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1.
目的合成一种一端为胺基一端为羟基的异双官能团聚乙二醇衍生物(NH2-PEG-OH)。方法以聚乙二醇为原料,采用氧化银和碘化钾催化系统催化聚乙二醇单磺酰化,通过氨基化反应将磺酰基转化为胺基,TLC、IR、1H-NMR等方法对产物结构进行表征。结果制备的产物与目标分子的结构相吻合,产率64.63%。结论本合成方法选择性高、操作简便,可用来制备更多的异双官能团聚乙二醇衍生物。  相似文献   

2.
目的研究抗肿瘤药物卡巴他赛的合成新方法。方法以10-脱乙酰基巴卡亭(10-DAB)和苯基异丝氨酸甲酯为原料,经过10-DAB的双甲基化、苯基异丝氨酸甲酯保护、酯解、酯化偶联、脱保护得到关键的中间体,最后再经Boc反应得到目标产物卡巴他赛。结果与结论以商品化的原料开始,共经7步反应得到卡巴他赛,总收率达到41.5%(以10-DAB计),纯度99%以上。部分中间体结构经~1H-NMR、~(13)C-NMR及HRMS表征。该合成路线操作简单、纯化方便、避免柱色谱分离,适合规模化生产。  相似文献   

3.
目的制备一种新型聚乙二醇化重组人生长激素(PEG-(rhGH)2),并对其理化性质及药理作用进行研究。方法以分子质量为2×104u的聚乙二醇二丙醛(PEG-(ALD)2)对重组人生长激素(rhGH)进行修饰,采用Sephacryl S-200凝胶过滤色谱、Q Sepharose FF离子交换色谱对修饰产物进行分离纯化,SDS-PAGE鉴定各组分,通过SEC-HPLC、IEF、MALDI-TOF-MS等方法对目标产物进行分析,并采用去脑垂体大鼠模型研究其体内生物活性与长效作用。结果获得了一种新型聚乙二醇化重组人生长激素(PEG-(rhGH)2)。其纯度质量分数达到97%以上,等电点为5.27,分子质量为6.6×104u。与未修饰的rhGH相比,PEG-(rhGH)2具有高效、长效的促进机体生长的药理作用。结论新型聚乙二醇化重组人生长激素PEG-(rhGH)2是一种具有开发前景的长效蛋白质药物,值得进一步深入研究。  相似文献   

4.
目的合成β-环糊精聚乙二醇羟基喜树碱高聚物(β-CD-PEG-HCPT)并研究其载药量。方法以β-环糊精和4-4′联苯二磺酰氯为起始原料,通过酰化反应、碘代反应、取代反应、酰化反应得到聚乙二醇-β-环糊精(β-CD-PEG)。采用羟基喜树碱(HCPT)为起始原料,利用乙酰基对10位羟基进行保护,再利用二氯甲烷/甲醇/乙酰氯这种温和的系统脱去乙酰基,得到乙酰羟基喜树碱甘氨酸酯(Ac-HCPT-Gly)。β-CD-PEG和Ac-HCPT-Gly反应得到目标产物β-CD-PEG-HCPT。结果合成了目标产物β-CD-PEG-HCPT,其结构通过1H-NMR确证。HCPT的载药量是4.3%。结论改进了β-CD-PEG-HCPT的合成工艺,操作简单、成本低、收率较高。  相似文献   

5.
目的改进抗肿瘤药物卡巴他赛的合成方法。方法以10-去乙酰基巴卡亭Ⅲ(10-DABⅢ)为起始原料,经过双甲醚化、酯化偶联、脱保护3步反应制得目标产物。结果与结论采用不同保护基的C-13侧链对酯化偶联反应具有重要的影响;确定了一条实用的制备卡巴他赛的合成路线,3步反应总收率达到41.7%(以10-DABⅢ计)。目标产物的结构经1H-NMR和MS谱确证。该合成路线适于批量合成。  相似文献   

6.
目的提高长效胸腺五肽(mPEG(10kD)-TP5)——定位单链聚乙二醇化修饰的胸腺五肽的合成产率。方法选用Fmoc-Tyr(tBu)-Wang树脂和Fmoc/t-Butyl策略完成所有氨基酸的缩合,三氟乙酸对Wang树脂、侧链切割脱除。在碱性条件下,单甲氧基聚乙二醇修饰物(mPEG(10kD)-SPA)定点连接到赖氨酸的侧链氨基(ε-NH2)上。中间产物经钯碳催化氢化,得到mPEG(10kD)-TP5。结果目标产物总收率为20%,新合成路线比我们之前报道的方法产率提高了10倍。结论路线操作简单,易于纯化,产率较高。  相似文献   

