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

---

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

---

(-)-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

Kosuke Shimizu Miki Takada Tomohiro Asai Kenji Irimura Kazuhiko Baba Naoto Oku

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.25, no.6, pp.783-786, 2002 (Released:2002-06-01)

参考文献数

19

被引用文献数

10 13

---

To enhance the therapeutic efficacy as well as to reduce the side effect, we attempted to liposomalize 4β-aminoalkyl-4′-O-demethyl-4-desoxypodophyllotoxin (TOP-53), a novel and effective topoisomerase II inhibitor. More than 90% of TOP-53 was efficiently incorporated into the liposomes composed of dipalmitoylphosphatidylcholine and cholesterol by remote-loading method. Anti-tumor activity of liposomal TOP-53 against solid tumor was examined in vivo using colon26 NL-17 carcinoma model mice. Three doses of liposomal TOP-53 (12 mg/kg/dose) showed significant tumor growth suppression (97.5% reduction determined at day 25) and the increase in life span (33%) of tumor-bearing mice. Furthermore, one mouse out of 5 was completely cured after treatment. Since similar efficacy was observed in the free TOP-53 treated group, liposomalization does not contribute much to the enhancement of therapeutic efficacy. However, a slight but measurable damage at the injection site was observed when free TOP-53 was injected, and the damage was diminished by the liposomalization. Taken together, liposomalization reduces the side effect rather than enhancing the therapeutic efficacy when TOP-53 is used.

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

---

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

---

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

---

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.

著者

矢島 治明 木曽 良明 小川 宏 藤井 信孝 入江 寛

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.23, no.5, pp.1164-1166, 1975-05-25 (Released:2008-03-31)

被引用文献数

27 37

---

Acidolytic cleavage of various protecting groups currently employed in peptide chemistry by fluorosulphonic and methanesulphonic acids was examined.

著者

木曽 良明 宇川 和子 中村 静夫 伊藤 薫 秋田 正

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.2, pp.673-676, 1980-02-25 (Released:2008-03-31)

参考文献数

18

被引用文献数

41 58

---

A thioanisole-trifluoroacetic acid (TFA) system was found to deprotect Tyr (Bzl) quantitatively at 25°within 3 hr by a push-pull mechanism without O-to-C rearrangements. This new deblocking system did not completely deprotect Ser (Bzl) and Thr (Bzl), but deprotected Lys (Z) quantitatively.

著者

Nobuko Mibu Kazumi Yokomizo Marina Sano Yuuna Kawaguchi Kenta Morimoto Syunsuke Shimomura Ryo Sato Nozomi Hiraga Aya Matsunaga Jian-Rong Zhou Tomonori Ohata Hatsumi Aki Kunihiro Sumoto

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.66, no.8, pp.830-838, 2018-08-01 (Released:2018-08-01)

参考文献数

15

被引用文献数

18

---

We report the preparation of new C3- and CS-symmetrical molecules constructed on a triazine (TAZ) template. Anti-herpes simplex virus type 1 (anti-HSV-1) and cytotoxic activities against Vero cells of synthesized TAZ derivatives were evaluated. The results suggested that the presence of an electron-donating group(s) on the benzene ring in benzylamine groups on the TAZ template is an important structural factor for expressing a high level of anti-HSV-1 activity and low cytotoxicity for these C3 types of TAZ derivatives. Among the tested TAZ derivatives, compounds 4f and 7h showed the highest anti HSV-1 activities (EC50=0.98 and 1.23 µM, respectively) and low cytotoxic activities to Vero cells (50% cytotoxic concentration (CC50)=292.2 and >200 µM, respectively).

著者

秋田 弘幸 古市 昭也 越地 弘子 堀越 弘毅 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.32, no.4, pp.1342-1348, 1984-04-25 (Released:2008-03-31)

参考文献数

12

被引用文献数

6 8

---

The synthesis of optically active α-hydroxy β-methyl esters V by means of microbiological reduction of the corresponding α-keto β-methyl esters IV was carried out. Methyl 3-phenyl-2-oxobutyrate 3 was found to be reduced by a variety of yeasts to the α-hydroxy β-methyl esters (7b and 8a) with (2R, 3S)-and (2R, 3R)-configurations, respectively, and by carrying out screening experiments, yeasts which give products with high optical purity were actually found.

