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4-羟基香豆素类化合物与4-羟基喹啉酮类化合物是一类重要的有机杂环化合物,因为其良好的生理活性,被广泛应用于抗菌、抗炎、抗HIV、抗肿瘤等药物结构中。 本文用4-羟基香豆素类化合物或4-羟基喹啉酮类化合物作为底物、以硫磺粉(S)为硫源、以碘苯类衍生物作为芳基源,在氯化铜催化作用下合成了3-芳硫基-4-羟基香豆素类化合物和3-芳硫基-4-羟基喹啉酮类化合物。 该方法使用环境友好的硫磺粉为硫源替代有机硫,操作简单、无污染、成本低廉,为该类化合物的绿色合成提供了新的方案。 相似文献
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异黄酮化合物具有心血管活性[1],雌激素活性[2]及抗骨质疏松[3]活性等。3 苯基 4(1H)喹啉酮衍生物是异黄酮化合物的等电子体,文献报道它具有与异黄酮化合物相似的心血管活性[4]和抗肿瘤[5]活性。结构中具有氟原子的化合物大多能改善脂溶性,增强生理活性,且能选择性作用于脑细胞及脑血管;喹诺酮类抗菌药中具有优良抗菌活性的化合物几乎都含有氟原子。我们对含氟的3 苯基 4(1H)喹啉酮类化合物进行了研究。以氟氯苯胺为原料,合成了其7 氯衍生物(化合物A1~A4),及5 氯衍生物(化合物B1~B4),其中7 氯衍生物为主产物,合成路线如下:化合… 相似文献
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异喹啉酮类化合物具有重要药理活性,本文在合成1,2,3,4-四氢-2-苄基异喹啉酮-4衍生物的基础上,参照Hinton方法制备2-异丙基-1,3-二氢-4(1H)异喹啉酮(1),用(1)进一步与芳醛、羟胺、酰氯及苯肼反应得到了相应的衍生物(3a-6e)。 相似文献
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使用廉价易得的邻烯基甲酰苯胺在可见光的诱导下发生自由基环化反应, 以良好至优秀的产率合成了15种2-喹啉酮衍生物. 该方法简单高效、 条件温和、 产率较高, 具有优异的官能团兼容性, 不仅拓展了邻烯基甲酰苯胺参与的新型有机反应, 也为光催化合成喹啉酮类化合物提供了一条新途径. 相似文献
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HIV-1整合酶是病毒复制所必需的三个基本酶之一, 为病毒所特有, 人体无对应的酶, 因此整合酶是理想的抗HIV药物设计的新靶标. HIV-1整合酶催化病毒DNA插入宿主染色体的过程涉及到整合酶与前病毒DNA形成整合前复合物、病毒DNA的3’末端切断和DNA链转移等步骤, 目前研究得最多的HIV-1整合酶抑制剂是抑制链转移反应的芳基二酮酸化合物, 其中的电子等排体衍生物Raltegravir (MK-0518)于2007年10月被美国食品药品管理局(FDA)批准上市, 而GS-9137处于三期临床试验, 此外还有多个处于临床前研究和临床阶段的药物. 根据抑制剂的不同作用机理, 本综述介绍了近年来所报道的HIV-1整合酶抑制剂的结构类型、药效团模型、研究进展及化学合成, 将整合酶抑制剂分为链转移反应抑制剂、整合酶-DNA结合抑制剂、整合酶3’端切除反应抑制剂、非专一性整合酶抑制剂以及多肽类抑制剂等几大类. 其中链转移反应抑制剂结构类型最丰富、发展最快. 整合酶抑制剂的出现丰富了高效抗逆转录病毒疗法(HAART), 为多重抗药性艾滋病患者提供了新的有效的治疗方案. 相似文献
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结构多样的HIV-1整合酶抑制剂:过去、现在和未来 总被引:2,自引:0,他引:2
HIV-1整合酶是逆转录病毒复制的必需酶,它催化病毒DNA与宿主染色体DNA的整合,而且在人类细胞中没有类似物,因此成为治疗艾滋病的富有吸引力和合理的靶标.最近十年,一大批HIV-1整合酶抑制剂被鉴定出来,其中一些化合物显示选择性的抑制HIV-1整合酶和阻断病毒复制的活性,而最有影响的两类抑制剂是含邻苯二酚的多羟基芳环化合物和最近报道的芳基β-二酮酸类化合物.全面综述了用于HIV-1整合酶抑制剂研究以发展抗HIV新药的不同种类的化合物,包括苯并咪唑类衍生物、核苷类、多肽、羟基取代的芳环化合物及二酮酸类化合物等,并阐述了这些化合物中对抑制活性重要的结构特征.同时也介绍了HIV-1整合酶的结构、功能以及HIV-1整合酶抑制剂的设计原理和作用机制. 相似文献
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Niloofar Parizadeh Eskandar Alipour Sepehr Soleymani Rezvan Zabihollahi Mohammad Reza Aghasadeghi 《Phosphorus, sulfur, and silicon and the related elements》2018,193(4):225-231
Novel quinolone derivatives featuring an 1,3,4-oxadiazole ring as a metal-chelating component and a benzyl group base on HIV-1 integrase inhibitors pharmacophore were designed and synthesized. An antiviral assay revealed that most analogues inhibited HIV-1 replication in the cell culture. Our results showed that compounds bearing small alkyl groups as R group were inactive in anti-HIV-1 assay, whereas compounds possessing benzyl or substituted benzyl at the same position showed good anti-HIV activity with the range of 20–57% at 100 μM concentration. Among them, 3-(5-((2-fluorobenzyl)thio)-1,3,4-oxadiazol-2-yl)-8-phenylquinolin-4-(1H)-one (compound 13) showed reasonable cell-based antiviral activity (EC50 = 50 μM) with no considerable cytotoxicity (CC50 > 100 μM) in the cell viability assay, suggesting that it may be amenable to further development for identifying new anti-HIV-1 agents. Docking studies using the later crystallographic data available for PFV integrase corroborate favorable binding to the active site of HIV integrase, providing a basis for the design of more potent analogues. 相似文献
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Winston Yan Wang Jack Ho Wong Denis Tsz Ming Ip David Chi Cheong Wan Randy Chifai Cheung Tzi Bun Ng 《Applied biochemistry and biotechnology》2016,179(7):1202-1212