7.
目的 改进威罗菲尼的合成工艺.方法 以2,6-二氟苯甲酸(2)为起始原料,经硝化、羧基保护、硝基还原、磺酰胺化、水解反应得到中间体9;5-溴-1H-吡咯并[2,3-b]吡啶与4-氯苯硼酸经Suzuki偶联反应得到中间体12;中间体9与12发生Friedel-Crafts酰基化反应得到目标产物威罗菲尼.结果 与结论本合成...  相似文献   

8.
目的研究gedatolisib的合成工艺。方法以三聚氯氰为起始原料,依次经取代、Suzuki偶联、异氰酸酯成脲、水解、缩合等5步反应得到目标化合物。结果与结论该合成路线总收率达43.6%(以三聚氯氰计),各步反应条件温和,操作简便,生产成本降低,为中试放大奠定基础。  相似文献   

9.
由马来酸酐、6 氨基正己酸及单甲氧基聚乙二醇为原料合成马来酸酐 6 氨基己酸 mPEG酯,用于蛋白质巯基的修饰。对原料的反应比例、柱层析洗脱剂等进行了研究。通过熔点测试、红外光谱分析、1H NMR鉴定和紫外扫描等对中间产物及终产物进行了初步结构鉴定,并以SDS PAGE分析活化mPEG修饰溶菌酶的情况。结果:建立了较简便的合成及分离纯化马来酸酐 6 氨基己酸 mPEG酯的方法。mal sac mPEG的熔点为 55~56℃,紫外吸收光谱在320 nm出现特征吸收峰,红外光谱有典型的特征吸收峰。活化mPEG可修饰溶菌酶。  相似文献   

10.
目的:合成磷酸二酯酶3B(PDE3B)选择性抑制剂N-羟乙基-2-(3′-硝基联苯基-4-亚甲磺酰基)乙酰胺。方法:以对溴苄溴为初始原料经Williamson成醚反应、氧化、酰化和Suzuki偶联4步反应合成了目标化合物。结果:目标产物的结构经核磁共振氢谱、碳谱、质谱及红外光谱等确证,4步反应的总收率为24.8%。结论:该合成路线原料易得,操作简便,可用于放大制备。  相似文献   

11.
甲磺酸伊马替尼有关物质的合成   总被引:1,自引:0,他引:1  
为了控制甲磺酸伊马替尼产品质量,分别合成了质量标准所载的5种有关物质:4-[(哌嗪-1-基)甲基]-N-[4-甲基-3-[ [4- (3-吡啶基)嘧啶-2-基]氨基]苯基]苯甲酰胺(A),4-[(4-甲基-1,4-二氧化哌嗪-1-基)甲基]-N-[4-甲基-3-[ [4- (3-吡啶基)嘧啶-2-基]氨基]苯基]苯甲酰胺(B),4-[(4-甲基-1-氧化哌嗪-1-基)甲基]-N-[4-甲基-3-[ [4- (3-吡啶基)嘧啶-2-基]氨基]苯基]苯甲酰胺(C),4-[ (4-甲基-4-氧化哌嗪-1-基)甲基]-N-[4-甲基-3-[ [4- (3-吡啶基)嘧啶-2-基]氨基]苯基]苯甲酰胺(D)和1,4-双[4-[4-甲基-3-[ [4- (3-吡啶基)嘧啶-2-基]氨基]苯基]氨甲酰基]苄基哌嗪(E),并经1H NMR、MS等确证结构.  相似文献   

12.
A series of 5-((3-(2-oxo-2H-chromen-3-yl)-1-phenyl-1H-pyrazol-4-yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-trione (4af) and dihydro-5-((3-(2-oxo-2H-chromen-3-yl)-1-phenyl-1H-pyrazol-4-yl)methylene)-2-thioxopyrimidine-4,6(1H,5H)-dione (5af) derivatives were synthesized by the condensation of 3-(2-oxo2H-chromen-3-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde (3af) with barbituric acid and thiobarbituric acid in acetic acid under microwave irradiation method. The newly synthesized compounds were evaluated for their antibacterial activity against Bcillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeoginosa, and Klebsiella pneumoniae. All the compounds were found to be moderately active against used microorganisms, whereas compounds (4d) and (4e) exhibited good antifungal activity against Aspergillus niger.  相似文献   

