3-甲胺基哌啶二醋酸盐的合成工艺改进

目的:合成3-甲胺基哌啶二醋酸盐.方法:以3-氨基吡啶为起始原料,经3步反应制得3-甲胺基哌啶二醋酸盐.结果:目标化合物经'H-NMR和MS确证,总收率为41.4%.结论:本方法优化了反应条件和投料比,缩短了反应时间,提高了收率,适合工业化生产.     

3-甲胺基哌啶二盐酸盐的合成

3-甲胺基哌啶（1）是合成氟喹诺酮类抗菌药巴洛沙星（balofloxacin）的重要中间体，文献以γ-丁内酯为原料，经胺解、水解、酯化、与溴乙酸乙酯缩合、环合、酯水解并脱羧、还原胺化和氢解脱苄基等反应得到1，步骤长，总收率低（仅11．5％）。文献用3-氨基吡啶（2）经甲酰化、氢化铝锂还原制得3-甲胺基吡啶（4）；或用2和原甲酸三乙酯缩合、硼氢化钠还原得到4，4再经Pd／C还原，     

巴洛沙星的合成

1-环丙基-6,7-二氟-1,4-二氢-8-甲氧基-4-氧代喹啉-3-羧酸乙酯在乙酐中与硼酸螯合后与3-甲胺基哌啶缩合,再经水解得到氟喹诺酮类抗菌药巴洛沙星,总收率74.4%.其合成关键中间体3-甲胺基哌啶可用γ-丁内酯经胺解、水解、酯化、与溴乙酸乙酯缩合、环合、酯水解并脱羧、还原胺化和氢解脱苄基等反应得到,收率11.5%.     

3-乙胺基丙酸乙酯的合成工艺改进

3-乙胺基丙酸乙酯是合成喹诺酮类抗菌药吡哌酸、依诺沙星的重要中间体,比较了分别以无水乙醇、氯仿、甲苯和环己烷为溶媒,用丙烯酸乙酯和无水乙胺在-5～0C制备目标物的结果,确定用环己烷做溶媒效果最好,收率85%,纯度98%.     

新一代氟喹诺酮类抗菌素--巴洛沙星的合成

目的合成新一代氟喹诺酮类抗菌素--巴洛沙星.方法以1-环丙基-6,7-二氟-1,4-二氢-8-甲氧基-4-氧代喹啉-3-羧酸为起始原料,在硼酸酯的作用下与3-甲胺基哌啶二醋酸盐缩合得到目标产物--巴洛沙星.以3-氨基吡啶为原料,分别通过甲酰化反应、氢化铝锂还原和原甲酸三乙酯缩合、硼氢化钠还原两种方法得到3-甲胺基吡啶,最后经催化氢化得到中间体3-甲胺基哌啶.结果合成巴洛沙星的总收率为60%,两种方法合成3-甲胺基哌啶的总收率分别为16%和32%.结论改进了合成路线,降低了成本,有助于巴洛沙星的合成.     

4-(2-甲胺基)乙氧基苄胺合成

目的合成4-(2-甲胺基)乙氧基苄胺,以降低生产成本。方法以N,N-二甲基乙醇胺为原料,经氯化、醚化、肟化、氢化反应得到目标化合物。结果成功得到目标化合物,经核磁共振氢谱确证结构正确。结论该方法三步反应总收率65.6%,且反应条件温和,原料廉价易得,适合工业化生产。     

以双（4—甲胺基安替比林）甲烷合成安乃近

以水作溶剂，由４－甲胺基安替比林与甲醛反应，缩合成双（４－甲胺基安替比林）甲烷，再以酒精作溶剂，与甲醛、亚硫酸氢钠缩合生成安乃近。     

(S)-2-甲氧亚胺基-2-呋喃乙酸的合成

以呋喃为原料，经乙酰化、肟重排、肟化合成(S)-2-甲氧亚胺基-2-呋喃乙酸。总收率达34％。     

3—环丙胺基丙烯酸乙酯的合成

3-环丙胺基丙烯酸乙酯(1)是合成环丙沙星(ciprofloxacin)的原料。我们采用廉价原料丙炔醇进行氧化、酯化,然后和环丙胺加成而制得。三步反应均作了改进,总收率为41%。     

(±)-反式-1-苄基-3-甲基-4-苯胺基哌啶的合成

采用金属钠还原Ｎ苄基３甲基４苯亚胺基哌啶,大大提高了反式产物的比例;将其制成草酸盐后,采用分步结晶的方法对（±）顺,反１苄基３甲基４苯胺基哌啶的混合物进行分离．     

芳烷醇哌啶类化合物的合成及抗抑郁活性研究

为寻找新型具有抗抑郁活性的单胺递质再摄取抑制剂, 设计合成了15个芳烷醇哌啶类未见文献报道的新化合物, 结构经¹H NMR及HR-MS分析确证。大鼠脑突触体对5-HT、NA和DA再摄取抑制作用体外活性测试结果表明, 化合物4、5和8对5-HT、NA和DA再摄取抑制作用较强。小鼠强迫游泳实验发现, 化合物4、5和13具有显著的体内抗抑郁效果, 化合物4和5值得进一步研究。     

3-环丁基丙酸的合成

目的合成3-环丁基丙酸.方法以溴甲基环丁烷和丙二酸二乙酯为起始原料,经缩合、脱羧得到3-环丁基丙酸.结果合成了3-环丁基丙酸,总收率为83%.结论该合成路线简洁,反应步骤少,适合工业化生产.     

