新型N-取代酰基-N-甲基-3-(1-萘氧基)-3-(2-噻吩基)-丙胺衍生物的设计与合成

(S)-N-甲基-3-(1-萘氧基)-3-(2-噻吩基)-丙胺(度洛西汀)分别与4个烷基酰氯反应,合成了4个新型的N-甲基-3-(1-萘氧基)-3-(2-噻吩基)-丙胺酰基衍生物,其结构经1H NMR,IR和MS表征。     

新型N-取代酰基-N-甲基-3-(1-萘氧基)-3-(2-噻吩基)丙胺的合成

为了得到具有更好抗抑郁活性的新型化合物,抗抑郁药度洛西汀通过N-酰化反应或N-烷基化反应与取代酰氯拼合,制得5个新型N-取代酰基-N-甲基-3-(1-萘氧基)-3-(2-噻吩基)丙胺,其结构经1H NMR,IR和MS表征.     

1-[二-(4-氟苯)甲基]-4-酰基取代哌嗪类衍生物的合成

1-[二-(4-氟苯)甲基]-4-取代哌嗪是一类重要的药物中间体,随着哌嗪环4-位引入不同的取代基可以产生不同的生物活性,如治疗偏头痛药物氟桂利嗪、洛美利嗪,抗氧化剂、钙拮抗剂、癌症治疗中多种抗药性的调节剂(modulator of MDR)等;此外,含有酰基结构单元的哌嗪     

4-N-{2-[4-(2-巯基乙氧基)苯氧基]乙基}-1-N-对甲苯磺酰基哌嗪的合成

以对苄氧基苯酚为原料,经三步反应合成了2-[4-(2-溴乙氧基)苯氧基]乙醇(3); 3与1-对甲苯磺酰基哌嗪反应制得4-N-{2-[4-(2-羟乙氧基)苯氧基]乙基}-1-N-对甲苯磺酰基哌嗪(5);在5上引入乙酰巯基后再经碱性水解,合成了新化合物4-N-{2-[4-(2-巯基乙氧基)苯氧基]乙基}-1-N-对甲苯磺...     

度洛西汀酰基衍生物的合成

抗抑郁药度洛西汀与取代酰氯反应合成了四个新的度洛西汀酰基衍生物——N-取代酰基-N-甲基-3-(1-萘氧基)-3-(2-噻吩基)丙胺,其结构经1H NMR,IR和MS表征。     

手性2-取代哌嗪类药物中间体的合成进展

手性2-取代哌嗪是一类重要的医药中间体,在药物合成领域有着广阔的应用前景。本文概述了当前手性2-取代哌嗪的合成方法。     

1-N-甲基哌嗪基-2-羟基丙胺的合成

以邻苯二甲酰胺为原料,经4步反应合成了1-N-甲基哌嗪基-2-羟基丙胺,其结构经NMR和MS表征,总收率34.3%。     

2-(取代哌嗪-1-甲基)-3-喹啉甲酸乙酯及其衍生物的合成、 表征及晶体结构

以邻硝基苯甲醛为起始原料, 经还原、Friedländer 缩合反应合成2-甲基-3-喹啉甲酸乙酯(2), 2经N-溴代丁二酰亚胺(NBS)溴代得到化合物3, 3再与N-取代哌嗪5a～5p 发生SN2亲核取代反应, 合成一系列2-(取代哌嗪-1-甲基)-3-喹啉甲酸乙酯及其衍生物6a～6p. 它们的结构通过元素分析, IR, 1H NMR, 13C NMR和MS进行了鉴定和表征, 并用X射线衍射法测定了化合物6n的晶体结构.     

N-取代苯基-N′-[6-(2-甲基苯并噻唑)基]脲类化合物的合成

以 2 -甲基苯并噻唑和取代苯胺为原料 ,合成了 7个 N-取代苯基 -N′-[6-( 2 -甲基苯并噻唑 )基 ]脲类新化合物 ,产率分别为 82 .0 % ,88.5% ,87.0 % ,90 .5% ,91 .0 % ,83.5%和 85.0 %。其结构经元素分析、IR和1 H NMR确定。     

N-{4-{N-甲基-N-[2-羟基-3-(2,4-二氧代-1,2,3,4-四氢嘧啶-5-基)氨基]丙基}氨基-3-溴}苯甲酰基-L-谷氨酸二乙酯及其衍生物的合成

报道了N-{4-{N-甲基-N-[2-羟基-3-(2,4-二氧代-1,2,3,4-四氢嘧啶-5-基)氨基]丙基}氨基-3-溴}苯甲酰基-L-谷氨酸二乙酯及其衍生物的简便合成方法. 分别以4-氨基苯甲酸乙酯和4-氨基苯甲酰基-L-谷氨酸二乙酯为起始物, 经甲基化、烯丙基化、溴羟基化、环氧化、开环、脱保护等反应首次合成了6个新型5-取代氨基嘧啶类化合物, 并通过¹H NMR, ¹³C NMR 和MS对其化学结构进行了表征. 初步生物活性结果表明, 苯环侧链的L-谷氨酸酯部分是此类化合物抑制人重组二氢叶酸还原酶的必需结构.     

