- HYDANTOIN CONTAINING DEOXYURIDINE TRIPHOSPHATASE INHIBITORS
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Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.
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- URACIL CONTAINING COMPOUNDS
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Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.
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- 6-MEMBERED URACIL ISOSTERES
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Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.
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- NITROGEN RING LINKED DEOXYURIDINE TRIPHOSPHATASE INHIBITORS
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Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.
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- HYDANTOIN CONTAINING DEOXYURIDINE TRIPHOSPHATASE INHIBITORS
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Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.
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- DEOXYURIDINE TRIPHOSPHATASE INHIBITORS
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Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.
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- HYDANTOIN CONTAINING DEOXYURIDINE TRIPHOSPHATASE INHIBITORS
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Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.
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- ANTI-TUMOR EFFECT POTENTIATOR
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There is provided an agent for potentiating the effects of an anti-tumor agent. An anti-tumor effect potentiator containing, as an active ingredient, a uracil compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof: wherein X represents a C1-5 alkylene group and one of methylene groups constituting the alkylene group is optionally substituted with an oxygen atom; R1 represents a hydrogen atom or a C1-6 alkyl group; R2 represents a hydrogen atom or a halogen atom; and R3 represents a C1-6 alkyl group, a C2-6 alkenyl group, a C3-6 cycloalkyl group, a (C3-6 cycloalkyl) C1-6 alkyl group, a halogeno-C1-6 alkyl group or a saturated heterocyclic group.
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- Discovery of a novel class of potent human deoxyuridine triphosphatase inhibitors remarkably enhancing the antitumor activity of thymidylate synthase inhibitors
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Inhibition of human deoxyuridine triphosphatase (dUTPase) has been identified as a promising approach to enhance the efficacy of 5-fluorouracil (5-FU)-based chemotherapy. This study describes the development of a novel class of dUTPase inhibitors based on the structure-activity relationship (SAR) studies of uracil derivatives. Starting from the weak inhibitor 7 (IC 50 = 100 μM), we developed compound 26, which is the most potent human dUTPase inhibitor (IC50 = 0.021 μM) reported to date. Not only does compound 26 significantly enhance the growth inhibition activity of 5-fluoro-2′-deoxyuridine (FdUrd) against HeLa S3 cells in vitro (EC 50 = 0.075 μM) but also shows robust antitumor activity against MX-1 breast cancer xenograft model in mice when administered orally with a continuous infusion of 5-FU. This is the first in vivo evidence that human dUTPase inhibitors enhance the antitumor activity of TS inhibitors. On the basis of these findings, it was concluded that compound 26 is a promising candidate for clinical development.
- Miyahara, Seiji,Miyakoshi, Hitoshi,Yokogawa, Tatsushi,Chong, Khoon Tee,Taguchi, Junko,Muto, Toshiharu,Endoh, Kanji,Yano, Wakako,Wakasa, Takeshi,Ueno, Hiroyuki,Takao, Yayoi,Fujioka, Akio,Hashimoto, Akihiro,Itou, Kenjirou,Yamamura, Keisuke,Nomura, Makoto,Nagasawa, Hideko,Shuto, Satoshi,Fukuoka, Masayoshi
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p. 2970 - 2980
(2012/05/31)
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- NOVEL URACIL COMPOUND HAVING INHIBITORY ACTIVITY ON HUMAN DEOXYURIDINE TRIPHOSPHATASE OR SALT THEREOF
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Provided is a uracil compound or a salt thereof, which has potent human dUTPase inhibitory activity and is useful as, for example, an antitumor drug. A uracil compound represented by the general formula (I) or a salt thereof: wherein n represents an integer of 1 to 3; X represents a bond, an oxygen atom, a sulfur atom, or the like; Y represents a linear or branched alkylene group having 1 to 8 carbon atoms, or the like; and Z represents -SO2NR1R2 or -NR3SO2-R4, wherein R1 and R2 each represent an alkyl group having 1 to 6 carbon atoms, an aralkyl group which is optionally substituted, or the like; R3 represents an alkyl group having 1 to 6 carbon atoms, or the like; and R4 represents an aromatic hydrocarbon group, an unsaturated heterocyclic group, or the like.
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- ARYLUREA DERIVATIVES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY
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A compound of formula (I), wherein substituents are as given above, useful in the treatment of a disease mediated by the action of CCR3, in particular inflammatory or obstructive airway diseases.
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Page/Page column 61
(2008/06/13)
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