著者

松永 康志 大田 涼子 坂東 信行 山田 博章 湯浅 宏 金谷 芳雄

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.720-724, 1993-04-15 (Released:2008-03-31)

参考文献数

10

被引用文献数

6 13

---

(E)-4-[1-[4-[2-(Dimethylamino)ethoxy]phenyl]-2-(4-isopropyl)phenyl]-1-butenyl]phenyl monophosphate (TAT-59) is a new drug for the treatment of breast cancer. Physical and chemical stability of a tablet consisting of TAT-59 powder and a few excipients (Formulated tablet), a tablet consisting of only TAT-59 power (TAT-59 tablet) and TAT-59 powder itself itself was evaluated based on water content, tensile strenght, porosity, the amount of TAT-59 and its hydrolysis product, DP-TAT-59.The water content of Formulated tablet increased with relative humidity (RH), whereas that of TAT-59 tablet and TAT-59 powder scarcely changed. The equilibrium water content of Formulated tablet was much greater than that of the TAT-59 tablet or TAT-59 powder due to adsorbed moisture by the excipients. The tensile strength and porosity of Formulated tablet decreased and increased linearly, respectively, with increasing water content. The degradation rate of TAT-59 decreased in the following order : Formulated tablet>TAT-59 tablet>TAT-59 powder. The relationship between equilibrium water content and degradation rate of the Formulated tablet was determined by the Carstensen equation, in which the interaction order between the durg and water content was 1.9, and the degration of TAT-59 in Formulated tablet was related to water content. Thus, it was found that the degradation of TAT-59 was accelerated by compression and addition of excipients.

著者

Akira OKU Kiichiro UETA KENJI ARAKAWA Tomomi KANO-ISHIHARA Mamoru MATSUMOTO Tetsuya ADACHI Koichiro YASUDA Kinsuke TSUDA Akira SAITO

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.23, no.12, pp.1434-1437, 2000-12-01 (Released:2008-04-10)

参考文献数

24

被引用文献数

17 26

---

T-1095, a derivative of phlorizin, is an orally active inhibitor of Na+ -glucose cotransporter (SGLT). We investigated the acute antihyperglycemic effect of T-1095 in streptozotocin-induced diabetic rats (STZ rats). T-1095 and its metabolite T-1095A inhibited the SGLT activity in brush border membranes prepared from kidneys of both normal and STZ rats, but the latter agent was approximately 10 times more potent than the former. Single oral administration of T-1095 (30-100 mg/kg) dose-dependently induced glycosuria in normal rats. The fed glucose levels in STZ rats were dose-dependently suppressed by single oral administration of T-1095 (3-100 mg/kg), whereas there was only marginal hypoglycemic effect in normal rats. Since there was no effect on blood glucose in nephrectomized STZ rats, inhibition of renal glucose reabsorption rather than intestinal glucose absorption mainly contributes to the antihyperglycemic effect of T-1095. In conclusion, T-1095 is the first orally active agent which has an acute antihyperglycemic action in the absence of endogeneous insulin secretion with a low risk of hypoglycemia and has therapeutic potential for treatment of diabetes mellitus.

著者

松田 彰 小尾 紀行 宮坂 貞

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.6, pp.2575-2578, 1985-06-25 (Released:2008-03-31)

参考文献数

21

被引用文献数

13 18

---

Reaction of 2', 3', 5'-tri-O-benzoyluridine (3) with 1-methylimidazole in the presence of phosphoryl chloride in acetonitrile afforded 3-methyl-1-imidazolium intermediate (4), from which a variety of 4-substituted pyrimidin-2 (1H)-one ribosides (5-12) were obtained in a one-pot manner by nucleophilic substitutions under mild conditions. Application of this method to 2'-deoxyriboside of several pyrimidines (13a, b, c) is also described.

著者

宮下 修 松村 興一 笠原 俊彦 島津 浩 橋本 直人

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.887-898, 1982-03-25 (Released:2008-03-31)

参考文献数

6

被引用文献数

3 8

---

Various derivatives of 5-fluoro-5, 6-dihydrouracil with an alkoxycarbonyl, substituted carbamoyl, or cyano group at C-5, and one of a variety of substituents, i.e., alkoxy, substituted mercapto, substituted amino, acyl amino, and alkylidene- and arylideneaminooxy at C-6, have been synthesized as a class of potential pro-drugs of autitumor agents, 5-fluorouracil (5-FU) and 1-(2-tetrahydrofuryl)-5-fluorouracil (Ftorafur). Antitumor activity of these compounds against leukemia P388 or L1210 in mice and antifungal activity against Botrytis cinerea are described.

