Synthesis and Structure-Activity Relationship of 1-(2-Furoyl)Piperazine Bearing Benzamides as Butyrylcholinesterase Inhi
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Pharmaceutical Chemistry Journal, Vol. 54, No. 6, September, 2020 (Russian Original Vol. 54, No. 6, June, 2020)
SYNTHESIS AND STRUCTURE-ACTIVITY RELATIONSHIP OF 1-(2-FUROYL)PIPERAZINE BEARING BENZAMIDES AS BUTYRYLCHOLINESTERASE INHIBITORS M. A. Abbasi,1,* M. Irshad,2 Aziz-ur-Rehman,1 S. Z. Siddiqui,1 H. M. Junaid,1 S. A. A. Shah,3 and M. Ashraf4 Original article submitted March 1, 1990. Four benzamide derivatives (5a, 5b, 8a, 8b) bearing heterocyclic furan and piperazine ring have been synthesized and evaluated for enzyme inhibition and hemolytic activity. Initial 4-(chloromethyl)benzoyl chloride (1) and 3-(chloromethyl)benzoyl chloride (6) were stirred with benzyl amine (2a) and cyclohexyl amine (2b), respectively, in aqueous medium at pH 9 – 10 maintained by aqueous sodium carbonate. The resulting benzamides (3a, 3b, 7a, 7b) were refluxed with 1-(2-furoyl)piperazine (4) in the presence of K2CO3 and CH3CN to acquire target compounds (5a, 5b, 8a, 8b). The spectroscopic techniques including 13C NMR, 1H NMR, IR and EI-MS corroborated the proposed molecular structures of final compounds. Among these, two compounds (5b, 8b) proved to be considerable inhibitors of butyrylcholinesterase enzyme. Study of the hemolytic activity potential revealed low toxicity level of compound 5b. Keywords: benzamides; enzyme inhibition; furan; hemolytic activity; piperazine.
types of compounds include peptides or proteins. At present, about 30% known drugs [14, 15] contain moieties of this type. When carboxylic acids and amines are coupled, then amide bond is formed as a key functional group [16 – 19]. The reaction of benzyl chloride with ammonia also yielded this moiety known as benzoic acid amide. Amide (RCO-NH2) is a compound which has C=O group and R substituent that may be hydrogen, linear chain or ring structures. It may also be a compound having metal replacing hydrogen in ammonia like sodium amide. Nitrogen admits various substituents which classify the amides into different classes exhibiting variable physical and chemical behavior [20]. Progress in the medicinal chemistry led to the development of many drugs for the cure and treatment of cancer. Benzamide, its derivatives and its other substituents are considered to be pharmacologically active. These compounds have interesting structures containing moieties which show diverse and remarkable activities. These compounds can be used for the treatment of different diseases including cancer [21 – 24]. Metoclopramide is an important benzamide derivative. This derivative has been reported to enhance the cisplatin effects [25, 26]. Anacardic acid has been used for the synthesis of many benzamide derivatives. In particular, cyano(acrylamido)benzamide is a benzamide derivative possessing anti-tumor activity against breast cancer cells [27]. Benzamides and their analogs exhibit different types of bio-
1. INTRODUCTION The bioactive nature of heterocyclic compounds is well known to researchers. Piperazine is a six membered nitrogen-containing heterocyclic compound, which has been modified
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