- Improved stereoselective synthesis of the β-anomer of 1-[3,5-bis-0-(p-chlorobenzoyl)-2-deoxy-D-ribofuranosyl]-5-iodo-2-pyrimidinone
-
The lack of stereochemical control has been a major hurdle in synthesizing β-nucleosides in large scale. This paper reports a study of the effects of different catalysts used in the synthesis of β-nucleosides. The effects of time and temperature on α- and β-anomers are illustrated in this paper. The yield and selectivity of the β-nucleoside have been improved vastly at temperatures between -30 and -40 °C and by using SnCl4 as the catalyst.
- Schure, Ralph,Mar, Aye Aye,Pease, Brian,Jones, Wyeth,Felt, Barb,Iyer, Mani S.
-
-
Read Online
- Radiosynthesis of [18F]-labelled pro-nucleotides (ProtIDes)
-
Phosphoramidate pro-nucleotides (ProTides) have revolutionized the field of anti-viral and anti-cancer nucleoside therapy, overcoming the major limitations of nucleoside therapies and achieving clinical and commercial success. Despite the translation of P
- Cavaliere, Alessandra,Probst, Katrin C.,Paisey, Stephen J.,Marshall, Christopher,Dheere, Abdul K.H.,Aigbirhio, Franklin,McGuigan, Christopher,Westwell, Andrew D.
-
-
- Efficient and selective catalytic N-Alkylation of pyrimidine by ammonium Sulfate?Hydro-thermal carbone under eco-friendly conditions
-
Abstract: An efficient and inexpensive method for the N-alkylation of pyrimidines using ammonium sulfate coated Hydro-Thermal-Carbone (HTC) (AS?HTC) as reused heterogeneous catalyst was developed. The catalyst was characterized by several analytical techniques such as SEM, XRD, and FTIR. The effect of various parameters was studied including catalyst loading, mole ratio, to achieve excellent selectivity and yields in 80–90%. Significantly, the present protocol offers the use of an inexpensive and environmentally friendly catalyst and simple workup. The simplicity of the procedure, excellent yield of the products, and the recyclability of the catalyst are the main advantages of this method. Graphic Abstract: Ammonium sulfate coated Hydro-Thermal-Carbone (HTC) (AS?HTC); an efficient and reused heterogeneous catalyst of the N-alkylation of pyrimidines was developed. Excellent selectivity and yields (80–90%) toward N1-alkylpyrimidines were achieved. Significantly, the present protocol offers the use of an inexpensive and environmentally friendly catalyst and simple workup.[Figure not available: see fulltext.]
- Ait Ali, Mustapha,Belkharchach, Soumia,Ighachane, Hana,Lachgar, Abdessadek,Lazrek, Hassan B
-
-
- HMDS/KI a simple, a cheap and efficient catalyst for the one-pot synthesis of N-functionalized pyrimidines
-
The syntheses of N-Alkylpyrimidine derivatives by reacting pyrimidin-2,4-diones with appropriate alkyl halide under microwave irradiation at 400 W were compared to the conventional synthesis route. These methodologies are regioselective and compatible with numerous substrates and furnish the corresponding N-alkylpyrimidines in good yields using a cheap catalyst HMDS/KI in MeCN. A comparison study between these two different modes of heating was investigated.
- Mansouri, Az-Eddine El,Zahouily, Mohamed,Lazrek, Hassan B.
-
supporting information
p. 1802 - 1812
(2019/05/15)
-
- A solid-supported acidic oxazolium perchlorate as an easy-handling catalyst for the synthesis of modified pyrimidine nucleosides via Vorbrüggen-type N-glycosylation
-
A solid-supported acidic oxazolium perchlorate was investigated as a heterogeneous catalyst in N-glycosylation reactions using silylated modified pyrimidines and an acylated ribose or glucose to afford the corresponding pyrimidine nucleosides. This salt is a nonhygroscopic and stable powder whose activity is comparable to that of 2-methyl-5-phenylbenzoxazolium perchlorate. A reaction with this polymer catalyst can be conducted on a gram scale. Reusability of the solid-supported catalyst was also investigated.
