Role of 1,4-Benzothiazine Derivatives in Medicinal Chemistry

Abstract

1,4-Benzothiazine (1,4-BT) derivatives have been reported to exhibit a wide range of pharmacological properties including antifungal, immunostimulating, anti-aldoso-reductase, anti-rheumatic, anti-allergic, vasorelaxant, anti-arrhythmic, anti-hypertensive, neuroprotective and cytotoxic activities. These different effects indicate that 1,4-BT is a template potentially useful in medicinal chemistry research and therapeutic applications.

Efficient synthesis of benzothiazine and acrylamide compounds

“…The present study describes the synthesis of substituted (2E)-Nalkyl-N-(2-hydroxy-5-nitrophenyl)-3-phenylacrylamides, (4-6), (2Z)-2-(4-methoxybenzylidene)-6-nitro-4H-benzo [1,4]thiazin-3-one, (7), (2Z)-2-(4-methoxybenzylidene)-4-methyl-6-nitro-4H-benzo [1,4]thiazin-3-one (8) and (2Z)-6-amino-2-(4-methoxybenzylidene)-4H-benzo [1,4] thiazin-3-one (9) or (2Z)-6-butylamino-2-(4-methoxybenzylidene)-4-methyl-4H-benzo [1,4]thiazin-3-one (12), Figure 1. The intermediary 6-nitro-4H-benzo [1,4]-oxazin-3-one, which were not isolated, were obtained as a result of the Knoevenagel condensation of activated 4-alkyl-6-nitro-4H-benzo [1,4]thiazin-3-one 2-3 with 4-methoxy or 4-bromobenzaldehydes in the presence of sodium methoxide in DMF.…”

“…The intermediary 6-nitro-4H-benzo [1,4]-oxazin-3-one, which were not isolated, were obtained as a result of the Knoevenagel condensation of activated 4-alkyl-6-nitro-4H-benzo [1,4]thiazin-3-one 2-3 with 4-methoxy or 4-bromobenzaldehydes in the presence of sodium methoxide in DMF. 9 The (2Z)-2-(4-methoxybenzylidene)-4-methyl-6-nitro-4H-benzo [1,4]thiazin-3-one 8 was first condensed in position 2; subsequently, alkylation was carried out at position 4.…”

“…These properties indicate that 1,4-benzothiazine is a template that may be potentially useful in medicinal chemistry research and therapeutic applications. 1 Gupta and Ojha 2 reviewed the chemical and pharmacological properties of phenothiazines and 1,4-benzothiazines. Some of the latter showed microbiological and antitumor activities.…”

“…Some of the latter showed microbiological and antitumor activities. 3,4 The synthesis, spectroscopic properties and microbiological activities of several 6-alkylacylamino-4-methyl-4H-benzo [1,4]thiazin-3-ones have also been reported. 5 Moreover, the reactivity of a methylene group activated by a carbonyl substituent or a thioxo has been studied by Guarda and Silva.…”

“…5 Moreover, the reactivity of a methylene group activated by a carbonyl substituent or a thioxo has been studied by Guarda and Silva. 6,7 Condensation of 1,4-benzothiazin-3-ones with arylaldehydes or Michael addition on cyanoacrylates leads to the formation of 2-arylidene-4H-benzo [1,4]thiazin-3-one compounds. 8 …”