180300-78-1

Basic information

• Product Name: ((3aR,5R,6R,6aR)-6-ethynyl-6-hydroxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)methyl benzoate
• Synonyms: ((3aR,5R,6R,6aR)-6-ethynyl-6-hydroxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)methyl benzoate
• CAS NO: 180300-78-1
• Molecular Weight: 318.326
• Mol File: 180300-78-1.mol

Chemical Properties

• CAS DataBase Reference: ((3aR,5R,6R,6aR)-6-ethynyl-6-hydroxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)methyl benzoate(CAS DataBase Reference)
• NIST Chemistry Reference: ((3aR,5R,6R,6aR)-6-ethynyl-6-hydroxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)methyl benzoate(180300-78-1)
• EPA Substance Registry System: ((3aR,5R,6R,6aR)-6-ethynyl-6-hydroxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)methyl benzoate(180300-78-1)

Safety Data

• Hazardous Substances Data: 180300-78-1(Hazardous Substances Data)

Upstream product

• 6698-46-0 5-O-benzoyl-1,2-O-isopropylidene-α-D-ribofuranos-3-ulose 
• 4301-14-8 acetylenemagnesium bromide 
• 98-88-4 benzoyl chloride 
• 6022-96-4 5-O-benzoyl-α-D-xylofuranose 
• 155470-62-5 5-O-tert-butyldimethylsilyl-1,2-O-isopropylidene-3-C-(2-trimethylsilylethynyl)-α-D-ribofuranose 
• 85951-12-8 1,2-O-isopropylidene-5-O-(tert-butyl)dimethylsilyl-α-D-xylofuranoside 
• 20031-21-4 1,2-O-isopropylidene-α-D-xylose 
• 103931-45-9 5-O-(tert-butyldimethylsilyl)-1,2-O-isopropylidene-α-D-erythro-pentofuranos-3-ulose 
• 155470-63-6 3-C-ethynyl-1,2-O-isopropylidene-α-D-ribo-pentofuranose 

Downstream Products

• 182825-15-6 methyl 5-O-benzoyl-3-C-ethynyl-α,β-D-ribofuranose 
• 180300-46-3 1-(2,3,5-tri-O-benzoyl-3-C-ethynyl-β-D-ribofuranosyl)uracil 
• 182825-17-8 1-O-acetyl-2,3,5-tri-O-benzoyl-3-C-ethynyl-D-ribofuranose 
• 182825-16-7 methyl 2,3,5-tri-O-benzoyl-3-C-ethynyl-α,β-D-ribofuranose 

Relevant articles and documents

Nucleosides and nucleotides. 152. 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)uracil as a broad spectrum antitumor nucleoside

1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)uracil (EUrd) has been designed as a potential multifunctional antitumor nucleoside antimetabolite. EUrd was synthesized by condensation of 1-O-acetyl-2,3,5-tri-O-benzoyl-3-C-ethynyl-α,β-D-ribo-pentofuranose (6) and bis(trimethylsilyl)uracil in the presence of trimethylsilyl triflate in CH3CN in good yield, followed by debenzoylation with NH3/MeOH. In vitro tumor cell growth inhibitory activity of EUrd against 14 human solid tumor cell lines was compared with 5-fluorouridine (FUrd), 2'-deoxy-5-fluorouridine (FdUrd), and 5-fluorouracil (5-FU) as positive controls. EUrd was a quite potent tumor cell growth inhibitor against almost all the tumor cell lines examined in this study except for human pancreas PANC-1 cells, and the potency of EUrd is about 6 to 650 times stronger than that of 5-FU and comparable to that of FUrd and FdUrd. EUrd showed also potent antitumor activity against human tumors as xenografts in nude mice when given in a daily intravenous dose of 2 mg/kg on consecutive days.

SELECTIVE INHIBITORS OF PROTEIN ARGININE METHYLTRANSFERASE 5

The disclosure is directed to methods of treating disease using compounds of Formula (I).

