99394-52-2

Usage

Uses

Used in Pharmaceutical Industry:
(E)-5-(2-CARBOXYVINYL)URIDINE is used as a key intermediate in the synthesis of 4-thioxo-5-(2-halovinyl)uridine, a sulfur-containing uridine anti-cancer compound. (E)-5-(2-CARBOXYVINYL)URIDINE holds promise in the development of novel cancer treatments due to its potential to target and inhibit cancer cell growth and proliferation.

Upstream product

• 123881-85-6 (E)-5-<2-(ethoxycarbonyl)vinyl>uridine 
• 58931-19-4 methyl 3-(5-uridinyl)propenoate 
• 1024-99-3 5-iodouridine 
• 58-96-8 uridine 

Downstream Products

• 123881-91-4 5-(1-hydroxy-2-iodoethyl)uridine 
• 123881-97-0 5-(1-methoxy-2-iodoethyl)uridine 
• 86391-68-6 (E)-5-(2-bromovinyl)uridine 
• 114494-92-7 5-(1,2-dibromo-2-succinimidoethyl)uridine 

Relevant academic research and scientific papers

Sulfur-containing uridine anticancer compound and intermediate and preparation method thereof

The invention relates to a 4-sulfur-5-(2-halogenated vinyl)uridine compound which has the higher sensibility to UVA light and the anticancer activity and an intermediate and a preparation method of the compound. The method comprises the following steps that an iodination reaction is performed, a halogenating reaction is performed, hydroxyl on a sugar ring is protected, oxygen is replaced by sulfur, an O protection group is removed, and then 4-sulfur-5-(2-halogenated vinyl)uridine is obtained. The method has the advantages of being short in reaction time and high in yield and product purity, and the defects that in a traditional synthesis method, time and energy are consumed, and the yield is low are overcome. Beneficial conditions are supplied for further developing sulfur-containing nucleoside drugs.

Synthesis and Antiviral and Cytotoxic Activity of Iodohydrin and Iodomethoxy Derivatives of 5-Vinyl-2'-deoxyuridines, 2'-Fluoro-2'-deoxyuridine, and Uridine

A series of new 5-(1-hydroxy-2-iodoethyl)-2'-deoxyuridine and uridine cpmpounds (11, 16) was synthesized by the regiospecific addition of HOI to the vinyl substituent of 5-vinyl-2'-deoxyuridine (10a), 5-vinyl-2'-fluoro-2'-deoxyuridine (10b), 5-vinyl-uridine (10c), and (E)-5-(2-iodovinyl)-2'-deoxyuridine (4b).Treatment of the iodohydrins 11a-c with methanolic sulfuric acid afforded the corresponding 5-(1-methoxy-2-iodoethyl) derivatives (12a-c).In contrast, reaction of 5-(1-hydroxy-2-iodoethyl)-2'-deoxyuridine (11a) with sodium carbonate in methanol afforded a mixture of 5-(1-hydroxy-2-methoxyethyl)-2'-deoxyuridine (13) and 2,3-dihydro-3-hydroxy-5-(2'-deoxy-β-D-ribofuranosyl)furanopyrimidin-6(5H)-one (14).The most active compound, 5-(1-methoxy-2-iodoethyl)-2'-deoxyuridine (12a, ID50 = 0.1 μg/mL) which exhibited antiviral activity (HSV-1) 100-fold higher than that of the 5-(1-hydroxy-2-iodoethyl) analogue (11a), was less active than IVDU or acyclovir (ID50 = 0.01 - 0.1 μg/mL range).The C-5 substituent in the 2'-deoxyuridine series was a determinant of cytotoxic activity, as determined in the in vitro L1210 screen, where the relative activity order was CH(OH)CHI2 (16) > CH(OH)CH2I (11a) ca.CH(OH)CH2OMe (13).The 2'-substituent was also a determinant of cytotoxic activity in the 5-(1-hydroxy-2-iodoethyl) (11a-c) and 5-(1-methoxy-2-iodoethyl) series of compounds, where the relative activity profile was 2'-deoxyuridine > 2'-fluoro-2'-deoxyuridine > uridine (11a > 11b 11c; 12a > 12b > 12c).The most active cytotoxic agent (16), possessing a 5-(1-hydroxy-2,2-diiodoethyl) substituent (ED50 = 0.77 μg/mL), exhibited an activity approaching that of melphalan (ED50 = 0.15 μg/mL).All compounds tested, except for 13 and 14, exhibited high affinity (Ki = 0.035 - 0.22 mM range relative to deoxyuridine, Ki = 0.125) for the murine NBMPR-sensitive erthyrocyte nucleoside transport system, suggesting that these iodohydrins are good permeants of cell membranes.

Synthesis and Antiviral Activity of (E)-5-(2-Bromovinyl)uracil and (E)-5-(2-Bromovinyl)uridine

(E)-5-(2-Bromovinyl)uracil (BVU) and (E)-5-(2-bromovinyl)uridine (BVRU) were synthesized starting from 5-formyluracil via (E)-5-(2-carboxyvinyl)uracil or starting from 5-iodouridine via (E)-5-(2-carbomethoxyvinyl)uridine and (E)-5-(2-carboxyvinyl)uridine, respectively.Depending on the choice of the cell system, BVU and BVRU exhibited a marked activity against herpes simplex virus type 1 (HSV-1) in vitro.Although BVU and BVRU were less potent than the reference compound (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), their antiviral activity spectrum was remarkably similar to that of BVDU.The latter findings suggest that BVU and BVRU are metabolically converted to BVDU or a phosphorylated product thereof.In vivo, BVU protected mice against a lethal disseminated HSV-1 infection.