著者

Shinji Oshima Kazuhiko Senoo Akio Negishi Hayato Akimoto Kousuke Ohara Naoko Inoue Shigeru Ohshima Nobuaki Kutsuma Kazuhiko Juni Daisuke Kobayashi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.39, no.3, pp.313-322, 2016-03-01 (Released:2016-03-01)

参考文献数

20

被引用文献数

2 6

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Article 25-2 of the Japanese Pharmacists’ Act was revised in June 2014, establishing the position of pharmacists as “advisors on the use of pharmaceuticals.” Prior to the Act’s revision, we investigated the perceptions of patients and pharmacists about pharmacists’ roles using a social science methodology. We also examined current opinions and necessary factors for the future growth and development of pharmacists. This questionnaire survey was conducted using an internet method. Patients and pharmacists answered 12 questions. Responses from 529 patients and 338 pharmacists were analyzed. For all items, pharmacists’ awareness of their roles exceeded patients’ awareness of the roles. In this study, the difference between pharmacist and patient awareness was larger than in similar research conducted in the United States. The greatest difference was observed in three items: “Understanding the effects of the drugs the patients are taking” (rate of high ratings: pharmacists 80.2%, patients 37.8%), “Understanding the health changes caused by the drugs dispensed to the patients” (pharmacists 80.2%, patients 28.4%), and “Consciously protecting patients from the adverse effects of drugs” (pharmacists 82.8%, patients 42.2%), indicating role discrepancy. Partition analysis indicated the three factors for a pharmacist to be regarded as a drug therapy or medication specialist: “The patient regards the pharmacist as his/her family or regular pharmacist,” “The pharmacist is making it easy for a patient to talk with him/her” and “The pharmacist is aware of a patient’s use of products other than prescribed drugs, such as over the counter (OTC) medications or health foods and nutritional supplements.” Future efforts are necessary to resolve role discrepancy and implement ongoing monitoring.

著者

Takashi Asada Masayoshi Omichi Tomoko Kimura Kikuo Oikawa

出版者

The Pharmaceutical Society of Japan

雑誌

Journal of Health Science (ISSN:13449702)

巻号頁・発行日

vol.47, no.4, pp.414-418, 2001 (Released:2002-03-29)

参考文献数

18

被引用文献数

4 7

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Both calcined shell calcium, which was recently reported to have bactericidal effects on Escherichia coli O157 : H7, Pseudomonas aeruginosa, and Staphylococcus aureus, and calcium oxide, which is the main component in calcined shell calcium, were examined as a bactericide against Legionella species. A calcined shell calcium solution of 0.025% or above reduced L. pneumophila counts from the original 7.0 × 106 CFU/ml to less than 300 CFU/ml after an incubation period of 1 hr. In water samples taken from the cooling tower of a prefabricated house, a calcined shell calcium solution of 0.05% or above reduced L. pneumophila counts to less than 10 CFU/ml after an incubation period of 1 hr. There was no difference between the bactericidal effects of the calcined shell calcium manufactured from the shells of surf clams and that manufactured from oysters; surf clams and oysters are equally effective. Calcium oxide also showed similar bactericidal effects against L. pneumophila, and thus we believe that the effect is not specific to calcined shell calcium, but rather to effects caused by the alkalinity of calcium oxide. The use of calcium oxide or calcined shell calcium as a bactericidal agent against Legionella species in the cooling tower water of hotels or other buildings is therefore expected.

著者

Insaf Bahrini Rikinari Hanayama

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.42, no.6, pp.977-981, 2019-06-01 (Released:2019-06-01)

参考文献数

26

被引用文献数

3

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Hepatitis C virus (HCV) infection leads to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma in 50–80% of the cases. Interferons (IFNs) and the nucleoside analog ribavirin form the basis of the treatment of this infection but are not considered sufficiently effective and cause several side effects. In this study, we developed a novel viral-specific drug delivery method. Enveloped viruses, including HCV, expose an anionic phospholipid, phosphatidylserine (PS), on their surface to mediate their binding and entry into cells for infection. To target such exposed PS on HCV, we developed a chimeric recombinant protein containing human IFN and mouse lactadherin (also known as milk fat globule epidermal growth factor 8), which binds with high affinity to PS. The IFN–lactadherin fusion protein showed a high binding affinity toward PS and HCV and consequently blocked viral replication in the infected cells more efficiently than conventional IFN. Overall, these data suggest that conjugation with lactadherin facilitates the delivery of any protein drug to PS-exposing enveloped viruses.

