Kato S, Morie T, Yoshida N
Discovery Research Laboratories I, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
Chem Pharm Bull (Tokyo). 1996 Aug;44(8):1484-92. doi: 10.1248/cpb.44.1484.
To confirm the proposed structures of the minor metabolites of a potential gastroprokinetic agent, mosapride, 4-amino-5-chloro-2-ethoxy-3-hydroxy-N-(2-morpholinylmethyl)benzamide (3) and the N-(5-oxo-2-morpholinyl)-methyl analogue 4 were prepared. As the common intermediate, 2-ethoxy-3-hydroxy-4-nitrobenzoic acid (15) was prepared via the regioselective ethylation of 2,3-dihydroxybenzaldehyde (10) and subsequent nitration of the resultant 2-ethoxy-3-hydroxybenzaldehyde (11). The key intermediate 15 was converted into the benzamides 3 and 4. After enzymatic treatment of the isolated metabolites, their structures were identified by comparison with the synthetic compounds. Serotonin-4 receptor binding affinity of these metabolites was found to be lower than that of mosapride.
为确证一种潜在的胃动力药莫沙必利的次要代谢产物的推测结构，制备了4-氨基-5-氯-2-乙氧基-3-羟基-N-(2-吗啉基甲基)苯甲酰胺(3)和N-(5-氧代-2-吗啉基)甲基类似物4。作为共同中间体，2-乙氧基-3-羟基-4-硝基苯甲酸(15)通过2,3-二羟基苯甲醛(10)的区域选择性乙基化以及所得2-乙氧基-3-羟基苯甲醛(11)的后续硝化反应制备而成。关键中间体15被转化为苯甲酰胺3和4。对分离得到的代谢产物进行酶处理后，通过与合成化合物比较鉴定其结构。发现这些代谢产物的5-羟色胺-4受体结合亲和力低于莫沙必利。
