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

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

---

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

---

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).

著者

ZHUO-FENG XIE YUKINOBU ICHIKAWA HIROSHI SUEMUNE 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.35, no.5, pp.1812-1816, 1987-05-25 (Released:2009-10-19)

参考文献数

9

被引用文献数

4 7

---

The conversion of (+) -limonen-10-ol (7) into the key intermediate for the synthesis of carbacyclin (1), (+) - (1S, 2R, 3R, 5R) -3-acetoxy-2-methoxycarbony1-7-oxobicyclo [3.3.0] octane (2), is described. The cis-3, 4-disubstituted cyclopentanone prepared from 7 via a sequence of reactions involving Rh (I) -catalyzed cyclization could be converted to the 3-acetylbicyclo [3.3.0] oct-2-ene skeleton, which was subjected to 1, 4-addition reaction with CN-. The resulting cyano compound was transformed into the key intermediate 2 through appropriate modification of the substituents on the five-membered ring. This synthetic method provides a new route to carbacyclin.

著者

飯森 隆昌 村井 安 脇坂 康尋 大塚 晏央 大内 章吉 児玉 佳男 大石 武

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.41, no.4, pp.775-777, 1993-04-15 (Released:2008-03-31)

参考文献数

14

被引用文献数

2 8

---

Conformational restrictions of sangivamycin (1) could be achieved by the use of the gauche effect of the substitutents on the ribofranose moiety. The conformational deviations obtained by this method were found to nicely correlate with the inhibitory activity of PKC.

著者

池原 森男 伊村 純子

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.29, no.11, pp.3281-3285, 1981-11-25 (Released:2008-03-31)

参考文献数

10

被引用文献数

11 17

---

The reaction of N2-isobutyryl-9-(2'-O-trifluoromethanesulfonyl-3', 5'-di-O-tetrahydrofuranyl-β-D-arabinofuranosyl) guanine with tetra-n-butylammonium fluoride or an appropriate metal halide in dimethylformamide aftorded N2-isobutyryl-3', 5'-di-O-tetrahydrofuranyl-2'-halogeno-2'-deoxyguanosines. The deprotection of these products led to 2'-halogeno-2'-deoxyguanosines. The ultraviolet absorption properties, 1H and 13C nuclear magnetic resonance spectral properties of the products were recorded.

著者

上杉 晴一 三木 弘子 池原 森男

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.29, no.8, pp.2199-2204, 1981-08-25 (Released:2008-03-31)

参考文献数

41

被引用文献数

3 7

---

^<13>C nuclear magnetic resonance spectra of various 2'-substituted 2'-deoxyadenosines are presented. The relative substituent chemical shifts of each sugar carbon are analyzed in terms of a substituent electronegativity parameter and compared with the data for substituted cyclohexanes. The relative substituent chemical shifts of C2' and C4' are controlled mainly by the inductive effect of the substituent. Those of C1' and C3' cannot be interpreted by inductive effect only. Some effect which is perturbed by the presence of a cis-substituent seems to be operating. A good linear correlation was observed between the substituent chemical shift of C2' and the N conformer population in the furanose puckering equilibrium.

著者

池原 森男 伊村 純子

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.29, no.4, pp.1034-1038, 1981-04-25 (Released:2008-03-31)

参考文献数

18

被引用文献数

15 16

---

2'-Deoxy-2'-fluoroguanosine (VII) was synthesized starting from 8, 2'-anhydro-8-oxy-9-β-D-arabinofuranosylguanine (8, 2'-O-cycloguanosine) (I). Compound I was protected at 2-NH2 with an isobutyryl group and at 3'- and 5'-OH with tetrahydrofuranyl groups. The protected compound III was derivatized to the arabino nucleoside V and thence converted to VII by treatment with trifluoromethanesulfonyl chloride and tetra-n-butylammonium fluoride. The resulting 2'-deoxy-2'-fluoroguanosine showed a 3'-endo favored conformation.

著者

/ 岩本 真承 青木 俊二 田中 直美 田嶋 清子 山原 條二 高石 喜久 吉田 雅昭 富松 利明 玉井 洋進 Yoshin TAMAI

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.39, no.2, pp.397-399, 1991-02-25 (Released:2008-03-31)

参考文献数

9

被引用文献数

40 73

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It has been reported that an acetone extract of ginger and its fractions have anti-5-HT (5-hydroxytryptamine; serotonin) effects. In the present study, guinea pig ileum, rat stomach fundus and rabbit aortic strips are used in order to determined the constituents of fraction 2 which are responsible for anti-5-HT effect and to examine their pharmacological properties.The analysis of fraction 2-3 indicated that galanolactone, a diterpenoid, is one of the active constituents. In guinea pig ileum, galanolactone inhibited contractile responses to 5-HT with a pIC50 value 4.93. pIC50 value of galanolactone against the response to 2-methyl-5-HT, a selective 5-HT3 agonist, in the presence of methysergide at 1×10-5M was 5.10. pIC50 values of ICS 205-930, a selective 5-HT3 antagonist, were 5.30 and 7.49, respectively. The concentration-response curve of 5-HT was shown as a biphasic curve and galanolactone caused a selective shift to the right of the second phase.In the same preparations, the pIC50 value of galanolactone and ICS 205-930 against the response to carbamylcholine (CCh) was 4.45 and 4.46.The inhibitory effect of galanolactone on the 5-HT response in the stomach fundus and aortic strips was less than that in the ileum.In addition, in the thoracic aorta precontracted with 50 mM K+, the relaxing effect of galanolactone was about 1/10 of that of papaverine.These results suggest that the anti-5-HT effect of galanolactone, a diterpenoid isolated from ginger, is related to antagonism of 5-HT3 receptors.

