著者

菅沢 勉 笹倉 和幸 日高 哲郎 豊田 達郎

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.22, no.4, pp.757-762, 1974-04-25 (Released:2008-03-31)

被引用文献数

1 2

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Attempted synthesis of 3-substituted (alkoxycarbonyl, hydroxymethyl or cyano)-2, 3-dihydro-2-benzyl (acyl or alkoxycarbonyl)-1H-pyrrolo [3, 4-b] quinolines (II), (III), and (VI) as potential ring A-B-C components for a total synthesis of dl-camptothecin (I) is described.

著者

菅沢 勉 豊田 達郎 笹倉 和幸 日高 哲郎

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.9, pp.1971-1974, 1971-09-25 (Released:2008-03-31)

被引用文献数

5 12

著者

豊岡 利正 山崎 壮 谷本 剛 佐藤 恭子 佐藤 道夫 豊田 正武 石橋 無味雄 義平 邦利 内山 充

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.3, pp.820-822, 1991-03-25 (Released:2008-03-31)

参考文献数

9

被引用文献数

27 42

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To identify chemical contaminant(s) associated with eosinophilia-myalgia syndrome (EMS), case and control lots of tryptophan were analyzed by HPLC with both UV and FL detection. Numerous contaminant peaks appeared on the chromatograms and some of them were identified as 5-hydroxytryptophan, indol aldehyde, indol, etc. from the retention time of authentic compounds. Among these, three peaks were significantly associated with case lots. One corresponds to di-tryptophan aminal of aldehyde (peak E). Ohters are unknown contaminants, UV-5 (FL-7) and UV-28 (FL-36). The structural elucidation and toxicological implication of UV-5 (FL-7) are currently in progress.

著者

中山 豊男 平良 盛三 池田 昌人 芦澤 広 織田 実 荒川 勝雅 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.1, pp.117-125, 1993-01-15 (Released:2008-03-31)

参考文献数

15

被引用文献数

5 10

---

By developing 6-amidino-2-naphthyl 4-guanidinobenzoate (I, FUT-175) as a basic structure, its various derivatives were synthesized and their inhibitory activities on trypsin, plasmin, kallikrein, thrombin, C1^- and C1s^- as well as on complement-mediated hemolysis were examined. The protective effect of these compounds on complement-mediated Forssman shock was also examined in guinea pigs. 6-Amidino-2-naphthyl 4-[(4, 5-dihydro-1H-imidazol-2-yl)amino]-benzoate (41, FUT-187) was found to be a suitable compound for oral administration with anti-complement activity superior to that of compound I.

著者

岡田 哲夫 江角 清志 山川 眞透 佐藤 久夫 辻 照二 津島 忠彦 元川 清司 小松 良英

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.1, pp.126-131, 1993-01-15 (Released:2008-03-31)

参考文献数

25

被引用文献数

19 24

---

Quantitative structure-activity relationships (QSAR) of various 7-(3-substituted-azetidin-1-yl)-1-cyclopropyl-6, 8-difluoro-1, 4-dihydro-4-oxoquinoline-3-carboxylic acids, 14-25, were studied to clarify the structural requirements for 3-substituted azetidines to potentiate antibacterial activity. A good parabolic relationship seemed to exist between the relative mean antibacterial activity indices against five representative gram-negative bacteria, GNM, and the calculated hydrophobic parameters, CLOG P, of these molecules. The CLOG P value of the most potent derivative was predicted to be around 2.3. On the other hand, against five representative gram-positive bacteria, the relative mean antibacterial activity indices, GPM, remained high and rather constant regardless of structural variation in the azetidine moiety. In order to confirm these findings, the QSAR analysis was extended with success to the quinolonecarboxylic acids, 26-34, which bear various substituted pyrrolidine, piperazine and piperidine derivatives instead of azetidines. The findings showed that the introduction of any amide substituent group to these heterocyclic amine moieties would lead to marked decrease in GNM, whereas incorporation of some amino substituent groups at a position two or three carbons remote from the N-1 position resulted in great enhancement of GNM. As azetidine quinolones exhibited somewhat low in vivo antibacterial activities, possibly reflecting their lesser bioavailability, we finally selected 3-amino-4-methoxypyrrolidine as one of the most promising C-7 substituent groups based on our QSAR analysis.

