多巴胺D3受体部分激动剂BP897的合成

目的：合成多巴胺D3受体部分激动剂BP897。方法：以二羟乙基胺为起始原料，经过氯化、环合、取代、肼解、缩合等反应合成BP897。结果：以总产率为40．2％合成了多巴胺D3受体部分激动剂BP897，结构经核磁氢谱（^1HNMR）、质谱（MS）和红外（IR）确证。结论：该法原料价廉易得，反应条件温和，收率较文献有所提高。     

多巴胺D3受体选择性激动剂PD128907的合成

目的合成多巴胺D3受体选择性激动剂PD128907.方法以对甲氧基苯酚为起始原料,经加成、酸解、环合、成肟、酯化、Neber重排、酰胺化、还原、环合、还原、烷基化以及脱甲基等12步反应制备了PD128907反式消旋体.结果以总收率4.75%合成了多巴胺D3受体选择性激动剂PD128907反式消旋体,结构经核磁氢谱(1H NMR)、质谱(MS)和红外光谱(IR)确证.结论对PD128907的合成进行了探讨,该法原料价廉易得,反应条件温和,收率较高.     

多巴胺D3受体选择性激动剂PD128907的合成

目的合成多巴胺D3受体选择性激动剂PD128907。方法以对甲氧基苯酚为起始原料，经加成、酸解、环合、成肟、酯化、Neber重排、酰胺化、还原、环合、还原、烷基化以及脱甲基等12步反应制备了PD128907反式消旋体。结果以总收率4．75％合成了多巴胺D3受体选择性激动剂PD128907反式消旋体，结构经核磁氢谱（^1H NMR、质谱（MS）和红外光谱（IR）确证。结论对PD128907的合成进行了探讨，该法原料价廉易得，反应条件温和，收率较高。     

多巴胺D3受体配体的研究和应用

综述有潜在治疗价值的多巴胺D3受体配体如多巴胺D3受体激动剂、部分激动剂和多巴胺D3受体拮抗剂的研究和应用近况。多巴胺D3受体与帕金森病、精神分裂症等神经性或精神性疾病及药物成瘾等有关。     

罗匹尼罗中间体2-甲基3-硝基苯乙腈的合成

以邻二甲苯为原料 ,经硝化、氧化、水解、还原、氯化和氰代等 6步反应制得 2 甲基 3 硝基 苯乙睛 (8) ,对其中还原、氯化和氰代等反应操作进行了改进 ,使用三氯化磷代替三溴化磷 ,结果较好 ,该法未见文献报道 .     

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。     

多巴胺D_3受体选择性配体治疗药物依赖的新进展

药物依赖是一种以复吸为特征的慢性脑病,迄今为止尚缺乏有效的防复吸药物。随着药物依赖及复吸神经生物学机制的研究不断深入,发现了一些潜在的药物干预靶点。靶向多巴胺D3受体(DAD3R)防复吸药物研究受到了广泛关注,DAD3R选择性分布在啮齿类动物及人脑内与药物依赖相关的中脑边缘多巴胺系统,在药物依赖发生发展过程中发挥着重要作用。本文重点介绍DAD3R在药物依赖中的作用及选择性配体治疗药物依赖研究的进展。     

6-氨基-3,4-二氢喹啉酮的合成改进

采用催化氢化还原的方法将６－硝基－３,４－二氢唑啉酮还原制得目标化合物,并对不同的氢压进行了考察,找出比较适合的反应条件。     

选择性D3受体拮抗剂抗精神分裂作用的研究进展

多巴胺（DA）3受体广泛影响DA的释放、DA能的效应和其它几个神经递质,已成为人们研发中枢类神经系统疾病的热点靶标。在动物模型试验中已证实,选择性D3受体拮抗剂具有诱导自发活动、改善认知障碍,并提高社交行为的抗精神分裂作用。但在体内研究中．临床几乎所有用于拮抗D3受体的抗精神分裂物药都有拮抗D2受体的作用,且无法达到对精神分裂症和认知功能障碍的最佳疗效。因此,高选择性D3拮抗剂很有希望被开发用于精神分裂症、认知障碍和药物成瘾性的治疗。     

6-甲氧基-1,2,3,9-四氢-4H-咔唑-4-酮的合成

4-甲氧基苯肼盐酸盐和1,3-环己二酮在乙酸催化下缩合得到3-[（4-甲氧基苯基）亚肼基]环己-1-烯醇盐酸盐,然后在二苯醚中经Fischer反应闭环生成6-甲氧基-1,2,3,9-四氢-4H-咔唑-4-酮,总收率约为57%。     

