著者

紺野 勝弘 尾島 克二 林 貴昭 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.5, pp.1120-1124, 1992-05-25 (Released:2008-03-31)

参考文献数

17

被引用文献数

15 24

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An alternative synthesis of the title compound 2, a highly potent analog of 1α, 25-dihydroxyvitamin D3 (1), is described. Starting with 1α, 3β-bis[(tert-butyldimethylsilyl)oxy]androst-5-ene (8), 2 was obtained in 3.8% total yield through 10 steps. This method provides compound 2 in much higher yield than that reported previously.

著者

Toshio Honda Hitoshi Wakabayashi Kazuo Kanai

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.50, no.2, pp.307-308, 2002 (Released:2002-06-30)

参考文献数

23

被引用文献数

33 44

---

Chiral β-amino esters are synthesized in one-pot from three components, amines, aldehydes, and ethyl bromoacetate, under the rhodium-catalyzed Reformatsky-type reaction condition, where complete diastereoselection is achieved in the nucleophilic addition step of ethyl bromoacetate to the imines prepared in situ.

著者

Koichiro Nishimura Toshikazu Saitoh

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.64, no.7, pp.1043-1046, 2016-07-01 (Released:2016-07-01)

参考文献数

3

被引用文献数

1 1

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The 5-bromo-2-methylamino-8-methoxyquinazoline (1) is a key intermediate in our drug discoveries. Compound 1 bears a monomethylamino group at the 2-position of the quinazoline ring. This compound has been synthesized from 6-bromo-2-fluoro-3-methoxybenzaldehyde by a synthetic route including a total of four isolation processes in the medicinal chemistry laboratories. Our process chemistry laboratories successfully improved the original synthetic route by introducing the telescoping process. We successfully reduced the isolation processes from four to two processes by using information extracted through design of experiment. The total yield of compound 1 increased by 18%, while maintaining the purity of compound 1 of the original synthetic route. Accordingly, we contributed to the quick supply of compound 1 to the medicinal laboratories.

著者

廣橋 満 木戸 勝 山本 栄仁 小島 裕 實川 浩一郎 藤井 節郎

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.9, pp.1498-1506, 1993-09-15 (Released:2008-03-31)

参考文献数

23

被引用文献数

6 10

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The reactivities of 5-fluorouracil (5-FUra) degradation inhibitors, 2, 4- (2) and 2, 6-dihydroxypyridines (3), were investigated. Acylation of 2 and 2, 4-bis(trimethylsilyloxy)pyridines with equimolar amounts of acid chlorides preferentially occurred at the 4-OH and 2-OH positions, respectively, and the structure of monobenzoylated 5-chloro-2, 4-dihydroxypyridine (2b) was determined as 4-benzoyloxy-5-chloro-2-pyridone (5b) by X-ray crystallo-graphic analysis. Compounds 2 and 3, as well as the N-2-tetrahydrofuryl (11), N-alkyl (12), and N-carbamoyl (14) derivatives of 2, exhibit dynamic keto-enol tautomerism. The acyl derivatives of these pyridines are labile and are thought to be active esters. Monoacyl ester derivatives of these pyridines were combined with 5-FUra analogs to develop novel antitumor agents containing an inhibitor of 5-FUra degradation. One of them, 3-[3-(6-benzoyloxy-3-cyano-2-pyridyloxycarbonyl)benzoyl]-1-ethoxymethyl-5-fluorouracil (BOF-A2) (22b), was the most effective and is currently undergoing late phase-II clinical trials.

著者

尾崎 庄一郎 渡辺 裕 星子 知範 水野 晴雄 石川 勝敏 森 春樹

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.2, pp.733-738, 1984-02-25 (Released:2008-03-31)

参考文献数

16

被引用文献数

20 24

---

The toxicity and tumor affinity of 5-fluorouracil (1) have been modified by the introduction of acyloxyalkyl group (s) at the 1-, 3- or 1, 3-position (s) of 1. 1-Acyloxyalkyl-5-fluorouracil (3), 3-acyloxyalkyl-5-fluorouracil (4) and 1, 3-bis (acyloxyalkyl)-5-fluorouracil (5) were obtained by three methods : i) the reaction of α-chloroalkyl carboxylate (2) with 1, ii) the reaction of alkylidene diacylate with 2, 4-bis (trimethylsilyloxy)-5-fluoropyrimidine, iii) partial hydrolysis of 5. Compounds 3, 4 and 5 showed antitumor activity.