- Basu, Nabamita,Oyama, Kin-ichi,Tsukamoto, Masaki
-
supporting information
p. 1921 - 1924
(2017/04/27)
-
- Synthesis of modified pyrimidine nucleosides via Vorbrüggen-type N-glycosylation catalyzed by 2-methyl-5-phenylbenzoxazolium perchlorate
-
Several acidic azolium salts prepared from oxazole, thiazole, and imidazole derivatives were investigated as catalysts in N-glycosylation reaction using a silylated modified pyrimidine and an acylated ribose or glucose to afford the corresponding pyrimidine nucleoside. Among the salts, 2-methyl-5- phenylbenzoxazolium perchlorate showed the highest catalytic activity. This salt is a nonhygroscopic crystalline compound that shows higher activity than the frequently used trimethylsilyl triflate. Reactions with this salt can be conducted in gram scales.
- Shirouzu, Hiroshi,Morita, Hiroki,Tsukamoto, Masaki
-
supporting information
p. 3635 - 3639
(2014/05/20)
-
- Synthesis and anti-HCMV activity of 1-[ω-(phenoxy)alkyl]uracil derivatives and analogues thereof
-
HCMV infection represents a life-threatening condition for immunocompromised patients and newborn infants and novel anti-HCMV agents are clearly needed. In this regard, a series of 1-[ω-(phenoxy)alkyl]uracil derivatives were synthesized and examined for antiviral properties. Compounds 17, 20, 24 and 28 were found to exhibit highly specific and promising inhibitory activity against HCMV replication in HEL cell cultures with EC50 values within 5.5-12 μM range. Further studies should be undertaken to elucidate the mechanism of action of these compounds and the structure-activity relationship for the linker region.
- Novikov, Mikhail S.,Babkov, Denis A.,Paramonova, Maria P.,Khandazhinskaya, Anastasia L.,Ozerov, Alexander A.,Chizhov, Alexander O.,Andrei, Graciela,Snoeck, Robert,Balzarini, Jan,Seley-Radtke, Katherine L.
-
p. 4151 - 4157
(2013/07/27)
-
- Synthesis and properties of 1-(3′-dihydroxyboryl-2′,3′- dideoxyribosyl)pyrimidines
-
Nucleoside analogues having a boronic acid in place of the 3-hydroxyl group of deoxyribose have been synthesized. The synthesis of 3′-dihydroxyboryl- 2′,3′-dideoxyribose was based on asymmetric homologation of boronic esters with (dihalomethyl)lithium, beginning from a (silyloxymethyl)boronic ester. A change of chiral director is required before introduction of the second stereocenter, and the direct displacement of (S,S)-1,2-dicyclohexyl-1,2- ethanediol by (1S,2S,3R,5S)-pinanediol was used for this purpose. Coupling of the pinanediol ester of the 1-acetoxy-3-dioxyboryl-5-tert-butylsilyloxy deoxyribose analogue with silylated pyrimidine bases was accomplished with trimethylsilyl bromide. The boronic acid nucleoside analogues were not cytotoxic toward Hep G2 (human hepatocarcinoma) cells. Decomposition occurred over a period of several hours at 37 °C, pH 7.4, with liberation of free pyrimidine base.
- Kim, Byung Ju,Zhang, Jinhua,Tan, Shenglan,Matteson, Donald S.,Prusoff, William H.,Cheng, Yung-Chi
-
p. 9349 - 9358
(2013/01/15)
-
- One-flow, multistep synthesis of nucleosides by Bronsted acid-catalyzed glycosylation
-
Nucleosides in flow: A general, scalable method of Bronsted acid-catalyzed nucleoside formation is described. Because of the high reaction temperatures readily available to the flow reaction format, mild Bronsted acids, particularly pyridinium triflates, can be used. A one-flow multistep synthesis of unprotected nucleosides is also reported (see scheme).
- Sniady, Adam,Bedore, Matthew W.,Jamison, Timothy F.
-
supporting information; body text
p. 2155 - 2158
(2011/04/23)
-
- Design, synthesis and biological evaluation of 2′-deoxy-2′, 2′-difluoro-5-halouridine phosphoramidate ProTides
-
We report the synthesis of a series of novel 2′-deoxy-2′, 2′-difluoro-5-halouridines and their corresponding phosphoramidate ProTides. All compounds were evaluated for antiviral activity and for cellular toxicity. Interestingly, 2′-deoxy-2′,2′-difluoro-5-iodo- and -5-bromo-uridines showed selective activity against feline herpes virus replication in cell culture due to a specific recognition (activation) by the virus-encoded thymidine kinase.