著者

Tomoki Yoshida Shuichi Hirono

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.67, no.6, pp.546-555, 2019-06-01 (Released:2019-06-01)

参考文献数

32

被引用文献数

13

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We report a three-dimensional quantitative structure–activity relationship (3D-QSAR) analysis of CDK2 inhibitors using fragment molecular orbital (FMO) calculations and partial least squares (PLS) regression. In our analysis, fragment binding energies of individual amino acids and fragment binding energy of a single ligand in a protein–ligand complex are evaluated by FMO calculations and used as descriptors in PLS regression to estimate biological activities of the ligands. The analysis was applied to the system of CDK2 protein and its inhibitors and the effectiveness of the method was tested. Application of the 3D-QSAR model demonstrated that it offered good predictive ability and was able to predict not only biological activity of ligands but also identify important amino acid residues which could be targeted in order to improve ligand activity.

著者

Kazuma Kaitoh Aki Nakatsu Shuichi Mori Hiroyuki Kagechika Yuichi Hashimoto Shinya Fujii

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.67, no.6, pp.566-575, 2019-06-01 (Released:2019-06-01)

参考文献数

33

被引用文献数

9

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We report here the development of phenylamino-1,3,5-triazine derivatives as novel nonsteroidal progesterone receptor (PR) antagonists. PR plays key roles in various physiological systems, including the female reproductive system, and PR antagonists are promising candidates for clinical treatment of multiple diseases. By using the phenylamino-1,3,5-triazine scaffold as a template structure, we designed and synthesized a series of 4-cyanophenylamino-1,3,5-triazine derivatives. The synthesized compounds exhibited PR antagonistic activity, and among them, compound 12n was the most potent (IC50 = 0.30 µM); it also showed significant binding affinity to the PR ligand-binding domain. Docking simulation supported the design rationale of the compounds. Our results suggest that the phenylamino-1,3,5-triazine scaffold is a versatile template for development of nonsteroidal PR antagonists and that the developed compounds are promising lead compounds for further structural development of nonsteroidal PR antagonists.

著者

浜田 康正 水野 章 大野 友靖 塩入 孝之

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.32, no.9, pp.3683-3685, 1984-09-25 (Released:2008-03-31)

参考文献数

12

被引用文献数

7 11

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Condensation of carboxylic acids with tert-butyl hydroperoxide has been smoothly achieved by the use of diethyl phosphorocyanidate and triethylamine under mild reaction conditions, giving tert-butyl peroxycarboxylates in good yields.

著者

川口 健夫 実吉 峯郎

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.36, no.5, pp.1899-1901, 1988-05-25 (Released:2008-03-31)

参考文献数

15

---

Inhibition constants (Ki) of pyrimidine acyclonucleosides and several normal pyrimidine metabolites for the phosphorolytic degradation of 5-fluoro-2'-deoxyuridine (FUdR) in rat and beagle tissue homogenates (liver and small intestine) were measured. Acyclothymidine (AcycTdR) showed the lowest Ki value for all the homogenates. The Ki/Km values of AcycTdR and acyclouridine (AcycUdR) depended on the homogenates, and the values (Ki/Km) in the rat liver homogenate were higher than those in all other homogenates.

著者

星 昭夫 飯郷 正明 実吉 峯郎 榑谷 和男

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.21, no.7, pp.1535-1538, 1973-07-25 (Released:2008-03-31)

被引用文献数

4 4

---

Deamination of cytidine derivatives especially of cyclocytidine by mouse kidney cytidine deaminase was examined. Cyclocytidine was not deaminated at either pH6.5 or pH7.3 by the enzyme. Furthermore, cyclocytidine did not inhibit the deamination of aracytidine and ([I]/[S])0.5 value for cyclocytidine was over 100. As a result, cyclocytidine is found to be markedly active compound with resistance against cytidine deaminase.

著者

濱田 福三郎 杉原 太助 津山 伸吾 平山 八彦 金井 貞 西村 昌数 榑谷 和男 星 昭夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.23, no.3, pp.586-591, 1975-03-25 (Released:2008-03-31)

被引用文献数

1 1

---

Newly synthesized 5-3H-cyclocytidine was injected intravenously in rhesus monkeys having a high level of cytidine deaminase which inactivates aracytidine, an antitumor substance analogous to cyclocytidine, in human plasma and tissues. After rapid distribution as intact molecule in the liver, kidney, spleen, and other organs, 46.5% of the administered radioactivity was excreted via the renal pathway within 160min. Metabolite analysis of 5-3H-cyclocytidine in plasma, tissues, and urine of the monkeys revealed that extensive or rapid degradation of cyclocytidine did not occur, and confirmed the resistance of cyclocytidine against the deaminase activity and its stability in biological condition in vivo. Phosphorylated derivatives of cyclocytidine were also detected in the monkey liver after injection.

