共查询到20条相似文献,搜索用时 31 毫秒
1.
Marc M. Greenberg Dong Jin Yoo Brian K. Goodman 《Nucleosides, nucleotides & nucleic acids》2013,32(1-2):33-40
Abstract ABSTRACT C1′ acylated derivatives of 2′-dcoxyuiidinc (1a-c) were synthesised from 1-[3-deoxy-β-D-psieofiiraiiosylliii.acil (6). The acyl group is introduced via the C1′ aldehyde (11). Following nucleophilic addition, the ketones (1a-c) are obtained via periodinane oxidation and desilylation with NH4F. 相似文献
2.
《Nucleosides, nucleotides & nucleic acids》2013,32(6-7):435-447
ABSTRACT A method has been found for the regioselective alkylation of the nitrogen at the 1-position of 2′-deoxyguanosine. This consists in the reaction, in tetrahydrofuran solution, of a fully protected form of dG, namely the 3′5′-O-bis(tert-butyldimethylsilyl)-N 2-dimethylaminomethylene derivative, with an alkyl halide in the presence of cesium carbonate. The yields of these previously unavailable derivatives of 2′-deoxyguanosine range from good to excellent. Confirmation of the structure of these substances comes from a comparison of their spectroscopic properties with those of the known 1-methyl homologue. In particular, the UV spectra of these new derivatives and the known 1-methyl homologue are essentially identical. 相似文献
3.
Shoujun Chen Lijun Sun Keizo Koya Noriaki Tatsuta Zhiqiang Xia Timothy Korbut Zhenjian Du Jim Wu Guiqing Liang Jun Jiang Mitsunori Ono Dan Zhou Andrew Sonderfan 《Bioorganic & medicinal chemistry letters》2013,23(18):5070-5076
A series of N′1,N′3-dialkyl-N′1,N′3-di(alkylcarbonothioyl) malonohydrazides have been designed and synthesized as anticancer agents by targeting oxidative stress and Hsp70 induction. Structure–activity relationship (SAR) studies lead to the discovery of STA-4783 (elesclomol), a novel small molecule that has been evaluated in a number of clinical trials as an anticancer agent in combination with Taxol. 相似文献
4.
From the gene library constructed with the chromosomal DNA of 6-mercaptoguanosine (MGS)-resistant strain Brevibacterium ammoniagenes IPR-1, a DNA fragment which conferred MGS-resistance to the wild-type strain B. ammoniagenes ATCC6872 was cloned. The purF gene encoding 5-phosphoribosyl-1-pyrophosphate amidotransferase was identified from this fragment and its nucleotide sequence was determined. Wild type purF gene was also cloned by polymerase chain reaction using chromosomal DNA of ATCC6872 as the template and its sequence was determined. Two nucleotides, 583 A and 1065 A, of MGS-resistant purF gene had been changed from 583 G and 1065 G by mutagenesis, respectively. Both changes at position 583 and 1065 were proved to be responsible for MGS-resistance by site-directed mutagenesis. 相似文献
5.
Arthur Van Aerschot Jan Balzarini Erik De Clercq Piet Herdewijn 《Nucleosides, nucleotides & nucleic acids》2013,32(5-6):1123-1124
Abstract It has generally proven difficult to synthesize ribonucleosides with sugar modifications at the 3′ position. We now present a practical route for the synthesis of ribonucleosides with a 3′ fluorine substituent. Nucleosides with the xylo configuration were prepared by sugar-base condensation. Tritylation of the unprotected nucleosides gave a mixture of 2′,5′ and 3′,5′ bistritylated nucleosides which were difficult to characterize. Therefore the necessary precursors were synthesized in a step-wise fashion, starting with selective deprotection of the 2′-acyl group, followed by tritylation. This gave the 2′,5′-tritylated xylonucleosides in good yield. Reaction with diethylaminosulfur trifluoride and deprotection with 80 % acetic acid provided the 3′-fluoro-3′-deoxyribonucleosides 1, 2 and 4. The cytidine derivative was synthesized from 1 by reaction with trifluoromethanesulfonic anhydride followed by ammonia. Treatment of 4 with adenosine deaminase yielded 5. 相似文献
6.