This study aimed to investigate fragments derived from human and bovine lactoferrins for ability to inhibit nuclear translocation of HIV-1 integrase. It was shown that human lactoferricin, human lactoferrin 1-11, and bovine lactoferrampin reduced nuclear distribution of HIV-1 integrase. Bovine lactoferrampin could inhibit both the activity and nuclear translocation of HIV-1 integrase. Human lactoferrampin, bovine lactoferricin, and bovine lactoferrin 1-11 had no effect on HIV-1 integrase nuclear translocation. Human lactoferrampin which inhibited the activity of integrase did not prevent its nuclear translocation. Human lactoferricin and lactoferrin 1-11 did not inhibit HIV-1 integrase nuclear translocation despite their ability to attenuate the enzyme activity. The discrepancy between the findings on reduction of HIV-1 activity and inhibition of nuclear translocation of HIV-1 integrase was due to the different mechanisms involved. A similar reasoning can also be applied to the different inhibitory potencies of the milk peptides on different HIV enzymes, i.e., nuclear translocation. 相似文献
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[reaction: see text] An alternative to the Friedlander condensation for the synthesis of naphthyridinones and quinolinones has been discovered. Palladium-catalyzed amidation of halo aromatics substituted in the ortho position by a carbonyl functional group or its equivalent with primary or secondary amides leads to the formation of substituted naphthyridinones and quinolinones. 相似文献
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Alves CN Martí S Castillo R Andrés J Moliner V Tuñón I Silla E 《Chemistry (Weinheim an der Bergstrasse, Germany)》2007,13(27):7715-7724
Human immunodeficiency virus type-1 integrase (HIV-1 IN) is an essential enzyme for effective viral replication. Diketo acids such as L-731,988 and S-1360 are potent and selective inhibitors of HIV-1 IN. In this study, we used molecular dynamics simulations, within the hybrid quantum mechanics/molecular mechanics (QM/MM) approach, to determine the protein-ligand interaction energy between HIV-1 IN and L-731,988 and 10 of its derivatives and analogues. This hybrid methodology has the advantage that it includes quantum effects such as ligand polarisation upon binding, which can be very important when highly polarisable groups are embedded in anisotropic environments, as for example in metal-containing active sites. Furthermore, an energy decomposition analysis was performed to determine the contributions of individual residues to the enzyme-inhibitor interactions on averaged structures obtained from rather extensive conformational sampling. Analysis of the results reveals first that there is a correlation between protein-ligand interaction energy and experimental strand transfer into human chromosomes and secondly that the Asn-155, Lys-156 and Lys-159 residues and the Mg(2+) ion are crucial to anti-HIV IN activity. These results may explain the available experimental data. 相似文献
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LI Xue-mei ZENG Cheng-chu NIU Li-ting YAN Hong ZHENG Da-wei ZHONG Ru-gang 《高等学校化学研究》2006,22(6):747-752
IntroductionSubstituted diketo acid derivatives possess a varie-ty of biological properties, such as analgesic[1—3], anti-bacterial[4]as well as anti-inflammatory[3]. Very re-cently, the results of random screening of millions ofcompounds have shown that… 相似文献
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Caiding Xu Lydie Yang Ashok Bhandari Christopher P. Holmes 《Tetrahedron letters》2006,47(28):4885-4888
A general method for the solid phase synthesis of 4-hydroxy quinolinones and subsequent Pd-catalyzed cross coupling to afford 4-substituted quinolinones has been developed. Conversion of support-bound 4-hydroxy quinolinones to 4-tosyl quinolinones and subsequent treatment with alkyl, aryl, benzylzinc halides, or arylboronic acids in the presence of catalytic amount of Pd(PPh3)4 provides 4-alkyl, aryl, or benzyl quinolinones. This method allows for the introduction of alkyl, aryl, and benzyl groups at the 4-position of the quinolinone ring, and is ideal for parallel and combinatorial chemistry library synthesis. 相似文献