3-取代-1,2,3,9-四氢-4H-咔唑-4-酮衍生物的合成

根据已知5-HT_3受体拮抗剂的结构特点,本文设计并合成了3-(2-烷基-1H-苯并咪唑-1-基)甲基-1,2,3,9-四氢-4H-咔唑-4-酮(Ⅶa-b)及3-(1H-苯并三唑-1-基)甲些-1,2,3,9-四氢-4H-咔唑-4-酮(IXa,b)衍生物共10个。目的物从相应的1,2,3,9-四氧-4H-咔唑-4-酮(Ⅳ,Ⅴ)经过Mannich反应,成盐反应、与2-烷基苯并咪唑或苯并三唑缩合反应制得,并经光谱确证。     

1,2,6,7-四甲氧基-9H-咔唑和2,3,6,7-四甲氧基-9H-咔唑的合成方法研究

目的 研究1，2，6，7-四甲氧基-9H-咔唑和2，3，6，7-四甲氧基-9H-咔唑的合成方法。方法 以4,5-二甲氧基-2-溴硝基苯和4-碘-1，2．二甲氧基苯为原料，经Ullmann反应得2-(3，4-二甲氧基苯基)-4．5．二甲氧基硝基苯(3)，再经亚磷酸三乙酯还原环合得1，2，6，7-四甲氧基-9H-咔唑(1)和2，3，6，7-四甲氧基-9H-咔唑(2)。结果 以4，5-二甲氧基-2-溴硝基苯和4-碘-1，2-二甲氧基苯为原料，制得3的收率为42％，3经环合制备l和2的收率分别为38％和39％。结论 化合物3经亚磷酸三乙酯还原环合时。等量得到l和2。研究发现化合物2还可由Ullmann反应的副产物4，4′，5，5′-四甲氧基-2，2′-二硝基联苯4经亚磷酸三乙酯还原环合制得。     

6-乙酰氨基-1,2,3,4-四氢-1-萘酮的合成

目的:合成中间体6-乙酰氨基-1,2,3,4-四氢-1-萘酮.方法:以苯甲酰基丙酸为原料,经过硝化、硝基还原、酰化、羰基还原、环合得到6-乙酰氨基-1,2,3,4-四氢-1-萘酮.结果与结论:只需经过5步反应就可以合成目标化合物,总收率14.7%.     

4-(4-甲氧基苯基)-3,4-二氢-2(1H)-喹啉酮的合成及抗惊厥作用研究

目的筛选抗惊厥活性的化合物,寻找新型抗癫痫药物。方法以肉桂酸为原料,对其化学结构进行优化,合成了4-(4-甲氧基苯基)-3,4-二氢-2(1H)-喹啉酮。采用最大电休克发作实验(MES)测定其抗癫痫活性。结果采用红外光谱、核磁共振氢谱和质谱确定了化学结构。经药理活性筛选发现4-(4-甲氧基苯基)-3,4-二氢-2(1H)-喹啉酮具有抗惊厥作用。结论本合成路线简单、产物易分离,为开发新的抗癫痫药物提供了新思路。     

5-氯-6-苯基-2H-哒嗪-3-酮的合成

6-苯基-2H-哒嗪-3-酮(2)经三氯化磷/氯气氯代制得3,5-二氯-6-苯基哒嗪,经氢氧化钠皂化,再用盐酸调至pH 8.5得到5-氯-6-苯基-2H-哒嗪-3-酮,总收率约24%(以2计).副产物3-氯-5-羟基-6-苯基哒嗪可作为氯代反应的原料回收使用.     

反式-八氢-1H-吲哚-2-羧酸苄酯盐酸盐的合成

环己酮与丙烯腈经Micheal加成环合得3,4,5,6,7,8-六氢喹啉-2(1H)-酮,经甲酸/甲酸钠还原、氯代、选择性脱氯、重排后得反式-八氢-1H-吲哚-2-羧酸,再经苄基化、手性分离和成盐反应得到4个反式-八氢-1H-吲哚-2-羧酸苄酯盐酸盐。     

6-甲基-4-苯基-3,4-二氢香豆素的合成工艺改进

目的:以浓磷酸为催化剂制备6-甲基-4-苯基-3,4-二氢香豆素.方法:以对甲酚和苯甲醛为主要原料,经脱水、环合等方法制备目标产物.结果:产品收率达74.2%.结论:该方法有效降低了酸对设备的腐蚀程度,使合成工艺条件得到了优化,利于工业化生产.     