著者

末宗 洋 田中 正一 尾葉石 浩 酒井 浄

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.1, pp.15-21, 1988-01-25 (Released:2008-03-31)

参考文献数

9

被引用文献数

9 18

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Synthesis of prostaglandin A2 (PGA2) by means of a route involving enzymatic reactions is described. Enantioselective reduction and hydrolysis of trans-3, 4-bis(methoxycarbonyl)cyclopentanone (1) were examined using yeasts or enzymes, and it was found that (+)- and (-)-1 are easily obtained by an enzymatic procedure. Compound (+)-1 was converted to the Corey intermediate for PGA2 via the regioselective hydrolysis of the (+)-diacetate (8) with porcine pancreatic lipase. This synthesis based on the enzymatic approach was proved to be useful for the synthesis of both PGA and PGE from (-)-1.

著者

Masayo SAKATA Takanori SUEDA Hirotaka IHARA Chuichi HIRAYAMA

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.44, no.2, pp.328-332, 1996-02-15 (Released:2008-03-31)

参考文献数

16

被引用文献数

2 3

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Novel copolymeric adsorbents for the selective removal of endotoxin from an acidic protein solution were prepared. The adsorbents comprise spherical copolymers derived from N, N-dimethylaminopropylacrylamide (DMAPAA) and divinylbenzene (DVB). When the molar ratio of DMAPAA to DVB was 80/20 (amino-group content : 5.1 meq/g) and the pore size (molecular mass exclusion of polysaccharide, Mlim) was 4000 to 10000, DMAPAA/DVB showed high endotoxin-adsorbing activity at pH 5.0 to 9.0 and ionic strengths of μ=0.05 to 0.4. The capacity of the adsorbent (Mlim : 4000) was 390 μg of endotoxin (lipopolysaccharide purified from E. coli O111 : B4) per ml of the adsorbent using the batchwise method. The apparent dissociation constant between endotoxin and the adsorbent was 2.2×10-12 M. On the other hand, the adsorption of bovine serum albumin, an acidic protein, by the adsorbent increased with an increase in Mlim from 4000 to 10000, but decreased with an increase in ionic strength (μ) from 0.05 to 0.2 As a result, DMAPAA/DVB (80/20)(Mlim : 4000)selectively removed endotoxin from various acidic protein solutions at pH 7.0 and μ=0.05. The residual concentration of endotoxin in the protein solution always decreased to a concentration lower than 0.1 ng/ml, and recovery of the protein was more than 97%.

著者

平山 忠一 坂田 眞砂代 大倉 幸洋 伊原 博隆 大隈 邦夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.40, no.8, pp.2106-2109, 1992-08-25 (Released:2008-03-31)

参考文献数

16

被引用文献数

10 10

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Attempts were made to prepare adsorbents having a high affinity for endotoxin in the culture supernatant of Bordetella pertussis. When poly(γ-methyl L-glutamate) (PMLG) was used as a matrix and amino groups as the ligand, the highest affinity for endotoxin was attained even at a high ionic strength (μ=0.2-0.4). PMLG beads containing amino groups of about 3.2 meq/g selectively removed endotoxin from the culture supernatant of B. pertussis without affecting the protective antigens. It was demonstrated that 1 ml of the wet adsorbent adsorbed 4.5 mg of endotoxin. The beads of PMLG derivatives, therefore, are considered to be a useful adsorbent for the removal of endotoxin from the pertussis vaccine, affecting neither filamentous hemagglutinin nor pertussis toxin.

著者

白石 忠義 亀山 啓司 今井 直博 堂本 剛史 勝見 郁男 渡辺 清

出版者

公益社団法人 日本薬学会

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.36, no.3, pp.974-981, 1988

被引用文献数

23

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A series of α-cyanocinnamamide derivatives was synthesized and evaluated for inhibitory activity against tyrosine-specific protein kinase using intact plasma membrane fractions from an epidermoid carcinoma cell line, A-431 cells. Among these compounds, several novel α-cyano-4-hydroxy-3, 5-disubstituted cinnamamide derivatives, e.g., α-cyano-3-ethoxy-4-gtdrixt-5-phenyl-thiomethylcinnamamide (ST 638), showed potent inhibitory activity. The studies on the structure-activity relationship revealed that the presence of the hydroxy group at the 4 position and the double bond in the α-cyano-4-hydroxycinnamamide skeleton was important for potent inhibitory activity, and that the presence of hydrophobic groups at the 3 and 5 positions on the benzene ring also enhanced the inhibitory activity of α-cyano-4-hydroxycinnamamide derivatives.