著者

岡田 哲夫 佐藤 久夫 辻 照二 津島 忠彦 中井 博 吉田 正 松浦 眞三

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.1, pp.132-138, 1993-01-15 (Released:2008-03-31)

参考文献数

12

被引用文献数

13 19

---

A new series of quinolone derivatives 3a-I bearing 3-amino-4-methoxypyrrolidines of different configurations and chirality were synthesized and their antibacterial activities as well as some of their toxicological properties were examined. As predicted by our previous quantitative structure-activity relationships (QSAR) analysis of C-7 heterocyclic amine substituted quinolonecarboxylic acid antibacterial agents, these pyrrolidine derivatives showed higher in vitro and in vivo antibacterial activities against both gram-positive and gram-negative bacteria than the analogs bearing various 3-substituted azetidines. Furthermore, the amino and methoxy substituent groups on the pyrrolidine ring exhibited strong configurational and chiral effects on the in vitro and in vivo antibacterial activities of these compounds : (1) cis compounds showed higher antibacterial activities against most of the pathogens examined : (2) N-methylation of the 3-amino group on the pyrrolidine ring lowered in vitro but not in vivo antibacterial activities, particularly leading to superior in vivo anti-pseudomonal activity; (3) the (3'S, 4'R)-derivative showed substantially higher activity that the (3'R, 4'S)-one. These findings led to the selection of compound 3k for further evaluation as it possessed the highest in vivo antibacterial activity and no cytotoxicity.

著者

TADASHI KIHO MASAHIKO ITO KATSUYUKI NAGAI CHIHIRO HARA SHIGEO UKAI

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.10, pp.4286-4293, 1987-10-25 (Released:2009-10-19)

参考文献数

34

被引用文献数

8 11

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A water-insoluble glucan (N-5P), [α] 23D +2.3° (c= 0.51, 0.5 M sodium hydroxide), was isolated from the alkaline extract of the fruit bodies of Yu er (Chinese name) (Auricularia species). N-5P was homogeneous as judged by gel filtration and electrophoresis. By gel filtration, the molecular weight of N-5P was estimated to be 5.6 × 105. The 13C-nuclear magnetic resonance and infrared spectra, together with the result of chromium trioxide oxidation, indicated that glucosidic linkages in N-5P have the β-D configuration. From the results of methylation analysis, periodate oxidation, Smith degradation (complete, as well as partial), partial acetolysis, and enzymic hydrolysis, it was concluded that N-5P has a main chain composed of β- (1→3) -linked D-glucopyranosyl residues, with single, β- (1→6) -linked D-glucopyranosyl groups attached as side chains, which account for a quarter of the total sugar residues. In addition, the results of enzymic hydrolysis indicated that the β- (1→6) -linked D-glucosyl side chains are mainly localized in the neighborhood of the nonreducing end of the main chain. Furthermore, N-5P showed potent antitumor activity against the solid form of sarcoma 180 in mice, and exhibited significant carbon clearance-enhancing activity in mice.

著者

Gyeong Han Jeong Tae Hoon Kim

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.65, no.7, pp.678-682, 2017-07-01 (Released:2017-07-01)

参考文献数

26

被引用文献数

4 5

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Rutin, a major flavonoid glycoside found in many higher plants, was exposed at 25 kGy of γ-ray and produced three new hydroxymethylated products 2–4 in the C-ring by γ-irradiation. Structures of the new compounds, including absolute configurations, were elucidated based on spectroscopic interpretation (NMR, UV, [α]D, MS, and circular dichroism (CD)). The new unusual rutin derivatives 2 and 3 exhibited significantly enhanced inhibitory effects against α-glucosidase with IC50 values of 23.1±1.2 and 11.2±0.7 µM, respectively, when compared to the parent rutin.