- Quintiliani, Maurizio,Persoons, Leentje,Solaroli, Nicola,Karlsson, Anna,Andrei, Graciela,Snoeck, Robert,Balzarini, Jan,McGuigan, Christopher
-
experimental part
p. 4338 - 4345
(2011/09/12)
-
- One-pot synthesis of azanucleosides from proline derivatives stereoselectivity in sequential processes
-
Common amino acid derivatives can be transformed in onestep fashion into N-azanucleosides. The method is a sequential process initiated, by a domino radical decarboxylation/ oxidation reaction; an acyliminium ion is formed as an intermediate and can be trapped by nitrogen bases (purines, pyrimidines, and benzotriazole). The mildness of the reaction conditions and the good, yields obtained make this procedure an interesting alternative to the conventional processes. Good stereoselectivities were obtained with 4-(silyloxy)proline derivatives as substrates.
- Boto, Alicia,Hernandez, Dacil,Hernandez, Rosendo
-
experimental part
p. 3847 - 3857
(2010/09/05)
-
- 2′-Fluorosugar analogues of the highly potent anti-varicella-zoster virus bicyclic nucleoside analogue (BCNA) Cf 1743
-
We report the preparation of 2′-α-F, 2′-β-F and 2′,2′-difluoro analogues of the leading anti-varicella zoster virus (VZV) pentylphenyl BCNA Cf 1743. VZV thymidine kinase showed the highest phosphorylating capacity for the β-fluoro derivative, that retaine
- McGuigan, Christopher,Derudas, Marco,Quintiliani, Maurizio,Andrei, Graciela,Snoeck, Robert,Henson, Geoffrey,Balzarini, Jan
-
scheme or table
p. 6264 - 6267
(2010/08/20)
-
- Synthesis and biological evaluation of carbon-11-labeled acyclic and furo[2,3-d]pyrimidine derivatives of bicyclic nucleoside analogues (BCNAs) for structure-brain uptake relationship study of BCNA tracers
-
We reported earlier on radiolabeled alkoxyphenyl bicyclic nucleoside analogues (BCNAs) as potential positron emission tomography (PET) reporter probes for imaging of varicella zoster virus thymidine kinase (VZV-tk) gene in vivo. Despite their favorable ph
- Chitneni, Satish K.,Balzarini, Jan,Celen, Sofie,Dyubankova, Natalia,Verbruggen, Alfons M.,Bormans, Guy M.
-
p. 159 - 166
(2008/09/19)
-
- One-pot synthesis of acyclic nucleosides from carbohydrate derivatives, by combination of tandem and sequential reactions
-
(Chemical Equation Presented) The design of processes which combine tandem and sequential reactions allows the transformation of readily available precursors into high-profit products. This strategy is illustrated by the one-pot synthesis of acyclic nucle
- Boto, Alicia,Hernandez, Dacil,Hernandez, Rosendo,Alvarez, Eleuterio
-
p. 9523 - 9532
(2008/03/28)
-
- Inhibition of hepatitis B virus (HBV) replication by pyrimidines bearing an acyclic moiety: Effect on wild-type and mutant HBV
-
Chronic hepatitis B virus (HBV) infection remains a major health problem worldwide. The main clinical limitation of a current antiviral drug for HBV, lamivudine, is the emergence of drug-resistant viral strains upon prolonged therapy. A group of 5-, 6-, or 5,6-substituted acyclic pyrimidine nucleosides with a 1-[(2-hydroxyethoxy)methyl] moiety were synthesized and evaluated for antiviral activities. The target compounds were prepared by the reaction of silylated uracils possessing a variety of substituents at the C-5 or C-6 positions or both with 1,3-dioxolane in the presence of potassium iodide and chlorotrimethylsilane by a convenient and single-step synthesis. Among the compounds tested, 5-chloro and 5-bromo analogues possessing an acyclic glycosyl moiety were the most effective and selective antiviral agents in the in vitro assays against wild-type duck HBV (EC50 = 0.4-2.2 and 3.7-18.5 μM, respectively) and human HBV-containing 2.2.15 cells (EC50 = 4.5-45.4 and 18.5-37.7 μM, respectively). These compounds were also found to retain sensitivity against lamivudine-resistant HBV containing a single mutation (M204I) and double mutations (L180M/M204V). The compounds investigated did not show cytotoxicity to host HepG2 and Vero cells, up to the highest concentration tested. The results presented here confirm and accentuate the potential of acyclic pyrimidine nucleosides as anti-HBV agents and extend our previous observations. We herein report the capability of acyclic pyrimidine nucleosides to inhibit the replication of both wild-type and drug-resistant mutant HBV.
