著者

Koichi Murano Hirofumi Ogino Tomofumi Okuno Tomohiro Arakawa Hitoshi Ueno

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.41, no.1, pp.92-98, 2018-01-01 (Released:2018-01-01)

参考文献数

43

被引用文献数

13

---

The role of supplementary selenium on the induction of insulin resistance and oxidative stress in a diabetic mouse model was investigated in NSY mice on a high fat diet (HFD) and administered seleno-L-methionine (SeMet)-containing water for 12 weeks. Significant increases in oral glucose tolerance-tested (OGTT), insulin tolerance-tested, and non-fasting blood glucose levels were observed in mice on a HFD, as well as the significant increases in OGTT and non-fasting plasma insulin levels. Mice on a HFD had decreased plasma adiponectin levels and increased free fatty acid (FFA) levels. Supplementary SeMet significantly augmented OGTT blood glucose levels in mice on a HFD and plasma FFA levels in mice on a normal diet. The mRNA levels of six selenoproteins were measured, and glutathione peroxidase (GPx) 1 and selenoprotein P (SelP) were selected as candidates that may be associated with insulin resistance or oxidative stress in the liver. Hepatic GPx1 expression was elevated in mice on a HFD and SeMet supplementation, and SelP expression increased in mice on a HFD. Histopathological observations in hepatic tissues showed hypertrophy of parenchymal cells and significant expression of 4-hydroxy-2-nonenal in mice on a HFD, indicating lipid accumulation and oxidative stress induction. Hepatic protein tyrosine phosphatase activity also increased by a HFD. These results suggest that hepatic lipid accumulation in NSY mice on a HFD promoted oxidative stress and hepatic SelP expression, and supplementary SeMet induced hepatic GPx1 expression.

著者

Yutaro Obara Kuniaki Ishii

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.41, no.1, pp.20-23, 2018-01-01 (Released:2018-01-01)

参考文献数

13

被引用文献数

7

---

We recently found that 10.5% of sporadic Parkinson’s disease (PD) patients lacked one copy of the midnolin (MIDN) gene. In addition, gene knock-down/out of MIDN caused down-regulation of parkin E3 ubiquitin ligase, indicating MIDN to be a novel PD-risk factor or causative gene. In this study, we performed RNA-sequencing and transcriptome analysis of Midn wild-type and knockout cells. Midn positively or negatively regulated the expression of a wide variety of genes, including causative familial PD genes, such as α-synuclein, parkin, and EIF4G1. However, EIF4G1 protein levels were not altered by the reduction of its mRNA by Midn loss, as seen that parkin protein levels were correlated to the mRNA down-regulation. Taken together, these findings indicate that MIDN regulates the expression of a wide variety of genes, including multiple PD-causative genes and is associated with PD onset.

著者

Akira Katsuyama Kousuke Sato Fumika Yakushiji Takanori Matsumaru Satoshi Ichikawa

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.1, pp.84-95, 2018-01-01 (Released:2018-01-01)

参考文献数

25

被引用文献数

11

---

A solid-phase synthesis of Park nucleotide as well as lipids I and II analogues, which is applicable to the synthesis of a range of analogues, is described in this work. This technique allows highly functionalized macromolecules to be modularly labeled. Multiple steps are used in a short time (4 d) with a single purification step to synthesize the molecules by solid-phase synthesis.

著者

大川原 正 堅原 宏 古川 潮

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.8, pp.3479-3483, 1985-08-25 (Released:2008-03-31)

参考文献数

9

被引用文献数

7 9

---

The reaction of thioamides (1) with various haloacyl halides (2, 7, 11, 14, 17, and 19) was carried out in sat. NaHCO3-CH2Cl2 and 5% NaOH-CH2Cl2 to give several kinds of 4-thiazolones (3-5, 10, 12 and 15), thiazin-4-one (18) and spiro compounds (21).

著者

渡辺 大一 福谷 俊 伊川 博 山浦 哲明 加瀬 則子 水谷 弘子

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.11, pp.4855-4858, 1986-11-25 (Released:2008-03-31)

参考文献数

8

被引用文献数

2 2

---

Two crystal forms of the new dihydropyridine derivative, methyl (E)-3-phenyl-2-propen-1-yl 1, 4-dihydro-2, 6-dimethyl-4-(3-nitrophenyl)pyridine-3, 5-dicarboxylate (FRC-8411), were obtained by recrystallization from methanol. These crystal forms were identified by using powder X-ray diffractometry, infrared spectroscopy, differential scanning calorimetry (DSC) and thermogravimetry. By means of DSC, the melting points of forms I and II were found to be 140 and 121°C, respectively.Forms I and II, having a similar particle size distribution, were administered orally or intravenously to spontaneously hypertensive rats. In the case of oral administration, the hypotensive action of form I was milder than that of form II and tachycardia was not observed after administration of form I.