著者

HIRAKU ONISHI TAKEO KAWAGUCHI TSUNEJI NAGAI

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.35, no.8, pp.3370-3374, 1987-08-25 (Released:2009-10-19)

参考文献数

22

被引用文献数

7 8

---

3'- (7-Carboxyheptanoyl) -5-fluoro-2'-deoxyuridine (C6-FUdR) was conjugated to decylenediamine-dextran T70 (T70-C10) or poly-L-lysine (PLL) by using 1-ethyl-3- (3-dimethylaminopropyl) -carbodiimide hydrochloride (EDC). Drug release patterns from the conjugates between C6-FUdR and T70-C10 (T70-C10-C6-FUdR) or PLL (PLL-C6-FUdR) by enzymatic and nonenzymatic processes were investigated at neutral and weakly acidic pHs. Under the nonenzymatic conditions, 5-fluoro-2'-deoxyuridine (FUdR) was released slowly only at neutral pH. This property is similar to that of C6-FUdR. Gradual drug release was observed enzymatically from T70-C10-C6-FUdR at both pHs, while PLL-C6-FUdR did not show enzymatic drug release. However, after the treatment of PLL-C6-FUdR with trypsin, FUdR was released enzymatically from the products; in this case, the release rate of FUdR was faster at neutral pH than at the weakly acidic pH. However, the release of FUdR by enzymatic processing was much slower from these conjugates than from C6-FUdR.

著者

川口 健夫 鈴木 嘉樹 南部 直樹 永井 恒司

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.33, no.7, pp.2956-2961, 1985-07-25 (Released:2008-03-31)

参考文献数

13

被引用文献数

6 8

---

Five acidic 3', 5'-diesters of 5-fluoro-2'-deoxyuridine (FUdR) including 3-carboxypropionate, 4-carboxybutyrate, 5-carboxypentanoate, 6-carboxyhexanoate and 7-carboxyheptanoate were synthesized, and their susceptibility to porcine liver, rat liver homogenate, rat intestinal homogenate and rat plasma esterase preparations was studied. The susceptibility of the derivatives to porcine liver esterase preparation increased as the number of methylene groups in the ester promoiety increased in both acidic (pH 5.0) and neutral (pH 7.0) solutions. The derivatives showed about 100 times higher reactivity to the esterase at pH 5.0 than at pH 7.0. With the rat tissue homogenates and plasma preparations, the longer the ester chain the higher the susceptibility, except for 3', 5'-bis (3-carboxypropionyl) FUdR (I) with rat liver homogenate. Though the reactivity of I was the lowest with porcine liver esterase preparation and not measurable with rat intestinal homogenate and plasma, I showed the highest reactivity with the rat liver homogenate.

著者

MINEO SANEYOSHI MOTOKO INOMATA TERUAKI SEKINE AKIO HOSHI FUMIKO FUKUOKA

出版者

The Pharmaceutical Society of Japan

雑誌

Journal of Pharmacobio-Dynamics (ISSN:0386846X)

巻号頁・発行日

vol.1, no.3, pp.168-174, 1978 (Released:2008-02-21)

参考文献数

12

被引用文献数

6 6

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Reaction of S-benzylthioisothiouronium hydrochloride with 6-mercaptopurine (1), 9-β-D-ribofuranosyl-6-mercaptopurine (2), 6-thioguanine (3) and 9-β-D-ribofuranosyl-6-thioguanine (4) afforded corresponding benzyl disulfide derivatives (5-8) in good yield. These compounds were converted easily to parent mercapto derivatives when they were treated with various reducing agents such as β-mercaptoethanol. Antitumor activity of compound 5 was higher than that of 1 both in ascites Sarcoma 180 and in Nakahara-Fukuoka sarcoma systems. However, toxicity and immunosuppressive activity of compound 5 and 6 were higher than those of 1 and 2, respectively.