- Semaine, Wassila,Johar, Monika,Tyrrell, D. Lorne J.,Kumar, Rakesh,Agrawal
-
p. 2049 - 2054
(2007/10/03)
-
- Nucleophilic substitution at the anomeric position of 1,2-O-isopropylidenefuranose derivatives. A novel stereoselective synthesis of cyclic phosphates analogous to cAMP
-
1,2-O-Isopropylidenefuranose derivatives were treated with various nucleophiles in the presence of either BF3·OEt2 or trimethylsilyl trifluoromethanesulfonate (TMSOTf) leading to substitution products in a regio- and stereoselective
- Romero, Miriam,Hernandez, Luis,Quintero, Leticia,Sartillo-Piscil, Fernando
-
p. 2883 - 2890
(2008/03/27)
-
- Template-directed DNA photoligation via α-5-cyanovinyldeoxyuridine
-
(Chemical Equation Presented) We describe an efficient template-directed photoligation of oligodeoxynucleotides (ODNs) using α-5- cyanovinyldeoxyuridine (αcU). An efficient photoligation was produced by photoirradiation of an ODN containing thymine at the 5′ end with an ODN containing thymine at the 5′ end in the presence of a template ODN. This photoligation method is a new and efficient way to synthesize branched ODNs.
- Ogino, Masayuki,Yoshimura, Yoshinaga,Nakazawa, Akio,Saito, Isao,Fujimoto, Kenzo
-
p. 2853 - 2856
(2007/10/03)
-
- Syntheses and structure-activity relationships of novel apio and thioapio dideoxydidehydronucleosides as anti-HCMV agents
-
On the basis of the fact that apio dideoxynucleosides, in which the furanose oxygen and the C2 of the 2,3-dideoxyribose are transposed, exhibited potent anti-HIV activity and 2′,3′-dideoxy-2′,3′-didehydronucleosides also showed potent anti-HIV activity, we synthesized apio dideoxydidehydronucleosides in which the oxygen atom and the double bond of the 2,3-dideoxy-2,3-didehydroribose are exchanged. The thioapio dideoxydidehydronucleosides were also synthesized since sulfur serves as a bioisostere of oxygen. Apio dideoxydidehydronucleosides 13a-f were synthesized starting from 1,3-dihydroxyacetone, utilizing phenylselenenyl chemistry as a key step. The ratio of the anomeric mixture was variable from 1:1 to 5:1 during the condensation of nucleosidic bases with the phenylselenyl acetate 11 in the presence of a Lewis acid. This is in contrast with other glycosyl donors such as 5-O-(tert-butyldiphenylsilyl)-2-phenylselenenyl-2,3-dideoxyribosyl acetate which shows excellent neighboring group effect (α:β = 1:99). Thioapio dideoxydidehydronucleosides 22a,b were synthesized from the lactone 9 via thiolactone 17 as a key intermediate which was synthesized from dicyclohexylcarbodiimide coupling of the mercapto acid produced from the basic hydrolysis of thioacetate 16. The majority of apio analogues synthesized in this study exhibited moderate to potent anti-HCMV activity, among which the 5-fluorouracil derivative 13c was found to be the most potent against HCMV, while thioapio analogues showed no activity against HCMV. However, all synthesized compounds did not exhibit any significant activities against HIV-1, HSV-1, and HSV-2. The fact that apio dideoxydidehydronucleosides were active against HCMV suggests that the apio dideoxydidehydro sugar moiety can serve as a novel template for the development of new antiviral agents.