著者

斎藤 勝 籔 晴夫 山崎 昌弘 松村 阜子 加藤 日出男

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.2, pp.652-658, 1982-02-25 (Released:2008-03-31)

参考文献数

17

被引用文献数

3 5

---

The existence of four crystalline forms (forms I, II and III, and a hydrate) and an amorphous form of tulobuterol hydrochloride was confirmed by X-ray powder diffraction, infrared spectroscopy and thermal analyses (DSC and TG). The hydrate was found to be the monohydrate by elemental analysis and measurement of water content. From the DSC measurement, it was found that forms I and II melted at 163°C and 170°C, and their heats of fusion were 5.15 kcal/mol and 4.76 kcal/mol, respectively. Form III, the amorphous form and the hydrate transformed into form II at 135°C, 90°C and 75°C, respectively. Activation energy for the dehydration of the hydrate determined by Kissinger's method was 56.1 kcal/mol. No crystal changes were observed in the four crystalline forms when they were ground in a mortar or compressed at high pressure ; however, after such mechanical treatments form I transformed into form II on being heated. The investigation of phase transitions of the four crystals showed that form II was the most stable among them.

著者

宮崎 正三 有田 隆一 堀 了平 伊藤 圭二

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.3, pp.638-642, 1974-03-25 (Released:2008-03-31)

被引用文献数

13 21

---

The existence of the two crystalline forms of chlortetracycline hydrochloride (CTC-HCI) was confirmed by infrared spectroscopy and X-ray diffraction. From the dissolution studies with crystalline powder and compressed disk, an appreciable difference in the dissolution behavior in water was detected between the two forms. In order to determine the effect of polymorphism on the gastrointestinal absorption of CTC-HCl, blood plasma levels obtained in rabbits after intraduodenal administration and cumulative amounts excreted in human subjects after oral administration of the two forms were compared. The results indicated that polymorphic state of CTC-HCl significantly influences bioavailability of the CTC-HCl.

著者

金庭 延慶 市川 順一 松本 崇弘

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.1063-1073, 1988-03-25 (Released:2008-03-31)

参考文献数

12

被引用文献数

5 8

---

Polymorphism of phenylbutazone was investigated in detail. Pure α form of phenylbutazone could not be obtained by conventional methods, but it was found that the β form was transformed to the stable α form in ethanol solution at 4°C. At 15 and 25°C, the β form was transformed to a mixture of the α and δ forms, while at 35°C, tha α form in the mixture was converted to the δ form. These results showed that the preparation of a pure polymorphic form by means of recrystallization in solution is not necessarily straightforward. The dissolution bethavior of each form in buffer solution was examined next. The transition temperatures of the pairs of α and δ forms and of α and β forms were 29.0 and 61.6°C, respectively, in buffer solution as determined by means of the non linear van't Hoff model proposed by Grant et al. The heats of fusion of the α, β and δ forms were 8.74, 6.48 and 6.85 kcal/mol, and their melting points were 91.2, 93.3 and 101.4°C, respectively. These results suggested that the pair of β and δ forms is in a monotropic relation and the pairs of a α and β forms and of α and β forms are in enantiotropic relationships.

著者

末宗 洋 川原 哲也 酒井 浄

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.2, pp.550-557, 1986-02-25 (Released:2008-03-31)

参考文献数

13

被引用文献数

13 20

---

Prostanoic acid (18) and 8-isoprostanoic acid (1) constitute the basic structures of primary prostaglandins and 8-isoprostaglandins. The conversion of commercially available (+)- and (-)-limonene to these compounds was accomplilshed by a sequence of reactions involving the Rh(I)-catalyzed cyclization of 3, 4-disubstituted 4-pentenals, which were easily prepared from (+)- or (-)-limonene, to cis-3, 4-disubstituted cyclopentanones and the appropriate modification of substituents on the five-membered ring.

