.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Details for Patent: 6,159,969

« Back to Dashboard

Details for Patent: 6,159,969

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)
Filing Date:Jan 12, 1998
Application Number:09/006,009
Claims:1. A uracil derivative represented by the following formula (1'): ##STR171## wherein R.sup.1 is selected from the group consisting of chlorine, bromine, iodine, cyano and a lower alkyl group; and R.sup.2 represents an amidinothio group, one or more of the hydrogen atom(s) on one or both of the nitrogen atoms of which may each be substituted by a lower alkyl group; a guanidino group, one or more of the hydrogen atom(s) on one, two or all of the nitrogen atoms of which may each be substituted by a lower alkyl or cyan group; a (lower alkyl) amidino group; a group --CH.sub.2 N(R.sup.a)R.sup.b in which R.sup.a and R.sup.b may be the same or different and each represents a hydrogen atom or a lower alkyl group or R.sup.a and R.sup.b may form a pyrrolidine ring together with the nitrogen atom to which R.sup.a and R.sup.b are bonded; a group --NH--(CH.sub.2).sub.m --Z in which Z represents an amino group, one or both of the hydrogen atoms on the nitrogen atom of which may each be substituted by a lower alkyl group or a cyano group, and m stands for an integer of from 0 to 3; a group NR.sup.c (CH.sub.2).sub.n --OH in which R.sup.c represents a hydrogen atom or a lower alkyl group, and n stands for a natural number of from 1 to 4; a group --X--Y in which X represents S or NH, and Y represents a 2-imidazolin-2-yl, 2-imidazolyl, 1-methylimidazol-2-yl, 1,2,4-triazol-3-yl, 2-pyrimidyl or 2-benzimidazolyl group which may be substituted by one or more lower alkyl groups; or a ureido or thioureido group, one or more of the hydrogen atom(s) on one or both of the nitrogen atoms of which may each be substituted by a lower alkyl group, with the proviso that R.sup.1 and R.sup.2 are not a bromine atom and an amino group, respectively, at the same time; or a salt thereof.

2. The uracil derivative or salt thereof according to claim 1, wherein in the formula (1'), the group represented by R.sup.2 is an amidinothio group, one or more of the hydrogen atom(s) on one or both of the nitrogen atoms of which may each be substituted by a lower alkyl group; a guanidino group, one or more of the hydrogen atom(s) on one, two or all of the nitrogen atoms of which may each be substituted by a lower alkyl or cyano group; or a (lower alkyl)amidino group.

3. The uracil derivative or salt thereof according to claim 1, wherein in the formula 1', the group represented by R.sup.2 is selected from the group consisting of an amidinothio, N.sup.1 -methylamidinothio, N.sup.1,N.sup.2 -dimethylamidinothio, 1-guanidino, 1-methylguanidino, 3-methylguanidino, 2,3-dimethylguanidino and an acetoamidino group.

4. The uracil derivative or salt thereof according to claim 2, wherein in the formula 1', the group represented by R.sup.2 is selected from the group consisting of an amidinothio, N.sup.1 -methylamidinothio, N.sup.1,N.sup.2 -dimethylamidinothio, 1-guanidino, 1-methylguanidino, 3-methylguanidino, 2,3-dimethylguanidino and an acetoamidino 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 selected from the group consisting of chlorine, bromine, and cyano, and the group represented by R.sup.2 is an amidinothio or 1-guanidino group.

6. The uracil derivative or salt thereof according to claim 1, which is selected from the group consisting of 2-(5-chlorouracil-6-ylmethyl)-isothiourea hydrochloride, 2-(5-cyanouracil-6-ylmethyl)isothiourea hydrochloride and 5-chloro-6-(1-guanidino)methyluracil hydrochloride.

7. A pharmaceutical composition comprising:

a uracil derivative represented by the following formula (1): ##STR172## wherein R.sup.1 is selected from the group consisting of chlorine, bromine, iodine, cyano and a lower alkyl group; and R.sup.2 represents an amidinothio group, one or more of the hydrogen atom(s) on one or both of the nitrogen atoms of which may each be substituted by a lower alkyl group; a guanidino group, one or more of the hydrogen atom(s) on one, two or all of the nitrogen atoms of which may each be substituted by a lower alkyl or cyano group; a (lower alkyl)amidino group; a group --CH.sub.2 N(R.sup.a)R.sup.b in which R.sup.a and R.sup.b may be the same or different and each represents a hydrogen atom or a lower alkyl group or R.sup.a and R.sup.b may form a pyrrolidine ring together with the nitrogen atom to which R.sup.a and R.sup.b are bonded; a group --NH--(CH.sub.2).sub.m --Z in which Z represents an amino group, one or both of the hydrogen atoms on the nitrogen atom of which may each be substituted by a lower alkyl group or a cyano group, and m stands for an integer of from 0 to 3; a group NR.sup.c (CH.sub.2).sub.n --OH in which R.sup.c represents a hydrogen atom or a lower alkyl group, and n stands for a natural number of from 1 to 4; a group --X--Y in which X represents S or NH, and Y represents a 2-imidazolin-2-yl, 2-imidazolyl, 1-methylimidazol-2-yl, 1,2,4-triazol-3-yl, 2-pyrimidyl or 2-benzimidazolyl group which may be substituted by one or more lower alkyl groups; or a ureido or thioureido group, one or more of the hydrogen atom(s) on one or both of the nitrogen atoms of which may each be substituted by a lower alkyl group; or a salt thereof; and

a pharmaceutically acceptable carrier.