- Lak Shin Jeong,Hea Ok Kim,Hyung Ryong Moon,Joon Hee Hong,Su Jeong Yoo,Won Jun Choi,Moon Woo Chun,Lee
-
p. 806 - 813
(2007/10/03)
-
- α-Oligodeoxynucleotides containing 5-propynyl analogs of α-deoxyuridine and α-deoxycytidine: Synthesis and base pairing properties
-
From propyne and 5-iodo-α,2-deoxyuridine, obtained by glycosylation, 5-propynyl-α,2'-deoxyuridine was synthesized following the procedure of Hobbs. One part was then transformed through displacement of its C4-triazolo derivative with ammonia into 5-propyn
- Morvan, Francois,Zeidler, Joanna,Rayner, Bernard
-
-
- Synthesis and reactions of some uracil and 5-halouracil nucleosides of 2-acetamido-2-deoxy-D-glucose
-
Silylated uracils react with 2-acetamido-1,3,4,6-tetra-?-acetyl-2-deoxy-D-glucose (5) under trimethylsilyl trifluoromethanesulfonate catalysis to give the nucleosides 6, 8, 10 and 12, respectively, as well as the diglycoside 14. Deblocking with sodium methoxide in methanol afforded the free nucleosides 7, 9, 11 and 13, respectively. Alternatively, the free nucleosides 11 and 13 were obtained directly by halogenation of 7 with N-bromosuccinimide or iodine monochloride, respectively. The structures of the synthesized compounds were confirmed by their 1H NMR, UV and mass spectra and elemental analyses. Acta Chemica Scandinavica 1997.
- Al-Masoudi, Najim A.,Issa, Fadhel B.
-
p. 958 - 962
(2007/10/03)
-
- Structure-activity relationships of 2'-deoxy-2',2'-difluoro-L-erythro- pentofuranosyl nucleosides
-
Following the recent discoveries that some L-nucleosides are more or equal potent than their D-counterparts, we synthesized 2'-deoxy-2',2'- difluoro-L-erythro-pentofuranosyl nucleosides as potential antiviral agents. The target compounds were synthesized via the key intermediates 7a or 7b from L-gulono γ-lactone. Compound 2 was oxidatively cleaved and coupled with ethyl bromodifluoroacetate in the presence of activated zinc under Reformatsky conditions to obtain a diastereomeric mixture of 4(R) and 4(S), in a 4:1 ratio. The major 4(R) isomer was cyclized and treated appropriately to obtain the mesylate 8a or 8b, which was condensed with various silyl- protected pyrimidines. Condensation of the alcohol 7a or 7b with 6- chloropurine under Mitsunobu conditions afforded the 6-chloropurine analogs 53a or 53b and 54a or 54b. Further treatment of the compounds 53a, 54a and 53b, 54b afforded the inosine and adenine derivatives 57-60, respectively. The condensation of 2-amino-6-chloropurine with compound 8a and subsequent treatment with 2-mercaptoethanol/sodium methoxide afforded the guanine analogs 63 and 64. All of the synthesized nucleosides 31-52, 57-60, 63, and 64 were evaluated for antiviral activity and for cellular toxicity. Adenine derivative 57 showed a moderate activity against HIV-1 in PBM cells (3.4 μM). None of the other compounds showed any significant activities against HIV-1, HBV, HSV-1, HSV-2, and toxicity in Veto, CEM, and PBM cell lines up to 100 μM. The X-ray structure of the 5-iodocytosine analog showed a 2'- exo/3'-endo conformation for the carbohydrate moiety, which is different from those of the biologically active compounds (-)-FTC and L-FMAU.
- Kotra, Lakshmi P.,Xiang, Yuejun,Gary Newton,Schinazi, Raymond F.,Cheng, Yung-C.,Chu, Chung K.
-
p. 3635 - 3644
(2007/10/03)
-
- A facile, alternative synthesis of 4'-thioarabinonucleosides and their biological activities
-
4'-Thioarabinonucleosides, which are potential antiviral agents, were synthesized from D-glucose. 1,4-Anhydro-4-thioarabitol (8), which can be derived from diacetone glucose in nine steps, was subjected to Pummerer rearrangement after protection of the hy
- Yoshimura, Yuichi,Watanabe, Mikari,Satoh, Hiroshi,Ashida, Noriyuki,Ijichi, Katsushi,Sakata, Shinji,Machida, Haruhiko,Matsuda, Akira
-
p. 2177 - 2183
(2007/10/03)
-
- A convenient one-pot synthesis of acyclonucleosides
-
Bis(trimethylsilyl)pyrimidine bases were treated directly with 1,3-dioxolane (or 2-methyl-1,3-dioxolane), chlorotrimethylsilane and a metal iodide, such as KI or NaI, in acetonitrile at room temperature to afford acyclopyrimidine derivatives, including 2-thiopyrimidine derivatives, in good yields. Introduction of an acyclic chain into 2-thiopyrimidine bases, however, necessitated the use of 2 eq of the reagents.