著者

細上 徹 榑谷 昌彦 東 邦彦 浅野 昌英 大屋 和美 高杉 紀雄 真船 英一 三木 藤作

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.10, pp.2712-2719, 1992-10-25 (Released:2008-03-31)

参考文献数

18

被引用文献数

12 14

---

A series of acyl derivatives of 2-(3, 4-dimethoxyphenyl)ethylamine (4) were synthesized and evaluated for their effectiveness to prevent water-immersion stress-induced gastric ulceration when given intraperitoneally to rats. Among them N-[2-(3, 4-dimethoxyphenyl)ethyl]-2-phenylaminoacetamide hydrochloride (15) had significant antiulcer activity. Further modification of the four parts of 15 revealed that only the introduction of a carbamoyl group into 2- or 3-position of the phenylamino part gave compounds (49-51, 54 and 55) which retained antiulcer activity comparable to the lead compound. However, the compounds (49-51 and 54) did not exert a prophylactic effect when administered orally except for the 3-substituted bezamide derivative 55. Alkyl substitution on the nitrogen of benzamide gave 3-[[[2-(3, 4-dimethoxyphenyl)ethyl]carbamoyl]methyl]amino-N-methylbenzamide (66, DQ-2511) and the related compounds (67, 70, 74 and 77) which all had potent antiuler activities at oral doses of 50-400 mg/kg.

著者

森田 正美 細上 徹 今野 勉 / 真船 英一 高杉 紀雄 Norio TAKASUGI

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.3, pp.476-482, 1995-03-15 (Released:2008-03-31)

参考文献数

7

---

Preliminary preformulation studies of a 2-(3, 4-dimethoxyphenyl)ethylamine derivative were investigated. The hydrochloride form showed incompatibility with the excipients used for oral dosage forms. There were several crystal forms of the free base, namely, α-anhydrate, β-anhydrate, monohydrate, and trihydrate. The trihydrate form was unstable. The degree of crystallinity of the β-anhydrate form was difficult to control. The monohydrate form was difficult to manufacture with constant quality.The serum levels of the compounds in rats were almost related to the dissolution rates in the JP 1st disintegration medium from the discs. The serum level of α-anhydrate was the lowest. However, the dissolution rates from the formulations of α-anhydrate were improved. After oral administration of the improved formulation, the serum level of α-anhydrate in beagle dogs was almost triple that after the oral administration of the capsule of the hydrochloride form.

著者

北岡 宏章 大屋 和美 伯水 英夫

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.10, pp.1744-1750, 1995-10-15 (Released:2008-03-31)

参考文献数

11

被引用文献数

6 6

---

Nafagrel hydrochloride exists as both a hemihydrate and monohydrate. Conversion from the hemihydrate to the monohydrate is not reversible, and both hydrates can coexist in stable equilibrium between 23% relative humidity (RH) and 64% RH. In order to clarify the dehydration behavior, the kinetics of the thermal dehydration of the hydrates was studied by means of isothermal gravimetry at atmospheric pressure with a controlled water vapor pressure. This revealed that dehydration did not depend on absolute humidity but on RH. The dehydration of the hemihydrate proceeded by two-dimensional gorwth of the nuclei, A2, but the mechanism of monohydrate dehydration changed from A2 to a two-dimensional phase boundary, R2, with an increase in RH. The dehydration of the monohydrate proceeded by R2, resulting in the production of the hemihydrate at 6.5% RH or above. These kinetic analyses showed that the monohydrate dehydrated faster than the hemihydrate.

著者

北岡 宏章 和田 千佐 諸井 黎明 伯水 英夫

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.4, pp.649-653, 1995-04-15 (Released:2008-03-31)

参考文献数

6

被引用文献数

16 35

---

Differential scanning calorimetry (DSC) curves of levofloxacin hemihydrate measured under various conditions showed different thermograms. These phenomena were attributed to be the dehydration. Dehydration caused a multiple-phase transition. Dehydration at a higher temperature (above 70°C) gave a sharp endothermic peak on the DSC curve due to the melting of the γ form, and at a lower temperature (below 50°C) gave a sharp endothermic peak due to the melting of the α form.In contrast, the thermal behavior of levofloxacin monohydrate was not affected by dehydration. The difference in the thermal behavior between the hemihydrate and the monohydrate might be attributed to a difference in the interaction between levofloxacin and crystal water. Observations by thermomicroscopy, the changes in powder X-ray diffraction patterns during heating, and single X-ray analysis all supported the above interpretation.