Synthesis,Bioactivity and Crystal Structure Analysis of 2-(Benzo[d]isothiazol-3-yloxy)-N-(3-cyano-1-(4-fluorophenyl)-1H-pyrazol-5-yl) Acetamide

A novel benzisothiazolin-3-one derivative, 2-(benzo[d]isothiazol-3-yloxy)-N-(3-cyano-1-(4-fluorophenyl)-1H-pyrazol-5-yl) acetamide(8), was synthesized from the initial compound benzo[d]isothiazol-3(2H)-one(BIT) 1 and 4-fluoroaniline 3. The structure of the target compound 8 was determined by elemental analyses, IR and 1H NMR. The single crystals of intermediate compound 6 and the target compound 8 were obtained and determined by X-ray diffraction analysis. The preliminary biological activity was also evaluated and the results showed the target compound exhibited a good anti-microbial activity.     

3-[(2-二甲基氨甲基)环己基]苯基乙酸酯盐酸盐的合成

以盐酸曲马多为起始原料,通过脱羟基,去甲基和乙酰化反应合成了一种新化合物3-[(2-二甲基氨甲基)环己基]苯基乙酸酯盐酸盐,其结构经1H NMR, MS和元素分析表征.     

Synthesis of 2-N-(benzo[b]thiophen-2-yl)benzo and heterofused-1,2,3-triazoles

A novel efficient synthesis of 2-N-(benzo[b]thiophen-2-yl)benzo and heterofused-1,2,3-triazoles was achieved by the diazotisation of 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile and ethyl-2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate and coupling with selected aromatic and heterocyclic amines followed by air oxidation in the presence of cupric acetate.     

Synthesis and Crystal Structure of N-(2-(1-butyl-3-phenylureido)-1H-indol-3-yl)-N-(4-chlorophenyl)benzamide

<正>The title compound N-(2-(1-butyl-3-phenylureido)-1H-indol-3-yl)-N-(4-chloro- phenyl)- benzamide (C_(32)H_(29)ClN_4O_2, M_r = 537.04) was synthesized by a sequential Ugi four com- ponent condensation (4CC)/aza-Wittig/carbodiimide-mediated cyclization, and the structure was characterized by NMR, IR, MS, elemental analysis and X-ray single-crystal diffraction analysis. The crystal belongs to orthorhombic, space group P2_12_12_1 with a = 11.3663(9), b = 13.3248(10), c = 18.7887(15), V = 2845.6(4)~3, Z = 4, D_c = 1.254 mg/m3, μ = 0.170 mm~(-1), F(000) = 1128, the final R = 0.0538 and wR = 0.1187. X-ray analysis reveals that the new five-membered ring (C(14)-C(15)-N(2)-C(16)-C(21)) and the benzene ring (C(16)-C(21)) are nearly coplanar.     

Synthesis and Crystal Structure of N-(1,3,4-Thiadiazol-2-yl)-1-[1-(6-chloropyridin-3-yl)methy]-5-methyl-1H-[1,2,3]triazol-4-carboxamide

The crystal structure of the title compound (C12H10ClN7OS,Mr=335.78) has been determined by single-crystal X-ray diffraction. The crystal is of triclinic,space group P1 with a=8.4093(11),b=9.4430(12),c=11.1454(14),α=95.508(2),β=111.366(2),γ=115.259(2)°,V=711.42(16) 3,Z=2,Dc=1.568 g/cm3,F(000)=344,μ(MoKα)=0.428 mm-1,the final R=0.0476 and wR=0.1243 for 2353 observed reflections (I > 2σ(I)). The dihedral angles between the pyridine and triazole,thiazole and triazole,and pyridine and thiazole rings are 69.2(1),9.2(1) and 72.7(1)o,respectively. Intramolecular C(8)-H(8B)…O(1) and N(5)-H(5A)…N(4) as well as intermolecular C(5)-H(5)…S(1),C(3)-H(3)…N(6) and N(5)-H(5A)…N(1) hydrogen bonds together with weak C-H…π hydrogen-bonding and π-π stacking interactions contribute to the stability of the structure. There is also evidence for significant electron delocalization in the triazolyl system.     

Parallel Solid-Phase Synthesis of disubstituted 3-(1H-benzo[d]imidazol-2-yl)imidazolidine-2,4-diones and 3-(1H-benzo[d]imidazol-2-yl)-2-thioxoimidazolidin-4-ones

A multistep approach to construct novel 3-(1H-benzo[d]imidazol-2-yl)imidazolidine-2,4-diones and 3-(1H-benzo[d]imidazol-2-yl)-2-thioxoimidazolidin-4-ones from commercially available amino acids, amines, and carboxylic acids is described. Coupling of Fmoc-amino acid to resin-bound aminobenzimidazole provided following Fmoc elimination free amine. Treatment of the free amine with 1,1′-carbonyldiimidazole or 1,1′-thiocarbonyldiimidazole furnished the corresponding hydantoins and thiohydantoins via intramolecular cyclization. The desired aminobenzimidazole tethered hydantoins or thiohydantoins were isolated in good yields.     

Synthesis and Crystal Structure of 1-[4-(Pyrimidin-2-yl)piperazin-1-ylmethyl]-1H-benzotriazole

1 INTRODUCTION Based on the reported 1.65 ? high resolution crystal structure of spinach KARI (ketol-acid reduc- toisomerase) complex[1], we obtained 279 molecules with low binding energy toward KARI from MDL/ ACD 3D database searching, using program DOCK 4.0[2]. These potential structures provide further information for the design of new KARI inhibitors, one of novel derivatives of which as the title com- pound has been synthesized. Its crystal structure will provide us more inf…