category B drug (Vardanyan and Hruby 2006, Siqueira et al. 2017, Posey and Stauffer 2007). The synthesis of praziquantel is reported in Scheme 4. Isoquinoline is reacted with a mixture of cyclohexanecarbonyl chloride/potassium cyanide. The obtained product is reduced by hydrogen over Raney nickel. After the acylation of the reduced compound with chloroacetyl chloride, praziquantel is synthesized with the heating of chloroacetyl derivative in the presence of diethylamine via intramolecular alkylation reaction (Vardanyan and Hruby 2006). The synthesis of Praziquantel (7).
1,3,4-Oxadiazole-naphthalene hybrids as potential VEGFR-2 inhibitors: design, synthesis, antiproliferative activity, apoptotic effect, and in silico studies
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Mohamed Hagras, Marwa A. Saleh, Rogy R. Ezz Eldin, Abdelrahman A. Abuelkhir, Emad Gamil Khidr, Ahmed A. El-Husseiny, Hesham A. El-Mahdy, Eslam B. Elkaeed, Ibrahim H. Eissa
The synthesis of the key starting material 1,3,4-oxadiazolyl scaffold 4 was achieved by the reaction of acid hydrazide 3 with carbon disulphide in an alcoholic potassium hydroxide solution. Different chloroacetinilides were obtained by the treatment of aromatic amines with chloroacetyl chloride47. The potassium salt of 4 was allowed to react with the substituted chloroacetinilides. Unfortunately, the required products couldn't be separated from the reaction mixture with the desirable purity. The presence of more than one product for each reaction was attributed to the high reactivity and/or basicity of the potassium salt. Alternatively, a less basic condition was adopted and the mercapto-containing structure 4 was directly allowed to react with chloroacetinilides in the presence of sodium acetate. This alternative route successfully afforded the final products in satisfying yields and reasonable purities.
Strained contacts with the cell membrane may influence ligand affinity to G protein coupled receptors: a case of free fatty acid receptor 1 agonists
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Alexey Lukin, Anna Bakholdina, Mikhail Chudinov, Oleksandra Onopchenko, Elena Zhuravel, Sergey Zozulya, Maxim Gureev, Mikhail Krasavin
To chloroacetyl chloride (4.1 mmol, 0.47 g) in anhydrous toluene (30 ml) 4′-chlorobiphenyl-3-amine (3.9 mmol, 0.80 g) was added with stirring. The reaction mixture was heated at reflux for 2 h. The progress of the reaction was monitored using thin-layer chromatography and 30% ethyl acetate in petroleum ether as eluent. The reaction mixture was cooled to room temperature and left without stirring until the formation of the precipitate was complete. The resulting precipitate was filtered off and the filtrate was concentrated in vacuo. To finely ground sulphur (7.9 mmol, 0.25 g), suspended in N,N-dimethylformamide (5.0 ml), was added triethylamine (7.9 mmol, 1.10 ml) and morpholine (5.3 mmol, 0.46 ml). After 15 min stirring at room temperature, the residue obtained in the first chemical operation was added and the mixture was stirred at room temperature for 3 h. The progress of the reaction was monitored using thin-layer chromatography and 1% methanol in chloroform as eluent. The reaction mixture was poured into water. The resulting precipitate was filtered off, 20 ml of acetone was added to the resulting precipitate, and undissolved excess sulphur was filtered off. The organic phase was separated, dried over anhydrous sodium sulphate, filtered, and concentrated in vacuo. The residue was taken up in N,N-dimethylformamide (5 ml), and treated with hydazine hydrate (4.1 µmol, 2.00 ml). The progress of the reaction was monitored using thin-layer chromatography and 1% methanol in chloroform as eluent. 100 ml of water was added to the reaction mixture and the resulting solution was acidified with 5% hydrochloric acid solution to pH = 5. The precipitate formed was filtered off and the filtrate was collected and concentrated in vacuo. The product was obtained by crystallisation of the residue from diethyl ether.