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Synthesis and antiulcer activity evaluation of conjugates of amino acids with N-aroyl- N, N'-dicyclohexyl urea.

Subudhi BB, Sahoo SP - Chem Cent J (2011)

Bottom Line: Amino acids are safe molecules with variable efficacy against ulceration.All these compounds were found to be safe and active.The promising efficacy and safety of these compounds is interesting for further investigation.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Pharmaceutical Sciences, Siksha O Anusandhan University Bhubaneswar, Orissa, 751003, India. bharatbhusans@gmail.com.

ABSTRACT
Amino acids are safe molecules with variable efficacy against ulceration. Considering the good antioxidant potential of N-aroyl- N, N'-dicyclohexyl urea and antiulcer activities of amino acids, a series of amino acid conjugates of N-aroyl- N, N'-dicyclohexyl urea was synthesized and the effect against ulceration in albino rats induced by pyloric ligation was screened. All these compounds were found to be safe and active. Reduction of ulcer index was significant for all compounds. Conjugates of methionine and histidine exhibited enhanced antiulcer activity comparable to omeprazole in terms of inhibition of release of gastric juice, hydrochloric acid and neutralization activity. The promising efficacy and safety of these compounds is interesting for further investigation.

No MeSH data available.


Related in: MedlinePlus

Synthesis of amino acid conjugates of N-aroyl- N, N'-dicyclohexyl urea.
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C1: Synthesis of amino acid conjugates of N-aroyl- N, N'-dicyclohexyl urea.

Mentions: The N-cyclohexyl-N-(cyclohexylcarbamoyl) benzamide (1) was prepared by reacting N, N'-dicyclohexylcarbodiimide (DCC) with benzoic acid in the reported manner [13]. Equimolar quantity of benzoic acid and DCC were used with triethylamine (TEA) as catalyst. Reaction of dry toluene in presence of TEA generated the carboxylate anion that acted as nucleophile to undergo nucleophillic addition with DCC to give the O-aryl intermediate that upon rearrangement yielded the urea analogue N-cyclohexyl-N-(cyclohexylcarbamoyl) benzamide (scheme 1). Acylation of N-cyclohexyl-N-(cyclohexylcarbamoyl) benzamide with chloroacetyl chloride was carried out following reported method [14,15]. The TEA acted as catalyst to enhance the nucleophilicity of the secondary amine to attack the nucleophillic centre of the chloroacetyl chloride to give N-((2-chloroacetyl) (cyclohexyl) carbamoyl)-N-cyclohexyl benzamide (scheme 1). The reaction between amino acids and halohydrocarbon has been reported being carried out in presence of K2CO3 using methanol as solvent [15]. To develop a simple method for substitution reaction of N-((2-chloroacetyl) (cyclohexyl) carbamoyl)-N-cyclohexyl benzamide with amino acids, we screened the effect of the base and solvent on the yield of the reaction (Table 1). In this reaction proton is abstracted from the amino group of the amino acids producing the anion that reacts with the nucleophillic centre of the halohydrocarbon. From the table it can be seen that methanol-TEA system effectively promoted this reaction. Other base-solvent systems were less effective in facilitating the reaction. This can be attributed to the good polarity of methanol and appropriate basicity of TEA.


Synthesis and antiulcer activity evaluation of conjugates of amino acids with N-aroyl- N, N'-dicyclohexyl urea.

Subudhi BB, Sahoo SP - Chem Cent J (2011)

Synthesis of amino acid conjugates of N-aroyl- N, N'-dicyclohexyl urea.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3275514&req=5

C1: Synthesis of amino acid conjugates of N-aroyl- N, N'-dicyclohexyl urea.
Mentions: The N-cyclohexyl-N-(cyclohexylcarbamoyl) benzamide (1) was prepared by reacting N, N'-dicyclohexylcarbodiimide (DCC) with benzoic acid in the reported manner [13]. Equimolar quantity of benzoic acid and DCC were used with triethylamine (TEA) as catalyst. Reaction of dry toluene in presence of TEA generated the carboxylate anion that acted as nucleophile to undergo nucleophillic addition with DCC to give the O-aryl intermediate that upon rearrangement yielded the urea analogue N-cyclohexyl-N-(cyclohexylcarbamoyl) benzamide (scheme 1). Acylation of N-cyclohexyl-N-(cyclohexylcarbamoyl) benzamide with chloroacetyl chloride was carried out following reported method [14,15]. The TEA acted as catalyst to enhance the nucleophilicity of the secondary amine to attack the nucleophillic centre of the chloroacetyl chloride to give N-((2-chloroacetyl) (cyclohexyl) carbamoyl)-N-cyclohexyl benzamide (scheme 1). The reaction between amino acids and halohydrocarbon has been reported being carried out in presence of K2CO3 using methanol as solvent [15]. To develop a simple method for substitution reaction of N-((2-chloroacetyl) (cyclohexyl) carbamoyl)-N-cyclohexyl benzamide with amino acids, we screened the effect of the base and solvent on the yield of the reaction (Table 1). In this reaction proton is abstracted from the amino group of the amino acids producing the anion that reacts with the nucleophillic centre of the halohydrocarbon. From the table it can be seen that methanol-TEA system effectively promoted this reaction. Other base-solvent systems were less effective in facilitating the reaction. This can be attributed to the good polarity of methanol and appropriate basicity of TEA.

Bottom Line: Amino acids are safe molecules with variable efficacy against ulceration.All these compounds were found to be safe and active.The promising efficacy and safety of these compounds is interesting for further investigation.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Pharmaceutical Sciences, Siksha O Anusandhan University Bhubaneswar, Orissa, 751003, India. bharatbhusans@gmail.com.

ABSTRACT
Amino acids are safe molecules with variable efficacy against ulceration. Considering the good antioxidant potential of N-aroyl- N, N'-dicyclohexyl urea and antiulcer activities of amino acids, a series of amino acid conjugates of N-aroyl- N, N'-dicyclohexyl urea was synthesized and the effect against ulceration in albino rats induced by pyloric ligation was screened. All these compounds were found to be safe and active. Reduction of ulcer index was significant for all compounds. Conjugates of methionine and histidine exhibited enhanced antiulcer activity comparable to omeprazole in terms of inhibition of release of gastric juice, hydrochloric acid and neutralization activity. The promising efficacy and safety of these compounds is interesting for further investigation.

No MeSH data available.


Related in: MedlinePlus