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1.
A summary delineating the large scale synthetic studies to prepare labeled precursors of ribonucleosides-3',4',5',5'-2H4 and -2',3',4',5',5'-2H5 from D-glucose is presented. The recycling of deuterium-labeled by-products has been devised to give a high overall yield of the intermediates and an expedient protocol has been elaborated for the conversion of 3-O-benzyl-alpha,beta-D-allofuranose-3,4-d2 6 to 1-O-methyl-3-O-benzyl-2-O-t-butyldimethylsilyl-alpha,beta-D-ribofuranose-3,4,5,5'-d4 16 (precursor of ribonucleosides-3',4',5',5'-2H4) or to 1-O-methyl-3,5-di-O-benzyl-alpha,beta-D-ribofuranose-3,4,5,5'-d4 18 (precursor of ribonucleosides-3',4',5',5'-2H4). 相似文献
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To develop novel biologically active organic compounds possessing a sugar moiety, a series of 2-phenylsulfonylhydrazono-3-(2',3',4',6'-tetra-O-acetyl-beta-d-glucopyranosyl)thiazolidine-4-one were synthesized via reaction of the thiosemicarbazide with ethyl bromoacetate. Their chemical structures were characterized by (1)H and (13)C NMR spectroscopy, elemental analysis and MS. The bioassay results indicated that some of these compound exhibit moderate fungicidal and herbicidal activities. Furthermore, the effect of various solvents at reflux temperature on the reactions of ethyl bromoacetate with the related thiosemicarbazides was investigated. 相似文献
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Zhao LX Kim TS Ahn SH Kim TH Kim EK Cho WJ Choi H Lee CS Kim JA Jeong TC Chang CJ Lee ES 《Bioorganic & medicinal chemistry letters》2001,11(19):2659-2662
For the development of new anticancer agents, 2,2':6',2"-, 2,2':6',3"- and 2,2':6',4"-terpyridine derivatives were designed and evaluated for their topoisomerase I inhibitory activity and antitumor cytotoxicity. Structure-activity relationship studies indicated that 2,2':6',2"-terpyridine derivatives were highly cytotoxic toward several human tumor cell lines, whereas 2,2':6',3"- and 2,2':6',4"-terpyridine derivatives were potent topoisomerase I inhibitors. 相似文献
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Zhou Y Li LS Dragovich PS Murphy DE Tran CV Ruebsam F Webber SE Shah AM Tsan M Averill A Showalter RE Patel R Han Q Zhao Q Hermann T Kissinger CR Lebrun L Sergeeva MV 《Bioorganic & medicinal chemistry letters》2008,18(4):1419-1424
5-Hydroxy-3(2H)-pyridazinone derivatives were investigated as inhibitors of genotype 1 HCV NS5B polymerase. The structure-activity relationship (SAR) associated with variation of the pyridazinone 2- and 6-substituents is discussed. The synthesis and metabolic stability of this new class of compounds are also described. 相似文献
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Sergeeva MV Zhou Y Bartkowski DM Nolan TG Norris DA Okamoto E Kirkovsky L Kamran R Lebrun LA Tsan M Patel R Shah AM Lardy M Gobbi A Li LS Zhao J Bertolini T Stankovic N Sun Z Murphy DE Webber SE Dragovich PS 《Bioorganic & medicinal chemistry letters》2008,18(11):3421-3426
5-Hydroxy-3(2H)-pyridazinone derivatives were investigated as potent inhibitors of genotype 1 HCV NS5B polymerase focusing on the optimization of their drug metabolism and pharmacokinetics (DMPK) profiles. This investigation led to the discovery of potent inhibitors with improved DMPK properties. 相似文献
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Li LS Zhou Y Murphy DE Stankovic N Zhao J Dragovich PS Bertolini T Sun Z Ayida B Tran CV Ruebsam F Webber SE Shah AM Tsan M Showalter RE Patel R Lebrun LA Bartkowski DM Nolan TG Norris DA Kamran R Brooks J Sergeeva MV Kirkovsky L Zhao Q Kissinger CR 《Bioorganic & medicinal chemistry letters》2008,18(11):3446-3455
5-Hydroxy-3(2H)-pyridazinone derivatives were investigated as inhibitors of genotype 1 HCV NS5B polymerase. Lead optimization led to the discovery of compound 3a, which displayed potent inhibitory activities in biochemical and replicon assays [IC(50) (1b)<10nM; IC(50) (1a)=22 nM; EC(50) (1b)=5nM], good stability toward human liver microsomes (HLM t(1/2)>60 min), and high ratios of liver to plasma concentrations 12h after a single oral administration to rats. 相似文献