著者

杉本 和朗 大木 貞雄

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.12, no.11, pp.1375-1378, 1964-11-25 (Released:2008-03-31)

被引用文献数

1 1

---

Aromatic nitrogen mustards containing an azo group (VII∼XV), a nitrogen mustard with a carrier and masking group, were synthesized in one step starting from p-amino-phenylalanine or aliphatic p-amino-phenyl acid.

著者

佐々木 正 源 勝麿

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.12, no.11, pp.1329-1338, 1964-11-25 (Released:2008-03-31)

被引用文献数

12 14

---

Im Rahmen der Untersuchungen der Synthesemoglichkeit von as-Triazin-N-oxyden, oxydierten wir 3-Amino- bzw. 3-Amino-5, 6-dimethyl-as-triazin durch Persaure, wobei sich die entsprechenden 5-Oxo-verbindungen und ein Mono-N-oxyd von 3-Amino-5, 6-dimethyl-as-triazin erhalten lieβen, deren Konstitutionen bzw. diejenigen der acetylierten Korpern durch Dipolmoment-Messungen sowie spektroskopisch diskutiert wurden.

著者

津田 恭介 生熊 晋 河村 正朗 太刀川 隆治 酒井 浄 田村 千尋 甘粕 治

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.12, no.11, pp.1357-1374, 1964-11-25 (Released:2008-03-31)

被引用文献数

126 208

---

The structures of both tetrodonic acid hydrobromide and 6, 11-diacetylanhydrotetrodotoxin hydroiodide were established by chemical and X-ray crystallographical research. Based upon structures of both these salts and upon other chemical information, we determined that tetrodotoxin and anhydrotetrodotoxin have zwitterionic hemilactal structures.

著者

田中 博道 高橋 隆子 富樫 浩之 上田 亨

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.11, pp.3322-3329, 1978-11-25 (Released:2008-03-31)

被引用文献数

5 8

---

Starting from 1-β-D-ribofuranosyl-2-oxo-4-imidazoline-4-carboxylic acid (1), obtained from uridine, various 2, 5'-O-cycloimidazole nucleosides have been prepared. The 2-oxo function of 1 was also converted to the 2-chloro and 2-thione functions. Whereas the circular dichroism (CD) spectra of 1 and related 2-oxo derivatives exhibited negative bands, their 5-bromo derivatives showed positive bands. All 2, 5'-O-cycloimidazole nucleosides showed strong negative CD bands which were in contrast to the results in the 8, 5'-O-cyclopurine nucleosides. The relationship between the sign of the CD bands and the orientation of the base moieties in imidazole nucleosides was discussed.

著者

宮澤 修平 岡野 和夫 下村 直之 川原 哲也 浅野 修 吉村 寛幸 河合 隆利 左右田 茂 吉田 豊 里 忠 町田 善正 山津 功

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.2, pp.521-523, 1992-02-25 (Released:2008-03-31)

参考文献数

14

被引用文献数

2 4

---

Optically active platelet-activating factor (PAF) receptor antagonist, (+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8, 11-dimethyl-2, 3, 4, 5-tetrahydro-8H-pyrido[4', 3' : 4, 5]thieno[3, 2-f][1, 2, 4]triazolo[4, 5-a][1, 4]diazepine (E6123), was synthesized on large-scale by optical resolution using (+)-dibenzoyl-D-tartaric acid. An X-ray crystallographic analysis clearly indicated that the absolute configuration of the synthesized E6123 was S.