著者

狐塚 寛 小山 又次郎 興津 知明

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.941-945, 1982-03-25 (Released:2008-03-31)

参考文献数

9

被引用文献数

5 6

---

The murexide reaction of caffeine was investigated to clarify the pathway of the coloration. From the reaction mixture of caffeine with nitric acid, 1, 3-dimethylalloxan (II) and 1, 3, 7-trimethyl-2, 6-dioxo-8-nitro-1H, 3H, 7H-xanthine (IV) were isolated. Compound II was found to be the key intermediate, since it was converted to a purple-red-colored substance, murexoin (III), by treatment with conc. ammonia. It was found that 1-hydroxy-5, 7-dimethyl-2, 4, 6-trioxo-1H, 5H, 7H-oxazolo [4, 5-d] pyrimidine (I), previously obtained by the oxidation of caffeine with hydrogen peroxide and hydrochloric acid, was also transformed to III with conc. ammonia. Consequently, the murexide reaction of caffeine was shown to have two pathways of coloration depending on the oxidizing agent employed. From the spectral data, a symmetrical structure (III) was assigned to murexoin in solution. Amalic acid, which has been reported as an intermediate of the murexide reaction of caffeine, can be ruled out on the basis of our experimental results.

著者

矢島 治明 藤井 信孝

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.29, no.2, pp.600-602, 1981-02-25 (Released:2008-03-31)

参考文献数

16

被引用文献数

1

---

Improved chemical synthesis of bovine pancreatic ribonuclease (RNase) A was achieved by applying a new deprotecting procedure with trifluoromethanesulfonic acidthioanisole in combination with a modified air oxidation procedure with glutathione for the disulfide formation. After purifications by affinity chromatography followed by ion-exchange chromatography, a protein with the full enzymatic activity was obtained and subsequently crystallized from 95% ethanol according to Kunitz. A totally synthetic enzyme with full RNase A activity was thus obtained in a crystalline form for the first time.

著者

福川 清史 上田 亨 平野 孝夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.29, no.2, pp.597-600, 1981-02-25 (Released:2008-03-31)

参考文献数

6

被引用文献数

8 18

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Neplanocin A (I) was treated with 1, 3-dichloro-1, 1, 3, 3-tetraisopropyldisiloxane to give 3', 5'-O-(tetraisopropyldisiloxane-1, 3-diyl) neplanocin A (II), which was converted to the 2'-O-trifluoromethanesulfonyl derivative (III). Nucleophilic substitution of III with a number of nucleophiles (AcO-, AcS-, N3-, Cl-, Br-, I-) in hexamethylphosphoric triamide afforded the respective 2' (R)-substituted derivatives in high yield. The halogenated derivatives were reduced with tri-n-butyltin hydride to the 2'-deoxy compound. 2'-O-Thiocarbonylimidazoyl-3', 5'-O-(tetraisopropyldisiloxane-1, 3-diyl) neplanocin A was also reduced to the 2'-deoxy derivative. The deprotection of the bifunctional silyl group with tetra-n-butylammonium fluoride afforded 2' (R)-AcO, -AcS, -N3, -Cl, -Br, -I, and 2'-deoxy neplanocin A's, respectively. Physical data of these compounds including nuclear magnetic resonance, mass spectrum, and circular dichroism were given.

