A series of novel acyclic nucleosides. IV. Synthesis of N1-sulfur analogues of acycolvir, directed toward improved antiviral activities.

Kaneko, Chisato; Hara, Shinjiro; Matsumoto, Hisakazu; Takeuchi, Tadao; Mori, Takeo; Ikeda, Kazuyoshi; Mizuno, Yoshihisa

doi:10.1248/cpb.39.871

Cited by 15 publications

(12 citation statements)

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“…Melting points were determined on a Yanagimoto micromelting point apparatus and are uncorrected. 1 H and 13 C NMR were recorded on JEOL JNL-GX270 (270 M Hz) and EX400 (400 MHz) spectrometers with Me4Si as the internal standard. Spectra were taken in DMSO-d6, and the chemical shifts are reported in parts per million (δ).…”

Section: Methodsmentioning

confidence: 99%

“…Previously, we described the synthesis of a variety of 5-substituted imidazo [1,5-a]thiazin-7(3H)-ones, e.g., the base moiety of 6-thiaoxanosine (1), as potential antiviral and anticancer agents. 1,2 During our attempts to synthesize the base moiety of 5-vinyl-7-thione analogue of 1, namely, 5-ethenylimidazo [4,5-d] [1,3]thiazin-7(3H)thione (3), via 2 by the known cyclization procedure (Chart 1), we unexpectedly discovered an interesting ring-closure reaction which led to the synthesis of imidazo [1,5-a]pyrimidin-2(1H)-ones.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis of 2,8-Disubstituted Imidazo[1,5-a]pyrimidines with Potent Antitumor Activity

et al. 1999

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Seventeen 1,2,3,4-tetrahydroimidazo[1,5-a]pyrimidine derivatives bearing electron-withdrawing substituents were designed and synthesized by novel ring closure as potential antitumor agents. They were screened for their activities against mouse leukemia L1210 and human oral epidermoid carcinoma KB cell lines, and relationships of structure and antitumor activity in vitro are discussed. It was found that 8-thiocarbamoyl-1,2,3,4-tetrahydroimidazo[1, 5-a]pyrimidin-2(1H)-thione (8c) exhibited activity comparable to that of 5-fluorouracil against both L1210 and KB cells. The existence of both 2-thioxo and 8-substituent with a thioxo group in the molecule is crucial for the cytotoxicity against L1210 and KB cells. A novel procedure for introduction of a double bond between C-3 and C-4 in 8c was developed. Introduction of the 3,4-double bond increased the activity against L1210, but against KB cells the activity decreased by 4-fold. Cytotoxicity of compounds 8c and 8-thiocarbamoyl-1,2-dihydroimidazo[1,5-a]pyrimidin-2(1H)-thione (11c) against human solid tumor and leukemia cell lines was further evaluated. The saturation of the 3,4-double bond led to a significant increase in cytotoxicity against tumor cell lines tested.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis of 2,8-Disubstituted Imidazo[1,5-a]pyrimidines with Potent Antitumor Activity

et al. 1999

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“…Vicentini et al described a reaction of trichloromethyl chloroformate with N -(1-alkyl/aryl-5-pyrazolyl)thiocarboxamides and N -(3-methyl-5-pyrazolyl)thiobenzamide in which pyrazolo[3,4- d ][1,3] thiazin-4-ones or pyrazolo[1,5- c ][1,3,5]thiadiazine-4-one were obtained, respectively [ 27 ]. Imidazo[4,5- d ][1,3]thiazine-7(3 H )-thiones were prepared from 5(4)-substituted amino-4(5)-ethoxycarbonyl-1(3 H )-imidazoles with the Lawesson reagent [ 28 ]. They were designed as acyclovir analogues but exhibited weak biological properties [ 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