著者

秋田 弘幸 古市 昭也 越地 弘子 堀越 弘毅 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.32, no.4, pp.1333-1341, 1984-04-25 (Released:2008-03-31)

参考文献数

13

被引用文献数

14 17

---

Microbiological asymmetric reduction of methyl 3-(2-furyl)-2-methyl-3-oxopropionate (5) by various yeasts was carried out. Four kinds of methyl 3-(2-furyl)-3-hydroxy-2-methyl propionates (6a-6d) could be obtained separately from the prochiral β-keto ester 5 by reduction with properly selected microorganisms. In particular, the desired syn-isomer 6a was obtained with high optical purity (>99% e.e.). Both the chemical yield and the optical purity of the reduction products (6a-6d) were significantly improved when fermentation was carried out on a large scale using a 30 1 jar fermentor or a 200 1 tank.

著者

秋田 弘幸 古市 昭也 越地 弘子 堀越 弘毅 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.31, no.12, pp.4384-4390, 1983-12-25 (Released:2008-03-31)

参考文献数

13

被引用文献数

10 13

---

In order to synthesize four optically active methyl 2-methylmalates (10-13), microbiological asymmetric reduction of the corresponding dimethyl 2-methyl-3-oxosuccinate (9) was carried out. The β-keto diester 9 was found to be reduced by fermenting baker's yeast (Saccharomyces cerevisiae) and Candida albicans to afford a mixture of the (2R, 3R)-isomer 10 and the (2S, 3R)-isomer 11. Although the optical purity of 10 produced by Candida albicans was reasonably high (95% e.e.), optical yields of other products were unexpectedly low. However, identification of the four possible isomers 14-17 was found to be easily carried out by means of nuclear magnetic resonance spectroscopy.

著者

秋田 弘幸 古市 昭也 越地 弘子 堀越 弘毅 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.31, no.12, pp.4376-4383, 1983-12-25 (Released:2008-03-31)

参考文献数

19

被引用文献数

18 30

---

The synthesis of optically active α-methyl β-hydroxy esters I by means of microbiological reduction of the corresponding β-keto esters II was carried out. Benzyl 2-methyl-3-oxobutyrate 1 was found to be reduced by a variety of yeasts to the α-methyl β-hydroxy esters with (2R, 3S)- and (2S, 3S)-configurations (2 and 3, respectively), and by carrying out screening experiments, yeasts which give each product with high optical purity were isolated. Moreover, the absolute configuration and the optical purity of the reduction products were found to be determinable from the 400 MHz nuclear magnetic resonance spectra of the (+)-α-methyoxy-α-trifluoromethylphenylacetyl esters of the alcohols produced.

著者

Naoto Okada Kazuyoshi Kawazoe Kazuhiko Teraoka Toshihide Kujime Masahiro Abe Yasuo Shinohara Kazuo Minakuchi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.36, no.10, pp.1622-1626, 2013-10-01 (Released:2013-10-01)

参考文献数

21

被引用文献数

27 43

---

Denosumab, a fully human monoclonal antibody that inhibits the receptor activator of nuclear factor-κB ligand, inhibits the activation of osteoclasts. Some clinical trials have shown that denosumab suppresses bone resorption in patients with advanced cancer, but hypocalcemia has been reported as a serious adverse effect after the administration of denosumab. It is difficult to predict hypocalcemia in such cases because the risk factors for denosumab-induced hypocalcemia have not been reported. Accordingly, the aim of the present study was to identify the risk factors for hypocalcemia induced by denosumab. We retrospectively reviewed the records of patients who had received denosumab at Tokushima University Hospital between April 2012 and May 2013. Fifty-three patients were analyzed and eleven patients had hypocalcemia after administration of denosumab. Univariate logistic regression analysis revealed that the patients who had not been administered zoledronic acid before receiving denosumab or had lower creatinine clearance (CCr) appeared to have a higher risk of hypocalcemia (p<0.05). The cut off value of CCr was 50.4 mL/min calculated by receiver-operator characteristics curves. Moreover, multivariate logistic regression analysis revealed that non-administration of zoledronic acid (odds ratio 10.43, p<0.05) and CCr less than 50.0 mL/min (odds ratio 5.90, p<0.05) were independent risk factors for denosumab-induced hypocalcemia. These findings provide useful information regarding the monitoring of hypocalcemia in patients receiving denosumab.

