著者

浜道 則光 宮坂 貞

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.38, no.12, pp.3253-3256, 1990-12-25 (Released:2008-03-31)

参考文献数

21

被引用文献数

1 3

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Substituent and solvent effects on the tautomeric equilibration (E/Z) of α-(N-alkyl and -arylaminomethylene)-9-(methoxymethyl)-9H-purine-6-acetonitriles (3a-q) have been studied by means of proton nuclear magnetic resonance spectroscopy in protic and aprotic solvents at 25°C. In chloroform-d these compounda (3a-q) exist mainly as the E-form. On the other hand, in methanol-d4 or dimethylsulfoxide-d6 the alkylamines (3a-c), phenylamine (3e), meta- or para-substituted phenylamines (3f-j) and 2, 6-disubstituted phenylamines (3p and q) exist mainly as the Z-form, while the trityl compound (3d), and ortho-substituted compounds (3k-o) showed a predominance of the E-form.

著者

浜道 則光 宮坂 貞

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.38, no.7, pp.2018-2019, 1990-07-25 (Released:2008-03-31)

参考文献数

7

被引用文献数

1 1

---

6-Dicyanomethylene-9-tetrahydrofuranylpurine (4), which was obtained by the reaction of 9H-1, 6-dihydropurine-Δ6, α-propanedinitrile (3) with 2, 3-dihydrofuran, has been catalytically hydrogenated to the α-(aminomethylene)-9-(tetrahydrofuran-2-yl)-9H-purine-6-acetonitrile (5) in good yield using N, N-dimethylformamide-benzene as a solvent over Pd-C under medium pressure. Substitution of 5 with amines gave the corresponding alkylaminomethylene purines (6 and 7). Reaction of 5 with hydrazine gave the pyrazole derivative (8).

著者

藤井 達也 西田 裕 阿比留 佳明 山本 雅司 黄瀬 正博

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.11, pp.1872-1877, 1995-11-15 (Released:2008-03-31)

参考文献数

13

被引用文献数

7 19

---

Diisopropylamine (DIPA), N, N-diisopropylethylamine (DIPEA), tributylamine (TNBA) and 7-(1-piperazinyl)-4-quinolone-3-carboxylic acid (2) were titrated in water-dimethylformamide (DMF) mixtures containing 45-98% DMF. Apparent pKa values in anhydrous DMF (pKDMF) were calculated by extrapolation from the variation in the half-neutralization pH values in aqueous DMF. The validity of the relative basicity derived from the pKDMFs was confirmed by examination of the kinetics of esterification of a derivative of 2 with 4-(bromomethyl)-5-methyl-1, 3-dioxol-2-one (DMDO-Br). Relative basicities in DMF were : the carboxylate anion of 2»DIPA>DIPEA>TNBA >the amino group in the piperazinyl part of 2. This order is clearly different from that observed in water.We concluded that DIPEA is a suitable agent to suppress the undesired esterification during the reaction to mask the amino group of 2 with a DMDO group, because it does not remove a proton from the carboxyl group, but only from the protonated amino group.

著者

瀬川 純 数野 憲二 松岡 正人 網本 功 尾崎 正邦 松田 真人 冨井 由文 北野 正彦 黄瀬 正博

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.7, pp.1238-1240, 1995-07-15 (Released:2008-03-31)

参考文献数

13

被引用文献数

3 7

---

Optically active isomers of 6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H-[1, 3]thiazeto[3, 2-a]quinoline-3-carboxylic acid (NM394, 3) were prepared through optical resolution of their racemic intermediate (±)-1 by high-performance liquid chromatography (HPLC). The absolute configuration at the C-1 position in the thiazetoquinolone ring of (-)-3 was confirmed by X-ray analysis of (-)-4 to be S. The in vitro antibacterial activity of (-)-3 was 2-8 times that of (+)-3.

著者

瀬川 純 数野 憲二 松岡 正人 白波瀬 一朗 尾崎 正邦 松田 真人 冨井 由文 北野 正彦 黄瀬 正博

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.1, pp.63-70, 1995-01-15 (Released:2008-03-31)

参考文献数

19

被引用文献数

6 13

---

A seried of 1, 8-disubstituted 6-fluoro-4-oxo-7-piperazinyl-4H-[1, 3]thiazeto[3, 2-a]quinoline-3-carboxylic acid derivatives was prepared and evaluated for antibacterial activity. In the 7-piperazinyl series, addition of a fluorine at C-8, which increased the in vitro activity for the 1-hydrogen and 1-methyl analogues and decreased it for the 1-phenyl analogue, improved the in vivo activity of all the analogues. Introduction of a methoxy group at C-8 of the 1-methyl-7-piperazinyl analogue also improved its in vivo antibacterial activity. The effect of 8-substituents on the in vitro and in vivo antibacterial activity of the 1-methyl-7-(4-methyl-1-piperazinyl) series is also discussed.