著者

杉浦 衛 加藤 憲二 足立 哲夫 伊藤 吉将 平野 和行 沢木 [シュン]二

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.29, no.2, pp.426-429, 1981-02-25 (Released:2008-03-31)

参考文献数

14

被引用文献数

5 5

---

We have established new colorimetric methods for the assay of adenosine deaminase, purine nucleoside phosphorylase and guanase activities in serum, based on the formation of hydrogen peroxide with xanthine oxidase as a coupling enzyme. [chemical formula] The proposed methods were found to be precise and convenient. Under the assay conditions, the mean levels of adenosine deaminase, purine nucleoside phosphorylase and guanase activities in the sera of normal subjects were 5.8±2.2 I. U./1, 3.7±2.1 I. U./1 and 0.5±0.3 I. U./1, respectively.

著者

杉浦 衛 加藤 憲二 足立 哲夫 伊藤 吉将 平野 和行

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.29, no.2, pp.430-432, 1981-02-25 (Released:2008-03-31)

参考文献数

18

被引用文献数

9 13

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A colorimetric method for the assay of xanthine oxidase activity, based on the production of hydrogen peroxide, is described. [chemical formula] The precision, accuracy, sensitivity and specificity of the method were found to be satisfactory for the rapid and reliable determination of xanthine oxidase activity.

著者

梅山 秀明 工藤 貴子

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.29, no.2, pp.554-558, 1981-02-25 (Released:2008-03-31)

参考文献数

26

---

Diborane as a molecular complex was studied by using a double zeta ab initio MO method and energy decomposition analyses. For diborane, a qualitatively major contribution of HOMO-LUMO transfers was reported by Yamabe et al. on the basis of configuration analyses by using a single zeta basis set. However, no quantitative work on the origin on the complex formation has been reported. In this note, we show that the charge transfer energy is the dominant contributor to the complex formation (2BH3→B2H6). The charge transfer energy and the exchange repulsion are analyzed at the molecular orbital (MO) levels.

著者

狐塚 寛 小山 又次郎 興津 知明

出版者

公益社団法人日本薬学会

雑誌

CHEMICAL & PHARMACEUTICAL BULLETIN (ISSN:00092363)

巻号頁・発行日

vol.29, no.2, pp.433-437, 1981

被引用文献数

7

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The murexide reaction was investigated to clarify the mechanism of the coloration, with caffeine as a model compound. From the reaction mixture of caffeine with hydrogen peroxide and hydrochloric acid, 1-hydroxy-5, 7-dimethyl-2, 4, 6-trioxo-1H, 5H, 7H-oxazolo-[4, 5-d] pyrimidine (yellow oil) (I) and 1, 3, 7-trimethyl-2, 6, 8-trioxo-9-hydroxy-1H, 3H, 7H-xanthine (red powder) (II) were isolated, and these two compounds were shown to be responsible for the murexide reaction of caffeine. Compound I was regarded as a key intermediate, since its purple coloration with dil. ammonia was similar to that of caffeine developed by the murexide reaction. The absorption maximum of II corresponds to that of the red-colored solution obtained from the reaction of caffeine with hydrogen peroxide and hydrochloric acid.

著者

狐塚 寛 小山 又次郎 興津 知明

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.29, no.2, pp.433-437, 1981-02-25 (Released:2008-03-31)

参考文献数

6

被引用文献数

4 7

---

The murexide reaction was investigated to clarify the mechanism of the coloration, with caffeine as a model compound. From the reaction mixture of caffeine with hydrogen peroxide and hydrochloric acid, 1-hydroxy-5, 7-dimethyl-2, 4, 6-trioxo-1H, 5H, 7H-oxazolo-[4, 5-d] pyrimidine (yellow oil) (I) and 1, 3, 7-trimethyl-2, 6, 8-trioxo-9-hydroxy-1H, 3H, 7H-xanthine (red powder) (II) were isolated, and these two compounds were shown to be responsible for the murexide reaction of caffeine. Compound I was regarded as a key intermediate, since its purple coloration with dil. ammonia was similar to that of caffeine developed by the murexide reaction. The absorption maximum of II corresponds to that of the red-colored solution obtained from the reaction of caffeine with hydrogen peroxide and hydrochloric acid.