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-Methoxy-5-(2',3',4'-trimethoxyphenyl) tropone is an active analog of colchicine, a mitotic spindle inhibitor, which is missing the middle "B" ring. This compound crystallizes in the triclinic system, space group P1, with Z = 2; a = 10.135(2), b = 10.166 (4), and c = 7.863(2) A; alpha = 82.15(3), beta = 103.49(3), and gamma = 107.16(2); degrees and V = 750.7(4) A. The structure was solved by direct methods and refined by full-matrix least-squares to a final R = 0.063, using 2503 observed reflections and 271 parameters. Despite the absence of the middle ring, the conformation of the molecule is similar to that of colchicine, isocolchicine , and their derivatives. The troponoid ring is dissimilar to the phenyl ring in that it is not aromatic and does have alternating short and long bond lengths. The dihedral angle between the least-squares planes of the two rings is -57.4 degrees. Van der Waals surface representations of the analog and colchicine are presented to demonstrate the similarity and differences of these two molecules . The structural information of the analog is consistent with the interpretation of thermodynamic parameters which govern the interactions between brain tubulin and the analog. 相似文献
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对巴西橡胶树(Hevea brasiliensis)新品种云研77-2和云研77-4及其亲本PR107和GT1的染色体进行了细胞学观察,并介绍了它们的育种历程.结果表明:PR107和GT1的染色体数为2n=2x=36,云研77-2和云研77-4的染色体数目为2n=3x=54,均为三倍体;利用特殊父母本建立杂交授粉园获取种子,设定合理的筛选标准在逆境中进行实生筛选是巴西橡胶树新品种选育的有效途径. 相似文献
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Okazaki R Oritani T Hara Y Yamamoto H 《Bioscience, biotechnology, and biochemistry》2001,65(4):943-946
Microbial hydroxylation of (+/-)-(2Z,4E)-5-(1',2'-epoxy-2',6',6'-trimethylcyclohexyl)-3-methyl-2,4-pentadienoic acid (3a) with Cercospora cruenta, a fungus producing (+)-abscisic acid, gave a four-stereoisomeric mixture consisting of (+)- and (-)-xanthoxin acid (4a), and (+)- and (-)-epi-xanthoxin acid (5a) by an HPLC analysis with a chiral column. Screening of the microorganisms capable of oxidizing (+/-)-3a showed that Cunninghamella echinulata stereoselectively oxidized (+/-)-3a to xanthoxin acid (4a) with the some degree of enantioselectivity as (-)-3a to (-)-4a. 相似文献
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Dragovich PS Blazel JK Ellis DA Han Q Kamran R Kissinger CR LeBrun LA Li LS Murphy DE Noble M Patel RA Ruebsam F Sergeeva MV Shah AM Showalter RE Tran CV Tsan M Webber SE Kirkovsky L Zhou Y 《Bioorganic & medicinal chemistry letters》2008,18(20):5635-5639
The synthesis of 4-(1',1'-dioxo-1',4'-dihydro-1'lambda(6)-benzo[1',2',4']thiadiazin-3'-yl)-5-hydroxy-2H-pyridazin-3-ones bearing 6-amino substituents as potent inhibitors of the HCV RNA-dependent RNA polymerase (NS5B) is described. Several of these agents also display potent antiviral activity in cell culture experiments (EC(50)<0.10 microM). In vitro DMPK data (microsome t(1/2), Caco-2 P(app)) for many of the compounds are also disclosed, and a crystal structure of a representative inhibitor complexed with the NS5B protein is discussed. 相似文献
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Zhou Y Webber SE Murphy DE Li LS Dragovich PS Tran CV Sun Z Ruebsam F Shah AM Tsan M Showalter RE Patel R Li B Zhao Q Han Q Hermann T Kissinger CR Lebrun L Sergeeva MV Kirkovsky L 《Bioorganic & medicinal chemistry letters》2008,18(4):1413-1418
5-Hydroxy-3(2H)-pyridazinone derivatives were investigated as inhibitors of genotype 1 HCV NS5B polymerase. The synthesis, structure-activity relationships (SAR), metabolic stability, and structure-based design approach for this new class of compounds are discussed. 相似文献
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An asymmetric synthesis route towards (3S,3'S)-(M,M)-(E)-(+)-1,1',2, 2',3,3',4,4'-octahydro-3,3',7,7'-tetramethyl-4,4'-biphenanthrylidene was developed using the Evans procedure as a key step. The absolute configurations of the title compound and of its parent ketone were determined by CD spectroscopy and could be correlated with the stereochemical results of the asymmetric alkylation. Furthermore, a comparison was made with the known (3R,3'R)-(P,P)-(E)-(-)-1,1',2,2', 3,3',4,4'-octahydro-3,3',7,7'-dimethyl-4,4'-biphenanthrylidene. Finally, the X-ray crystallographic analysis of (3S,3'S)-(M, M)-(E)-(+)-1,1',2,2',3,3',4,4'-octahydro-3,3',7,7'-tetramethyl-4, 4'-biphenanthrylidene is presented. 相似文献
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Lavandera I Fernández S Ferrero M De Clercq E Gotor V 《Nucleosides, nucleotides & nucleic acids》2003,22(5-8):833-836
(E)-3',5'-diamino-5-(2-bromovinyl)-2',3',5'-trideoxyuridine (5), the diamino analogue of BVDU (1), was synthesized from BVDU. In contrast with BVDU, compound 5 did not show activity against herpes simplex virus or varicella-zoster virus. 相似文献
17.