著者

原田平 輝志 前田 稔 金沢 洋子 桃園 裕子 小嶋 正治

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.3, pp.1407-1410, 1986-03-25 (Released:2008-03-31)

参考文献数

9

被引用文献数

6 7

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Interconversion of 2-deoxy-2-fluoro-D-glucose (FDG) and 2-deoxy-2-2-fluoro-D-mannose (FDM) catalyzed by acid has been detected by 19F-NMR method. Although FDG and FDM were stable towards 1 N hydrochloric acid, in stronger acidic media the two hexoses underwent epimerization at C-2.

著者

小嶋 正治 栗原 悟 金沢 洋子 原田平 輝志 前原 喜彦 遠藤 英也

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.3, pp.1194-1197, 1988-03-25 (Released:2008-03-31)

参考文献数

16

被引用文献数

8 11

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The metabolic products of 2-deoxy-2-fluoro-D-glucose (FDG) and 2-deoxy-2-fluoro-D-mannose (FDM) in sarcoma 180 cells transplanted in mice were investigated by fluorin-19 nuclear magnetic resonance (19F-NMR) spectroscopy. It became apparent that the administered FDG was converted to FDM (and/or FDM-6-phosphate) in tumor cells, and also the administered FDM was converted to FDG (and/or FDG-6-phosphate). At 9h after administration of FDM, the ratio of FDG (and/or FDG-6-phosphate) and FDM (and/or FDM-6-phosphate) reached equilibrium. On the other hand, it took more than 48h in the case of FDG administration. The equilibrium amount of FDM (and/or FDM-6-phosphate) was approximately four times as much as that of FDG (and/or FDG-6-phosphate) in both cases.

著者

Yoko Kanazawa Yuko Momozono Hideki Yamane Terushi Haradahira Minoru Maeda Masaharu Kojimaa

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.2, pp.895-897, 1987-02-25 (Released:2009-10-19)

参考文献数

5

被引用文献数

8 8

---

2-Deoxy-2-fluoro-D-glucose (FDG) or its 6-phosphate (FDG-6-P) was detected by19F NMR in the organs and urine of mice previously injected with 2-deoxy-2-fluoro-D-mannose (FDM). This conversion of FDG (-6-P) to FDM (-6-P) in vivo was reversible.

著者

原田平 輝志 前田 稔 甲斐 康信 尾前 裕子 小嶋 正治

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.165-172, 1985-01-25 (Released:2008-03-31)

参考文献数

22

被引用文献数

26 34

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Methyl 3-O-benzyl-4, 6-O-benzylidene-2-O-(trifluoromethanesulfonyl)-β-D-mannopyranoside (7) was examined as a substrate for the preparation of 2-deoxy-2-fluoro-D-glucose (1) by fluoride ion treatment. The triflate (7) reacted rapidly with tetraalkylammonium fluorides in acetonitrile or tetrahydrofuran to give methyl 3-O-benzyl-4, 6-O-benzylidene-2-deoxy-2-fluoro-β-D-glucopyranoside (10) in 52-57% yield. Removal of the protecting groups from 10 by the use of 50% methanesulfonic acid afforded the required 1 in good yield. This synthetic sequence may provide an effective alternative to known methods for preparing 18F-labeled 1.

著者

原田平 輝志 前田 稔 矢野 裕二 小嶋 正治

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.8, pp.3317-3319, 1984-08-25 (Released:2008-03-31)

参考文献数

9

被引用文献数

15 18

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A nucleophilic displacement reaction of methyl 3, 4-O-isopropylidene-2-O-(trifluoromethanesulfonyl)-6-O-trityl-β-D-talopyranoside (10) with tetraalkylammonium fluorides in acetonitrile gave methyl 2-deoxy-2-fluoro-3, 4-O-isopropylidene-6-O-trityl-β-D-galactopyranoside (11). Excellent conversion of 11 into 2-deoxy-2-fluoro-D-galactose (1) was achieved by hydrolysis with 5 N hydrochloric acid.

著者

菊川 清見 佐藤 史子 鶴尾 隆 井村 伸正 浮田 忠之進

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.16, no.6, pp.1110-1115, 1968-06-25 (Released:2008-03-31)

被引用文献数

13 23

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2'-O-Benzyl-4-methylthiouridine (III) and 2'-O-benzylcytidine (VI) were obtained by respective treatment of 4-methylthiouridine (II) and cytidine (V) with benzyl bromide in the presence of sodium hydride. By this reaction, highly specific benzylation of 2'-hydroxyl group of the ribonucleosides was achieved. The both compounds (III) and (VI) could easily be converted to 2'-O-benzyluridine (IV) which is an important intermediate in the synthesis of oligonucleotide.