“…Imidazo[4,5- d ][1,3]thiazine-7(3 H )-thiones were prepared from 5(4)-substituted amino-4(5)-ethoxycarbonyl-1(3 H )-imidazoles with the Lawesson reagent [ 28 ]. They were designed as acyclovir analogues but exhibited weak biological properties [ 28 , 29 ]. Other derivatives showed antibacterial [ 30 ] or fungicidal activity [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, characterization, and pharmacological evaluation of novel azolo- and azinothiazinones containing 2,4-dihydroxyphenyl substituent as anticancer agents

et al. 2015

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We reported the synthesis and characterization of a series of azolo- and azino[1,3]thiazinones containing the 2,4-dihydroxyphenyl substituent. The compounds were prepared by a new one-step reaction of aryl-modified sulfinylbis[(2,4-dihydroxyphenyl)methanethione]s and the corresponding aminoazolo(azino)carboxamides. Their chemical structures were confirmed by IR, NMR: 1H, 13C, HSQC, and EI-MS spectral data. The compounds inhibited proliferation and viability of lung cancer A549, colon cancer HT-29, and glioma C6 cells in a structure- and concentration-dependent manner. The activity of some analogues was below 10 μmol dm−3 (IC50). Glioma C6 cells were the most sensitive to tested compounds. Generally, the derivatives were not toxic for the skin fibroblast HSF culture. Moreover, some of them exerted a protective effect on the treated normal cells. Evaluation of compound properties in silico showed that they possess significant drug-like characteristics and most of them display a low toxicity.Graphical abstract

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Synthesis Of Nucleosides

Vorbrüggen¹,

1999

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This chapter deals with the synthesis of nucleosides (e.g., the formation of N ‐glycosides of sugars such as D ‐ribose or 2‐deoxy‐D‐ribose with heterocyclic nitrogen bases). The methods of nucleoside synthesis have been treated in a number of reviews and monographs. It is now generally accepted that nucleosides were among the first organic compounds formed at the start of evolution in the early history of our planet earth. To support this point, guanine and adenine were heated with D ‐ribose in seawater, which contains the Lewis acid magnesium chloride as catalyst. One thus obtained the nucleosides guanosine and adenosine together with comparable yields of unnatural α‐nucleosides. The latter were gradually photoanomerized to the thermodynamically more stable compounds in overall yields of 5–6%. The furanose form of ribose reacts faster than the pyranose form. Corresponding syntheses of the pyrimidine nucleosides uridine and cytidine from uracil , cytosine and ribose are more problematic and remain an enigma. The recent conversion of glycolaldehyde‐ O ‐phosphate and formaldehyde to ribose‐2,4‐di‐ O ‐phosphate might give new insights into the prebiotic syntheses of uridine and cytidine. The evidence and hypotheses for these prebiotic conversions and the evolution of RNA, as well as the implications of an “RNA World,” have been reviewed. These RNA nucleosides are reduced in vivo as 5′‐ O ‐diphosphates by ribonucleotide reductases to the corresponding 2′‐deoxynucleosides—the building blocks of DNA such as 2′‐deoxyguanosine. The thermodynamically controlled synthesis of these four building blocks of RNA has implications for the design of efficient, high yielding, new methods for the synthesis of the naturally occurring nucleosides, nucleoside antibiotics, and modified nucleosides that may serve as antimetabolites to fight viral and parasitic diseases and cancer. The nucleoside rings in this chapter are depicted arbitrarily in the anti conformation, as occurs predominantly in the crystal and solution (based primarily on NOE‐ 1 H‐ and 13 C‐NMR measurements) forms of pyrimidine nucleosides. Only a few nucleosides, such as 6‐methyluridine, occur with the heterocyclic ring predominantly in the syn conformation. The synthesis of C ‐nucleosides has been reviewed previously and is not covered in this review.

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A series of novel acyclic nucleosides. IV. Synthesis of N1-sulfur analogues of acycolvir, directed toward improved antiviral activities.

Cited by 15 publications

References 0 publications

Synthesis of 2,8-Disubstituted Imidazo[1,5-a]pyrimidines with Potent Antitumor Activity

Synthesis of 2,8-Disubstituted Imidazo[1,5-a]pyrimidines with Potent Antitumor Activity

Synthesis, characterization, and pharmacological evaluation of novel azolo- and azinothiazinones containing 2,4-dihydroxyphenyl substituent as anticancer agents

Synthesis Of Nucleosides

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