Conformational analysis of (2R,3S,4R)-(+)-3,3',4,4',7-flavanpentol, a flavonoid compound displaying both antioxidant and pro-oxidant properties, is performed by molecular mechanics and density functional theory calculations both in the gas phase and in methanol solution by using the Polarizable Continuum Model. Nine different conformations are identified. Absorption (UV) and circular dichroism (CD) spectra and optical rotations are calculated by means of time dependent density functional theory (TDDFT) and compared with experiments. The effects of a complex environment formed by water and proline-rich peptide molecules on the conformational characteristics of (2R,3S,4R)-(+)-3,3',4,4',7-flavanpentol and therefore on its UV and CD spectra are investigated by atomistic molecular dynamics simulations. 相似文献
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Nicolaou KC Ellery SP Rivas F Saye K Rogers E Workinger TJ Schallenberger M Tawatao R Montero A Hessell A Romesberg F Carson D Burton D 《Bioorganic & medicinal chemistry》2011,19(18):5648-5669
Most nucleosides in solution typically exist in equilibrium between two major sugar pucker forms, N-type and S-type, but bridged nucleosides can be locked into one of these conformations depending on their specific structure. While many groups have researched these bridged nucleosides for the purpose of determining their binding affinity for antisense applications, we opted to look into the potential for biological activity within these conformationally-locked structures. A small library of 2',4'- and 3',4'-bridged nucleoside analogues was synthesized, including a novel 3',4'-carbocyclic bridged system. The synthesized compounds were tested for antibacterial, antitumor, and antiviral activities, leading to the identification of nucleosides possessing such biological activities. To the best of our knowledge, these biologically active compounds represent the first example of 2',4'-bridged nucleosides to demonstrate such properties. The most potent compound, nucleoside 33, exhibited significant antiviral activity against pseudoviruses SF162 (IC(50)=7.0 μM) and HxB2 (IC(50)=2.4 μM). These findings render bridged nucleosides as credible leads for drug discovery in the anti-HIV area of research. 相似文献
20.
Non-covalent interaction of 2', 4', 5', 7'-tetrabromo-4, 5, 6, 7-tetrachlorofluorescein with proteins and its application 总被引:1,自引:0,他引:1
The interactions of 2', 4', 5', 7'-tetrabromo-4, 5, 6, 7-tetrachlorofluorescein (TBTCF) with BSA, ovalbumin (OVA) and poly-L-lysine (PLYS) at pH 3.70 have been investigated by combination of the spectral correction technique and the Langmuir isothermal adsorption. The active connection actions such as ion pairs, van der Waals' force, hydrogen bond, hydrophobic bond were proposed to explain the non-covalent interaction between TBTCF and BSA, OVA and PLYS. Effects of the electrolyte and high temperature indicated that union of the active connections between TBTCF and BSA and OVA was too firm to be destroyed. The relationship between the binding number of TBTCF and variety fraction of the amino acid residues was analyzed. The binding number of TBTCF depended on the number of positively charged amino acid residues. The other amino acid residues surrounded and seized TBTCF by hydrogen bonds and hydrophobic bonds when the electrostatic attraction pulled TBTCF to link protein. In addition, a novel method named the absorbance ratio difference was established for determination of protein in trace level and was applied with much higher sensitivity than the ordinary method. 相似文献