4-甲基-1.3-二氢-2H-咪唑-2-酮合成方法改进

4一甲基一13－H氢一ZH一咪娃一2一阴（I）是一种治疗心力衰竭药物5一取代一4一甲基一1．3－H氢一ZH一咪哇一2一酮类药物的重要中间体！’］，有多种合成方法，分别以乙酸乙酸乙酸、p一羟基丙胺、氨基乙酸为原料，经过不同的化学反应制得氨基丙酮（Ill），然后和氨酸钾作用进行环会反应制得（l）。在本文，我们则选择以环氧丙烷为原料经加成，氧化得l一氯丙酮（11），再定位氨化向样得到氨基丙团（Ill）．然后与尿素进行环会反应，使得到（l）．新的合成路线用反应式表示如下．实验部分在装有搅拌器、摄度计和回流冷反管的250Inl三口瓶中…     

5-乙基-2,4-二氢-4-(2-苯氧乙基)-3H-1,2,4-三唑-3-酮的合成

丙酰肼与三光气缩合环化得到5-乙基-1,3,4-噁二唑-2(3H)-酮,继与2-苯氧乙胺反应后在碱性条件下环合得到抗抑郁药奈法唑酮中间体5-乙基-2,4-二氢-4-(2-苯氧乙基)-3H-1,2,4-三唑-3-酮,总收率66.3%.     

1,4,5,8-四甲氧基萘-2-甲醛的合成

对紫草素合成中间体1,4,5,8-四甲氧基萘-2-甲醛的制备工艺进行了改进,由萘茜在溴化四丁基铵催化下进行还原甲基化的收率由文献报道的44%提高到90%,标题化合物总收率72%(以对二甲氧基苯计).     

Synthesis and anticonvulsant properties of 2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-one derivatives.

A number of novel 1H-pyrrolo[1,2-a]benzimidazol-1-one derivatives were prepared and their anticonvulsant properties evaluated. The new synthesized compounds proved to possess anticonvulsant effects depending on the nature of substituents at C-6, C-2, and C-3a positions of the polycyclic system. In particular, the 6-chloro-3a-(p-tolyl)-2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-one derivative (22) displayed potency fivefold higher than unsubstituted compound (13).     

Synthesis and anticonvulsant evaluation of some new 1,3,4,5-tetrahydro-6-alkoxy-2H-1-benzazepin-2-one derivatives

A series of new 1,3,4,5-tetrahydro-6-alkoxy-2H-1-benzazepin-2-one derivatives were synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test, subcutaneous pentylenetetrazol (scPTZ) test, and their neurotoxicity was evaluated by the rotarod neurotoxicity test. The results of these tests showed that 1,3,4,5-tetrahydro-6-octyloxy-2H-1-benzazepin-2-one (4f) was the most promising compound, with median effective dose (ED₅₀) of 20.4 mg/kg, and protective index (PI) value of 20.1 in the MES test, which is much higher than the PI value of the prototype antiepileptic drug carbamazepine (PI = 8.1), phenytoin (PI = 6.9), phenobarbital (PI = 3.2), and sodium valproate (PI = 1.6). The scPTZ test displayed that 1,3,4,5-tetrahydro-6-heptyloxy-2H-1-benzazepin-2-one (4e) was the most active compound (ED₅₀ = 64.4, PI = 2.6). The possible structure–activity relationship was discussed.     

6-氯-苯并二氢-γ-吡喃酮的合成研究

目的:合成氧杂非甾体雌激素类似物制备的关键中间体6 -氯-苯并二氢-γ-吡喃酮。方法:以对氯苯酚为起始原料经亲核加成、水解和环合反应合成了6 -氯-苯并二氢-γ-吡喃酮。结果:合成产物的结构经熔点、红外光谱、核磁共振氢谱和质谱确证。结论:该合成工艺简单,产品质量好且成本低     

Distribution of 1,2,3,4-Tetrahydro-β-carboline and 6-Methoxy-1,2,3,4-tetrahydro-β-carboline in Mice

Abstract: The distribution of radioactivity after intravenous injection of ¹⁴C-labelled 1,2,3,4-tetrahydro-β-carboline (THBC) and 6-methoxy-1,2,3,4-tetrahydro-β-carboline (6-MeO-THBC) was studied on mice by whole-body autoradiography and by liquid scintillation counting (LSC). Following intravenous injection they rapidly distributed into different organs and were excreted into urine and the gut contents. A considerable uptake of the compounds was seen in the lungs, kidney, liver, bone marrow, urinary bladder, gastrointestinal tract and in various glands e.g. adrenal, Harderian and salivary glands. THBC moderately penetrated the blood-brain barrier and the placenta but 6-MeO-THBC seemed to penetrate poorly both. At early stages of the experiment the values of tissue radioactivity in LSC were generally much higher in the THBC group but 24 hours following injections the reverse was true with higher activities in the 6-MeO-THBC group. The initial excretion of 6-MeO-THBC seemed to be more rapid judged by the superfluous accumulation of activity in the bladder and a high accumulation of activity into the gut contents.:     

6-甲氧基-2-萘丙酮的萘1-取代占位制备

2—甲氧基荼通过溴化、丙酰化和脱溴三步反应合成了6—甲氧基—2—萘丙酮。研究并优化了溴化反应中溶剂的用量和丙酰化的工艺条件。结果表明，经优化工艺能明显减少溴化反应的溶剂用量，6—甲氧基—2—萘丙酮的得率达到87．8％。