著者

沢田 誠吾 宮坂 貞 荒川 基一

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.25, no.12, pp.3370-3375, 1977-12-25 (Released:2008-03-31)

被引用文献数

5 5

---

Seventeen 3-(substituted-phenyl) thiazolo [2, 3-b] benzothiazolium perchlorates (3) were synthesized by acid-cyclization of the ketosulfides (2), which were prepared by alkylation of 2-mercaptobenzothiazole sodium salt with substituted phenacyl halides (1). Some of the phenacyl halides were prepared by chloroacetylation of substituted benzenes, and the others by bromination of the corresponding substituted acetophenones.

著者

沢田 誠吾 八重樫 隆 古田 富雄 横倉 輝男 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.41, no.2, pp.310-313, 1993-02-15 (Released:2008-03-31)

参考文献数

22

被引用文献数

13 20

---

7-Ethylcamptothecin (1d), a model which does not have any site on the A-ring for further modification was converted into water-soluble derivatives by opening the E-ring lactone. 1d was heated in N, N-dimethylenediamine to yield amide 2a, and this was then acylated to furnish 3a-q, which were soluble in water as their HCl salts. The propionyl (3b), butyryl (3c) and methylthiopropionyl (3h) derivatives showed higher activity than the sodium salt of 1d. The acyl group makes the derivatives more lipophilic, and ease of hydrolysis of amide 2a to 1d is thought to be necessary for significant activity.

著者

八重樫 隆 沢田 誠吾 古田 富雄 横倉 輝男 山口 健太郎 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.41, no.5, pp.971-974, 1993-05-15 (Released:2008-03-31)

参考文献数

10

被引用文献数

6 10

---

The structure of the N-amino pyridone (4a) obtained by the reaction of camptothecin (1a) with hydrazine was determined by X-ray crystallography. A mixture of 7-etylcamptothecin (1b) and hydrazine hydrate was stirred at room temperature, and the hydrazide (2b) was isolated as its diacetate 2c. Treatment of the 17-O-acetyl amide (5a) with hydrazine gave 1b (74% yield) and the N-amino lactam 6 (11% yield). Compounds with bulky acyl groups, 5c-e, gave 6 in modest yields. The N-amino lactam 6 was smoothly dehydrated into the pyridone 4d by refluxing in hydrazine hydrate.

著者

八重樫 隆 野方 健一郎 沢田 誠吾 古田 富雄 横倉 輝男 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.40, no.1, pp.131-135, 1992-01-25 (Released:2008-03-31)

参考文献数

19

被引用文献数

9 10

---

Water-soluble derivatives having the lactone ring intact were synthesized starting from 7-ethyl-10-hydroxycamptothecin (1). Glycosides (2) of the phenolic hydroxyl group of 1 were obtained by reaction with acetylated α-bromosugars in acetone or aqueous acetone in the presence of potassium carbonate, followed by deprotection.Phosphates (3) were prepared by reaction of 1 with phosphoryl chloride in pyridine or with dibenzylchlorophosphoridate.Sulfates (4) were obtained by reaction of 1 with sulfur trioxide-pyridine complex in the presence of a tertiary amine.The organic ammonium salts of monophosphate (3p) and sulfates (4a and 4b) showed significant activity against L1210 in vivo.

著者

沢田 誠吾 松岡 俊一 野方 健一郎 永田 洋 古田 富雄 横倉 輝男 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.39, no.12, pp.3183-3188, 1991-12-25 (Released:2008-03-31)

参考文献数

28

被引用文献数

39 57

---

20(S)-Camptothecin derivatives having nitro, amino, chloro, bromo, hydroxyl and methoxyl groups in the A-ring were synthesized. B-Ring hydrogenated camptothecin (2a) was converted into 10-hydroxycamptothecin (6e) by treatment with lead tetraacetate in trifluoroacetic acid. 10-Substituted derivatives (6) were obtained by a photoreaction of N-oxides (9). The cytotoxicity o the A-ring modified camptothecins was evaluated against KB cells in vitro and leukemia L1210 in mice. 7-Ethyl-10-hydroxycamptothecin (6i) was identified as a potential derivative for further modification.

著者

HIROYUKI HAYAKAWA KAZUHIRO HARAGUCHI HIROMICHI TANAKA TADASHI MIYASAKA

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.1, pp.72-79, 1987-01-25 (Released:2009-10-19)

参考文献数

16

被引用文献数

29 43

---

The sugar moiety of adenosine, inosine, or guanosine was protected with a tert-butyldimethylsilyl group. The C-8 lithiation of these protected nucleosides was carried out with lithium diisopropylamide in tetrahydrofuran at below -70°C. The reactions of the C-8-lithiated species with MeI, HCO2Me, and ClCO2Me were examined. The resulting products having a carbon substituent at the C-8 position were converted to the corresponding 8-carbon-substituted purine nucleosides by treatment with tetrabutylammonium fluoride. The whole sequence constitutes a simple method for the preparation of 8-carbon-substituted purine nucleosides from intact purine nucleosides.