8. The pharmaceutical composition according to claim 7, wherein in the formula (1), the group represented by R.sup.2 is an amidinothio group, one or more of the hydrogen atom(s) on one or both of the nitrogen atoms of which may each by substituted by a lower alkyl group; a guanidino group, one or more of the hydrogen atom(s) on one, two or all of the nitrogen atoms of which may each by substituted by a lower alkyl or cyano group; or a (lower alkyl)amidino group.

9. The pharmaceutical composition according to claim 7, wherein in the formula (1), the group represented by R.sup.2 is selected from the group consisting of an amidinothio, N.sup.1 -methylamidinothio, N.sup.1,N.sup.2 -dimethyl-amidinothio, 1-guanidino, 1-methylguanidino, 3-methylguanidino, 2,3,-dimethylguanidino and an acetoamidino group.

10. The pharmaceutical composition according to claim 8, wherein in the formula (1), the group represented by R.sup.2 is selected from the group consisting of an amidinothio, N.sup.1 -methylamidinothio, N.sup.1,N.sup.2 -dimethyl-amidinothio, 1-guanidino, 1-methylguanidino, 3-methylguanidino, 2,3,-dimethylguanidino and an acetoamidino group.

11. The pharmaceutical composition according to claim 7, wherein in the formula (1), the group represented by R.sup.1 is selected from the group consisting of chlorine, bromine, and cyano, and the group represented by R.sup.2 is an amidinothio or 1-guanidino group.

12. The pharmaceutical composition according to claim 7, wherein the compound represented by the formula (1) is selected from the group consisting of 2-(5-chlorouracil-6-ylmethyl)isothiourea hydrochloride, 2-(5-cyanouracil-6-ylmethyl)isothiourea hydrochloride and 5-chloro-6-(1-guanidino)methyluracil hydrochloride.

13. A method for potentiating an antitumor 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): ##STR173## wherein R.sup.1 is selected from the group consisting of chlorine, bromine, iodine, cyano and a lower alkyl group; and R.sup.2 represents an amidinothio group, one or more of the hydrogen atom(s) on one or both of the nitrogen atoms of which may each be substituted by a lower alkyl group; a guanidino group, one or more of the hydrogen atom(s) on one, two or all of the nitrogen atoms of which may each be substituted by a lower alkyl or cyano group; a (lower alkyl)amidino group; a group --CH.sub.2 N(R.sup.a)R.sup.b in which R.sup.a and R.sup.b may be the same or different and each represents a hydrogen atom or a lower alkyl group or R.sup.a and R.sup.b may form a pyrrolidine ring together with the nitrogen atom to which R.sup.a and R.sup.b are bonded; a group --NH--(CH.sub.2).sub.m --Z in which Z represents an amino group, one or both of the hydrogen atoms on the nitrogen atom of which may each be substituted by a lower alkyl group, or a cyano group, and m stands for an integer of from 0 to 3; a group NR.sup.c (CH.sub.2).sub.n --OH in which R.sup.c represents a hydrogen atom or a lower alkyl group, and n stands for a natural number of from 1 to 4; a group --X--Y in which X represents S or NH, and Y represents a 2-imidazolin-2-yl, 2-imidazolyl, 1-methylimidazol-2-yl, 1,2,4-triazol-3-yl, 2-pyrimidyl or 2-benzimidazolyl group which may be substituted by one or more lower alkyl groups; or a ureido or thioureido group, one or more of the hydrogen atom(s) on one or both of the nitrogen atoms of which may each be substituted by a lower alkyl group; or a salt thereof.

14. A therapeutic method for treating cancer, which comprises administering to a patient in need of treatment an effective amount of a uracil derivative represented by the following formula ##STR174## wherein R.sup.1 is selected from the group consisting of chlorine, bromine, iodine, cyano and a lower alkyl group; and R.sup.2 represents an amidinothio group, one or more of the hydrogen atom(s) on one or both of the nitrogen atoms of which may each be substituted by a lower alkyl group; a guanidino group, one or more of the hydrogen atom(s) on one, two or all of the nitrogen atoms of which may each be substituted by a lower alkyl or cyano group; a (lower alkyl)amidino group; a group --CH.sub.2 N(R.sup.a)R.sup.b in which R.sup.a and R.sup.b may be the same or different and each represents a hydrogen atom or a lower alkyl group or R.sup.a and R.sup.b may form a pyrrolidine ring together with the nitrogen atom to which R.sup.a and R.sup.b are bonded; a group --NH--(CH.sub.2).sub.m --Z in which Z represents an amino group, one or both of the hydrogen atoms on the nitrogen atom of which may each be substituted by a lower alkyl group or a cyano group, and m stands for an integer of from 0 to 3; a group NR.sup.c (CH.sub.2).sub.n --OH in which R.sup.c represents a hydrogen atom or a lower alkyl group, and n stands for a natural number of from 1 to 4; a group --X--Y in which X represents S or NH, and Y represents a 2-imidazolin-2-yl, 2-imidazolyl, 1-methylimidazol-2-yl, 1,2,4-triazol-3-yl, 2-pyrimidyl or 2-benzimidazolyl group which may be substituted by one or more lower alkyl groups; or a ureido or thioureido group, one or more of the hydrogen atom(s) on one or both of the nitrogen atoms of which may each be substituted by a lower alkyl group; or a salt thereof; and a 2'-deoxypyrimidine nucleoside.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

How are People Using DrugPatentWatch?

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 verifification 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.

`abc