The Effective Synthesis of N-(Arylalkyl)-1-R-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides as Promising Analgesics of a New Chemical Class

Igor V. UKRAINETS; Lidiya A. PETRUSHOVA; Sergiy P. DZYUBENKO; Galina SIM; Lina A. GRINEVICH

doi:10.3797/scipharm.1506-04

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Article

17 July 2015

The Effective Synthesis of N-(Arylalkyl)-1-R-4-hydroxy-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxamides as Promising Analgesics of a New Chemical Class

and

Department of Pharmaceutical Chemistry, National University of Pharmacy, 53 Pushkinska St., 61002, Kharkiv, Ukraine

Department of Pharmaceutical Chemistry, N. I. Pirogov Vinnitsa National Medical University, 56 Pirogov St., Vinnitsa, 21018, Ukraine

Department of Pharmaceutical Chemistry, Far Eastern State Medical University, 35 Murav'eva-Amurskogo St., 680000, Khabarovsk, Russia

Author to whom correspondence should be addressed.

Sci. Pharm.2015, 83(4), 549-566;https://doi.org/10.3797/scipharm.1506-04

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Abstract

A new, effective preparative method has been proposed and the synthesis of a series of N-(arylalkyl)-1-R-4-hydroxy-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-car-boxamides has been carried out. It has been shown that amidation of alkyl 1-R-4-hydroxy-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxylates with arylalkyl-amines in boiling xylene proceeds with good yield and purity to the corresponding N-(arylalkyl)-amides. However, the presence of water in the reaction mixture has been shown to cause the formation of specific impurities: N-(arylalkyl)-1-R-2,2-dioxo-1H-2λ⁶,1-benzothiazin-4-amines. According to the results of the pharmacological studies, powerful analgesics have been found among the substances synthesized.

Keywords:

Amidation; Analgesia; Arylalkylamines; Synthesis; Pain syndrome; 4-Hydroxy-2,2-dioxo-1,2-dihydro-2λ⁶,1-benzothiazine-3-carboxamides; 2,1-Benzothiazines

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