著者

Abdel-Rahim Sayed Ibrahim Ahmed Mohamed Galal Mohammed Shamim Ahmed Gabir Salem Mossa

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.51, no.2, pp.203-206, 2003 (Released:2003-02-01)

参考文献数

24

被引用文献数

30 54

---

Metabolism of 7-O-methylnaringenin (sakuranetin) by Cunninghamella elegans NRRL 1392 yielded naringenin and naringenin-4′-sulfate. C. elegans also converted 5, 3′, 4′-trihydroxy-7-methoxyflavanone into eriodictyol-4′-sulfate. Furthermore, incubation of 5, 4′-dihydroxy-7, 3′-dimethoxyflavanone with the same fungus gave homoeriodictyol (5, 7, 4′-trihydroxy-3′-methoxyflavanone) and homoeriodicytol-7-sulfate. The structures of the new metabolites were established by spectral analysis including 2D-NMR, HR-ESI-FT-MS beside hydrolysis by acid.

著者

今井 欣一 丸本 龍二 小林 邦夫 吉岡 義夫 戸田 準 本庄 美喜男

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.19, no.3, pp.576-586, 1971-03-25 (Released:2008-03-31)

被引用文献数

11 19

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Ring closure of 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide (AICA-riboside) with phenyl isothiocyanate afforded 2-mercaptoinosine (I) in good yield. Similarly, the ring closure of AICA-riboside 5'-phosphate (AICAR) led to the formation of 2-mercaptoinosine 5'-phosphate (II). Various 2-substituted inosine 5'-phosphates were prepared from I and II or starting with AICA-riboside. It was found that 2-furfuryl-thioinosine 5'-phosphate possessed a flavor enhancing activity of about 17-times that of inosine 5'-phosphate. The chemical structure-flavor enhancing activity relationship was presented.

著者

松田 彰 野本 裕二 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.27, no.1, pp.183-192, 1979-01-25 (Released:2008-03-31)

被引用文献数

16 31

---

A facile displacement of a methylsulfonyl group in adenosines with cyanide ion is described. Treatment of protected 8-methylsulfonyladenosines with sodium cyanide in dimethylformamide gave the 8-cyanoadenosines. The conversion of the cyano group to the methyl imidate, methoxycarbonyl, carbamoyl, and carboxylic acid, respectively, was achieved. Similar reaction was carried out with 2-methylsulfonyladenosines to give the 2-cyanoadenosines and their derivatives. The nuclear magnetic resonance (NMR) and circular dichroism (CD) spectra of these 2-and 8-substituted adenosines are given. The 8-substituted adenosines possess syn-conformations while the 2-substituted derivatives prefer to possess anti-conformations, as confirmed by the CD and NMR spectra.

著者

松田 彰 篠崎 操 宮坂 貞 町田 治彦 畔蒜 藤一

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.4, pp.1766-1769, 1985-04-25 (Released:2008-03-31)

参考文献数

24

被引用文献数

19 30

---

Reaction of 2-iodoadenosine (2) with terminal alkynes in the presence of bis (triphenylphosphine) palladium dichloride and cuprous iodide in triethylamine and N, N, -dimethylformamide gave 2-alkynyl-adenosines (3a-h) in excellent yields. Several compounds showed high activity as inhibitors in rat passive cutaneous anaphylaxis (PCA) reaction. Among them, 2-(3-hydroxypropynyl)- and 2-(3-hydroxybutynyl)-adenosines (3d, f) are much more potent than disodium cromoglycate (DSCG).

著者

松田 彰 佐藤 和恵 宮坂 貞 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.32, no.5, pp.2048-2051, 1984-05-25 (Released:2008-03-31)

参考文献数

8

被引用文献数

4 4

---

2-Aminomethylinosine (1), a one-carbon extended homolog of an exocyclic amino group of guanosine, was synthesized from guanosine by the use of a newly developed protection and deprotection method. Introduction of a methoxy group into the 6-position of 2-benzenesulfonyl-purine riboside facilitated a nucleophilic substitution with cyanide to afford 2-cyano-6-methoxypurine riboside (11) which was subsequently hydrogenated and demethylated with trimethylsilyl iodide to afford 1.

著者

坂田 紳二 米井 清志郎 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.30, no.7, pp.2583-2585, 1982-07-25 (Released:2008-03-31)

参考文献数

11

被引用文献数

7 10

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A new method for the synthesis of 2-substituted 6-methylpurine ribosides from guanosine is described. Reaction of N (2), O (2'), O (3'), O (5')-tetraacetyl-O (6)-p-toluenesulfonylguanosine with carbanion from ethylacetoacetate gave the 6-ethoxycarbonylmethyl derivative, which was further converted to 2-amino-6-methylpurine riboside by deacetylation and decarboxylation. Replacement of the amino group of the compound by the fluoro group was achieved by the Schiemann reaction. The fluoro group could easily be replaced by several nucleophiles. As a result, 2-methylthio-, and 2-dimethylamino-6-methyl-9-β-D-ribofuranosylpurines could be effectively prepared.