Synthesis and Biological Evaluation of New 2-(4,5-Dihydro-1H-imidazol-2-yl)-3,4-dihydro-2H-1,4-benzoxazine Derivatives

Abstract

2-(4,5-Dihydro-1H-imidazol-2-yl)-3,4-dihydro-2H-1,4-benzoxazine derivatives and tricyclic analogues with a fused additional ring on the nitrogen atom of the benzoxazine moiety have been prepared and evaluated for their cardiovascular effects as potential antihypertensive agents. The imidazoline ring was generated by reaction of the corresponding ethyl ester with ethylenediamine. Affinities for imidazoline binding sites (IBS) I(1) and I(2) and alpha(1) and alpha(2) adrenergic receptors were evaluated as well as the effects on mean arterial blood pressure (MAP) and heart rate (HR) of spontaneously hypertensive rats. With few exceptions the most active compounds on MAP were those with high affinities for IBS and alpha(2) receptor. Among these, compound 4h was the most interesting and is now, together with its enantiomers, under complementary pharmacological evaluation.

Redox potentials, laccase oxidation, and antilarval activities of substituted phenols

“…o -Aminophenols 7 [23] and 8 [24] were readily prepared from the reduction of both nitro and aldehyde functions of 4-hydroxy-3-nitrobenzaldehyde ( 31 ) using a catalytic amount of palladium under 30 psi of hydrogen in ethanol (Scheme 3). The two products (1:1) were separated by silica gel column chromatography.…”

Microwave-assisted One-pot Efficient Synthesis of Functionalized 2-Oxo-2-phenylethylidenes-linked 2-Oxobenzo[1,4]oxazines and 2-Oxoquino[1,4]oxalines: Synthetic Applications, Antioxidant Activity, SAR and Cytotoxic Studies

“…Benzo [1,4]oxazines 1-8, a sub-class of benzo fused heterocycles, are endowed with a wide range of biological activities such as anti-inflammatory, 1 analgesic, 2 antibacterial, 3 neuroprotective, 4 D2 receptor antagonists, 5 antimycobacterial, 6,7 antihypertensive, 8 antifungal, 9 herbicidal, 10 antiarrhythmic, 11 thrombin inhibitor and fibrinogen receptor antagonists, 12 5-HT receptor antagonists, 13 potent inhibitor of tumor-driven angiogenesis 14a and selective non-steroidal mineralocorticoid receptor antagonists 14b etc. Some marine secondary metabolites such as, Arcticoside 5a (potent antifungal agent) and C-1027 chromophore-III & V 5b (potent antitumor antibiotic), 15 which were isolated from a culture of an arctic marine actinomycete Streptomyces strain; possess as benzo [1,4]oxazines substructures in their active scaffolds (figure 1).…”

Synthesis of 2,3‐dihydro‐6H‐1‐oxa‐3a‐aza‐phenalene and its benzo/hetero‐fused analog

“…Recently, Mérour and coworkers have used the benzoxazine framework for the synthesis of number of imidazolinic derivatives, which showed pronounced cardiovascular effects on both blood pressure and heart rate either after intraperitoneal (ip) or oral (po) administration. Among them, 6-fluoro-2-(4,5-dihydro-1H-imidazol-2-yl)-4-methyl-3,4-dihydro-2H-1,4-benzoxazine was considered to be a potential antihypertensive agent [3]. Some tricylic benzoxazines are synthetic analogs of antibacterial fluoroquinolones, exemplified by norfloxacin and ciprofloxacin [4][5][6][7][8].…”