Selective Inhibitors Of Protein Arginine Methyltransferase 5 (PRMT5)

The disclosure is directed to compounds of Formula I Pharmaceutical compositions comprising compounds of Formula I, as well as methods of their use and preparation, are also described.

Nucleosides and nucleotides. Part 212: Practical large-scale synthesis of 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine (ECyd), a potent antitumor nucleoside. Isobutyryloxy group as an efficient anomeric leaving group in the Vorbrüggen glycosylation reaction

A practical synthetic route to the antitumor nucleoside, 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine (ECyd, 1) from 1,2-O-isopropylidene-D-xylofuranose (3) has been developed. Since most of the compounds were obtained as crystals, the target ECyd was prepared without any chromatographic purification in 31% overall yield from compound 3. The isobutyryloxy group was found to be an effective leaving group at the anomeric position of the 3-β-C-ethynyl glycosyl donors in the key Vorbru?ggen glycosylation reaction. Using a similar procedure without chromatographic purification, the uracil congener EUrd [1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)uracil (2), which also has a potent antitumor effect, was synthesized from 3 in 39% overall yield.

3'-substituted nucleoside derivatives

The invention relates to a 3'-substituted nucleoside derivative represented by the following general formula (1): STR1 wherein B means a nucleic acid base which may have a substituent, Z represents a lower alkynyl or lower alkenyl group which may be subst

Nucleosides and nucleotides. 158. 1-(3-C-ethynyl-β-D-ribo- pentofuranosyl)-cytosine, 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)uracil, and their nucleobase analogues as new potential multifunctional antitumor nucleosides with a broad spectrum of activity

We previously designed 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)uracil (EUrd) as a potential multifunctional antitumor nucleoside antimetabolite. It showed a potent and broad spectrum of antitumor activity against various human tumor cells in vitro and in vivo. To determine the structure-activity relationship, various nucleobase analogues of EUrd, such as 5-fluorouracil, thymine, cytosine, 5-fluorocytosine, adenine, and guanine derivatives, were synthesized by condensation of 1-O-acetyl-2,3,5-tri-O-benzoyl-3-C-ethynyl- α-β-D-ribo-pentofuranose (6) and the corresponding pertrimethylsilylated nucleobases in the presence of SnCl4 or TMSOTf as a Lewis acid in CH3CN followed by debenzoylation. The in vitro tumor cell growth inhibitory activity of these 3'-C-ethynyl nucleosides against mouse leukemia L1210 and human nasopharyngeal KB cells showed that 1-(3-C-ethynyl-β-D-ribo- pentofuranosyl)cytosine (ECyd) and EUrd were the most potent inhibitors in the series, with IC50 values for L1210 cells of 0.016 and 0.13 μM and for KB cells of 0.028 and 0.029 μM, respectively. 5-Fluorocytosine, 5- fluorouracil, and adenine nucleosides showed much lower activity, with IC50 values of 0.42.5 μM, while thymine and guanine nucleosides did not exhibit any activity up to 300 μM. We next evaluated the tumor cell growth inhibitory activity of ECyd and EUrd against 36 human tumor cell lines in vitro and found that they were highly effective against these cell lines with IC50 values in the nanomolar to micromolar range. These nucleosides have a similar inhibitory spectrum. The in vivo antitumor activities of ECyd and EUrd were compared to that of 5-fluorouracil against 11 human tumor xenografts including three stomach, three colon, two pancreas, one renal, one breast, and one bile duct cancers. ECyd and EUrd showed a potent tumor inhibition ratio (73-92% inhibition relative to the control) in 9 of 11 and 8 of 11 human tumors, respectively, when administered intravenously for 10 consecutive days at doses of 0.25 and 2.0 mg/kg, respectively, while 5- fluorouracil showed potent inhibitory activity against only one tumor. Such excellent antitumor activity suggests that ECyd and EUrd are worth evaluating further for use in the treatment of human cancers.