- Ubasawa,Takashima,Sekiya
-
p. 142 - 143
(2007/10/02)
-
- Synthesis and reactions of 1-(5-azido-5-deoxy-3-O-p-toluenesulfonyl-β-D-xylofuranosyl) derivatives of 5-alkyl- and 5-halo-pyrimidines
-
Chemical syntheses of 1-(2-O-acetyl-5-azido--5-deoxy-3-O-p-toluenesulfonyl-β-D-xylofuranosyl)-5-iodo,- -5-fluoro-, and -5-trifluoromethyl-uracil nucleosides (11-13) as well as the thymine analogue 10 were performed from a sugar precursor and the correspon
- Al-Masoudi, Najim A.,Pfleiderer, W.
-
-
- Asymmetric Synthesis and Biological Evaluation of β-L-(2R,5S)- and α-L-(2R,5R)-1,3-Oxathiolane-Pyrimidine and -Purine Nucleosides as Potential Anti-HIV Agents
-
In order to study the structure-acivity relationships of L-oxathiolanyl nucleosides as potential anti-HIV agents, a series of enantiomerically pure L-oxathiolanyl pyrimidine and purine nucleosides were synthesized and evaluated for anti-HIV-1 activity in human peripheral blood mononuclear (PBM) cells.The key intermediate 8 was synthesized starting from L-gulose via 1,6-thiaanhydro-L-gulopyranose.The acetate 8 was condensed with thymine, 5-substituted uracils and cytosines, 6-chloropurine, and 6-chloro-2-fluoropurine to give pyrimidine and purine nucleosides.Upon evaluation of these final nucleosides, the 5-fluorocytosine derivative 51 was found to be the most potent compound among those tested.In the case of 5-substituted cytosine analogues, the antiviral potency was found to be in the following decreasing order: cytosine (β-isomer) > 5-iodocytosine (β-isomer) > 5-fluorocytosine (α-isomer) > 5-methylcytosine (α-isomer) > 5-methylcytosine (β-isomer) > 5-bromocytosine (β-isomer) > 5-chlorocytosine (β-isomer).Among the thymine, uracil, and 5-substituted uracil derivatives, thymine (α-isomer) and uracil (β-isomer) derivatives exhibited moderate anti-HIV activity.In the purine series, the antiviral potency is found to be in the following decreasing order: adenine (β-isomer) > 6-chloropurine (β-isomer) > 6-chloropurine (α-isomer) > 2-NH2-6-Cl-purine (β-isomer) > guanine (β-isomer) > N6-methyladenine (α-isomer) > N6-methyladenine (β-isomer).The cytotoxicity was also determined in human PBM cells as well as Vero cells.None of the synthesized nucleosides was toxic up to 100 μ in PBM cells.
- Jeong, Lak S.,Shinazi, Raymond F.,Beach, J. Warren,Kim, Hea O.,Nampalli, Satyanarayana,et al.
-
p. 181 - 195
(2007/10/02)
-
- Synthesis of some novel 1-(5-thio-β-D-xylopyranosyl)-lumazine and -pyrimidine nucleosides
-
1,2,3,4-tetra-O-acetyl-5-thio-D-xylopyranose (1) reacts with the silylated lumazine bases (2-5) under trimethylsilyl trifluoromethylsulfonate catalysis to give the nucleosides 6, 8, 10, and 12 respectively, which face deblocking with potassium carbonate i
- Al-Masoudi,Pfleiderer
-
p. 7579 - 7592
(2007/10/02)
-
- Novel uracil derivatives: Newly synthesized centrally acting agents
-
A series of 1-amino-5-substituted uracils and their 4-thio or 2,4-dithio substituted analogues were synthesized and assayed for anti-conflict activity in rats and anesthetic activity in mice. 1-Amino-5-halogenouracils 3b-e, 1-amino-4-thiouracil (9a), and 1-amino-5-halogeno-4-thiouracils 9c, d showed both anti-conflict and anesthetic activities. The most active compound was 1-amino-5-chloro-4-thiouracil (9d) which showed anxiolytic activity at 2 mg/kg of oral administration (p.o.) on a modified Geller-Seifter conflict schedule. Its minimum effective dose (MED) was lower than that of diazepam. The 50 percent effective dose (ED50) for anesthetic activity in mice of the compound (9d) was 32.9 mg/kg, p.o.