Muhammad Azymah Claude Chavis Alain Fruchier Marc Lucas Jean-Louis Imbach 《Nucleosides, nucleotides & nucleic acids》2013,32(9):1607-1620
Abstract Reaction of (±)but-3-en-1,2-diol (3) with ethyl diazoacetate afforded two cyclopropyl compounds (5) and (6). Their relative trans stereochemistry at C-2 and C-3 has been determined by high-field and computational NMR spectroscopy. (±)Trans-1-(1′,5′-dihydroxy-3′,4′-methylenyl-pent-2′-oxy)methyl]thymine (1d) or -cytosine (1b) and (±)trans-9-(1′,5′-dihydroxy-3′,4′-methylenylpent-2′-oxy)-methyl]adenine (la) or -guanine (1c) have been obtained through a regiospecific alkylation procedure and their antiviral evaluation is reported. 相似文献
7.
Alexander A. Krayevsky Natalie B. Tarussova Qing-Yu Zhu Pedro Vidal Ting-Chao Chou Penny Baron 《Nucleosides, nucleotides & nucleic acids》2013,32(2-4):177-196
Abstract A number of nucleoside 5′-hydrogerphosphonates and nucleoside 5′-methylphosphonates were prepared, to study their ability to inhibit replication of HIV-1. Two compounds, the 5′-hydrogenphosphonate of 3′-azido-3′-deoxythymidine (AZT-HP, IVc) and of 3′-deoxy-3′-fluorothymidine (FLT-HP, IVa), exhibit potent anti-HIV-1 activity with selectivity indices similar to or better than those of their parent nucleosides. 相似文献
8.
The first synthesis of 1-deaza-pyridoxal 5′-phosphate (2-formyl-3-hydroxy-4-methylbenzyl phosphate) is described. The chemoenzymatic approach described here is a reliable route to this important isosteric pyridoxal phosphate analogue. This work enables elucidation of the role of the pyridine nitrogen in pyridoxal 5′-phosphate dependent enzymes. 相似文献
9.
Tongchao Liu Wuchen Xie Cong Li Huanming Ren Yudong Mao Guohua Chen Maosheng Cheng Dongmei Zhao Jingkang Shen Jia Li Yubo Zhou Bing Xiong Yue-Lei Chen 《Bioorganic & medicinal chemistry letters》2017,27(22):4960-4963
From a readily available 5-C-Me ribofuranoside, we have realized a reliable route to valuable 5′-deoxy-5′-amino-5′-C-methyl adenosine derivatives at gram scale with confirmed stereochemistry. These adenosine derivatives are useful starting materials for the preparation of 5′-deoxy-5′-amino-5′-C-methyl adenosine derivatives with higher complexity. From one of the new adenosine derivatives, some 5′-deoxy-5′-amino-5′-C-methyl adenosine DOT1L inhibitors were prepared in several steps. Data from DOT1L assay indicated that additional 5′-C-Me group improved the enzyme inhibitory activity. 相似文献
10.
Abstract Two C-1′-branched acyclic thymine derivatives, 1-[2-hydroxy-1-(2-hydroxyethoxy)ethyl]thymine and 1-[3-hydroxy-1-(2-hydroxyethoxy)-propyl]thymine were synthesized by a novel iodine-activated reaction of a tolylthio derivative with ethylene glycol. This synthetic method provides a potentially versatile synthetic entry to C-1′-branched acyclic nucleosides. 相似文献
11.
12.
