著者

西村 卓三 清水 文治 岩井 一成

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.11, no.11, pp.1470-1472, 1963-11-25 (Released:2008-03-31)

被引用文献数

35 55

著者

Shu-Hua Qi Si Zhang Cheng-Hai Gao Qin-Xing Li

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.58, no.6, pp.884, 2010-06-01 (Released:2010-06-02)

被引用文献数

2 3

著者

Hajime KATAYAMA Yusuke KAWADA Kimiyoshi KANEKO Takamitsu OSHIYAMA Noriyuki TAKATSU

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.47, no.1, pp.48-53, 1999-01-15 (Released:2008-03-31)

参考文献数

31

被引用文献数

9 17

---

A new type of synthetic inhibitor of DNA topoisomerase I and II was examined and several of these derivatives exhibited strong dual activity against these enzymes. This series of compounds showed high cytotoxic activities against cancer cells, but only a limited number of compounds showed any noticeable activity in an in vivo test against murine P388. Non-specific toxicity was observed in the in vivo tests.

著者

Judith RAZAFIMBELO Genevieve BAUDOUIN Francois TILLEQUIN Pierre RENARD Stephane LEONCE Alain PIERRE Ghanem ATASSI

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.46, no.1, pp.34-41, 1998-01-15 (Released:2008-03-31)

参考文献数

33

被引用文献数

3 4

---

Condensation of 5-amino, 6-amino, 7-amino and 8-amino-2, 2-dimethyl-2H-chromenes with either 6-bromo-veratraldehyde or 6-chloropiperonal afforded the corresponding Schiff bases, which were subsequently reduced to the corresponding benzylchromenylamines 30-33 and 36-39. Lithium diisopropylamide-mediated cyclization of those amines, followed by spontaneous air oxidation, afforded pyranophenanthridines 3-14. The cytotoxicity of compounds 3-14 was evaluated against L1210 and HT29 cell lines. 9, 9-Dimethyl-9H-pyrano[3, 2-b]phenanthridines appear to be the most promising compounds of the series, since both the dimethoxy derivative 11 and the methylenedioxy derivative 12 exhibit significant cytotoxic activity. Compound 12 was the most active and induced a massive accumulation of cells in G2+M phases, suggesting that the cytotoxicity is due to a perturbation of the integrity or function of DNA.

著者

山脇 一郎 鈴木 雅博 小川 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.42, no.4, pp.963-971, 1994-04-15 (Released:2008-03-31)

参考文献数

23

被引用文献数

1 1

---

Piperazinealkanol ester derivatives of indomethacin were prepared and tested for inhibitory activities against 5-lipoxygenase (5-LO) and cyclooxygenase (CO). They inhibited 5-hydroxyeicosatetraenoic acid (5-HETE) formation by the cytosol of guinea pig polymorphonuclear leukocytes and thromboxane B2 (TXB2) formation by washed rabit platelet suspension. Of the test compounds, 2-[4-(2-hydroxyethyl)-1-piperazinyl]-1-phenylethyl 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-3-indolylacetate dimaleate (II-8) was found to be the most active dual inhibitor of 5-LO and CO, and its inhibitory potency was higher than that of 2-[4-(3-hydroxypropyl)-1-piperazinyl]-ethyl [1-(4-chlorobenzoyl)-5-methoxy-2-methyl]-3-indolylacetate (CR-1015) (I), the lead compound.

著者

秋山 稔 大石 順一 白井 孝 明石 景泰 吉田 浩一 錦戸 条二 林 絋 白淵 穣 西村 大吉 伊藤 平隆 渋屋 千征 石田 寅夫

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.3, pp.981-984, 1978-03-25 (Released:2008-03-31)

被引用文献数

14 21

---

In order to obtain 1-β-D-arabinofuranosylcytosine derivatives with better antitumor effect, 12 kinds of saturated fatty acyl groups were introduced at the N4-position of 1-β-D-arabinofuranosylcytosine. The presence of a great excess of water and about two-fold equivalents of carboxylic anhydride was found to be most desirable for selective N4-acylation. This simple method of one-step N4-acylation should be generally applicable to cytosine nucleosides and a variety of carboxylic anhydrides.

