阿立哌唑的合成

4-（2，3-二氯苯基）-1-哌嗪盐酸盐与1，4-二溴丁烷缩合得到1-（4-溴丁基）-4-（2，3-二氯苯基）哌嗪，再与3-氯-N-（3-羟基苯基）丙酰胺反应得3-氯-N-[3-[4-[4-（2，3-二氯苯基）]-1-哌嗪基]丁氧基]苯丙酰胺，最后经闭环制得阿立哌唑，总收率25％。     

阿立哌唑的合成

间氨基酚和3-氯丙酰氯制得的酰胺在无水三氯化铝作用下环合得7-羟基-3,4-二氢-2(1H)-喹诺酮,与1,4-二溴丁烷成醚后与1-(2,3-二氯苯基)哌嗪进行取代反应制得抗精神病药阿立哌唑,总收率25%.     

阿立哌唑的合成

7-羟基-3,4-二氢-2（1H）-喹诺酮和4-溴-1-丁醇经醚化制得7-（4-羟基丁氧基）-3,4-二氢-2（1H）-喹诺酮，再经磺酰化、1-（2，3-二氯苯基）哌嗪取代制得抗精神病药阿立哌唑，总收率77．5％。     

阿立哌唑的合成

目的合成抗精神病药阿立哌唑,并验证所用路线的中间体的螺环季铵盐结构。方法1-（2,3-二氯苯基）哌嗪盐酸盐与1,4-二溴丁烷反应后,再与7-羟基-3,4-2（1H）-喹喏啉酮反应。结果总收率达45%,目标化合物经核磁共振氢谱和红外确证结构,并验证了中间体结构,化学名为5,8-二氮杂螺[4,5]癸烷溴化物。结论此工艺路线生产成本低,反应条件温和、适宜工业化生产。并确证了中间体是5,8-二氮杂螺[4,5]癸烷溴化物,而非1-（4-溴丁基）-4-（2,3-二氯苯基）哌嗪。     

阿立哌唑的合成

目的：合成阿立哌唑。方法：以7-羟基-3，4-二氢喹啉酮、1-氯-4-溴-丁烷及2，3-二氯苯基哌嗪盐酸盐为原料，经2步缩合反应得到纯度99％以上的阿立哌唑。结果：目标化合物经核磁共振、氢谱等确证其化学结构，总收率65％。结论：该路线反应条件温和，后处理简单，产率较高，适合工业化生产。     

非典型抗精神病新药阿立哌唑的合成

目的：研究非典型抗精神病药阿立哌唑的合成路线及工艺。方法：通过优化反应溶剂、反应温度、反应时间及加料方式，以1-(2，3-二氯苯基)哌嗪盐酸盐为起始原料，经N-溴丁基化和O-烃基化合成了阿立哌唑。结果：合成了目标化合物，总收率85％，其化学结构经元素分析、红外光谱、核磁共振氢谱及质谱确证。结论：该方法适合工业化生产。     

月桂酰阿立哌唑合成工艺改进

以7-{4-[4-(2,3-二氯苯基)-l-哌嗪基]丁氧基}-3,4-二氢-2(1H)-喹啉酮（2）为起始原料,与甲醛水溶液进行羟基亚甲基化反应合成中间体7-{4-[4-(2,3-二氯苯基)哌嗪-1-基]丁氧基}-1-(羟甲基)-3,4-二氢喹啉-2(1H)-酮（3）,然后再与月桂酸进行酯化反应得到（7-{4-[4-(2,3-二氯苯基)-1-哌嗪基]丁氧}-3,4-二氢-2-氧-1(2H)-喹啉基）甲酯（1）。本研究建立的合成路线操作简单,原料易得,总收率约62%,最终化合物1的纯度在99.9%以上,具有工业化生产的前景。     

抗精神病药阿立哌唑的合成工艺改进

目的改进抗精神病药阿立哌唑的合成工艺。方法以间氨基苯甲醚为原料,经酰胺化、傅-克烃化、醚化、N-烷基化四步反应合成阿立哌唑。结果通过优化条件合成了阿立哌唑,总收率40%,目标化合物的结构经元素分析、质谱、氢谱、红外光谱确证。结论改进后的工艺操作简便,易于控制,且节省了反应时间,降低了生产成本,更有利于工业化生产。     