著者

宮澤 修平 岡野 和夫 下村 直之 / 川原 哲也 浅野 修 吉村 寛幸 宮本 光明 佐久間 義範 村本 賢三 尾葉石 浩 原田 耕吉 梶間 隆 山田 浩司 角田 創 片山 敏 阿部 信也 浅川 直樹 左右田 茂 堀江 透 里 忠 町田 善正 片山 幸一 山津 功 Isao YAMATSU

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.12, pp.3215-3220, 1991-12-25 (Released:2008-03-31)

参考文献数

27

被引用文献数

6 9

---

A series of triazolodiazepines was synthesized and evaluated for anti-platelet activating factor (PAF) activities. Structure-activity relationship (SAR) studies on this series revealed that the introduction of a methyl group into the 8-position of the thienodiazepine nucleus can lead to a lengthening of the duration of action. Introduction of a methyl group produced an asymmetric center and the enantiomers so formed were separated with an optical resolving column. In the in vitro assay system, the (+)-isomers displayed 50-200 times more potent anti-PAF activity than the (-)-isomers. After comparison of toxicology and pharmacokinetics, (+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8, 11-dimethyl-2, 3, 4, 5-tetrahydro-8H-pyrido[4', 3' : 4, 5]thieno[3, 2-f][1, 2, 4]triazolo[4, 3-a][1, 4]diazepine (35(+)-isomer, E6123) was selected from among the compounds synthesized as a candidate for clinical study.

著者

Shigehiro Yanagihara Yuya Taniguchi Mareto Hosono Eiji Yoshioka Rika Ishikawa Yoshihiro Shimada Toshihiko Kadoya Kazuhiro Kutsukake

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.33, no.9, pp.1596-1599, 2010-09-01 (Released:2010-09-01)

参考文献数

22

被引用文献数

10 11

---

Assessment of biological potency and its comparison with clinical effects are important in the quality control of therapeutic glycoproteins. Animal models are usually used for evaluating bioactivity of these compounds. However, alternative methods are required to simplify the bioassay and avoid ethical issues associated with animal studies. Negatively charged sialic acid residues are known to be critical for in vivo bioactivity of recombinant human erythropoietin (rhEPO). In this study, we used capillary zone electrophoresis, a charge-based separation method, to estimate the sialic acid content for predicting in vivo bioactivity of rhEPO. In vivo bioactivities of rhEPO subfractions were measured and compared with sialylation levels. The results obtained indicated that in vivo bioactivity of rhEPO is not simply correlated with the sialylation level, which suggests that it is difficult to predict biological potency from the sialic acid content alone. N-Glycan moieties as well as sialic acid residues may have a significant impact on in vivo bioactivity of rhEPO.

著者

平山 晃久 中田 晴美 渡辺 徹志

出版者

The Pharmaceutical Society of Japan

雑誌

衛生化学 (ISSN:0013273X)

巻号頁・発行日

vol.38, no.5, pp.431-436, 1992-10-31 (Released:2008-05-30)

参考文献数

6

被引用文献数

1

---

The effect of nicotinamide on 7 kinds of mutagenic alkylating agents was investigated in Salmonella typhimurium TA100 without S9 mix, and its mechanism was studied. The mutagenic potency of alkylating agents other than N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was reduced to less than 50% by the addition of about 50-fold molar ratio of nicotinamide to alkylating agent. The mutagenic potency of MNNG was only reduced to 60-70% by the addition of more than 200-fold molar ratio of nicotinamide. To investigate the mechanism of the suppressive effect of nicotinamide, alkylating agents (1.0 μmol) (methyl methanesulfonate and dimethyl sulfate) were reacted with nicotinamide (1.0 μmol) alone or together with DNA or 5 kinds of nucleotides in phosphate buffer (pH 7.4) at 30°C for 24 h, and the resulting N1-methylnicotinamide (NMN) was analyzed by HPLC with fluorometric detection after derivatization. With the addition of DNA (0.2 molar ratio or more), the amount of NMN by methyl methane-sulfonate was reduced to 80% compared with nicotinamide alone, whereas that by dimethyl sulfate was unchanged. With the addition of nucleotides like guanosine-5'-phosphate, the amount of NMN by methyl methanesulfonate was reduced to 75%, whereas no reducing effect was seen by the other 4 nucleotides. The present results strongly suggest that nicotinamide is more easily alkylated than nucleic bases in DNA or nucleotides by methyl methanesulfonate and dimethyl sulfate, and that nicotinamide scavenged alkyl species derived from them, thereby showing a suppressive effect on the mutagenicity of alkylating agents. In MNNG, nicotinamide did not act as des-mutagen in Salmonella assay.