著者

上田 修一 武田 節夫 山脇 一郎 山下 純一 安本 三治 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.1, pp.125-131, 1982-01-25 (Released:2008-03-31)

参考文献数

20

被引用文献数

5 8

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A hydroxylated metabolite of 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT), 1-(trans-3-hydroxytetrahydro-2-furanyl)-5-fluorouracil (trans-3'-OH-FT, VIII) and its isomer, 1-(cis-3-hydroxytetrahydro-2-furanyl)-5-fluorouracil (cis-3'-OH-FT, VI), were synthesized and isolated at high purity. As compounds related to FT metabolites, 2, 3'-anhydro-1-(cis-3-hydroxytetrahydro-2-furanyl)-5-fluorouracil (2, 3'-anhydro-FT, V), 1-(2, 5-dihydro-2-furanyl)-5-fluorouracil (3', 4'-dehydro-FT, XII) and 1-(5-acetoxytetrahydro-2-furanyl)-5-fluorouracil (5'-AcO-FT, XI) were also synthesized. The antitumor activities of these compounds against sarcoma 180 and L 1210 were examined. The activities of cis-3'-OH-FT (VI) and 2, 3'-anhydro-FT (V) were found to be lower than that of FT. The activity of 5'-AcO-FT (XI) was the same as that of FT. 3', 4'-Dehydro-FT (XII) showed much greater activity than FT.

著者

JUN-ICHI YAMASHITA SETSUO TAKEDA HIROSHI MATSUMOTO TADAFUMI TERADA NORIO UNEMI MITSUGI YASUMOTO

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.2090-2094, 1987-05-25 (Released:2009-10-19)

参考文献数

14

被引用文献数

6 6

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Various O-acyl and N-acyl derivatives of 2'-deoxy-5-trifluoromethyluridine (F3Thd) were synthesized; namely 5'-O-acyl, 3', 5'-di-O-acyl, N3-acyl, 3', 5'-di-O-acetyl-N3-acyl, 3', 5'-di-O-carbamoyl and 3', 5'-di-O-ethoxycarbonyl compounds. 5'-O-Acyl derivatives of 2'-deoxy-5-trifluoromethylcytidine were also synthesized.The antitumor activities of these compounds against sarcoma 180 were examined by oral administration to mice. Among the 5'-and 3', 5'-diester compounds with aliphatic acids, the 5'-O-hexanoyl compound showed the highest activity. Full protection of the sugar moiety with aroyl or carbamoyl groups considerably decreased the activities, and those of the 3', 5'-di-O-m-fluorobenzoyl and 3, 5'-di-O-butylcarbamoyl compounds were the smallest. N3-Benzoyl compounds were slightly more effective than F3Thd but none of them showed higher activity than the effective O-acyl compounds. In the case of 5'-O-acylates of 2'-deoxy-5-trifluoromethylcytidine, the 5'-O-benzoyl compound showed the highest activity.

著者

Atsuhiko UEMURA Yukio TADA Setsuo TAKEDA Junji UCHIDA Jun-ichi YAMASHITA

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.1, pp.150-155, 1996-01-15 (Released:2008-03-31)

参考文献数

20

被引用文献数

3 3

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Various O-alkyl derivatives of 2'-deoxy-5-fluorouridine (FUdR) were synthesized and their antitumor activities in mice bearing sarcoma 180 (s.c.-p.o.) were evaluated in terms of the ED50 values (mg/kg/d). Most of these compounds were superior to FUdR in antitumor activity. In particular, the antitumor activity of 3'-O-(p-chloro-benzyl)-FUdR (3e) (ED50 =0.87mg/kg/d) was as much as 100 times that of FUdR (ED50=84mg/kg/d). Further, various 5'-O-aminoacyl derivatives of 3e were synthesized and evaluated in terms of ED50 value and therapeutic index (T.I.). Both the ED50 value (0.41mg/kg/d) and the T.I. (4.18) of 3'-O-(p-chlorobenzyl)-5'-O-glycyl-FUdR hydrochloride (6a) were significantly improved, compared with those of 3e and FUdR. FUdR plasma concentration after a single p.o. dosing of 6a was maintained for as long as 24h.

