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Author

Nobuo Shimma

Other affiliations: Chugai Pharmaceutical Co.
Bio: Nobuo Shimma is an academic researcher from Hoffmann-La Roche. The author has contributed to research in topics: Alkyl & Capecitabine. The author has an hindex of 24, co-authored 92 publications receiving 3160 citations. Previous affiliations of Nobuo Shimma include Chugai Pharmaceutical Co..


Papers
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Journal ArticleDOI
TL;DR: Capecitabine, which is finally converted to 5-FU by dThdPase in tumours, should be much safer and more effective than5-FU, and this was indeed the case in the HCT116 human colon cancer and the MX-1 breast cancer xenograft models.

1,214 citations

Journal ArticleDOI
TL;DR: In tests with various human cancer xenograft models, capecitabine was more efficacious at wider dose ranges than either 5-FU or 5'-DFUR and was significantly less toxic to the intestinal tract than the others in monkeys.

156 citations

Patent
21 Aug 2001
TL;DR: The use of compounds of formula (I) is defined in this paper, where the use of I is defined as the mixture of two or more carbon atoms, each of which is substituted with four different substituents.
Abstract: Use of compounds of formula (I), wherein R1 is hydrogen, hydroxy, alkyl, hydroxyalkyl, alkoxy, halogen, cyano, isocyano or azido; R2 is hydrogen, hydroxy, alkoxy, chlorine, bromine or iodine; R3 is hydrogen; or R?2 and R3? together represent =CH?2?; or R?2 and R3? represent fluorine; X is O, s or CH?2?; a, b, c, d denoting asymmetric carbon atoms each of which is substituted with 4 different substituents; and B signifies a purine base B1 which is connected through the 9-nitrogen of formula (B1), wherein R?4? is hydrogen, hydroxyl, alkyl, alkoxy, alkylthio, aryloxy, arylthio, heterocyclyl, NR7R8, halogen or SH; R5 is hydrogen, hydroxy, alkyl, haloalkyl, cycloalkyl, alkoxy, alkylthio, aryl, aryloxy, arylthio, heterocyclyl, heterocyclylamino, halogen, NR?7R8, NHOR9, NHNR7R8? or SH; R6 is hydrogen, hydroxy, alkyl, alkoxy, alkylthio, aryloxy, arylthio, heterocyclyl, NR7R8, halogen, SH or cyano; R?7 and R8? are independently of each other hydrogen, alkyl, aryl, hydroxyalkyl, alkenylalkyl, alkynylalkyl, cycloalkyl or acyl; R9 is hydrogen, alkyl or aryl; or B signifies an oxidised purine base B2 which is connected through the 9-nitrogen of formula (B2), wherein R?4, R5 and R6? are as defined above; or B signifies a purine base B3 which is connected through the 9-nitrogen of formula (B3), wherein R?4 and R6? are as defined above; R10 is hydrogen, alkyl or aryl; Y is O, S or NR11; R11 is hydrogen, hydroxy, alkyl, OR9, heterocyclyl or NR?7R8; R7, R8 and R9? are as defined above; or B signifies a pyrimidine base B4 which is connected through the 1-nitrogen of formula (B4), wherein Z is O or S; R12 is hydrogen, hydroxy, alkyl, alkoxy, haloalkyl, alkylthio, aryl, aryloxy, arylthio, heterocyclyl, heterocyclylamino, halogen, NR?7R8, NHOR9, NHNR7R8? or SH; R13 is hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, haloalkyl, cycloalkyl or halogen; R?7, R8 and R9? are as defined above; or B signifies a pyrimidine base B5 which is connected through the 1-nitrogen of formula (B5), wherein Y, Z, R10 are as defined above for the treatment of diseases mediated by the Hepatitis C Virus (HIV) or for the preparation of a medicament for such treatment. The invention is concerned with novel and known purine and pyrimidine nucleoside derivatives, their use as inhibitors of subgenomic Hepatitis C Virus (HCV) RNA replication and pharmaceutical compositions of such compounds.

146 citations

Patent
14 Sep 2009
TL;DR: In this article, the use of nucleoside derivatives of formula I for the treatment of diseases mediated by the hepatitis C Virus (HCV) for the preparation of a medicament for such treatment and to pharmaceutical compositions containing such compounds.
Abstract: The present invention relates to the use of nucleoside derivatives of formula I wherein B signifies a 9-purinyl residue B1 of formula or a 1-pyrimidyl residue B2 of formula wherein the symbols are as defined in the specification, and of pharmaceutically acceptable salts thereof; for the treatment of diseases mediated by the Hepatitis C Virus (HCV), for the preparation of a medicament for such treatment and to pharmaceutical compositions containing such compounds.