Sachin S. Chaudhari Ashok B. Kadam Neelima Khairatkar-Joshi Indranil Mukhopadhyay Pallavi V. Karnik Anupindi Raghuram Shobha S. Rao Thamil Selvan Vaiyapuri Dinesh P. Wale Vikram M. Bhosale Girish S. Gudi Ramchandra R. Sangana Abraham Thomas 《Bioorganic & medicinal chemistry》2013,21(21):6542-6553
A novel series of N-aryl-3,4-dihydro-1′H-spiro[chromene-2,4′-piperidine]-1′-carboxamides was identified as transient receptor potential melastatin 8 (TRPM8) channel blockers through analogue-based rational design, synthesis and screening. Details of the synthesis, effect of aryl groups and their substituents on in-vitro potency were studied. The effects of selected functional groups on the 4-position of the chromene ring were also studied, which showed interesting results. The 4-hydroxy derivatives showed excellent potency and selectivity. Optical resolution and screening of alcohols revealed that (R)-(–)-isomers were in general more potent than the corresponding (S)-(+)-isomers. The isomer (R)-(–)-10e (IC50: 8.9 nM) showed a good pharmacokinetic profile upon oral dosing at 10 mg/kg in Sprague–Dawley (SD) rats. The compound (R)-(–)-10e also showed excellent efficacy in relevant rodent models of neuropathic pain. 相似文献
13.
The synthesis of constrained nucleosides has become an important tool to understand the SAR in the interaction between biological and synthetic nucleotides in the context of antisense oligonucleotide therapy. The incorporation of a cyclopropane into a furanose ring of a nucleoside induces some degree of constrain without affecting significantly the steric environment of a nucleoside. Here, we report a new, short and stereocontrolled synthesis of two constrained nucleosides analogues, 1′,2′- methano-2′,3′-dideoxyuridine 9, and the corresponding cytidine analog 12. X-ray crystallography revealed that the furanose ring in the constrained uridine and cytidine analogues was flattened with virtual loss of pseudorotation. The phosphoramidate esters of the novel constrained uridine and cytidine nucleosides, intended as prodrugs, were tested in cell-based assays for viral replication across the herpes virus family and HIV inhibition courtesy of Merck laboratories, Rahway. They were also tested in antiproliferative assays against colorectal and melanoma cell lines. Unfortunately, none of the compounds showed activity in these assays. 相似文献
14.
Hyo-Joong Kim Nicole A. Leal Steven A. Benner 《Bioorganic & medicinal chemistry》2009,17(10):3728-3732
2′-Deoxy-5-methylisocytidine is widely used in assays to personalize the care of patients infected with HIV, hepatitis C, and other infectious agents. However, oligonucleotides that incorporate 2′-deoxy-5-methylisocytidine are expensive, because of its intrinsic chemical instability. We report here a C-glycoside analog that is more stable and, in oligonucleotides, pairs with 2′-deoxyisoguanosine, contributing to duplex stability about as much as a standard 2′-deoxycytidine and 2′-deoxyguanosine pair. 相似文献
15.
Zahid H. Chohan Andrea Scozzafava Claudiu T. Supuran 《Journal of enzyme inhibition and medicinal chemistry》2013,28(4):261-266
Condensation reactions of 1,1"-diacetylferrocene with different heteroaromatic amines such as, 2-amino-1,3,4-thiadiazole, 5-aminotetrazole and 3-amino-1,2,4-triazole to form unsymmetrically 1,1′-disubstituted ferrocenes have been studied. The obtained compounds have been further investigated for their liganding and biological properties upon chelation with Co(II), Cu(II), Ni(II) and Zn(II) metal ions. The synthesized compounds have been characterized by physical, spectral and analytical data and have been screened against pathogenic bacterial strains e.g., Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus, showing moderate activity as antibacterials in vitro. 相似文献
16.
《Bioscience, biotechnology, and biochemistry》2013,77(8):1694-1696
We investigated the activation of transient receptor potential cation channel (TRP) subfamily V, member 1 (TRPV1) and TRP subfamily A, member 1 (TRPA1) by 1′-acetoxychavicol acetate (ACA), the main pungent component in galangal. ACA did not activate TRPV1-expressing human embryonic kidney (HEK) cells, but strongly activated TRPA1-expressing HEK cells. ACA was more potent than allyl isothiocyanate, the typical TRPA1 agonist. 相似文献
17.