著者

山根 晃 井上 英夫 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.28, no.1, pp.157-162, 1980-01-25 (Released:2008-03-31)

参考文献数

12

被引用文献数

10 19

---

Treatment of 4-thiouridine with phenacyl bromide, bromoacetone, and ethyl bromoacetate gave the corresponding 4-thioalkylcarbonyl derivatives. The sulfur extrusion reactions of these compounds afforded ribosides of 4-phenacylidene-2 (3H)-pyrimidinone, 4-acetonylidene-2 (3H)-pyrimidinone, and 2-pyrimidinone-4-acetic ester, respectively. The ease of sulfur extrusion depends on the electron-withdrawing ability of the carbonyl group attached to the 4-S-methylene group. Sulfur extrusion reactions starting from 6-thioinosine similarly gave the ribofuranosides of 6-phenacylpurine and 6-acetonylpurine. These purine ribosides exist meinly as the enol form rather than the keto form.

著者

山根 晃 松田 彰 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.28, no.1, pp.150-156, 1980-01-25 (Released:2008-03-31)

参考文献数

13

被引用文献数

13 26

---

Treatment of 6-methylsulfonyl-9-(2, 3, 5-tri-O-benzoyl-β-D-ribofuranosyl) purine with ethyl acetoacetate and sodium hydride in tetrahydrofuran afforded, after deblocking, 6-ethoxycarbonylmethyl-9-β-D-ribofuranosylpurine. Similarly, replacement of the 6-methylsulfonyl moiety with other carbanions derived from diethyl malonate, ethyl cyanoacetate, malononitrile, nitromethane, and sodium cyanide gave the corresponding 6-C-substituted purine nucleosides. Most of these derivatives exist as the 6-(1H)-exomethylene tautomeric forms. 6-Ethoxycarbonylmethylpurine riboside was further converted to 6-methyl, ethyl, propyl, butyl, and pentyl-purine ribosides by decarboxylation or prior alkylation of the methylene group followed by de-carboxylation. This reaction sequence facilitated the preparation of hitherto almost inaccessible alkyl or C-substituted purine nucleosides.

著者

沢田 誠吾 岡島 悟 相山 律男 野方 健一郎 古田 富雄 横倉 輝雄 杉野 栄一 山口 健太郎 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.39, no.6, pp.1446-1454, 1991-06-25 (Released:2008-03-31)

参考文献数

18

被引用文献数

144 197

---

Nevel 36 derivatives (6), bonding the phenolic hydroxyl group of 7-ethyl-10-hydroxycamptothecin (4) with diamines through a monocarbamate linkage, were synthesized and their antitumor activity was evaluated in vivo. The derivatives were soluble in water as their HC1 salts wiht the E lactone ring intact and exhibited significant antitumor activity. One of the derivatives, 6-27 showed excellent activity against L1210 leukemia and other murine tumors.The structure of its hydrochloride trihydrate (CPT-11) was determined by spectroscopic and crystallographic methods.

著者

沢田 誠吾 野方 健一郎 古田 富雄 横倉 輝男 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.39, no.10, pp.2574-2580, 1991-10-25 (Released:2008-03-31)

参考文献数

14

被引用文献数

44 56

---

A radical substitution reaction of 20(S)-camptothecin (1) with methanol furnished 7-hydroxymethylcamptothecin (2). Reaction of 1 with primary alcohols higher than methanol gave 7-alkylcamptothecins (4), of which alkyl groups were one carbon less than the alcohols used and also 7-hydroxyalkylcamptothecins (5). For the preparation of 7-alkylcamptothecin (4), aldehydes were used as a radical source and several alkylated derivatives were synthesized. 7-Acyloxymethyl derivatives (6), 7-carbaldehyde (7), iminomethyl derivatives (10), acid (11), esters (12) and amides (13) were synthesized starting from 2. 7-Ethyl-(4b) and 7-propylcamptothecin (4c), acyloxymethyl compounds 6a, 6c and ethyl ester (12b) exhibited higher antitumor activity than 1 against L1210 in mice.

著者

山村 初雄 藤田 佳平衛

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.10, pp.2505-2508, 1991-10-25 (Released:2008-03-31)

参考文献数

24

被引用文献数

26 33

---

Heptakis(6-O-(p-tosyl))-β-cyclodextrin and heptakis(6-O-(p-tosyl))-2-O-(p-tosyl)-β-cyclodextrin were prepared by the reaction of β-cyclodextrin with p-tosyl chloride in pyridine. They were converted to heptakis(3, 6-anhydro)-β-cyclodextrin, constituted from alternative (1C4) glucose units.