著者

FUMIHIKO KANZAWA AKIO HOSHI KAZUO KURETANI

出版者

The Pharmaceutical Society of Japan

雑誌

Journal of Pharmacobio-Dynamics (ISSN:0386846X)

巻号頁・発行日

vol.3, no.8, pp.390-394, 1980 (Released:2008-02-19)

参考文献数

20

被引用文献数

1 1

---

5-Fluorouracil-resistant cell line designated as L5178Y/FU was established in this experiment. This is one of the colonies derived from the subculture which acquired resistance to 5-fluorouracil by passaging the L5178Y cells through ten successive episodes of culture in Fischer's medium containing 5-fluorouracil, in which each 5-fluorouracil treatment was followed by recovery intervals. The resistance of this line is about 80-fold that of the IC99 of 5-fluorouracil, and also shows a cross resistance to both 5-fluorouridine and 5-fluoro-2'-deoxyuridine. 5-Fluoro-2'-deoxyuridine resistant subline designated as L5178Y/FUdR was also isolated from the subculture which acquired resistance to 5-fluoro-2'-deoxyuridine by using the same selection procedure. The resistance of this line is about 650-fold that of the IC99 of 5-fluoro-2'-deoxyuridine, and shows a partial cross-resistance to 5-fluorouridine, but not to 5-fluorouracil.

著者

川口 健夫 鈴木 嘉樹 中原 葉子 南部 直樹 永井 恒司

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.33, no.1, pp.301-307, 1985-01-25 (Released:2008-03-31)

参考文献数

17

被引用文献数

13 16

---

The activity of porcine liver esterase towards diesters of 5-fluoro-2'-deoxyuridine with saturated aliphatic acids including acetic, propionic, butyric, hexanoic, octanoic, decanoic and dodecanoic acids was investigated. The susceptibility of the 3', 5'-diesters increased as the acyl chain was lengthened up to octanoyl, but further increase in the acyl chain length resulted in a sharp decrease in the susceptibility. The susceptibility of 3'-and 5'-monoesters increased as the chain was lengthened to decanoyl and slightly decreased on going to dodecanoyl. These results suggest that the higher antitumor activity of longer alkyl chain diesters of 5-fluoro-2'-deoxyuridine is partly due to their slow rates of hydrolysis by non-specific esterase.

著者

川口 健夫 斉藤 政彦 鈴木 嘉樹 南部 直樹 永井 恒司

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.33, no.4, pp.1652-1659, 1985-04-25 (Released:2008-03-31)

参考文献数

18

被引用文献数

21 24

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The bioactivation characteristics of 3', 5'-diesters of 5-fluoro-2'-deoxyuridine (FUdR) esterified with saturated aliphatic acids, including acetic, propionic, butyric, hexanoic, octanoic, decanoic, dodecanoic and trimethylacetic acids, were studied by using rat tissue homogenates and plasma. The susceptibility of the esters to hydrolysis by the biological media increased as the acyl promoiety was lengthened up to octanoyl. Further elongation resulted in decreasing susceptibility. Antitumor activity against L1210 of the esters with a longer chain or branched acyl group administered intraperitoneally and orally to tumor-bearing mice was also examined. Both the antitumor activity and the therapeutic index (ILSmax/ILS30) of the esters improved as the acyl promoiety was lengthened from octanoyl to dodecanoyl. These results suggested that the higher antitumor activities of longer alkyl chain diesters of FUdR are due to their slow rates of FUdR regeneration with esterases.

著者

実吉 峯郎 両角 正海 小玉 健次郎 町田 治彦 国中 明 吉野 宏

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.28, no.10, pp.2915-2923, 1980-10-25 (Released:2008-03-31)

参考文献数

24

被引用文献数

16 26

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Enzymatic selective dephosphorylation of 1-β-D-arabinofuranosylcytosine 3', 5'-diphosphate (1) with nuclease-3'-nucleotidase P1 at 60° for 24 hr gave 1-β-D-arabinofuranosylcytosine 5'-phosphate (Ara CMP) (2) in good yield. The acylation of both N4- and the 2', 3'-hydroxyl groups of 2 followed by coupling with various alcohols and phenols in the presence of 2, 4, 6-triisopropylbenzenesulfonyl chloride and subsequent alkaline hydrolysis afforded the title compounds (4). The resulting 32 kinds of Ara CMP alkyl or aryl esters were examined to determine their biological activities, such as antiviral activity against herpes simplex type 1 in cultured human embryonic lung fibroblast cells, growth inhibitory activity against mouse leukemic L5178Y cells in culture and antileukemic activity against L-1210 in mice. Ara CMP esters were active in these assay systems.

