共查询到20条相似文献,搜索用时 31 毫秒
1.
Gray JL Almstead JI Gallagher CP Hu XE Kim NK Taylor CJ Twinem TL Wallace CD Ledoussal B 《Bioorganic & medicinal chemistry letters》2003,13(14):2373-2375
Quinolones without the usual 6-fluorine substituent have been recently described as potent antibacterial agents. A series of non-fluorinated analogues of the antibacterial quinolone Levofloxacin were synthesized and tested. 相似文献
2.
Pchelintseva AA Skorobogatyj MV Petrunina AL Andronova VL Galegov GA Astakhova IV Ustinov AV Malakhov AD Korshun VA 《Nucleosides, nucleotides & nucleic acids》2005,24(5-7):923-926
Eight 5-alkynyl-2'deoxyuridines containing different bulky substituents have been prepared and tested against HSV-1 in Vero cells. The compounds show positive antiviral activity. There is no obvious correlation between activity and substituent size. The nature of the linker between uracil and a substituent appears to be more important for antiviral properties: nucleosides containing arylethynyl groups show higher activity. 相似文献
3.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-7):923-926
Eight 5-alkynyl-2′deoxyuridines containing different bulky substituents have been prepared and tested against HSV-1 in Vero cells. The compounds show positive antiviral activity. There is no obvious correlation between activity and substituent size. The nature of the linker between uracil and a substituent appears to be more important for antiviral properties: nucleosides containing arylethynyl groups show higher activity. 相似文献
4.
《Bioorganic & medicinal chemistry》2016,24(21):5158-5161
The antiviral activity of 4-hydroxy-hexahydro-2H-chromenes and 4-fluorine-hexahydro-2H-chromenes with an aromatic substituent, synthesized from monoterpene (−)-verbenone, was studied for the first time. Five of 11 (45 per cent) of 4-hydroxy-hexahydro-2H-chromene-type compounds have been found to exhibit antiviral activity against influenza A virus of subtype H1N1pdm09. Although a portion of active compounds among 4-fluorine-containing series was fewer, just compound 5i that contains a fluorine substituent exhibited more potent anti-influenza activity along with low cytotoxicity. Thus two new promising types of antiviral compounds were identified. 相似文献
5.
Synthesis and antiviral activities of 1,3-oxathiolanyl nucleosides with 5-hydroxymethyl substituent.
M W Chun S P Choi M J Kim C J Bae H R Moon H D Kim L S Jeong 《Nucleosides & nucleotides》1999,18(4-5):615-616
Novel 1,3-oxathiolanyl pyrimidine nucleosides with 5-hydroxymethyl substituent were synthesized starting from D-mannose and evaluated for antiviral activities against HIV-1, HSV type 1,2 and HCMV. 相似文献
6.
Siddiqui A McGuigan C Ballatore C Srinivasan S De Clercq E Balzarini J 《Bioorganic & medicinal chemistry letters》2000,10(4):381-384
A range of polyether para-substituted phosphoramidates were synthesised and found to have substantially elevated aqueous solubilities compared to the underivatised parent prodrug. A 30-fold increase in aqueous solubility could be achieved without a substantial decrease of in vitro activity against HIV-1. Replacement of the aryl (i.e. phenolic) moiety by tyrosine led to a substantial enhancement in aqueous solubility but also to a decrease in antiviral potency. A previously unobserved trend was identified, relating increased aryl substituent steric bulk to decreased antiviral activity. 相似文献
7.
Al-Masoudi NA Al-Soud YA Eherman M De Clercq E 《Bioorganic & medicinal chemistry》2000,8(6):1407-1413
Reaction of the quinolone carboxylic acids 1 and 2 with (2-acetoxyethoxy)methyl chloride 3 in the presence of n-Bu4NI afforded the N-alkylated products 4 and 6, which could be deblocked to the free nucleoside analogues 5 and 7, respectively. The alkylated quinolone carboxylic acids 9 and 10 were obtained by condensation of I and 2 with 1,4-dichlorobut-2-ene 8 in the presence of NaH. Hydrolysis of 9 gave the alcohol 11. Similar treatment of 1 with 8 in the presence of K2CO3 at relatively high temperature furnished 12. Prolonged heating of the ester 13 with 8 in NaH/DMF afforded the conjugated-diene 15. Treatment of 1 and 2 with dimethyl acetylenedicarboxylate 16 furnished the pyrano[4,3-b]quinolones 17 and 18, respectively. Antibacterial and antiviral evaluations of the new products are reported. 相似文献
8.