阿立哌唑的合成工艺

目的　考察阿立哌唑的合成路线。方法　以7-羟基- 3,4 -二氢- 2 (1H) -喹喏酮为原料,经O -溴丁基化和缩合反应合成阿立哌唑。结果　阿立哌唑总收率为81%,经元素分析、红外光谱确证化学结构正确。结论　该合成路线适于工业化生产。     

Aripiprazole

Aripiprazole is a quinolinone derivative and the first of a new class of atypical antipsychotics. The drug has partial agonist activity at dopamine D(2) and serotonin 5-HT(1A) receptors, and is also an antagonist at 5-HT(2A) receptors. In patients with acute relapse of schizophrenia or schizoaffective disorder, aripiprazole 15 to 30 mg/day was at least as effective as haloperidol 10 mg/day and had similar efficacy to risperidone 6 mg/day in well designed, 4-week, placebo-controlled trials. Negative symptoms improved earlier in the aripiprazole than the risperidone group. Efficacy of aripiprazole was observed at week 1 in several trials and was sustained throughout the study periods. Aripiprazole was superior to placebo in a 26-week trial in patients with stable, chronic schizophrenia. In a 52-week trial involving patients with acute relapsing disease, aripiprazole was similar to haloperidol as assessed by time to failure to maintain response and was superior in ameliorating negative and depressive symptoms. The incidence of extrapyramidal symptoms during aripiprazole therapy was similar to that with risperidone and placebo but lower than with haloperidol. Compared with placebo, the proportion of patients with increased plasma prolactin levels and QTc prolongation was similar in patients treated with aripiprazole 15 to 30 mg/day but was significantly increased with haloperidol and risperidone.     

Aripiprazole

Aripiprazole is a new chemical entity with a unique pharmacological profile. It has strong affinities for certain dopamine receptors, and intermediate affinity for serotonin, adrenergic and histamine receptors. Partial agonism of the D2 dopamine and 5HT1A serotonin receptors, and antagonism of the 5HT2 serotonin receptor are believed to be the functional basis of its therapeutic efficacy. Its clinical effects are best documented in patients suffering from schizophrenia and bipolar disorder, in which it has been demonstrated to have antipsychotic and antimanic properties superior to placebo in dose ranges of 10 – 30 mg/day. Two published longer term trials document maintenance of antipsychotic effects and relapse prevention in schizophrenia patients. In general, aripiprazole seems to be a well-tolerated drug, especially with regard to metabolic side effects. The most commonly reported side effects include restlessness/akathisia, somnolence and nausea. These may be dose-dependent and usually occur early on during treatment, with many patients developing tolerance. Aripiprazole is an interesting and important addition to the currently available spectrum of antipsychotic drugs. Further studies in other indications and clinical trials that confirm results from the Phase II and III clinical development programme are eagerly awaited.     

Aripiprazole

Aripiprazole is a new chemical entity with a unique pharmacological profile. It has strong affinities for certain dopamine receptors, and intermediate affinity for serotonin, adrenergic and histamine receptors. Partial agonism of the D2 dopamine and 5HT1A serotonin receptors, and antagonism of the 5HT2 serotonin receptor are believed to be the functional basis of its therapeutic efficacy. Its clinical effects are best documented in patients suffering from schizophrenia and bipolar disorder, in which it has been demonstrated to have antipsychotic and antimanic properties superior to placebo in dose ranges of 10-30 mg/day. Two published longer term trials document maintenance of antipsychotic effects and relapse prevention in schizophrenia patients. In general, aripiprazole seems to be a well-tolerated drug, especially with regard to metabolic side effects. The most commonly reported side effects include restlessness/akathisia, somnolence and nausea. These may be dose-dependent and usually occur early on during treatment, with many patients developing tolerance. Aripiprazole is an interesting and important addition to the currently available spectrum of antipsychotic drugs. Further studies in other indications and clinical trials that confirm results from the Phase II and III clinical development programme are eagerly awaited.