- Imaizumi,Kano,Sakata
-
p. 1808 - 1813
(2007/10/02)
-
- Asymmetric Synthesis of 1,3-Dioxolane-Pyrimidine Nucleosides and Their Anti-HIV Activity
-
In order to study the structure-activity relationships of dioxolane nucleosides as potential anti-HIV agents, various enantiomerically pure dioxolane-pyrimidine nucleosides have been synthesized and evaluated against HIV-1 in human peripheral blood mononuclear cells.The enantiomerically pure key intermediate 8 has been synthesized in nine steps from 1,6-anhydro-D-mannose (1), which was condensed with 5-substituted pyrimidines to obtain various dioxolane-pyrimidine nucleosides.Upon evaluation of these compounds, cytosine derivative 19 was found to exhibit the most potent anti-HIV agent although it is the most toxic.The order of anti-HIV potency was as follows: cytosine (β-isomer) > thymine > cytosine (α-isomer) > 5-chlorouracil > 5-bromouracil > 5-fluorouracil derivatives.Uracil, 5-methylcytosine, and 5-iodouracil derivatives were found to be inactive.Interestingly, α-isomer 20 showed good anti-HIV activity without cytotoxicity.As expected, other α-isomers did not exhibit any significant antiviral activity. (-)-Dioxolane-T was 5-fold less effective against AZT-resistant virus than AZT-sensitive virus.
- Kim, Hea O.,Ahn, Soon K.,Alves, Antonio J.,Beach, J. Warren,Jeong, Lak S.,et al
-
p. 1987 - 1995
(2007/10/02)
-
- 5-(5-Bromothien-2-yl)-2'-deoxyuridine and 5-(5-Chlorothien-2-yl)-2'-deoxyuridine Are Equipotent to (E)-5-(2-Bromovinyl)-2'-deoxyuridine in the Inhibition of Herpes Simplex Virus Type I Replication
-
2'-Deoxyuridines with a five-membered heterocyclic substituent in the 5-position were synthesized by palladium-catalyzed coupling reactions of 5-iodo-2'-deoxyuridine with the activated heteroaromatics.Further modification of the compound with the 5-thien-
- Wigerinck, P.,Pannecouque, C.,Snoeck, R.,Claes, P.,Clercq, E. De,Herdewijn, P.
-
p. 2383 - 2389
(2007/10/02)
-
- Antiviral Nucleosides. A Stereospecific, Total Synthesis of 2'-Fluoro-2'-deoxy-β-D-arabinofuranosyl Nucleosides
-
A general, total synthesis of (2'-fluoro-2'-deoxy-β-D-arabinofuranosyl)uracils 1a-d is described.A study of the coupling reaction beetwen 3,5-di-O-benzoyl-2-deoxy-2-fluoro-α-D-arabinofuranosyl bromide (7) and silylated pyrimidines 11a-d has resulted in a high overall yield for the five-step stereospecific synthesis of β-nucleosides.
- Howell, Henry G.,Brodfuehrer, Paul R.,Brundidge, Steven P.,Benigni, Daniel A.,Sapino, Chester
-
-
- SYNTHESIS OF 1-(3-HALOTETRAHYDRO-2-FURYL) DERIVATIVES OF URACIL, 5-SUBSTITUTED URACILS, AND CYTOSINE
-
The cis and trans isomers of 1-(3-halotetrahydro-2-furyl) derivatives of uracil, 5-substituted uracils, and cytosine were obtained by alkylation of 2,4-bis(trimethylsilyl) derivatives of uracil, 5-substituted uracils, and cytosine with 2,3-dihalotetrahydrofurans . 2,3'-Anhydro compounds are also formed in the alkylation of 5-halouracil derivatives.The physicochemical properties of the compounds obtained and the antineoplastic activities of the 5-fluorouracil derivatives were studied.
- Kaulinya, L. T.,Lidak, M. Yu.
-
-