著者

赤羽 健司 永野 泰夫 梅山 秀明

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.37, no.1, pp.86-92, 1989-01-25 (Released:2008-03-31)

参考文献数

26

被引用文献数

4 8

---

Two empirical indices accounting for the hydrophobic interaction are described. The first index is a "hydrophobic field-effect (Hf) index, "which indicates the hydrophobic nature of the binding site of a host molecule such as an enzyme, and the second index is a "hydrophobic correlation (Hc) index", which indicates the hydrophobic correspondency between a host molecule and its guest molecule such as a ligand. Furthermore, a method to calculate the surface area of a molecule is described, in which the molecular surface is treated as a set of area-preserving spherical triangles. The hydrophobic effects on the interaction between papain and its inhibitor benzyloxycarbonyl-L-phenylalanyl-L-alanyl-methylene (Z-Phe-Ala-CH2-), which is covalently bound to catalytic Cys Sγ of the enzyme, were investigated by using these indices. It is quantitatively shown that the binding sites interacting with the benzene rings of P2 Phe and P3 Z are more hydrophobic, while the site of the carbonyl group of P1 Ala is more hydrophilic. The substrate specificity of papain can be explained in part by these indices. Both the Hc and Hf indices are visualized by using computer graphics. These indices would be useful as quantitative structure-activity relationship (QSAR) parameters.

著者

Yasuki YAMADA Koji ANDO Yukishige IKEMOTO Hiroki TADA Eiji SHIRAKAWA Eiji INAGAKI Saizo SHIBATA Ikuro NAKAMURA Yoshiharu HAYASHI Kiyoteru IKEGAMI Itsuo UCHIDA

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.45, no.10, pp.1631-1641, 1997-10-15 (Released:2008-03-31)

参考文献数

32

被引用文献数

4 4

---

A series of renin inhibitors containing the (2S, 3S, 5S)-2-amino-1-cyclohexyl-6-methyl-3, 5-heptanediol (2-amino-3, 5-anti-diol) fragment as a novel transition-state mimic was synthesized, and their biological activities were evaluated. All of the synthesized compounds containing the 2-amino-3, 5-anti-diol fragment at the P1-P1' position showed high in vitro renin-inhibitory activity with IC50 values in the 10-8-10-10M range, and most of them caused a reduction of blood pressure when administered orally to salt-depleted, conscious marmosets. The inhibitor (29) with the 4-hydroxypiperidine residue at the P4 position showed the highest activity in terms of both potency and duration of the blood pressure-lowering effect.

著者

赤羽 健司 上條 哲聖 飯塚 欣二 田口 武夫 小林 義郎 木曽 良明 梅山 秀明

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.9, pp.3447-3452, 1988-09-25 (Released:2008-03-31)

参考文献数

31

被引用文献数

3 4

---

The structure-activity relationship of acyl-His-trifluorinated leucinol derivatives as inhibitors of human renal renin is discussed based upon the tertiary structure of human renin, which was deduced from the crystal structure of penicillopepsin by assuming structural similarity. The structural requirements for the inhibitors and possible interactions at the renin binding site are discussed.

著者

飯塚 欣二 上條 哲聖 原田 弘 赤羽 健司 久保田 哲弘 島岡 巌 梅山 秀明 木曽 良明

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.6, pp.2278-2281, 1988-06-25 (Released:2008-03-31)

参考文献数

11

被引用文献数

4 4

---

New human renin inhibitors were designed from transition-state analogues of angiotensinogen, synthesized and evaluated. The peptide derovative, which contained 1-naphthylmethylsuccinylamide residue (P3) with a retro-inverso amide bond and a norstatine isoamylamide residue (P1-P1'), was stable to proteases and had potent human renin inhibitory activity. This compact inhibitor exhibited hypotension when administered orally to a monkey.

