2'-deoxy-5-fluorouridine derivatives

• US 5,032,680 A
• Filed: 02/24/1989
• Issued: 07/16/1991
• Est. Priority Date: 02/29/1988
• Status: Expired due to Fees

• Current Assignee: Taiho Pharmaceutical Company Limited (Otsuka Holdings Company Limited)
• Original Assignee: Kuraray Company Limited, Taiho Pharmaceutical Company Limited (Otsuka Holdings Company Limited)
• Inventors: Saito, Hitoshi, Mori, Fumio, Kawai, Tsutomu, Unemi, Norio, Takeda, Setsuo
• Primary Examiner(s): Wax, Robert A.
• Assistant Examiner(s): TSUNG, FREDERICK
• Application Number:
  US07/314,924
• Time in Patent Office: 872 Days
• Field of Search: 536/23, 536/29, 514/50, 514/51, 544/243, 544/311, 544/313
• US Class Current: 536/26.8
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids

Abstract

2'"'"'-Deoxy-5-fluorouridine derivatives of the formula ##STR1## wherein, R¹ is hydrogen atom or an acyl group and R² and R³ are respectively hydrogen atom, an acyl group or a group of the formula ##STR2## wherein X¹ and X² are respectively oxygen atom or sulfur atom; R⁴ is a phenyl group, a benzyl group or a naphthyl group each of which may be substituted by an alkyl group, an alkoxyl group, an alkoxycarbonyl group, an alkylthio group, and acyl group, a halogen atom, trifluoromethyl group, nitro group, cyano group, carboxyl group and/or methylenedioxy group and R⁵ is an alkyl group, an alkenyl group or one of the groups represented by R⁴ which is the same as or different from R⁴, at least one of R² and R³ being a group of the formula ##STR3## which exhibit excellent antitumour activities and have lower toxicity, methods of the production thereof and antitumour compositions containing said 2'"'"'-deoxy-5-fluorouridine derivatives.

Claims

1. A 2'"'"'-deoxy-5-fluorouridine derivative of the formula ##STR36## wherein, R¹ is hydrogen atom or an acyl group and R² and R³ are respectively hydrogen atom, an acyl group or a group of the formula ##STR37## wherein X¹ and X² are respectively oxygen atom or sulfur atom;

R⁴ is a phenyl group, a benzyl group or a naphthyl group each of which may be substituted by an alkyl group, an alkoxyl group, an alkoxycarbonyl group, an alkylthio group, an acyl group, a halogen atom, trifluoromethyl group, nitro group, cyano group, carboxyl group and/or methylenedioxy group and R⁵ is an alkyl group, an alkenyl group or one of the groups represented by R⁴ which is the same as or different from R⁴, at least one of R² and R³ being a group of the formula ##STR38##

2. The 2'"'"'-deoxy-5-fluorouridine derivative as claimed in claim 1 wherein R² is a group of the formula ##STR39## wherein the symbols are as defined in claim 1.

3. The 2'"'"'-deoxy-5-fluorouridine derivative as claimed in claim 1 wherein R¹ and R³ are respectively hydrogen atom or an acyl group.

4. The 2'"'"'-deoxy-5-fluorouridine derivative as claimed in claim 1 wherein R² is a group of the formula ##STR40## wherein each of X¹ and X² is oxygen atom and R⁴ and R⁵ are respectively a phenyl group substituted by one or two chlorine atom, fluorine atom, bromine atom and/or trifluoromethyl group.

5. The 2'"'"'-deoxy-5-fluorouridine derivative as claimed in claim 1, wherein R¹ is a hydrogen atom;

R² is a group of the formula ##STR41## wherein each of X¹ and X² is oxygen atom and R⁴ and R⁵ are respectively a phenyl group substituted by one or two chlorine atom, fluorine atom, bromine atom and/or trifluoromethyl group;

R³ is hydrogen atom or an acyl group.

6. The 2'"'"'-deoxy-5-fluorouridine derivative as claimed in claim 1 selected from the group consisting of di-p-chlorophenyl 2'"'"'-deoxy-5-fluoro-5'"'"'-uridylate, di-m-chlorophenyl 2'"'"'-deoxy-5-fluoro-5'"'"'-uridylate, di(2,4-dichlorophenyl) 2'"'"'-deoxy-5-fluoro-5'"'"'-uridylate, di-p-fluorophenyl 2'"'"'-deoxy-5-fluoro-5'"'"'-uridylate, di-p-bromophenyl 2'"'"'-deoxy-5-fluoro-5'"'"'-uridylate, de-p-trifluoromethylphenyl 2'"'"'-deoxy-5-fluoro-5'"'"'-uridylate and di-p-chlorophenyl 3'"'"'-acetyl-2'"'"'-deoxy-5-fluoro-5'"'"'-uridylate.

7. A composition comprising an amount of a 2'"'"'-deoxy-5-fluorouridine derivative, as claimed in claim 1, effective to treat Sarcoma 180 tumor cells transplanted to mice, and a pharmaceutically acceptable carrier.