Sála M Hřebabecký H Leyssen P Dejmek M Dračínský M De Palma AM Neyts J Nencka R 《Bioorganic & medicinal chemistry letters》2012,22(5):1963-1968
We report on the synthesis and the study of the structure-activity relationship of novel 9-norbornyl-6-chloropurine derivatives, which exert selective antiviral activity on the replication of Coxsackievirus B3. In particular, the synthetic approaches towards norbornyl derivatives bearing diverse side chains were studied. The main goal of the study was to determine the influence of the norbornane moiety substitution at positions 5' and 6' on selective antiviral activity with special regard to the liphophilicity profile of the substituent. 相似文献
9.
Kim MJ 《Nucleosides, nucleotides & nucleic acids》2008,27(10):1097-1106
Based on the biological importance of conformationally restricted nucleoside analogues, we have efficiently synthesized 3,6-anhydro sugar moiety with 3-C-hydroxymethyl substituent from 1,2;5,6-di-O-isopropylidene-D-glucose and condensed 15 with silylated nucleobases to afford the bicyclic nucleoside with 3,6-anhydro skeleton as potential antiviral agent. 相似文献
10.
A recently disclosed series of pyrazolo[1,5-a]pyridine inhibitors of herpes virus replication has been closely examined herein for effects of the C3 substituent on antiviral activity. Significant changes in activity are observed by alterations of the heteroatom basicity and orientation of the group at C3. These results in combination with previous studies have served to further elaborate the minimal pharmacophore required for potency of this novel series of antiviral agents. During the course of these studies, several novel synthetic approaches were developed and are described. 相似文献
11.
Stuart Bailey Colin T. Shanks Michael R. Harnden 《Nucleosides, nucleotides & nucleic acids》2013,32(5):565-585
Abstract Novel pyrimidine nucleoside analogues in which the N-1 ribosyl moiety is replaced by a 2,3-dihydroxy-1-methoxypropyl or 3-hydroxy-1-methoxypropyl substituent have been synthesized and tested for antiviral activity. 相似文献
12.
Moon Woo Chun Sung Pil Choi Myong Jung Kim Chol Joon Bae Hyung Ryong Moon Hee-Doo Kim 《Nucleosides, nucleotides & nucleic acids》2013,32(4-5):615-616
Abstract Novel 1,3-oxathiolanyl pyrimidine nucleosides with 5-hydroxymethyl substituent were synthesized starting from d-mannose and evaluated for antiviral activities against HIV-1, HSV type 1,2 and HCMV. 相似文献
13.
Abstract Novel purine nucleoside analogues in which the N-9 ribosyl moiety is replaced by a 2,3-dihydroxy-1-methoxypropyl or 3-hydroxy- 1-methoxy-propyl substituent and their N-7 substituted isomers have been synthesized and tested for antiviral activity. 相似文献
14.
Abstract Novel purine nucleoside analogues in which the N-9 ribosyl moiety is replaced by a 2,3-dihydroxy-1-methoxypropyl or 3-hydroxy-1-methoxypropyl substituent and their N-7 substituted isomers have been synthesized and tested for antiviral activity. 相似文献
15.
Tabarrini O Sissi C Fravolini A Palumbo M 《Nucleosides, nucleotides & nucleic acids》2000,19(8):1327-1336
A new 6-desfluoroquinolone derivative, characterized by the presence of a 6-hydroxyl group instead of the usual fluorine atom at the C-6 position, was synthesized with the aim to better understand the mechanistic role of the C-6 substituent in the quinolone/DNA/DNA-gyrase interaction. The antibacterial activity unambiguously shows that the hydroxyl group is a good substitute for the C-6 fluorine atom, especially against Gram-positive bacteria. On the contrary, it is a very weak inhibitor of the target DNA gyrase, displaying the highest IC50 value observed for all the C-6 substituted analogues. This behaviour could be explained on the basis of its DNA binding properties. 相似文献
16.