著者

仲井 由宣 山本 恵司 寺田 勝英 内田 武 清水 昶幸 西垣 貞男

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.2629-2632, 1982-07-25 (Released:2008-03-31)

参考文献数

5

被引用文献数

9 14

---

The crystal structure of ftorafur, C8H9FN2O3, has been determined by single-crystal X-ray diffraction techniques. The crystal is triclinic, space group P1 ; its unit-cell dimensions are a=8.994 (8), b=16.612 (9), c=5.981 (5) Å, α=86.40 (6), β=94.06 (15), γ=80.29 (8)°, Z=4. The structure was solved by the direct method and the final R value was 0.056.

著者

内田 武 米持 悦生 小口 敏夫 寺田 勝英 山本 恵司 仲井 由宣

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.1632-1635, 1993-09-15 (Released:2008-03-31)

参考文献数

15

被引用文献数

13 20

---

Four crystalline forms of tegafur were prepared by recrystallization from different solvents (α-, β-, δ-forms) and by heating (γ-form). They have been characterized using powder X-ray diffraction, thermal analysis, microscopy, density measurements and infrared spectroscopy. From differential scanning calorimetry measurements, it was confirmed that the γ- and δ-forms melted at 175°C and 165°C, whereas the α- and β-forms transformed into the γ-form at about 162°C and 120°C, respectively. The infrared absorption spectral differences observed between the α- and β-forms were discussed in relation to their intermolecular hydrogen bonding systems. It was also found that the difference in crystal forms significantly altered the dissolution rate of tegafur.

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:13475223)

巻号頁・発行日

vol.64, no.7, pp.961-965, 2016-07-01 (Released:2016-07-01)

被引用文献数

14

著者

Yoshinori Ochiai Kunio Itoh Eiichi Sakurai Mayuko Adachi Yorihisa Tanaka

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.29, no.12, pp.2362-2366, 2006 (Released:2006-12-01)

参考文献数

24

被引用文献数

11 22

---

The substrate selectivity of monoamine oxidase A (MAO-A), monoamine oxidase B (MAO-B), diamine oxidase (DAO), and semicarbazide-sensitive amine oxidase (SSAO) was investigated in the absence of chemical inhibitors using the COS-1 cells expressed with respective amine oxidase. Serotonin (5-hydroxytryptamine), 1-methylhistamine, and histamine were preferentially oxidized by MAO-A, SSAO, and DAO, respectively, at a low substrate concentration. In contrast, benzylamine, tyramine, and β-phenylethylamine served as substrates for all of MAO-A, MAO-B, and SSAO. Each amine oxidase showed broad substrate selectivity at a high substrate concentration. The cross-inhibition was remarkable in MAO-A and MAO-B, especially in MAO-A, but not in SSAO and DAO. A study of the substrate selectivity of amine oxidases should include consideration of the effects of substrate concentration and specific chemical inhibitors.

著者

Nathan Ray Alim Shiki Miyazaki Yasushi Shimoda Masaharu Sugiura Makoto Nakajima Shunsuke Kotani

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.10, pp.989-993, 2017-10-01 (Released:2017-10-01)

参考文献数

19

被引用文献数

8

---

Chiral phosphine oxide sequentially activates silicon tetrachloride and trichlorosilyl enol ethers to facilitate asymmetric aldol/vinylogous aldol reaction of 4-methoxy-3-penten-2-one and conjugated aldehydes in a highly enantioselective fashion, and the subsequent cyclization produced optically active 2,6-disubstituted 2,3-dihydro-4-pyranones bearing stereogenic centers at a remote position in a single operation.

著者

菅沢 勉 豊田 達郎 笹倉 和幸

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.771-781, 1974-04-25 (Released:2008-03-31)

被引用文献数

6 13

---

dl-Camptothecin (XXX) and two epimeric N-formyl-1, 2, 6, 7-tetrahydrocamptothecins (XXIIIa, b) have been synthesized from 3-oxo-1H-pyrrolo [3, 4-b] quinoline IIIa by using following two key reactions. 1) An intramolecular aldol condensation of the imido-ester (VIIIb→IXb). 2) Vilsmeier reaction on a 4-methoxy-2-pyridone ring (XVIb→XVII) followed by nucleophilic attack of a malonate carbanion onto the formyl-pyridone ring (XVII→XVIII).

著者

菅沢 勉 笹倉 和幸 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.763-770, 1974-04-25 (Released:2008-03-31)

被引用文献数

7 12

---

A D-E ring analog (XX) of camptothecin (I) was synthesized from 4-methoxy-1-methyl-2 (1H)-pyridone by using Vilsmeier reaction followed by nucleophilic direct introduction of di-tert-butyl malonate onto the pyridone ring, ethylation and hydroxylation.