著者

FUMIHIKO KANZAWA YUKA MATSUSHIMA JUNICHI ISHIHARA AKIO HOSHI TAKEO OHBA KENZO WATANABE

出版者

The Pharmaceutical Society of Japan

雑誌

Journal of Pharmacobio-Dynamics (ISSN:0386846X)

巻号頁・発行日

vol.9, no.8, pp.688-693, 1986 (Released:2008-02-19)

参考文献数

16

被引用文献数

5 5

---

A series of twenty six 5'-substituted FdUMP (5-fluoro-2'-deoxyuridine 5'-monophosphate) have been evaluated for their inhibitory effects on the proliferation of murine lymphoma L5178Y cells sensitive or resistant to FUdR (5-fluoro-2'-deoxyuridine). 5'-Octylphenylene-FdUMP was the most active among these active derivatives against the parent cell line (L5178Y/P). Several other FdUMP derivatives also proved as potent as FUdR in their antiproliferating activity on the L5178Y/P cell line. Activity of these derivatives was decresed considerably by a substituent with a long aliphatic chain and the introduction of acyl groups on the C-3' position. Eicosyl-FdUMP was found to show no or low cross-resistance on the L5178Y/FUdR subline which was about 19000-fold resistant to FUdR compared with the parent cell line. This derivative might penetrate cell membrane in an intact form and be converted into FdUMP by a phosphodiesterase inside the cell, because an anabolic enzyme, deoxyuridine kinase, was defective in cells of the L5178Y/FUdR subline. The derivatives were promising as antitumor agents for the treatment of relapsed patients following 5-fluorouracil therapy.

著者

吉田 光二 星 昭夫 / 実吉 峯郎 MINEO SANEYOSHI

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.30, no.3, pp.1018-1023, 1982-03-25 (Released:2008-03-31)

参考文献数

23

被引用文献数

4 6

---

The mode of antiproliferative action of two 5-fluorocytosine nucleosides, 5-fluoro-cytidine (FCR) and 5-fluoro-2'-deoxycytidine (FCdR), was examined using mouse leukemia L5178Y cells in vitro. FCR and FCdR were markedly active against L5178Y cells, though the cells were deficient in cytidine deaminase activity. Both compounds increased the incorporation of 14C-labeled thymidine into the acid-insoluble fraction of L5178Y cells and decreased labeled deoxycytidine incorporation. In reversal studies, the antiproliferative effects of both compounds were almost abolished by simultaneous addition of thymidine or deoxyuridine. Deoxycytidine completely reversed the growth inhibition caused by FCdR, but not that caused by FCR. These results demonstrate that the cytotoxicity of both compounds is due to inhibition of thymidylate synthetase, presumably through formation of 5-fluoro-2'-deoxyuridine monophosphate (FdUMP) after deamination by deoxycytidylate deaminase in the pyrimidine de novo pathway.

著者

吉田 光二 榑谷 和男 星 昭夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.26, no.2, pp.429-434, 1978-02-25 (Released:2008-03-31)

被引用文献数

2 3

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5-Fluorouridine and 1-β-D-arabinofuranosylcytosine are active against various tumors as antimetabolites. Antitumor activity and mode of action of their nucleotides, 5-fluorouridine 5'-phosphate and 1-β-D-arabinofuranosylcytosine 5'-phosphate, were examined. 5-Fluorouridine 5'-phosphate was active similar to the nucleoside against L1210 leukemia, but the nucleotide showed higher therapeutic ratio than 5-fluorouracil and 5-fluorouridine. The mode of action of these nucleotides was examined by the incorporation of labeled precursors into acid-insoluble fraction of the cells for 30 min. Inhibition patterns of these nucleotides were the same as those of the nucleosides, but the potency of the nucleotides was very weak, and increased with time. Analysis showed that these nucleotides were dephosphorylated on the cell surface and the dephosphorylation was greater than that of phenolphthalein monophosphate. 5-Fluorouridine 5'-phosphate was considered to be a good candidate for an antitumor agent.

著者

/ 船越 和久 末宗 洋 大石 武 秋田 弘幸 酒井 浄 Kiyoshi Sakai

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.34, no.7, pp.3058-3060, 1986-07-25 (Released:2008-03-31)

参考文献数

9

被引用文献数

7 9

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Microbial reduction of 7-methoxycarbonyl bicyclo[4. 3. 0]non-3-en-8-one ((±)-3) afforded the optically active (-)-3, which was efficiently converted by ring contraction using thallium (III) nitrate to the intermediate (11) used to synthesize carbacyclin (1).