间苯二酚常压催化氢化得到1，3环己二酮，经缩台、Reformatsky反应、脱氢反应，得到4苯并呋喃乙酸乙酯，再水解酸化后，得到依那朵林合成中的关键中间体4苯并呋喃乙酸。

选用苄基氯，经过芳香族烯烃的游离基加成、缩台、氢解脱苄基等反应以及光学异构体的拆分，合成了福辛普利（fosinopril）的重要中间体[R（R*, S*）[（2甲基1丙酰氧基丙氧基）（4苯基丁基）氧腾基]乙酸，并改进了部分反应条件。

Purpose To prepare 1-metyh1-3-ethy1-3(3-hydroxyhenyl)-hexahydro-1 H-azepin hy-drochloride (I) from m-methoxyacetophenone. Methods 1-methy1-3-(3-hydrox yphenyl)-hex-ahydro-1 H-azepin hydrochloride (I) was synthesized by eight steeps with m-methoxyacetophenone as start-ing material. The eight steps were willgerodt rearrangement, formation of acyl chloride, acylride and salt for-mation. Results 1-methy1-3-ethy1-3(3-hydroxypheny1)-hexahydro-1 H-azepin Hydrochlorde (I) was prepared in eight steps from cheap material and reagent on normal condition. Conclusions This method is applicable to industrial production.

Using the latency of paw withdrawal (PWL) from a noxious thermal stimulus as a measure of hyperalgesia, the effects of i.p. injection of meptazinol and its isomers, 112824 and 112825, on carrageenan-induced thermal hyperalgesia were studied in awaked carrageenan-inflamed rats. Peripheral inflammation was induced by intraplantar (i.pl.) injection of carrageenan (2mg/100μl) into one hindpaw in rats. Carrageenan produced marked inflammation (edema and erythema) and thermal hyperalgesia in the injected paws, which peaked at 3 h after injection and showed little change in magnitude for another 3h. Injection of 0.1mg/kg meptazinol (i.p.) at 3h after carrageenan had no effect on the PWLs of either inflamed or non-inflamed hindpaw during the next 100 min (P>0.05, n=8). At the dosage of 1 and 10mg/kg, meptazinol produced marked anti-nociception and anti-hyperalgesia in non-inflamed and inflamed hindpaw, respectively (P<0.05, n=8～11). The prolonging effect of meptazinol on PWL in inflamed hindpaw was more potent than that in non-inflamed hindpaw. Pre-administration of 1.5mg/kg naloxone significantly antagonized meptazinol-induced anti-nociception and anti-hyperalgesia. Intraperitoneal injection of an isomer of meptazinol, 112825 (1.5mg/kg), but not 112824 (1mg/kg), markedly increased the PWL of the non-inflamed hindpaw. Nevertheles, both the isomers produced similar anti-hyperalgesic effect to that of meptazinol (P<0.05, n=8), which was completely reversed by naloxone (1.5mg/mg). The results suggest that meptazinol and its isomers have anti-nociceptive and anti-hyperalgesic properties with the former more potent. The effects are mainly mediated by mu opioid receptors. This study provides an important clue for extending clinical utilization of meptazinol and its isomers.

对具有很高kappa受体亲和性和选择性的依那朵林进行了合成研究。以1，4环己二酮为原料，经缩合、环合、还原、环氧化等16步反应得到关键中间体1-[8-甲氨基-1-氧杂螺[4，5]癸烷-7-基]吡咯烷（16），再和4苯并呋喃乙酸在偶合剂CDI催化下得到目标化合物依那朵林。