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     

Autoradiographic localisation of D3-dopamine receptors in the human brain using the selective D3-dopamine receptor agonist (+)-[3H]PD 128907

The selective D₃-dopamine receptor agonist 4aR,10bR-(+)-trans-3,4,4a,10b-tetrahydro-4-[N-propyl-2,3-³H]-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-ol ([³H]PD 128907) was used to visualise D₃-dopamine receptors in whole hemisphere cryosections from post-mortem human brain. [³H]PD 128907 has an 18- to 40-fold selectivity for D₃- over D₂-dopamine receptors as compared to a 7- to 24-fold selectivity of the more commonly used ligand [³H]7-OH-DPAT. [³H]PD 128907 accumulated markedly in the nucleus accumbens and in the ventral parts of caudate nucleus and putamen, with a slightly heterogeneous (patch-matrix like) distribution. The binding in the lateral parts of caudate nucleus and putamen was much less dense. No binding was obtained in any other regions. A very high proportion of [³H]PD 128907 was specifically bound, as judged from the low binding remaining in the presence of the D₂/D₃-dopamine receptor antagonist raclopride. This gives the ligand a potential for the detection of low density D₃-dopamine receptors in the human brain. The binding obtained with [³H]PD 128907 was qualitatively similar to that using [³H]7-OH-DPAT in the presence of GTP. However, [³H]7-OH-DPAT labelled, in contrast to [³H]PD 128907, also D₃-dopamine receptors in neocortex. The new compound [³H]PD 128907 appears to be a suitable radioligand for autoradiographic examination of the D₃-dopamine receptor localisation in the human brain, and should also be useful for pharmacological studies of this receptor subtype. Received: 20 November 1995/Final version: 2 May 1996     

Synthesis and antihypertensive activity of substituted trans-4-amino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-3-ols

A series of novel substituted trans-4-amino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-3-ols was prepared and tested for antihypertensive activity in the conscious deoxycorticosterone acetate (DOCA)/saline treated hypertensive rat. Optimum blood pressure lowering activity requires 6-substitution by a strong electron-withdrawing group, together with a pyrrolidino or piperidino group at the 4 position. Exceptions to this were the 7-nitro-4-pyrrolidine analogue and the 6-nitro-3-chloropropylamine, which retained marked antihypertensive activity. All of these compounds were direct vasodilators and had comparable antihypertensive activity to hydralazine and to the calcium antagonist, nifedipine. The synthetic route to these compounds involves cyclization of of propargyl ethers to 2H-1-benzopyrans, followed by conversion via bromohydrins to 3,4-epoxides, which were ring opened with the appropriate amines. Meta-substituted propargyl ethers gave both 5- and 7-substituted benzopyrans on thermal cyclization, the former predominating. A new route to 2,2-dimethyl-7-nitrobenzopyran is described.     

Synthesis and antihypertensive activity of 6,7-disubstituted trans-4-amino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-3-ols

A series of novel 6,7-disubstituted trans-3,4-dihydro-2, 2-dimethyl-4-pyrrolidino-(or piperidino)-2H-1-benzopyran-3-ols was prepared and tested for antihypertensive activity in the conscious spontaneously hypertensive rat (SHR) and compared with certain of their monosubstituted analogues. The potent blood pressure lowering activity of the 6-monosubstituted compounds was enhanced by incorporation of an acetylamino or amino group at C(7) and that of the 7-nitro-substituted compound by incorporation of an amino (but not an acetylamino group) at C(6). The combination of 6-nitro or 6-cyano with 7-(acetylamino) or 7-amino groups and 6-amino with 7-nitro groups in trans-4-pyrrolidino- or -4-piperidino-2,2-dimethyl-2H-1-benzopyranols conferred superior antihypertensive activity to hydralazine and to the calcium antagonist, nifedipine, in SHR. The synthetic route to these compounds involves the conversion of 2H-1-benzopyrans to bromohydrins that were treated with pyrrolidine or piperidine. Preparation of the 6-cyano-7-amino analogue was accomplished when 6-cyano-7-[(trifluoroacetyl)amino]-2,2-dimethylbenzopyran was used as starting material.     

Synthesis of new N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H-thieno[2,3-h]-1-benzopyran-2-ones

The synthesis of some N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H-thieno[2,3-h]-1-benzopyran-2-ones (4a-f), by reaction of phenylchloroketene with a series of N,N-disubstituted (E)-5-aminomethylene-6,7-dihydrobenzo[b]thiophen-4(5)-ones, followed by dehydrochlorination in situ of the primary adducts with DBN, is described. A moderate local anaesthetic activity was observed in the title compounds, particularly in 4e.