Yutaka Kubota Nobuhide Ishizaki Kazuhiro Haraguchi Takayuki Hamasaki Masanori Baba Hiromichi Tanaka 《Bioorganic & medicinal chemistry》2010,18(20):7186-7192
Synthesis of the 4′-ethynyl and 4′-cyano phosphonates 8–11, which mimic the 5′-monophosphate of 4′-branched 2′,3′-didehydro-2′,3′-dideoxy nucleosides, was investigated by employing the 3′,4′-unsaturated nucleosides (13 and 28) as the starting material. The synthesis was initiated by the electrophilic addition of NIS/(EtO)2P(O)CH2OH to these unsaturated nucleosides. After introduction of the 2′,3′-double bond, the 4′-hydroxylmethyl group of the resulting adducts was transformed into the ethynyl or cyano group. While the 4′-cyano phosphonates 9 and 11 were not sufficiently stable to be isolated, the 4′-ethynyl counterparts (8 and 10) were obtained as their mono-ammonium salts. The adenine derivative 8 showed almost comparable anti-HIV-1 activity to that of d4T. 相似文献
18.
Florence Gaudin Françoise Paquet Luc Chanteloup Jean-Marie Beau Nguyen T. Thuong Gérard Lancelot 《Journal of biomolecular NMR》1995,5(1):49-58
Summary In order to examine the internal dynamic processes of the dodecamer d(CGCAAATTTGCG)2, the 13C-enriched oligonucleotide has been synthesized. The three central thymines were selectively 13C-labeled at the C1′ position and their spin-lattice relaxation parameters R(CZ), R(CX,Y), R(HZ→CZ), R(2HZCZ), R(2HZCX,Y) and R(H
infZ
supC
) were measured. Density functions were computed for two models of internal motions. Comparisons of the experimental data
were made with the spin-lattice relaxation rates rather than with the density functions, whose values were altered by accumulation
of the uncertainties of each relaxation rate measurement. The spin-lattice relaxation rates were computed with respect to
the motions of the sugar around the C1′-N1 bond. A two-state jump model between the anti- and syn-conformations with P(anti)/P(syn)=91/9
or a restricted rotation model with Δχ=28° and an internal diffusion coefficient of 30×107 s-1 gave a good fit with the experimental data. Twist, tilt or roll base motions have little effect on 13C1′ NMR relaxation. Simulation of spin-relaxation rates with the data obtained at several temperatures between 7 and 32 °C,
where the dodecamer is double stranded, shows that the internal motion amplitude is independent of the temperature within
this range, as expected for internal motion. Using the strong correlation which exists in a B-DNA structure between the χ
and δ angle, we suggest that the change in the glycosidic angle value should be indicative of a sugar puckering between the
C1′-exo and C2′-endo conformations. 相似文献
19.
G. Cristalli S. Vittori A. Eleuteri R. Volpini E. Camaioni G. Lupidi 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):835-848
Abstract 5, 7-Dichloro-3H-imidazo[4, 5-b]pyridine (4) is a versatile base which can be coupled with a variety of sugar moieties and transformed in a series of 7-alkyl(aryl)amino-derivatives by reacting with the corresponding amines. In this paper synthesis, structure elucidation and ADA inhibitory activity of 2′-deoxyribonucleoside derivatives of N6-substituted 1-deazaapurines are described. 相似文献
20.
Véronique Faivre-Buet Annie Grouiller Gérard Descotes 《Nucleosides, nucleotides & nucleic acids》2013,32(7):1411-1424
Abstract Various routes to the targets 1, 2, 3, 1-deoxy-psicofuranosyl nucleoside analogues related to anti-HIV agents, are reported. Two routes afforded their 6′-benzylated derivatives 9, 10 and 15. Only the epoxide 12 and deoxynucleosides 19 and 22 were able to be deprotected leading in the first case to 16 and its ring opening derivative 17 and in the second case to 20 and to the target 3. 相似文献