Novel Potassium Channel Activators. III. Synthesis and Pharmacological Evaluation of 3,4-Dihydro-2H-1,4-benzoxazine Derivatives: Modification at the 2 Position.

Abstract

A new series of 3,4-dihydro-2H-1,4-benzoxazine derivatives, where various substituents were introduced into one of the geminal dimethyl groups at the 2 position, were synthesized and their potassium channel-activating activity was evaluated. Introduction of a hydroxyl group, as in compound 5, resulted in good solubility in water and a long duration of action compared with the parent compound 1. Introduction of a nitrato group, as in compound 8, produced typical nitrate activity such as exhibited by nitroglycerine in addition to potassium channel-activating activity. X-ray structural analysis of compound 5 showed that the sum of the bond angles around the N atom at the 4 position was 357.8 degrees, suggesting that the N atom had an approximately sp2-like planar bond configuration.

Dualistic actions of cromakalim and new potent 2H‐1,4‐benzoxazine derivatives on the native skeletal muscle KATP channel

“…The 2 H ‐1,4‐benzoxazine derivatives are known to be structural analogues of benzopyrans, the difference being the replacement of the carbon atom at position 4 of the benzopyran ring with a nitrogen atom. Structure–activity relations performed on isolated organs have shown that the introduction of the nitro or amino group in positions 6 and 7 of the 2 H ‐1,4‐benzoxazine nucleus, respectively, or the synthesis of tricyclic derivatives by condensing an oxadiazole ring to the same part of the nucleus give rise to molecules more potent than cromakalim or levcromakalim in relaxing the arterial smooth muscle or in reducing the arterial mean blood pressure (Matsumoto et al ., 1996, 1999, 2000; Caliendo et al ., 1998). In most cases, the vasodilating effects of these compounds were antagonised ‘ in vitro ’ by glibenclamide, the well known K ATP channel blocker, suggesting that the K ATP channel is the main target of the action of these molecules in smooth muscle cells.…”

Highly Potent 1,4-Benzothiazine Derivatives as KATP-Channel Openers

“…However, it seems that this strong influence on activity given by cyclopentenone moiety is peculiar to the 1,4-benzothiazine series. In fact the same moiety in the closed 1,4-benzoxazine series increases the activity but not to the same extent 24b…”

Ultrasound-assisted synthesis and antimicrobial evaluation of some novel benzoxanonyhyldrazone derivatives

“…1,4-Benzoxazin-3-(4H)-one derivatives, on the other hand, are known to possess diverse interesting biological activities such as antimicrobial, [33][34][35][36] anticancer, 37 herbicidal, 38 non-steroidal anti-inflammatory 39,40 and neuroprotective antioxidants. [41][42] Thus, a large number of compounds based on benzoxazinone scaffold has been described and evaluated for their antifungal and antibacterial activities.…”