122 citations

Patent
26 Mar 2002
TL;DR: In this paper, the use of known 2′-deoxy-2′-fluoro nucleoside derivatives as inhibitors of hepatitis C virus (HCV) RNA replication and pharmaceutical compositions of such compounds are described.
Abstract: The present invention comprises nucleoside derivatives for use in the treatment or prophylaxis of hepatitis C virus infections. In particular, the present invention discloses the novel use of known 2′-deoxy-2′-fluoro nucleoside derivatives as inhibitors of hepatitis C virus (HCV) RNA replication and pharmaceutical compositions of such compounds. The compounds of this invention have potential use as therapeutic agents for the treatment of HCV infections.

119 citations


Cited by
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Journal ArticleDOI
TL;DR: This work has shown that novel genes identified in DNA microarray profiling have the potential to identify novel genes that are involved in mediating resistance to 5-FU, and these genes might prove to be therapeutically valuable as new targets for chemotherapy, or as predictive biomarkers of response to5-FU-based chemotherapy.
Abstract: 5-fluorouracil (5-FU) is widely used in the treatment of cancer. Over the past 20 years, increased understanding of the mechanism of action of 5-FU has led to the development of strategies that increase its anticancer activity. Despite these advances, drug resistance remains a significant limitation to the clinical use of 5-FU. Emerging technologies, such as DNA microarray profiling, have the potential to identify novel genes that are involved in mediating resistance to 5-FU. Such target genes might prove to be therapeutically valuable as new targets for chemotherapy, or as predictive biomarkers of response to 5-FU-based chemotherapy.

4,177 citations

Journal ArticleDOI
TL;DR: Introduced to the Market in the Last Decade (2001−2011) Jiang Wang,† María Sańchez-Rosello,́‡,§ Jose ́ Luis Aceña, Carlos del Pozo,‡ and Hong Liu.
Abstract: Introduced to the Market in the Last Decade (2001−2011) Jiang Wang,† María Sańchez-Rosello,́‡,§ Jose ́ Luis Aceña, Carlos del Pozo,‡ Alexander E. Sorochinsky, Santos Fustero,*,‡,§ Vadim A. Soloshonok,* and Hong Liu*,† †Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China ‡Department of Organic Chemistry, Faculty of Pharmacy, University of Valencia, Av. Vicente Andreś Estelleś, 46100 Burjassot, Valencia, Spain Laboratorio de Molećulas Orgańicas, Centro de Investigacioń Príncipe Felipe, C/ Eduardo Primo Yuf́era 3, 46012 Valencia, Spain Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel Lardizab́al 3, 20018 San Sebastian, Spain IKERBASQUE, Basque Foundation for Science, Alameda Urquijo, 36-5 Plaza Bizkaia, 48011 Bilbao, Spain Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Murmanska Street 1, 02660 Kyiv-94, Ukraine

3,368 citations

Journal ArticleDOI
TL;DR: Capecitabine and oxaliplatin are as effective as fluorouracil and cisplatin, respectively, in patients with previously untreated esophagogastric cancer, in a two-by-two design.
Abstract: For the capecitabine–fluorouracil comparison, the hazard ratio for death in the capecitabine group was 0.86 (95% confidence interval [CI], 0.80 to 0.99); for the oxaliplatin–cisplatin comparison, the hazard ratio for the oxaliplatin group was 0.92 (95% CI, 0.80 to 1.10). The upper limit of the confidence intervals for both hazard ratios excluded the predefined noninferiority margin of 1.23. Median survival times in the ECF, ECX, EOF, and EOX groups were 9.9 months, 9.9 months, 9.3 months, and 11.2 months, respectively; survival rates at 1 year were 37.7%, 40.8%, 40.4%, and 46.8%, respectively. In the secondary analysis, overall survival was longer with EOX than with ECF, with a hazard ratio for death of 0.80 in the EOX group (95% CI, 0.66 to 0.97; P = 0.02). Progression-free survival and response rates did not differ significantly among the regimens. Toxic effects of capecitabine and fluorouracil were similar. As compared with cisplatin, oxaliplatin was associated with lower incidences of grade 3 or 4 neutropenia, alopecia, renal toxicity, and thromboembolism but with slightly higher incidences of grade 3 or 4 diarrhea and neuropathy. Conclusions Capecitabine and oxaliplatin are as effective as fluorouracil and cisplatin, respectively, in patients with previously untreated esophagogastric cancer. (Current Controlled Trials number, ISRCTN51678883.)

1,987 citations

Journal Article
29 Jun 1993-Genomics
TL;DR: In this paper, a genotypic screen was developed to identify a heterozygous recessive mutation at the URA3 locus, which was introduced by targeted mutagenesis, homologous integration of transforming DNA, to avoid introduction of extraneous mutations.

1,595 citations