著者

Yoko Kanazawa Satoru Kuribayashi Masaharu Kojima Terushi Haradahira

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.10, pp.4213-4216, 1988-10-25 (Released:2011-02-08)

参考文献数

9

被引用文献数

9 10

---

The metabolic pathway of 2-deoxy-2-fluoro-D-galactose (FDGal) in mice was studied by 19F NMR. Efficient accumulation of FDGal in liver was demonstrated by NMR, which is consistent with the results of Ishiwata et al. using radioactive 18FDGal. The new discovery is that this fluorinated hexose was converted to 2-deoxy-2-fluoro-D-glucose (FDG) through UDP-FDGal and UDP-FDG apparently by the action of UDP-Gal epimerase.

著者

斉藤 仁 好川 博 西村 吉雄 近藤 信一 竹内 富雄 梅澤 濱夫

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.9, pp.3733-3740, 1986-09-25 (Released:2008-03-31)

参考文献数

42

被引用文献数

8 14

---

D-(and L-)Aminoglycosidic variants of 4'-O-demethyl-1-epipodophyllotoxin were synthesized by glycosidation of 4'-O-benzyloxycarbonyl- or 4'-O-chloroacetyl-4'-O-demethyl-1-epipodophyllotoxin (8 or 22) with the corresponding aminosugar derivatives. Cyclic acetals of 1-O-(2-amino-2-deoxy- and 3-amino-3-deoxy-β-D-glucopyranosyl)-4'-O-demethyl-1-epipodophyllotoxins (13 and 21) gave a significant survival time increase in mice with leukemia L-1210, and showed superior activity to VP-16-213 (etoposide, 5).

著者

神戸 敏江 土屋 香誉子 堀 誠 浴本 久雄 高橋 良和 竹内 富雄

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.17, no.4, pp.527-530, 1994-04-15 (Released:2008-04-10)

参考文献数

5

被引用文献数

1

---

Several antitumor anthracyclines, including those in preclinical stages, were examined for their action in reversing tumorous phenotypes of H- or K-ras 3T3 cells (NIH3T3 cells transformed by human H- or K-ras oncogene) into normal phenotypes, such as flattened cell morphology, anchorage dependent cell growth, etc. (referred to as anti-ras activity). The study elucidated relationships between the chemical structure of anthracyclines and the anti-ras activity. The human tumor cell line T24, which has a mutated H-ras gene, responded to the anthracyclines, as did K- or H-ras 3T3 cells, in respect to the phenotypic alterations. Pirarubicin was more than 4 times as active as aclarubicin in inhibiting the growth of solid tumors of K-ras 3T3 cells in nude mice, possibly reflecting a difference in anti-ras activity between the two antibiotics.

著者

埜渡 裕義 黒田 泰男 速水 宏 岡本 一也 浴本 久雄 高橋 克俊

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.9, pp.2406-2409, 1989-09-25 (Released:2008-03-31)

参考文献数

15

被引用文献数

14 18

---

Novel alkyl-1, 4-butanediamine Pt(II) complexes having a seven-membered ring structure were synthesized and characterized by fast atom bombardment mass and infrared spectra and elemental analysis. Their antitumor activities in vivo toward lymphoid leukemia L1210 and LEwis lung carcinoma LL were studied in the case where the leaving group was either dichloride or cyclobutane-1, 1-dicarboxylate. 1, 4-Butanediamine Pt(II) complexes (seven-membered ring) showed higher antitumor activities than those of ethylenediamine Pt(II)(five-membered ring) and 1, 3-propanediamine Pt(II)(six-membered ring) complexes toward L1210 for both leaving groups. Alkyl-1, 4-butanediamine Pt(II) complexes showed high antitumor activities toward L1210, except for 1, 1-dimethyl-1, 4-butanediamine Pt(II) complexes. In particular, 2, 2-dimethyl-1, 4-butanediamine and 2, 3-dimethyl-1, 4-butanediamine Pt(II) complexes exhibited excellent antitumor activities with T/C% values higher than 300. None of the dichloro Pt(II) complexes showed antitumor activities toward LL, but the cyclobutane-1, 1-dicarboxylato Pt(II) complexes, which were moderately active toward L1210 with T/C% values aroung 200, also showed high antitumor activities toward LL with T/C% values of more than 200. Alkyl-1, 4-butanediamine Pt(II) complexes with a seven-membered ring structure were found to be stable and to have antitumor activities in vivo.