著者

大島 悦男 佐藤 秀幸 小場瀬 宏之 内村 達雄 桑原 隆 小林 智

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.9, pp.2552-2554, 1992-09-25 (Released:2008-03-31)

参考文献数

8

被引用文献数

2 6

---

(Z)-11-[3-(Dimethlamino)propylidene]-2-(methoxycarbonyl)methyl-6, 11-dihydrodibenz[b, e]oxepin-9-acrylic acid (5) was prepared for application to the radiommunoassay of KW-4679 (1, (Z)-11-[3-(dimethylamino)propylidene]-6, 11-dihydrodibenz[b, e]oxepin-2-acetic acid hydrochloride). The acrylic acid moiety in the 9-position of 5 was employed for coupling with an amino group of bovine serum albumin (BSA) to provide 17. Subsequently, the conjugate 17 was treated with aquenus NaOH to hydrolyze the terminal methoxycarbonyl group in the 2-position of the BSA conjugated 5. Antiserum raised against the antigenic BSA-conjugate 4 finally obtained was specific for 1.

著者

熊沢 利昭 大島 悦男 原川 洋行 佐藤 秀幸 小場瀬 宏之 生地 由昌 石井 昭男 石井 秀衛 大森 健守

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.10, pp.2729-2733, 1991-10-25 (Released:2008-03-31)

参考文献数

14

被引用文献数

2 4

---

New methods for the preparation of multi-functionallized-6, 11-dihydrodibenz[b, e]oxepins were developed. The structural requirements of KW-4994 (1), a promising orally active antiallergic agent, were defined. A carboxyl group at C-2 was critical for enhanced antiallergic of 1. The introduction of bromine atom at C-9 of 1 could elongate the duration of the action of the parent. Antiplatelet acetivity, a new pharmacological property of this series of compounds, was observed in one of the derivatives of 1.

著者

大島 悦男 熊沢 利昭 滝沢 博 原川 洋行 佐藤 秀幸 小場瀬 宏之 生地 由昌 石井 昭男 石井 秀衛 大森 健守

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.10, pp.2724-2728, 1991-10-25 (Released:2008-03-31)

参考文献数

28

被引用文献数

2 3

---

A new series of 11-substituted 6, 11-dihydrodibenz[b, e]oxepin derivatives was synthesized and evaluated for antiallergic activity. Convenient methods for the preparation of sulfides from alcohols were developed. Structure-activity relationships are described. Compound 7, 11-[2-(dimethylamino)ethyl]thio-6, 11-dihydrodibenz[b, e]oxepin-2-carboxylic acid hydrochloride, was the most potent in the rat passive cutaneous anaphylaxis test (ED50=0.92 mg/lg p.o.). It had a potent inhibitory effect on anaphylactic bronchoconstriction in guinea pigs (ED50=0.029 mg/kg p.o.) and H1 receptor antagonistic effect (Ki=14 nM) with few central nervous system side effects. Additionally, an antagonistic effect against prostagrandin D2-induced contraction of isolated guinea pig trachea (pA2=5.73) was an attractive mechanism of action of the new antiallergic agent. Compound 7 was selected for further evaluation as KW-4994.

著者

山下 純一 山脇 一郎 上田 修一 安本 三治 采見 憲男 橋本 貞夫

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.12, pp.4258-4267, 1982-12-25 (Released:2008-03-31)

参考文献数

32

被引用文献数

15 18

---

Six types of 5-fluorouracil (5-FU) derivatives were synthesized ; namely, 2, 4-di-O-substituted, 2-O-substituted, 4-O-substituted, 1, 3-disubstituted, 1-substituted and 3-substituted compounds. After oral administration of these compounds to rats, the blood levels of 5-FU were determined. Among O-substituted derivatives, a 4-O-substituted derivative was most easily activated to 5-FU and 2-O-substituted derivatives were next most easily activated. Among N-substituted derivatives, acyl and sulfonyl derivatives showed the highest 5-FU releasing abilities and 1-alkoxymethyl substituted derivatives showed low ability. N-Alkyl substituted derivatives were not activated to 5-FU. Several compounds which gave higher blood levels of 5-FU than that obtained with 1-(tetrahydro-2-furyl)-5-fluorouracil (Thf-FU), as well as same related compounds, were selected and their antitumor activities were examined. The 2-O-substituted derivatives, 2-butoxy-5-fluoro-4 (1H)-pyrimidone (11) and 2-benzyloxy-5-fluoro-4 (1H)-pyrimidone (19), were as effective as Thf-FU. The activities of 2, 4-di-O-substituted derivatives, 2, 4-dibutoxy-5-fluoropyrimidine (1) and 2, 4-dibenzyloxy-5-fluoropyrimidine (6), against Ehrlich carcinoma and against sarcoma 180, respectively, were the same as those of Thf-FU. The 1-substituted derivatives, 1-ethoxymethyl-5-fluorouracil (49) and 1-(1-ethoxy-1-phenylmethyl)-5-fluorouracil (50), were found to be as effective as Thf-FU.