著者

香野 敬喜 小川 千穂子 下村 由紀子 矢野 弘重 上田 陽

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.29, no.2, pp.301-307, 1981-02-25 (Released:2008-03-31)

参考文献数

9

被引用文献数

11 13

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The interaction between imidazole and p-benzoquinone in acetonitrile was investigated at both low temperature (below 0°) and room temperature. The step of formation of the charge-transfer complex between two intact molecules could not be detected. Instead, the two compounds were found to react with each other fairly quickly at room temperature to form 2, 5-bis (imidazol-1-yl) hydroquinone, 2, 3-bis (imidazol-1-yl) hydroquinone and hydroquinone.

著者

梅山 秀明 工藤 貴子 中川 節子

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.29, no.2, pp.287-292, 1981-02-25 (Released:2008-03-31)

参考文献数

32

被引用文献数

7 10

---

The heat of complex formation of H3PBH3 was calculated to be -15.3 kcal/mol by double zeta ab initio LCAO MO SCF calculations ; this is very similar to the experimental values for (CH3)3PB(CH3)3 and (CH3)3PBF3. The origin of complex formation of H3PBH3 was elucidated by energy decomposition methods. The order of contributions is ES-(41%)>CT (37%)> PL (22%). The d atomic orbitals on phosphorus play a role in increasing the polarization energy upon complex formation. The barrier to internal rotation of H3PBH3 was calculated to be 2.4 kcal/mol, which is in very good agreement with the experimental value of 2.47kcal/mol. The exchange repulsion and the charge transfer energy related to the staggered form contribute to the barrier to internal rotation. The change of the charge transfer energy corresponds to the difference of the barrier heights between H3PBH3 and H3SiCH3. The energies of complex formation of F3PBH3 and (CH3)3PBH3 were calculated, to investigate the origin of the barrier to internal rotation.

著者

岡本 康 原野 一誠 安田 昌巳 大沢 映二 兼松 顕

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.7, pp.2526-2529, 1983-07-25 (Released:2008-03-31)

参考文献数

6

被引用文献数

8 11

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The cage triketone 2 revealed different reactivities toward the thermal condition according to the substituents : the cyclobutane ring cleavage for alkyl substituents and the decarbonylation for methoxycarbonyl ones. The X-ray crystallographic study for the derivative of 2b showed a significantly long (1.635 (7) Å) C (Ph)-C (Ph) σ bond. The reaction mechanisms are discussed in terms of frontier molecular orbital (FMO) theory combined with the results of molecular mechanics and semiempirical MNDO molecular calculations.

著者

Yasushi MATSUNAGA Nobuyuki BANDO Hiroshi YUASA Yoshio KANAYA

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.10, pp.1931-1934, 1996-10-15 (Released:2008-03-31)

参考文献数

12

被引用文献数

7 12

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The effects of grinding and tableting on the physicochemical stability of TAT-59, (E)-4-[1-[4-[2-(dimethylamino)ethoxy]phenyl]-2-(4-isopropyl)phenyl]-1-butenyl]phenyl monophosphate, were studied. The crystallinity of TAT-59 ground in a planetary ball mill for 0-120 min or compressed at 0-4500 kg/cm2 was evaluated by X-ray diffraction analysis and differential scanning calorimetry (DSC). The surface of TAT-59 was measured under a scanning electron microscope (SEM). The physicochemical stability of TAT-59, ground or compressed, was determined by measurements of water content, crystallinity and the amount of hydrolysis product, DP-TAT-59, formed. The crystallinity of ground TAT-59 decreased with increasing grinding time, and the amount of DP-TAT-59 increased with decrease in the crystallinity. Similar to ground TAT-59, the crystallinity of TAT-59 tablet gradually decreased with increasing compression pressure, and the amount of DP-TAT-59 tended to increase with decreasing crystallinity. These findings suggested that the dacrease of the crystallinity of TAT-59 by mechanical force, such as grinding and tableting raised the drug's reactivity and affected its stability.