著者

尾崎 庄一郎 秋山 隆彦 池 祥雅 森 春樹 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.37, no.12, pp.3405-3408, 1989-12-25 (Released:2008-03-31)

参考文献数

13

被引用文献数

14 15

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With the aim of diminishing the toxicity of 5-fluorouridine (1) and obtaining biologically active derivatives of 1, various kinds of 5'-O-acyl-8-fluorouridines 2 were synthesized. The antitumor activity of the compounds against L-1210 leukemia in mice was examined. The 5'-O-heptanoyl derivative 2h showed the highest antitumor activity.

著者

小林 義郎 熊懐 稜丸 大沢 昭緒 山田 猛

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.20, no.8, pp.1839, 1972-08-25 (Released:2008-03-31)

被引用文献数

15 20

著者

小林 義郎 熊懐 稜丸 大沢 昭緒 村上 慎一 中野 隆治

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.4, pp.1247-1249, 1978-04-25 (Released:2008-03-31)

被引用文献数

31 45

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Photochemical trifluoromethylation of pyridine gave a mixture of three (trifluoromethyl) pyridines. Pyrrole and N-methylpyrrole were trifluoromethylated in α-position. Benzene gave very low yield of benzotrifluoride.

著者

小林 義郎 熊懐 稜丸 佐藤 進 原 伸祀 近見 永一

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.18, no.11, pp.2334-2339, 1970-11-25 (Released:2008-03-31)

被引用文献数

39 65

---

Trifluoromethyl iodide reacts with aryl halide in the presence of copper powder to give aryltrifluoromethane derivatives in a fairly good yield. This newly observed reaction is applicable to heterocyclic halides as well as benzene derivatives. Activities of halides are in the following order of readiness : iodide>bromide>chloride. Effects of solvents and natures of copper were examined.

著者

織田 範一 小林 和弘 植田 泰誠 伊藤 磯雄

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.8, pp.2578-2581, 1978-08-25 (Released:2008-03-31)

被引用文献数

1 3

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Diels-Alder reaction of 5-nitro-1, 4-naphthoquinone (1) and unsymmetrical butadienes was carried out. Reaction of 1 and 2-methyl-1, 3-butadiene gave 1, 4, 4a, 9a-tetrahydro-2-methyl-5-nitro-anthraquinone (2) and its 3-methyl analogue (3) at the ratio of 9.2 : 1. Reaction of 1 and 1, 3-pentadiene gave 1, 4, 4a, 9a-tetrahydro-1-methyl-8-nitroanthraquinone (8) and its 5-nitro analogue (9) at the ratio of 10 : 7. Their structures have been determined by aromatization to methyl-nitroanthraquinones.

著者

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.27, no.12, pp.3180-3182, 1979-12-25 (Released:2008-03-31)

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Closed shell LCAO-SCF-MO calculations were carried out for the chloride anion cryptate, which is of interest in connection with organic anion receptors and carriers. In the Cl- cryptate of [(C9H18)3(NH)2Cl]+Cl-, Cl- is encapsulated in the host molecule. Since the positions of the two protons bonded to the two nitrogens of the host molecule were not determined in the reported X-ray diffraction analyses, the positions of the two protons in the inclusion complex were decided by calculation using the ab initio molecular orbital method. A structure N+-H…Cl-…H-N+ in which Cl- is in between the two nitrogens was most stable at values of γ(NN) less than 7.0 Å. The structure N+-H…Cl-…H-N+ was most stable at γ(NN)=6.023 Å. In the most stable structure, the two protons are covalently bonded to the two nitrogens. The structure obtained by geometry optimization for the two ammonium ions and Cl- was similar to that determined by X-ray diffraction analysis.

著者

山田 幸子 大森 正幸 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.27, no.12, pp.3196-3198, 1979-12-25 (Released:2008-03-31)

被引用文献数

11 14

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24, 24-Difluoro-1α, 25-dihydroxyvitamin D3 (1) has been synthesized from 24, 24-difluoro-5β-cholestane-3α, 25-diol (2) as an antimetabolic analogue of 1α, 25-dihydroxyvitamin D3 to study the role of the 24-hydroxylation in the metabolism of vitamin D3.