著者

Hidetoshi Nakatake Hisao Ekimoto Mariko Aso Atsushi Ogawa Asami Yamaguchi Hiroshi Suemune

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.59, no.6, pp.710-713, 2011-06-01 (Released:2011-06-01)

参考文献数

20

被引用文献数

9 17

---

Bisphosphonates have high affinity for hydroxyapatite (HA), which is abundantly present in bone. Also, platinum complexes are known that have a wide spectrum of antitumor activities. The conjugate of bisphosphonate and a platinum complex might have HA affinity and antitumor activity, and become a drug for metastatic bone tumor. In this study, the authors synthesized platinum complexes that had dialkyl bisphosphonic acid as a ligand, and evaluated the possibility of the synthesized complexes as a drug for metastatic bone tumor. The synthesized dialkyl bisphosphonate platinum(II) complex was characterized, and its stability in an aqueous solution was also confirmed. The synthesized platinum complex showed higher HA affinity than other platinum complexes such as cisplatin and carboplatin in an experiment of adsorption to HA. In vitro, the platinum complex showed tumor growth inhibitory effect stronger than or equal to cisplatin, which is the most commonly used antitumor agent. Moreover, the platinum complex showed a bone absorption inhibitory effect on the osteoclast. These results suggest potential of dialkyl bisphosphonate platinum(II) complexes as a drug for metastatic bone tumor.

著者

門田 重利 高森 靖 / 菊池 徹 田中 謙 浴本 久雄 Hisao EKIMOTO

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.10, pp.2687-2697, 1990-10-25 (Released:2008-03-31)

参考文献数

22

被引用文献数

28 54

---

Woodfruticosin (woodfordin C), a new cyclic dimeric hydrolyzable tannin having an inhibitory activity toward deoxyribonucleic acid (DNA) topoisomerase II, has been isolated from the leaves of Woodfordia fruticosa KURZ (Lythraceae) along with three known flavonol glycosides and three known flavonol glycoside gallates. The structure of woodfruticosin (woodfordin C) was determined by the use of two-dimensional nuclear magnetic resonance (2-D NMR) spectroscopy including heteronuclear multiple quantum coherence (HMQC) and heteronuclear mucltiple bond connectivity (HMBC) techniques. Detailed analyses of the proton and carbon-13 NMR (1H-and 13C-NMR) spectra of six known flavonoids were performed.

著者

松田 彰 伊藤 弘子 竹貫 健二 佐々木 琢磨 上田 亨

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.945-953, 1988-03-25 (Released:2008-03-31)

参考文献数

21

被引用文献数

32 55

---

The reaction of 4-ethoxy-1-(3, 5-O-tetraisopropyldisiloxanyl-1, 3-diyl-β-D-erythro-pentofuran-2-ulosyl)-2(1H)-pyrimidinone (11) with various organometallic reagents yielded corresponding 2'-branched-chain sugar pyrimidine nucleosides. Only in the reactions with MeMgBr and EtMgBr was the more hindered β-attack observed to afford and 2'-alkyl ribofuranosides (13a, b). In the reaction of 11 with MeLi, Me3, Al, or PhMgBr, 2'-methyl or phenyl arabinosides (12a, b, c)were obtained stereoselectively. Conversion of these pyrimidine nucleosides into cytosine derivatives is also described and their antileukemic and antiviral activities are discussed.

著者

Tetsuji Noguchi Naoki Tanaka Toyoki Nishimata Riki Goto Miho Hayakawa Atsuhiro Sugidachi Taketoshi Ogawa Yoichi Niitsu Fumitoshi Asai Tomoko Ishizuka Koichi Fujimoto

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.57, no.1, pp.22-33, 2009-01-01 (Released:2009-01-01)

参考文献数

25

被引用文献数

10 13

---

To develop a novel and effective anticoagulant with potent and selective factor Xa (FXa) inhibitory activity, a new series of cinnamyl derivatives with enhanced lipophilicity and prodrug forms were synthesized and their biological activities were evaluated. As a result, we found that cinnamyl derivative (N-{4-[1-(acetimidoyl)piperidin-4-yloxy]-3-carbamoylphenyl}-N-[(Z)-3-(3-amidinophenyl)-2-fluoro-2-propenyl]sulfamoyl)acetic acid dihydrochloride (26d, R-142086) with a fluorine atom on the double bond exhibited potent anticoagulant activity and no mutagenic potential. Moreover, orally administered R-142086 exhibited potent anti-FXa activity and anticoagulant activity in dogs.