Guadalupe Herrera Vicente Aleixandra Amparo Urios Manuel Blanco 《FEMS microbiology letters》1993,106(2):187-191
Abstract We have isolated spontaneous mutant strains of Escherichia coli KL16 showing different levels of nalidixic acid (NAL) resistance. From 40 independent mutants, 36 had gyrA and four had gyrB mutations. Most of the gyrA mutations (30/36) conferred high level NAL resistance. In contrast, the only gyrB mutation that conferred a relatively high level of NAL resistance also determined enhanced susceptibility to quinolones with a piperazinyl substituent at C7 position of the quinolone ring (amphoteric quinolones). This gyrB mutation (denoted gyrB1604 ), jointly with a gyrA mutation (denoted gyrA972 ) which confers a high level of quinolone resistance, were used to construct strain IC2476, carrying the two gyr mutant alleles. The susceptibility of this strain to amphoteric quinolones (pipemidic acid, norfloxacin and ciprofloxacin) was similar to that of the gyrA972 single mutant. This result indicates that the change in GyrA subunit which determines a high level of quinolone-resistance has the capacity to mask the hypersusceptibility to amphoteric quinolones promoted by the GyrB1604 mutant subunit. This capacity was further confirmed by studying the effects of ciprofloxacin (CFX) on gyrase inhibition in the gyrA972 gyrB1604 strain. 相似文献
17.
Combrink KD Gulgeze HB Thuring JW Yu KL Civiello RL Zhang Y Pearce BC Yin Z Langley DR Kadow KF Cianci CW Li Z Clarke J Genovesi EV Medina I Lamb L Yang Z Zadjura L Krystal M Meanwell NA 《Bioorganic & medicinal chemistry letters》2007,17(17):4784-4790
The effect of structural variation of the benzimidazol-2-one ring of RSV fusion inhibitors related to BMS-433771 (1) was examined in conjunction with side chain modifications and the introduction of an aminomethyl substituent at the 5-position of the core benzimidazole moiety. Replacement of the benzimidazol-2-one moiety with benzoxazole, oxindole, quinoline-2-one, quinazolin-2,4-dione and benzothiazine derivatives provided a series of potent RSV fusion inhibitors 4. However, the intrinsic potency of 6,6-fused ring systems was generally less than that of comparably substituted 5,6-fused heterocycles of the type found in BMS-433771 (1). The introduction of an aminomethyl substituent to the benzimidazole ring enhanced antiviral activity in the 6,6-fused ring systems. 相似文献
18.
Shu M Loebach JL Parker KA Mills SG Chapman KT Shen DM Malkowitz L Springer MS Gould SL DeMartino JA Siciliano SJ Salvo JD Lyons K Pivnichny JV Kwei GY Carella A Carver G Holmes K Schleif WA Danzeisen R Hazuda D Kessler J Lineberger J Miller MD Emini EA 《Bioorganic & medicinal chemistry letters》2004,14(4):947-952
Extensive SAR studies in our benzylpyrazole series of CCR5 antagonists have shown that both lipophilic and hydrophilic substituents on the phenyl of the benzyl group increase antiviral potency. However, improvements in pharmacokinetic profiles were generally only observed with more lipophilic substitutions. 4-Biphenyl (51) performed the best in this regard. Highly lipophilic substituents impart undesirable ion channel activity to these CCR5 antagonists. Alkoxy substituents provide a good balance of antiviral activity, pharmacokinetic parameters, and selectivity. Compounds 42b and 42d, containing a 3,4-dimethoxy substituent, are considered the most promising improvements over parent compounds 9. They demonstrate improved antiviral activity while retaining good pharmacokinetic profile and selectivity. 相似文献
19.
Myong Jung Kim 《Nucleosides, nucleotides & nucleic acids》2013,32(10-11):1097-1106
Based on the biological importance of conformationally restricted nucleoside analogues, we have efficiently synthesized 3,6-anhydro sugar moiety with 3-C-hydroxymethyl substituent from 1,2;5,6-di-O-isopropylidene-D-glucose and condensed 15 with silylated nucleobases to afford the bicyclic nucleoside with 3,6-anhydro skeleton as potential antiviral agent. 相似文献
20.
Oriana Tabarrini Claudia Sissi Arnaldo Fravolini Manlio Palumbo 《Nucleosides, nucleotides & nucleic acids》2013,32(8):1327-1336
Abstract A new 6-desfluoroquinolone derivative, characterized by the presence of a 6-hydroxyl group instead of the usual fluorine atom at the C-6 position, was synthesized with the aim to better understand the mechanistic role of the C-6 substituent in the quinolone/DNA/DNA-gyrase interaction. The antibacterial activity unambiguously shows that the hydroxyl group is a good substitute for the C-6 fluorine atom, especially against Gram-positive bacteria. On the contrary, it is a very weak inhibitor of the target DNA gyrase, displaying the highest IC50 value observed for all the C-6 substituted analogues. This behaviour could be explained on the basis of its DNA binding properties. 相似文献