著者

舟越 和久 稲田 治明 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.12, pp.4731-4739, 1984-12-25 (Released:2008-03-31)

参考文献数

14

被引用文献数

3 5

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Isoquinoline 2-oxide (1) reacts with cyanoacetic acid in the presence of Ac2O to afford various types of 1-substituted isoquinolines (2, 4, 6, and 7) and N-ylides (3 and 5a) depending upon the reaction conditions and processing procedures (Table I). The reaction in Ac2O gives initially α-acetoxycarbonyl-1-isoquinolineacetonitrile (2) and 2-isoquinolinio-acetoxycarbonylcyanomethylide (3), and that in Ac2O-dimethylformamide yields only 3. Products 2 and 3 are readily convertible into α-acetyl-1-isoquinolineacetonitrile (4) and 2-isoquinolinio-acetylcyanomethylide (5a), respectively, by processing involving heating. The reaction in ethanol gives ethyl α-cyano-1-isoquinolineacetate (6) and di (1-isoquinolyl) acetonitrile (7). The reaction of 1 with benzoylacetonitrile affords both the corresponding 1-substituted isoquinoline (10) and N-ylide (11). Reactions with ethyl benzoylacetate and, methyl and ethyl acetoacetates produce 1-substituted isoquinolines (12 and 14a, b) and 4-acetoxyisoquinoline (13), no ylide being formed.

著者

亀谷 哲治 川村 邦昭 津吹 政可 本多 利雄

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.11, pp.4821-4828, 1985-11-25 (Released:2008-03-31)

参考文献数

32

被引用文献数

15 20

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(-)-α-Cuparenone, (17) was synthesized from the olefinic aldehyde (9) by utilizing a rhodium-catalyzed cyclization as a key step. The optically active aldehyde (7) was prepared by employing an asymmetric [2, 3] sigmatropic rearrangement of a quaternary L-prolinol derivative. The aldehyde (7) was also converted into its antipodal form (24) in several steps.

著者

黄 永 豊田 英尚 輿石 一郎 戸井田 敏彦 今成 登志男

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.12, pp.2182-2186, 1995-12-15 (Released:2008-03-31)

参考文献数

28

被引用文献数

5 7

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Depolymerized holothurian glycosaminoglycan (DHG) produced artificially from sea cucumber has an anticoagulant and antithrombotic activity. In the present study, we attempted to determine the plasma level of DHG using a chemical procedure. A general method for determination of chondroitin sulfates by forming unsaturated disaccharides with chondroitinase digestion was difficult to apply to DHG, because it was resistant to any chondroitinase digestion. We therefore developed a highly sensitive postcolumn HPLC method for determination of intact DHG. DHG was applied to Asahipak NH2P-50, an amino-bonded column, eluted by alkaline solution and then detected with arginine under a strong alkaline condition as a postcolumn reagent. The limit of detection for DHG was 10ng. The present method was applicable to the determination of DHG in plasma after intravenous administration.

著者

Surat Laphookhieo John Keith Syers Rattana Kiattansakul Kan Chantrapromma

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.54, no.5, pp.745-747, 2006 (Released:2006-05-01)

参考文献数

12

被引用文献数

40 64

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A new prenylated xanthone, 5-O-methylcelebixanthone (1), together with six known compounds; celebixanthone (2), 1,3,7-trihydroxy-2,4-di(3-methylbut-2-enyl)xanthone (3), cochinchinone A (4), α-mangostin (5), β-mangostin (6) and cochinchinone C (7) were isolated from roots of Cratoxylum cochinchinense. Their structures were elucidated by spectroscopic methods. Compounds 2 and 4—7 showed cytotoxic activity against the human lung cancer cell line (NCI-H187) with IC50 values ranging from 0.65 to 5.2 μg/ml. Compounds 1, 2, 6 and 7 also showed antimalarial activity against Plasmodium falciparum with IC50 values of 3.2, 4.9, 7.2 and 2.6 μg/ml, respectively.

著者

矢島 治明 小川 博 藤井 信孝 船越 奨

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.4, pp.740-747, 1977-04-25 (Released:2008-03-31)

被引用文献数

12 21

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Among various dilute sulfonic acids tested, 2 to 4N ethanesulfonic acid in acetic acid or methylenechloride was found suitable as a deprotecting reagent for the acid labile α-amino protecting groups, such as Boc and Z(OMe), which are currently removed by trifluoroacetic acid or dilute hydrochloric acid, since the deprotection occured selectively within 60 minutes at room temperature leaving intact other side chain protecting groups, such as Z, benzyl ester, S-p-methoxybenzyl and NG-p-methoxybenzenesulfonyl groups. This reagent was applied to the synthesis of three model peptides ; Met and Leu-enkephalin and endorphin.