You’re using a public version of DrugPatentWatch with 5 free searches available | Register to unlock more free searches. CREATE FREE ACCOUNT

Last Updated: March 29, 2024

Claims for Patent: 5,744,475


✉ Email this page to a colleague

« Back to Dashboard


Summary for Patent: 5,744,475
Title: Uracil derivatives, and antitumor effect potentiator and antitumor agent containing the same
Abstract:The invention relates to novel uracil derivatives having excellent inhibiting effects of human derived thymidine phosphorylase and anti-tumor activity. The pharmaceutical compositions, anti-tumor potentiators, antitumor agents containing such novel compounds, and a process for their preparation and use is described. The novel compounds satisfy the general formula (1): ##STR1##
Inventor(s): Yano; Shingo (Kawagoe, JP), Tada; Yukio (Higashimatsuyama, JP), Kazuno; Hideki (Hanno, JP), Sato; Tsutomu (Hanno, JP), Yamashita; Junichi (Honjo, JP), Suzuki; Norihiko (Hidaka, JP), Emura; Tomohiro (Iruma, JP), Fukushima; Masakazu (Hanno, JP), Asao; Tetsuji (Tokorozawa, JP)
Assignee: Taiho Pharmaceutical Co., Ltd. (Tokyo, JP)
Application Number:08/737,677
Patent Claims: 1. A uracil derivative represented by the following formula (1): ##STR170## wherein R.sup.1 represents a chlorine, bromide or iodine atom or a cyano or lower alkyl group; and R.sup.2 is selected from the group consisting of a 4-5 membered heterocyclic group having 1-3 nitrogen atoms, piperidine and piperazine, which may be substituted by one or more lower alkyl, imino, hydroxyl, hydroxymethyl, methanesulfonyloxy, amino or nitro groups; or a salt thereof.

2. The uracil derivative or salt thereof according to claim 1, wherein in formula (1), the 4-5 membered heterocyclic group represented by R.sup.2 is selected from the group consisting of 1-3 nitrogen atoms, piperidine and piperazine, or R.sup.2 is a 1-azetidinyl, 1-pyrrolidinyl, 2-pyrrolin-1-yl, 3-pyrrolin-1-yl, 1-pyrrolyl, 1-pyrazolidinyl, 2-pyrazolin-1-yl, 3-pyrazolin-1-yl, 4-pyrazolin-1-yl, 1-pyrazolyl, 1-imidazolidinyl, 2-imidazolin-1-yl, 3-imidazolin-1-yl, 4-imidazolin-1-yl, 1-imidazolyl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, piperidino, or 1-piperazyl group.

3. The uracil derivative or salt thereof according to claim 1, wherein in formula (1), R.sup.2 may be substituted by one or more lower alkyl, imino, hydroxy, hydroxymethyl, methanesulfonyloxy, amino or nitro groups, and is a 1-azetidinyl, 1-pyrrolidinyl, 2,5-dimethylpyrrolidin-1-yl, 2-iminopyrrolidin-1-yl, 3-hydroxypyrrolidin-1-yl, 2-hydroxymethylpyrrolidin-1-yl, 3-methanesulfonyloxypyrrolidin-1-yl, 3-aminopyrrolidin-1-yl, 1-pyrrolyl, 2-pyrazolin-1-yl, 1-pyrazolyl, 2-iminoimidazolidin-1-yl, 2-imino-3-methylimidazolidin-1-yl, 2-imino- 3-ethylimidazolidin-1-yl, 2-imino-3-isopropylimidazolidin-1-yl, 2-imidazolin-1-yl, 2-imino-3-methyl-4-imidazolin-1-yl, 2-imino-3-ethyl-4-imidazolin-1-yl, 1-imidazolyl, 2-methylimidazol-1-yl, 2-nitroimidazol-1-yl, 4-nitroimidazol-1-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, 3-nitro-1,2,4-triazol-1-yl, piperidino or 4-methylpiperazin-1-yl group.

4. The uracil derivative or salt thereof according to claim 1, wherein in the formula (1'), the group represented by R.sup.2 is a 1-azetidinyl, 1-pyrrolidinyl, 2-iminopyrrolidin-1-yl, 2-iminoimidazolidin-1-yl, 2-imino-3-methylimidazolidin-1-yl, 2-imino-3-ethylimidazolidin-1-yl, 2-imino-3-isopropylimidazolidin-1-yl, 2-imidazolin-1-yl, 2-imino-3-methyl-4-imidazolin-1-yl, 2-imino-3-ethyl-4-imidazolin-1-yl, or 1-imidazolyl group.

5. The uracil derivative or salt thereof according to claim 1, wherein in the formula (1'), the group represented by R.sup.1 is a chlorine or bromine atom or a cyano group, and the group represented by R.sup.2 is a 1-pyrrolidinyl, 1-azetidinyl, 2-iminopyrrolidin-1-yl, 2-iminoimidazolidin-1-yl, or 1-imidazolyl group.

6. The uracil derivative or salt thereof according to claim 1, which is selected from 5-chloro-6-(1-pyrrolidinylmethyl)uracil, 5-bromo-6-(1-pyrrolidinyl-methyl)uracil, 5-chloro-6-(1-azetidinylmethyl)uracil, 5-chloro-6-(1-(2-iminopyrrolidinyl)methyl)uracil hydrochloride, 5-bromo-6-(1-(2-iminopyrrolidinyl)methyl)-uracil hydrochloride, 5-cyano-6-(1-(2-iminopyrrolidinyl)methyl)uracil, 5-chloro-6-(1-(2-iminoimidazolidinyl)methyl)uracil, 5-bromo-6-(1-(2-iminoimidazolidinyl)methyl)uracil, or 5-chloro-6-(1-imidazolylmethyl)-uracil hydrochloride.