著者

飯塚 欣二 上條 哲聖 原田 弘 赤羽 健司 久保田 哲弘 江藤 裕夫 島岡 厳 椿 敦 村上 真 山口 敏章 伊與部 亮 梅山 秀明 木曽 良明

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.38, no.9, pp.2487-2493, 1990-09-25 (Released:2008-03-31)

参考文献数

33

被引用文献数

7 11

---

The synthesis and the structure-activity relationships of renin inhibitors designed from the angiotensinogen transition state are described. These inhibitors contained residues modified at P1-P1, , P2, and P4-P3. Decrease in the size of side chain alkyl group in norstatine analog at P1 diminished the inhibitory activities of the compounds. Compound 5j, which contained valine residue instead of histidine residue at P2, inhibited potently cathepsin D (IC50=6.0×10-9 M) and pepsin (IC50=3.5×10-7 M) to the same extent as renin (IC50=8.5×10-10 M), and thus was not specific for renin. The reduction of the β-carbonyl group to methylene group in β-carbonylpropionyl residue at P4-P3 decreased the potency about 2 orders against human renin (5i : IC50=1.1×10-7 M vs. 1 : IC50=2.4 ×10-9 M). These results confirmed the rationality of our analysis of the interaction between an orally potent human renin inhibitor 1 and the active site of human renin using modeling techniques, showing that 1 fits the active site of renin favorably. The experimental details of the synthesis are presented.

著者

富田 真雄 新宮 徹朗 冨士谷 憲徳 古川 宏

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.13, no.8, pp.921-926, 1965-08-25 (Released:2008-03-31)

被引用文献数

25 32

---

The proton magnetic resonance spectra of N-methylcoclaurine type bases were examined and assignment of the alkoxyl groups and aromatic protons was presented. Correlations of the Chemical shifts with stereochemistry of the molecule were discussed.

著者

袖岡 幹子 小川 裕司 間瀬 俊明 柴崎 正勝

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.37, no.3, pp.586-598, 1989-03-25 (Released:2008-03-31)

参考文献数

48

被引用文献数

11 19

---

An efficient and useful synthesis of isocarbacyclins, potent carbon analogs of Prostacyclin(PGI2), has been accomplished.Three synthetic routes to isocarbacyclins using intramolecular thermal ene reaction or intramolecular aldol condensation as a key step are described.

著者

伊関 克彦 間瀬 俊明 岡崎 徳二 柴崎 正勝 池上 四郎

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.31, no.12, pp.4448-4455, 1983-12-25 (Released:2008-03-31)

参考文献数

21

被引用文献数

7 9

---

Biologically interesting 9 (O)-methano-△6-prostaglandin I1 (9 (O)-methano-△6-PGI1), a chemically stable analog of prostacyclin (PGI2), was efficiently synthesized from 1, 3-cyclooctadiene with high stereo- and regiochemical control. In all three biological test systems examined, 9 (O)-methano-△6-PGI1 was found to be considerably less active than prostaglandin E1 (PGE1).

著者

長尾 善光 萩原 裕一 山田 省三 落合 正仁 藤田 榮一

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.11, pp.4686-4689, 1984-11-25 (Released:2008-03-31)

参考文献数

15

被引用文献数

3 4

---

As a new extention of monitored aminolysis of 3-acyl-1, 3-thiazolidine-2-thione (ATT), a convenient procedure for the synthesis of αβ-unsaturated carboxylic acid amides has been developed using a new hetero-bifunctional reagent, 3-dimethylphosphonoacetyl-1, 3-thiazolidine-2-thione (DMPATT). DMPATT was effectively used as the bridging reagent between amino (or imino) compounds and aldehydes (or ketone) to afford various olefinic amides in good yields.

著者

藤井 澄三 小川 和男 板谷 泰助 伊達 忠正 稲垣 甚一郎 野原 富士夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.43, no.3, pp.408-413, 1995-03-15 (Released:2008-03-31)

参考文献数

25

被引用文献数

2 3

---

A full account is given of the first syntheses of 6-mercaptopurine 7-N-oxide (4) and 6-methylthiopurine 7-N-oxide (5). The synthesis of 4 followed a "phenacylamine route", which started from condensation of 4, 6-dichloro-5-nitropyrimidine (15) with N-(4-methoxybenzyl)phenacylamine to form the phenacylaminopyrimidine derivative (11) and proceeded through conversion into the mercapto derivative, intramolecular cyclization between the NO2 nitrogen atom and the phenacyl carbanion to give 6-mercapto-9-(4-methoxybenzyl)purine 7-N-oxide (12), and removal of the 4-methoxybenzyl group. S-Methylation of 12 and removal of the 4-methoxybenzyl group afforded 5. The location of the oxygen function in 4, 5, and 12 was confirmed by X-ray crystallographic analysis of 5·H2O, which was shown to exist in the N(7)-OH form (19). A UV spectroscopic approach suggested that the neutral species of 4 exists in HO as the N(7)-OH tautomer (21), whereas that of 5 exists as an equilibrated mixture of the N(7)-oxide (5) and the N(7)-OH (19) tautomers. In the in vitro bioassay of antileukemic activity against murine L5178Y cells, the N-oxides 4 and 12 were found to be weakly cytotoxic.

