Steroidal Dihydro-1,3-oxazines as Antitumor Agents

Abstract

Dihydro-m-oxazines were prepared by condensation of hexestrol, stilbestrol, equilenin and 17 -ethynylestradiol with formaldehyde and primary amines.Estrogenic activity was retained only by the products derived from 17a-ethynylestradiol, where some members also showed maximum inhibition of experimental adenocarcinoma E0771 in mice. Condensation of 3, 17, 20, 23 and 24-aminosteroids with formaldehyde and phenols gave dihydro-m-oxazines with steroidal .V-substituents. Moderate inhibition of E0771 tumors was found in each class of steroids. The A-(3a,7a,12a-trihydroxycholan-24-yl)-dihydro-m-oxazines demonstrated bacteriostatic and antifungal activity in vitro..

Design and Synthesis of Two Oxazine Derivatives Using Several Strategies

“…176-178 ∘ C; IR ( max , cm −1 ): 1718, 1228, 1140; 1 H NMR (300 MHz, CDCl 3 ) H : 2.10 (s, 3H), 2.80 (s, 3H), 5.20-5.70 (m, 4H), 7.01 (m, 1H), 7.10 (m, 1H), 7.30 (m, 1H), 7.40 (m, 2H), 7.44 (m, 2H), 7.58 (m, 2H), 7.60-7.66 (m, 3H) ppm. 13 [1,2-e] [1,3]oxazin-2-yl)-2-phenyl-1,2-dihydro-pyrazol-3-ylidene]-ethane-1,2-diamine (4). A solution of 3 (100 mg, 0.27 mmol), ethylenediamine (100 L, 1.50 mmol), and boric acid (90 mg, 1.45 mmol) in 10 mL of methanol was stirred for 72 h at room temperature.…”

“…Oxazine derivatives are very important heterocyclic compounds with several biological activities [1,2]. Several years ago, some oxazine derivatives have been synthesized; for example, the synthesis of 1,2-dihydro-1-arylnaphtho [1,2-e] [1,3]oxazine-3-one using the three-component system ( -naphthol, benzaldehyde, and urea) in presence of HClO 4 -SiO 2 [3]. Other report [4] showed the preparation of dirithromycin (9-N-11-O-oxazine derivative) by condensation of 9(S)erythromycylamine with 2-(2-methoxy-ethoxy)acetaldehyde.…”

“…Other studies showed the condensation of 2-naphthol with heteroarylaldehydes or substituted benzaldehydes in the presence of ammonia [5]. In addition, a study [6] showed the synthesis of 3,4-dihydro-3-substituted-2H-naphtho [2,1e] [1,3]oxazine derivatives catalyzed by zirconium (IV) chloride. Other data [7] showed the reaction of substituted aryl and heteroarylaldehydes to give a series of 8-bromo-1,3-diaryl-2,3-dihydro-1H-naphth [1,2e] [1,3]oxazines.…”

“…In addition, a study [6] showed the synthesis of 3,4-dihydro-3-substituted-2H-naphtho [2,1e] [1,3]oxazine derivatives catalyzed by zirconium (IV) chloride. Other data [7] showed the reaction of substituted aryl and heteroarylaldehydes to give a series of 8-bromo-1,3-diaryl-2,3-dihydro-1H-naphth [1,2e] [1,3]oxazines. Also an other oxazine derivative (1,3-diphenyl-1H-naphtho [1,2-e] [1,3]oxazine) was developed by the reaction of N-arylidene-1-(aminoarylbenzyl)-2-naphthol with iodobenzene diacetate [8].…”

“…Other data [7] showed the reaction of substituted aryl and heteroarylaldehydes to give a series of 8-bromo-1,3-diaryl-2,3-dihydro-1H-naphth [1,2e] [1,3]oxazines. Also an other oxazine derivative (1,3-diphenyl-1H-naphtho [1,2-e] [1,3]oxazine) was developed by the reaction of N-arylidene-1-(aminoarylbenzyl)-2-naphthol with iodobenzene diacetate [8]. All these experimental results show several procedures which are available for synthesis of several oxazine derivatives; nevertheless, expensive reagents and special conditions are required.…”