7. A pharmaceutical composition comprising:

a uracil derivative represented by the following formula (1): ##STR171## wherein R.sup.1 represents a chlorine, bromide or iodine atom or a cyano or lower alkyl group; and R.sup.2 is selected from the group consisting of a 4-5 membered heterocyclic group having 1-3 nitrogen atoms, piperidine and piperazine, which may be substituted by one or more lower alkyl, imino, hydroxyl, hydroxymethyl, methanesulfonyloxy, amino or nitro groups; or a salt thereof; and

a pharmaceutically acceptable carrier.

8. The pharmaceutical composition according to claim 7, wherein in formula (1), R.sup.2 is a 1-azetidinyl, 1-pyrrolidinyl, 2-pyrrolin-1-yl, 3-pyrrolin-1-yl, 1-pyrrolyl, 1-pyrazolidinyl, 2-pyrazolin-1-yl, 3-pyrazolin-1-yl, 4-pyrazolin-1-yl, 1-pyrazolyl, 1-imidazolidinyl, 2-imidazolin-1-yl, 3-imidazolin-1-yl, 4-imidazolin-1-yl, 1-imidazolyl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, piperidino or 1-piperazyl group.

9. The pharmaceutical composition according to claim 7, wherein in formula (1), R.sup.2 is a 1-azetidinyl, 1-pyrrolidinyl, 2,5-dimethylpyrrolidin-1-yl, 2-iminopyrrolidin-1-yl, 3-hydroxypyrrolidin-1-yl, 2-hydroxymethylpyrrolidin-1-yl, 3-methanesulfonyloxypyrrolidin-1-yl, 3-aminopyrrolidin-1-yl, 1-pyrrolyl, 2-pyrazolin-1-yl, 1-pyrazolyl, 2-iminoimidazolidin-1-yl, 2-imino-3-methylimidazolidin-1-yl, 2-imino-3-ethylimidazolidin-1-yl, 2-imino-3-isopropylimidazolidin-1-yl, 2-imidazolin-1-yl, 2-imino-3-methyl-4-imidazolin-1-yl, 2-imino-3-ethyl-4-imidazolin-1-yl, 1-imidazolyl, 2-methylimidazol-1-yl, 2-nitroimidazol-1-yl, 4-nitroimidazol-1-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, 3-nitro-1,2,4-triazol-1-yl, piperidino or 4-methylpiperazin-1-yl group.

10. The pharmaceutical composition according to claim 7, wherein in the formula (1), the group represented by R.sup.2 is a 1-azetidinyl, 1-pyrrolidinyl, 2-iminopyrrolidin-1-yl, 2-iminoimidazolidin-1-yl, 2-imino-3-methylimidazolidin-1-yl, 2-imino-3-ethyl-imidazolidin-1-yl, 2-imino-3-isopropylimidazolidin-1-yl, 2-imidazolin-1-yl, 2-imino-3-methyl-4-imidazolin-1-yl, 2-imino-3-ethyl-4-imidazolin-1-yl, or 1-imidazolyl group.

11. The pharmaceutical composition according to claim 7, wherein in the formula (1), the group represented by R.sup.1 is a chlorine or bromine atom or a cyano group, and the group represented by R.sup.2 is a 1-pyrrolidinyl, 1-azetidinyl, 2-iminopyrrolidin-1-yl, 2-iminoimidazolidin-1-yl, or 1-imidazolyl group.

12. The pharmaceutical composition according to claim 7, wherein the compound represented by the formula (1) is selected from 5-chloro-6-(1-pyrrolidinyl-methyl)uracil, 5-bromo-6-(1-pyrrolidinylmethyl)uracil, 5-chloro-6-(1-azetidinylmethyl)uracil, 5-chloro-6-(1-(2-iminopyrrolidinyl)methyl)uracil hydrochloride, 5-bromo-6-(1-(2-iminopyrrolidinyl)methyl)uracil hydrochloride, 5-cyano-6-(1-(2-iminopyrrolidinyl)-methyl)uracil, 5-chloro-6-(1-(2-iminoimidazolidinyl)-methyl)uracil, 5-bromo-6-(1-(2-iminoimidazolidinyl)-methyl)uracil, or 5-chloro-6-(1-imidazolylmethyl)uracil hydrochloride.

13. A method for inducing the effect of an antitumor agent containing a 2'-deoxypyrimidine nucleoside, which comprises administering to a patient an effective amount of a uracil derivative represented by the following formula (1): ##STR172## wherein R.sup.1 represents a chlorine, bromide or iodine atom or a cyano or lower alkyl group; and R.sup.2 is selected from the group consisting of a 4-5 membered heterocyclic group having 1-3 nitrogen atoms, piperidine and piperazine, which may be substituted by one or more lower alkyl, imino, hydroxyl, hydroxymethyl, methanesulfonyloxy, amino or nitro groups; or a salt thereof.

14. A therapeutic method for treating cancer, which comprises administering to a patient an effective amount of a uracil derivative represented by the following formula (1): ##STR173## wherein R.sup.1 represents a chlorine, bromide or iodine atom or a cyano or lower alkyl group; and R.sup.2 is selected from the group consisting of a 4-5 membered heterocyclic group having 1-3 nitrogen atoms, piperidine and piperazine, which may be substituted by one or more lower alkyl, imino, hydroxyl, hydroxymethyl, methanesulfonyloxy, amino or nitro groups; or a salt thereof; and a 2'-deoxypyrimidine nucleoside.

Make Better Decisions: Try a trial or see plans & pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.