药物中间体3-噻吩丙二酸的合成研究

利用铜锂试剂在酯基存在下选择性发生亲核取代反应的特征,将溴代丙二酸二乙酯引入噻吩环的3-位,设计了合成3-噻吩丙二酸(TM A)的新路线。     

Multiple sites of action of ( +)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine (( +)-3PPP) in blood vessels

Functional effects of the σ ligand, (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3PPP), were explored in perfused rat tail and rabbit ear arteries in vitro. In the rat tail artery (+)-3PPP inhibited contractile responses to adrenergic nerve stimulation, an effect which was reversed to potentiation by the dopamine D₂ receptor antagonist sulpiride. In the rabbit ear artery, however, (+)-3PPP potentiated contractile responses to nerve stimulation, an effect which was unchanged by sulpiride. In the rat tail artery, blockade of norepinephrine uptake by cocaine and deoxycorticosterone in the presence of sulpiride revealed two additional actions of (+)-3PPP. First, an inhibitory action on the monoamine uptake site was confirmed by direct measurement of [³H]norepmephrine accumulation. Second, at higher concentrations, an action to inhibit contractile responses to adrenergic nerve stimulation was manifested at a still unidentified site. These studies demonstrate that the observed functional effect of (+)-3PPP results from its combined actions on three individual sites with the net effect dependent on the relative densities of these different receptor sites in each type of vessel.     

巴洛沙星的合成

目的 合成巴洛沙星（Balofloxacin），并进行工艺优化。方法 以1-环丙基-6，7-二氟-8-甲氧基-4-氧代-1，4二氢喹啉-3-羧酸乙酯为起始原料，经保护、缩合、水解等反应制得抗菌药巴洛沙星。结果 合成目标化合物，总收率为54．9％。结论 本工艺反应条件平和，成本较低，收率较高。     

巴洛沙星的合成

目的合成巴洛沙星(Balofloxacin),并进行工艺优化。方法以1-环丙基-6,7-二氟-8-甲氧基-4-氧代-1,4二氢喹啉-3-羧酸乙酯为起始原料,经保护、缩合、水解等反应制得抗菌药巴洛沙星。结果合成目标化合物,总收率为54.9%。结论本工艺反应条件平和,成本较低,收率较高。     

Dual-acting diether derivatives of piperidine and homopiperidine with histamine H(3) receptor antagonistic and anticholinesterase activity

The study presents novel biological properties of diether derivatives of homo‐ or substituted piperidine ligands of the histamine H₃ receptor. The compounds were evaluated for their inhibitory potency against acetylcholinesterase (AChE) from the electric eel and butyrylcholinesterase (BuChE) from horse serum. The most interesting multifunctional compound 13 displayed high affinity for the cloned hH₃R (K_i = 3.48 nM) and moderate inhibitory potency against both enzymes (IC₅₀ AChE = 7.91 µM and BuChE = 4.97 µM). Molecular modeling studies revealed interactions with key amino acid residues in the homology model of histamine H₃ receptor ligands, as well as the binding model for AChE and BuChE in the catalytic and peripheral active sites.     

N-吲哚烷基哌啶类化合物及其类似物的合成和活性研究

摘 要：目的 以5-羟色胺转运体和5-HT2A受体为靶点,设计合成N-吲哚烷基哌啶类化合物及其类似物,研究它们的体内外生物活性。方法 以苯并五元氮杂化合物为原料,经烷基化反应,再与相应的哌啶或哌嗪类化合物进行缩合制备系列化合物。经5-羟色胺再摄取抑制实验和5-HT_2A受体结合实验进行体外筛选,采用小鼠醋酸扭体法和小鼠热板法对其中优选化合物10c、10e进行体内镇痛活性实验;通过阿片受体结合试验和小鼠急性毒性试验,考察目标化合物作为新型非阿片类镇痛剂的潜在开发价值。 结果与结论 共合成了18个未见文献报道的新化合物, 经高分辨质谱及核磁共振氢谱确证结构。体内外药理研究表明：化合物10c和10e具有较强的5-羟色胺再摄取抑制作用,且与5-HT_2A受体有较高亲和力;10c、10e在两种镇痛模型上均显示出很强的镇痛活性;与阿片μ、δ、κ受体无明显亲和力;毒性较小,具有作为非阿片类新型镇痛剂的开发价值。     

Synthesis of new hydantoin-3-ethanethiol derivatives

5-sec-Butylthiomethyl-5-alkyl (methyl or phenyl) hydantoins (3−x) were prepared by the reaction of sec-butylthiomethyl alkyl (methyl or phenyl) ketone (1–2), potassium cyanide and ammonium carbonate. 3-(2-Bromoethyl) hydantoins (5–6) were the reaction products of 5-sec-butylthiomethyl-5-alkyl (methyl or phenyl) hydantoin and 1,2-dibromoethane in the presence of potassium hydroxide. Alkylation of5 and6 with an excess of alkyl (methyl or ethyl) iodide in THF with sodium hydride as base gave three 1-alkyl (methyl or ethyl)-3-(2-bromoethyl) hydantoins (7–9). Treatment of the 2-bromoethyl group with potassium thioacetate and triethylamine gave three 1-alkyl (methyl or ethyl)-3-(2-acetylthioethyl) hydantoins (10–12). Hydrolysis of the 2-acetylthioethyl group with sodium hydroxide in methanol afforded the three 1-alkyl (methyl or ethyl)-3-(2-mercaptoethyl) hydantoins.     

Two new piperidine alkaloids from the leaves of Microcos paniculata

Two new piperidine alkaloids, microcosamines A (1) and B (2), were isolated from the leaves of Microcos paniculata. Their structures were elucidated by spectroscopic analysis. Both new compounds showed significant larvicidal activity against Culex quinquefasciatus.