著者

板谷 泰助 小川 和男 松本 浩郎 渡辺 朝子

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.9, pp.2819-2824, 1980-09-25 (Released:2008-03-31)

参考文献数

11

被引用文献数

7 8

---

Heating N, N-diethyl-3, 9-dialkyladeninium halides (Ig-j) in aqueous sodium hydroxide gave 1-alkyl-5-(alkylamino)imidazole-4-carboxamides (IV) together with minor amounts of 1-alkyl-5-(alkylamino)imidazole-4-carbonitriles (III), which were converted into IV on further heating. N, N-Dimethyl-3, 9-dialkyladeninium halides (Ia-d) underwent hydrolysis more rapidly to provide IV selectively in 90-94% yields.

著者

藤井 澄三 小川 和男 斎藤 徹 板谷 泰助 伊藤 忠正 岡村 公生

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.43, no.2, pp.321-324, 1995-02-15 (Released:2008-03-31)

参考文献数

26

---

Oxidation of 1-benzyladenine (12) with m-chloroperoxybenzoic acid in MeOH or in MeOH-0.5 M phosphate buffer (pH 6.6) has been found to afford 1-benzyladenine 7-oxide (13) as the main product. Nonreductive debenzylation of 13 gave adenine 7-oxide (14) in 63% yield. The structure of 13 was unequivocally established by an X-ray crystallographic analysis.

著者

/ 藤井 澄三 斎藤 徹 TOHRU SAITO

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.5, pp.2037-2043, 1986-05-25 (Released:2008-03-31)

参考文献数

28

被引用文献数

9 14

---

A detailed account is given of the final step of the general 7-alkalation procedure for adenine (1), which consists of the preferential benzylation at the 3-position of 1, regioselective alkylation of the resulting 3-benzyladenine (2) to give 7-alkyl-3-benzyladenine salts (3a-c), and debenzylation of 3a-c leading to 7-alkyladenines (4a-c). Debenzylation of 3a-c (X=Cl or ClO4) has been achieved by hydrogenolysis using hydrogen and Pd-C catalyst at atmospheric pressure, producing 7-alkyladenines (4a-c) in 38-74% yields. The use of the allyl or γ, γ-dimethylallyl group at the 3-position instead of the benzyl group for the synthesis of 7-methyladenine (4a) by this procedure has no practical value. Alternatively, the salts 3a-c (X=Br, ClO4, or I) have been debenzylated efficiently by treatment with conc. H2SO4 in the presence of toluene at room temperature for 3-6h or at 60°C for 0.5-2h, giving 4a-c in 73-93% yields.

著者

藤井 澄三 小川 和男 斎藤 徹 小林 恵子 板谷 泰助 伊達 忠正 岡村 公生

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.43, no.1, pp.53-62, 1995-01-15 (Released:2008-03-31)

参考文献数

49

被引用文献数

3 4

---

A detailed account is given of the first unequivocal synthesis of adenine 7-oxide (8). The synthesis started with peroxycarboxylic acid oxidation of 3-benzyladenine (6), readily obtainable from adenine (1) by benzylation, and proceeded through nonreductive debenzylation of the resulting 3-benzyladenine 7-oxide (7). The location of the oxygen function in 7 and 8 was confirmed by their chemical reactions including deamination and methylation and by X-ray crystallographic analysis. A UV spectroscopic approach suggested that the neutral species of 8 exists in H2O as an equilibrated mixture of the N(7)-oxide (8) and N(7)-OH (21) tautomers. Treatment of 6 with 30% aqueous H2O2 in MeOH in the presence of MeCN and KHCO3 at 30°C produced the N(7)-oxide 7 and 7-acetamido-3-benzyladenine (15) in 12% and 1% yields, respectively.