著者

伊藤 豊 矢野 真吾 渡辺 和夫 山中 悦二 相見 則郎 坂井 進一郎

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.38, no.6, pp.1702-1706, 1990

被引用文献数

19

---

We investigated the selectivities and structure requirements for alpha-1 and alpha-2 adrenoceptor blocking activities of yohimbine (YO) and its 12 related analogs, such as β-yohimbine (β-YO), dihydrocorynantheine (DHC) and (-)indoloquinolizidine ((-)IQ). The affinity of YO analogs to alpha-adrenoceptor was assessed by measuring their blockade of pressor responses to epinephrine in pithed rats. Among YO structure groups, the potency order was YO>DHC=β-YO>geissoschizine methylether>14β-hydroxy YO>14β-benzoyloxy YO (inactive). (-)IQ was slightly less potent than YO, but much stronger than (+)IQ. Among (±)IQ structure groups, the potency order was (±)IQ>(±)1, 12b-trans-1-hydroxy IQ»(±)1, 12b-cis-1-hydroxy IQ (imactive). (±)Borrerine was active, but (±)desmethylborrerine was inactive. The alpha-1 blocking activities of the four compounds YO, β-YO, DHC and (-)IQ, were assessed in experiments of pressor responses to methoxamine in pithed rats and contractile responses to methoxamine in the rat vas deferens. The potency order was (-)IQ>YO>DHC>β-YO. Furthermore, the alpha-2 blocking activities of the four analogs were assessed in experiments of pressor responses to clonidine and inhibition of electrically driven cardioacceleration by clonidine, in pithed rats. The potency order was YO>β-YO>(-)IQ>DHC. Based on the potency ratio between alpha-1 and alpha-2 blocking activities, DHC or YO was most selective for alpha-1 or alpha-2 subtype, respectively, among the four YO analogs. These results suggest that the A, B, C and D rings of YO analogs and their planarity are necessary for the affinity to alpha-adrenoceptors and that the predominant conformation of the carboxymethyl or hydroxy group on the E ring of YO structure determines the selectivity for alpha-1 and alpha-2 blocking activities.

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

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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.

著者

Zhang Bingyu Lv Chao Li Weibo Cui Zhiming Chen Dongdong Cao Fangjun Miao Fang Zhou Le

出版者

公益社団法人 日本薬学会

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

2015

被引用文献数

17

---

This paper reported the synthesis, structure-activity relationship (SAR) and acaricidal activity in vitro against Psoroptes cuniculi, a mange mite, of 25 ethyl cinnamate derivatives. All target compounds were synthesized and elucidated by means of MS, 1H- and 13C-NMR analysis. The results showed that 24 out of 25 tested compounds at 1.0 mg/mL demonstrated acaricidal activity in varying degrees. Among them, 6, 15, 26, 27 and 30 showed significant activity with median lethal concentration values (LC50) of 89.3, 119.0, 39.2, 29.8 and 41.2 μg/mL, respectively, which were 2.1- to 8.3-fold the activity of ivermectin (LC50 = 247.4 μg/mL), a standard drug in the treatment of Psoroptes cuniculi. Compared with ivermectin, with a median lethal time value (LT50) of 8.9 h, 27 and 30 showed smaller LT50 values of 7.9 and 1.3 h, respectively, whereas 6, 15 and 26 showed slightly larger LT50 values of 10.6, 11.0 and 10.4 h at 4.5 μmol/mL. SARs showed that the presence of o-NO2 or m-NO2 on the benzene ring significantly improved the activity, whereas the introduction of a hydroxy, methoxy, acetoxy, methylenedioxy, bromo or chloro group reduced the activity. (E)-Cinnamates were more effective than their (Z)-isomer. Nevertheless, the carbon-carbon double bond in the acrylic ester moiety was proven not to be essential to improve the activity of cinnamic acid esters. Thus, the results strongly indicate that cinnamate derivatives, especially their dihydro derivatives, should be promising candidates or lead compounds for the development of novel acaricides for the effective control of animal or human acariasis.

著者

Shuichi Mori Ryohei Takagaki Shinya Fujii Ko Urushibara Aya Tanatani Hiroyuki Kagechika

出版者

公益社団法人日本薬学会

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.65, no.11, pp.1051-1057, 2017-11-01 (Released:2017-11-01)

参考文献数

39

被引用文献数

3

---

The progesterone receptor (PR) controls various physiological processes, including the female reproductive system, and nonsteroidal PR ligands are considered to be drug candidates for treatment of various diseases without significant adverse effects. Here, we designed and synthesized m-carborane-based secondary alcohols and investigated their PR-ligand activity. All the synthesized alcohols exhibited PR-antagonistic activity at subnanomolar concentration. Among them, alcohols having a small alkyl side chain and a 4-cyanophenyl group also exhibited PR-agonistic activity in a relatively high concentration range. Optical resolution of secondary alcohols having a methyl side chain was performed, and the PR-ligand activity and PR-binding affinity of the purified enantiomers were examined. The chirality of the secondary alcohol appears to have a more significant influence on PR-agonistic activity than on antagonistic activity.

著者

Kosuke Chiba Yuichi Hashimoto Takao Yamaguchi

出版者

公益社団法人日本薬学会

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.65, no.10, pp.994-996, 2017-10-01 (Released:2017-10-01)

参考文献数

16

被引用文献数

3

---

We recently developed 4-azidophthalimide (AzPI) as a compact fluorogenic photoreactive tag that can be attached to ligands to achieve selective fluorescence labeling of target proteins even in the presence of a large excess of non-target proteins. To further establish the utility of the AzPI tag, we focused here on streptavidin labeling with biotin–AzPI conjugates, and evaluated the relation between the amount of covalently labeled streptavidin (labeling rate) and fluorescence intensity. The labeling rate was proportional to the fluorescence intensity under standardized photo-irradiation conditions. Prolongation of the photo-irradiation time led to a marked increase in the labeling rate, but this was accompanied by a gradual decrease in the fluorescence intensity, which appeared to be due at least in part to photo-induced degradation of the target streptavidin. These findings should be helpful for achieving sensitive fluorescence detection of target proteins by using the AzPI tag.

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.