13.
Zaleplon is a pyrazolopyrimidine derivative and possesses sedative and hypnotic properties. Seven unknown impurities in zaleplon bulk drug at levels below 0.1% were detected by reverse-phase high performance liquid chromatography (HPLC). The starting material, 3-amino-4-cyanopyrazole and an intermediate, N-[3-[3-(dimethylamino)-1-oxo-2-propenyl]-phenyl]-N-ethylacetamide (DOPEA) were also present in the sample at a level below 0.1%. The molecular weights of impurities were determined by LC-MS analysis. These impurities were isolated from crude samples of zaleplon using reverse-phase preparative HPLC. Based on the spectral data the structures of these impurities were characterized as, N-(3-(3-(4-amino-2H-pyrazolo [3,4-d]pyrimidin-6-yl) pyrazolo[1,5-a] pyrimidin-7-yl)phenyl)-N-ethylacetamide (impurity I); N-[3-(3-carboxamidopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-N-ethylacetamide (impurity II); N-[3-(3-cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]acetamide (impurity III); N-[3-(3-cyanopyrazolo [1,5-a]pyrimidin-7-yl)phenyl]-N-methylacetamide (impurity IV); N-[3-(3-cyanopyrazolo[1,5-a] pyrimidin-5-yl)phenyl]-N-ethylacetamide (impurity V); N-[3-(3-cyanopyrazolo[1,5-a] pyrimidin-7-yl)phenyl]-N-ethylamine (impurity VI); N-[3-(3-cyano-6-[(E)-3-((N-ethyl-N-acetyl)amino)phenyl-3-oxoprop-1-enyl] pyrazolo[1,5-a]pyrimidin-7-yl) phenyl]-N-ethylacetamide (impurity VII). Structural elucidation of all impurities by spectral data ((1)H NMR, (13)C NMR, MS and IR) and formation of these impurities are discussed in detail.  相似文献   

14.
Bidentate chelators such as hydroxypyridinones and hydroxypyranones are highly iron selective. The synthesis of two novel fluorescent probes N-[2-(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)ethyl]-2-(7-methoxy-2-oxo-2H-chromen-4-yl)acetamide (CP600) and N-[(3-hydroxy-6-methyl-4-oxo-4H-pyran-2-yl)methyl]-2-(7-methoxy-2-oxo-2H-chromen-4-yl)acetamide (CP610) is reported. The method involves coupling the bidentate ligands, 3-hydroxypyridin-4-one and 3-hydroxypyran-4-one, with the well-characterised fluorescent probe methoxycoumarin. Fluorescence emission of both probes at 380 nm is readily quenched by Fe(3+). The fluorescence was quenched to a greater extent by Fe(3+) than by Mn(2+), Co(2+), Zn(2+), Ca(2+), Mg(2+), Na(+) and K(+) and to approximately the same extent as Cu(2+). Comparison of the fluorescence-quenching ability by a range of metal ions on CP600 and CP610 and the hexadentate chelator, calcein, under in-vitro conditions, demonstrated advantages of the two novel fluorescent probes with respect to both iron(III) sensitivity and selectivity. Chelation of iron(III) by CP600 and CP610 leads to the formation of a complex with a metal-to-ligand ratio of 1:3. Fluorescence is quenched on formation of such complexes. These probes possess a molecular weight less than 400 and thus they are predicted to permeate biological membranes by passive diffusion, and have potential for reporting intracellular organelle labile iron levels.  相似文献   

15.
Pharmaceutical Chemistry Journal - The anticonvulsant activity of hydroxycoumarin derivatives and 4-[(3-nitro-2-oxo-2H-chromen-4-yl)amino] butanoic acid was studied using nicotine and corazole...  相似文献   

16.
Reaction of ethyl-6-methyl-2-oxo-4-aryl-1,2,3,4-tetrahydropyrimidin-5-carboxylates (1a-i) with hydrazine hydrate yielded 6-methyl-2-oxo-4-aryl-1,2,3,4-tetrahydropyrimidin-5-carbohydrazides (2a-i). These products, on reaction with cyanogen bromide, gave 5-(5-amino-1,3,4-oxadiazol-2-yl)-6-methyl-4-aryl-3,4-dihydropyrimidin-2 (1H)-ones (3a-i). The resultant aminooxadiazolylpyrimidinones were condensed with isatin to obtain various 3-{[5-(6-methyl-4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidin-5-yl)-1,3,4-oxadiazol-2-yl]-imino}-1,3-dihydro-2H-indol-2-ones (4a-i). These products were characterized by IR, 1H NMR, mass spectra and elemental analysis. Products (4a-i) revealed promising antibacterial, antifungal and antioxidant activity.  相似文献   

17.
2-[2-(3-Methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)-2-oxoethyl]-2H-1,4-benzoxazin-3(4H)-one (3) was obtained starting from methyl-(3,4-dihydro-3-oxo-2H-1,4-benzoxazin-2-yl) acetate (1) through the corresponding hydrazide (2). Condensation of (3) with different aromatic aldehydes under Knoevengel condensation afforded 2-{2-[3-methyl-4-(2-methylbenzylidine)-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]-2-oxoethyl}-2H-1,4-benzoxazin-3(4H)-ones (4ak). The structures of the compounds were determined by FT-IR, 1H NMR, 13C NMR, mass spectral data, and elemental analysis. All the synthesized compounds were screened for their in vitro antimicrobial and antioxidant studies.  相似文献   

