Synthesis and Pharmacological Activity of S(-)-2-Amino-2-Methyl-3-Phenylpropanoic Acid

• Published in: Pharmaceutical chemistry journal 2019-10, Vol.53 (7), p.620-623
• Main Authors: Grigoryan, S. H., Zhamharyan, A. G., Saghyan, A. S., Chitchiyan, A. A., Balyan, L. S., Poghosyan, A. S., Topchyan, H. V., Balasanyan, M. G.
• Format: Article
• Language: English
• Subjects: Amino acids; Health aspects; Medicine; Organic Chemistry; Pharmacology/Toxicology; Pharmacy
• ISSN: 0091-150X; 1573-9031
• DOI: 10.1007/s11094-019-02049-1

Taking into account the high efficacy of 2-arylpropionic acid derivatives among NSAIDs and based on their SARs, we have evaluated the anti-inflammatory, antinociceptive, and antiaggregant activity and ulcerogenic properties of a new synthesized non-protein amino acid (NPAA) derivative S(-)-2-amino-2-methyl-3-phenylpropanoic acid (NPAA-36). A new method of NPAA-36 synthesis was developed and experiments were carried out, which showed that this compound injected in a dose of 10 mg/kg (i.p.) inhibited xylene-induced ear oedema by about 31.1%, which proved its anti-inflammatory properties. The antinociceptive activity of NPAA-36 was assessed in tail-flick test by the ability to increase the tail cut-off latency by 36.78% within 60 min after injection at the same dose. Investigation of the ulcerogenic properties of NPAA-36 demonstrated that it exhibited lower gastrointestinal toxicity than a well-known arylpropionic acid derivative NSAID. Results of in vitro experiments showed the antiplatelet activity registered not in all (only in 41.2%) cases, which might imply lower bleeding. The obtained data indicate that the new NPAAderivative can be a potential basis for the development of new anti-inflammatory drugs with weak side effects.