著者

川瀬 雅子 鮫島 啓二郎 岡田 正志 越智 清成 松永 功

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.2395-2402, 1985-06-25 (Released:2008-03-31)

参考文献数

14

被引用文献数

2 5

---

Derivatives of 5-fluorouracil (5-FU) substituted at the N-1 position were synthesized in order to investigate their enzymatic conversion to N1-(2-formylethyl)-5-FU, which is expected to give 5-FU with concomitant release of acrolein. Proton nuclear magnetic resonance spectroscopic studies of authentic N1-(2-formylethyl)-5-FU suggested that the compound exists in an equilibrium mixture of free aldehyde and cyclic hemiacetal forms. Spontaneous liberation of 5-FU from N1-(2-formylethyl)-5-FU at neutral pH was demonstrated by thin-layer chromatography using both the authentic compound and N1-(3-aminopropyl)-5-FU after treatment with amine oxidase, but the release of 5-FU seemed to be limited. Cytotoxicity was observed with N1-(2-formylethyl)-5-FU and N1-(3-aminopropyl)-5-FU, but none of the derivatives of 5-FU presently prepared showed a positive effect on P388 leukemia inoculated into mice.

著者

佐伯 清太郎 林 貴昭 浜名 政和

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.6, pp.2154-2159, 1984-06-25 (Released:2008-03-31)

参考文献数

2

被引用文献数

1 6

---

The pseudo-Gomberg reaction of 1-substituted pyrrole derivatives with substituted anilines was examined. Pyrrole derivatives with electron-attracting groups at the 1-position, i.e., ethoxycarbonyl, methanesulfonyl, and benzoyl groups, were found to react smoothly with nitroaniline, chloroaniline and aniline. In each case, 2-arylated pyrrole derivatives were obtained in good or moderate yields.

著者

佐伯 清太郎 近藤 幸子 林 貴昭 浜名 政和

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.5, pp.1780-1789, 1984-05-25 (Released:2008-03-31)

参考文献数

6

被引用文献数

2 6

---

The 1-oxido-4-pyridyl radical generated by the reaction of 4-aminopyridine 1-oxide with amyl nitrite reacted smoothly with aromatic hydrocarbons, including five-membered heterocycles, i.e. thiophene, furan and pyrrole, to give the arylated products when acetic acid was used as the solvent. The relative rates of reaction with the 1-oxido-4-pyridyl radical indicated that this radical is electrophilic, and this finding was supported by a comparison of molecular orbital energy levels. 2-Aminopyridine 1-oxide also undergoes a similar reaction.

著者

Katsuhiro KONNO Katsuji OJIMA Takaaki HAYASHI Miyuki TANABE Hiroaki TAKAYAMA

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.1, pp.185-188, 1997-01-15 (Released:2008-03-31)

参考文献数

15

被引用文献数

4 6

---

Synthesis of a 1α, 25-dihydroxyvitamin D2 analog (3), in which the double bond in the side-chain in replaced by an amide group, is described. Condensation of a carboxylic acid (8) with an amine (6) gave an amide (9), which in turn led to 3 via several steps. The analog (3) could not bind to the chick cytosol vitamin D receptor, which indicated the importance of the hydrophobic interaction of the C(22)-C(23) double bond in 1α, 25-dihydroxyvitamin D2 (2) with the vitamin D receptor.

著者

林 貴昭 尾島 克二 紺野 勝弘 間中 明彦 山口 健太郎 山田 幸子 高山 浩明

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.11, pp.2932-2936, 1992-11-25 (Released:2008-03-31)

参考文献数

16

被引用文献数

5 4

---

A new synthesis of 24-fluoro-1α, 25-dihydroxyvitamin D2 (4a) and its 24-epimer (4b) is described. Starting with 1α, 3β-bis[(tert-butyldimethylsilyl)oxy]-24-norchol-5, 7-dien-23-al (5), a mixture of 4a and 4b was obtained in 3% overall yield in 6 steps. Reversed-phase HPLC cleanly separated the mixture into the two C-24 epimers. The X-ray crystallographic analysis of the 4-phenyl-1, 2, 4-triazoline-3, 5-dione (PTAD) adduct 11b, which was derived from the ester 6, unambiguously determined the configuration at C-24 of this compound. Based on the X-ray analysis, the configuration at C-24 of 4a and 4b was unequivocally determined.