18.
This paper outlines the synthesis of selected acid mimics of the non-peptide CCK-B selective antagonist CI-988, 1. CCK-B and CCK-A binding affinities of these analogues are described and their CCK-B affinity and selectivity rationalized by consideration of the pK(a) values, charge distribution, and geometry of the respective acid mimics. Several of the compounds have CCK-B binding affinities similar to the parent carboxylic acid 1 (CCK-B, IC50 = 1.7 nM; pK(a) = 5.6) and span a pK(a) range of less than 1 (sulfonic acid 27) to greater than 9.5 (5-thio-1,2,4-triazole 24). Among the more active compounds synthesized are tricyclo[3.3.1.1(3,7)]dec-2-yl [R-(R*,R*)]-[2-[[2-[[(3-hydroxy-5-isoxazolyl)acetyl]-amino]-2- phenylethyl]amino]-1-(1H-indol-3-ylmethyl)-1-methyl-2-oxoethyl+ ++]carbamate (15), tricyclo[3.3.1.1(3,7)]dec-2-yl [R-(R*,R*)]-[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[[2-[(1-oxo- 3-sulfopropyl)amino]-2-phenylethyl]amino]-ethyl]carbamate, monosodium salt (27), and tricyclo[3.3.1.1(3,7)]dec-2-yl [R-(R*,R*)]-[1-(1H-indol-3-ylmethyl)-1- methyl-2-oxo-2-[[2-[[(1H-1,2,4-triazol-5-ylsulfinyl)acetyl]a mino]-2-phenylethyl]amino]ethyl]carbamic acid (34) which have CCK-B binding affinities of IC50 = 2.6, 1.3, and 1.7 nM, CCK-A/-B ratios of 650, 780, and 550 and pK(a) values of 6.5, less than 1, and 7.0, respectively.  相似文献   

19.
In an attempt to circumvent resistance to and toxicity of clinically used folate-based thymidylate synthase (TS) inhibitors that require folylpoly-gamma-glutamate synthetase (FPGS) for their antitumor activity, we designed and synthesized two classical 6-5 ring-fused analogues, N-[4-[(2-amino-6-methyl-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)thio]-2'-fluorobenzoyl]-l-glutamic acid (4) and N-[4-[(2-amino-6-methyl-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)thio]-2'-chlorobenzoyl]-l-glutamic acid (5), as TS inhibitors and antitumor agents. The key intermediates in the synthesis of these classical analogues were the mercaptans 10 and 11, which were obtained from the corresponding nitro compounds 6 and 7 respectively, by reduction of the nitro groups followed by diazotization of the amines. The syntheses of analogues 4 and 5 were achieved via the oxidative addition of the sodium salt of ethyl 2-halo-substituted-4-mercaptobenzoate (16 or 17) to 2-amino-6-methyl-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidine (18) in the presence of iodine. The esters obtained from the reaction were deprotected and coupled with diethyl-l-glutamate followed by saponification. Compounds 4 and 5 were both more potent inhibitors of human TS (IC(50) values of 54 and 51 nM, respectively) than were PDDF and the clinically used ZD1694 and LY231514. Compounds 4 and 5 were not substrates for human FPGS up to 250 muM. In addition, 4 and 5 were growth inhibitory against CCRF-CEM cells as well as a number of other tumor cell lines in culture, and protection studies established TS as the principal target of these analogues.  相似文献   

20.
A series of some derivatives of 2-xanthone was synthesized and evaluated for their activity against M. tuberculosis in primary and/or secondary microbiological assays. The cytotoxic activity of some compounds was also evaluated. The most active compounds were: [I] 2-(2-(4-(2-(4-chloro-3-methylphenoxy)ethyl)piperazin-1-yl)ethoxy)-9H-xanthen-9-one, [III] 2-((4-(2-(4-chlor-3-methylphenoxy)ethyl)piperazin-1-yl)methyl)-9H-xanthen-9-one dihydrochloride and [XVIII] ethyl 4-(2-hydroxy-3-(9-oxo-9H-xanthen-2-yloxy)propyl) piperazine-1-carboxylate, which displayed 98%, 98% and 94% inhibition of M. tuberculosis growth, respectively. Furthermore, compounds III and XVIII revealed their cytotoxic activity (SI < 1). Other structures varied greatly in their anti M. tuberculosis activity, however, several trends in their structure in relation to their antituberculous activity have been observed.  相似文献   

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