著者

三巻 祥浩 神本 敏弘 黒田 明平 指田 豊 西野 敦子 里見 佳子 西野 輔翼

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.7, pp.1190-1196, 1995-07-15 (Released:2008-03-31)

参考文献数

25

被引用文献数

17 31

---

Phytochemical study on the underground parts of Hosta longipes gave six new steroidal saponins together with a known one. The structures of the new compounds were determined by detailed analysis of their 1H-and 13C-NMR spectra including two-dimensional NMR spectroscopy, acid-catalyzed hydrolysis followed by chemical correlation, and by comparison with spectral data of known compounds. The isolated saponins and their aglycones were examined for inhibitory activity on 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated 32P-incorporation into phospholipids of HeLa cells to identify new antitumor-promoter compounds.

著者

今泉 宏之 南部 直樹 永井 恒司

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.9, pp.2565-2569, 1980-09-25 (Released:2008-03-31)

参考文献数

13

被引用文献数

66 96

---

An X-ray diffraction method for determination of the degree of crystallinity of indomethacin was established, and the transition rate of indomethacin from amorphous to crystalline form was investigated. The transition of the amorphous form to crystalline form at 20°, 30°and 40°followed first-order kinetics and the Arrhenius plot showed good linearity. The amorphous form was shown to change to form I at 100% relative humidity (RH), to form I or II at 89% RH and to form I at 79% and 69% RH at 30°. The transition rate of the amorphous form to form II at 100% RH was larger than that at 89% RH. A good linear relation was observed between the maximum amount of water absorbed (log scale) and the degree of crystallinity at 100% or 89% RH at 30°. The dissolution rate of the amorphous form was higher than those of forms I and II. The amorphous form showed better tablet-forming properties than the crystalline form.

著者

Ryosuke Koyama Wataru Hakamata Takako Hirano Toshiyuki Nishio

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

pp.c17-01009, (Released:2018-03-13)

参考文献数

29

被引用文献数

9

---

Three Golgi mannosidases (GMs), namely Golgi α-mannosidases IA, IB, and IC, remove mannose residues from N-glycans and regulate the quality control and transportation of nascent proteins. GM inhibitors regulate several biological events such as cell–cell communication, differentiation, and apoptosis in cancer cells. As a result, GM inhibitor-based therapies have gained significant attention for cancer treatment. However, to date, no GM inhibitor has been approved and none is in clinical development for anti-cancer treatment. Meanwhile, drug repositioning plays an important role in identifying potential inhibitors that vary in molecular structure and properties to bypass much of the early cost and time. We performed a drug repositioning screen of a compound library that included approved drugs. The estrogen receptor antagonists tamoxifen and raloxifene inhibited human GMs at the cellular level. Sulindac, a nonsteroidal anti-inflammatory drug, also inhibited GMs. Our results demonstrated the efficacy of this screening strategy and revealed lead compounds for anti-cancer drug development.

著者

木山 竜一 林 邦雄 原 真里子 藤本 正文 川畑 友二 川上 勝 中島 成元 藤下 利夫

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.6, pp.960-965, 1995-06-15 (Released:2008-03-31)

参考文献数

12

被引用文献数

3 8

---

A novel series of 6-alkyl-7-oxo-4, 7-dihydropyrazolo[1, 5-a]pyrimidine-3-carboxylic acid derivatives was prepared as angiotensin II (AII) receptor antagonists. When evaluated in an in vitro binding assay using COS cells transfected with a cDNA encoding a human AT1 angiotensin II receptor, the compounds in this series showed Ki values in the range of 0.4-4.0 nM. In anesthetized spontaneously hypertensive rats (SHRs), administration of the 6-propyl derivative 4d (1 mg/kg, i.v.) reduced the mean blood pressure (MBP) by a maximum of more than 30 mmHg from the normal value.

著者

木山 竜一 冨士 雅弘 原 真里子 藤本 正文 川畑 友二 中村 益久 藤下 利夫

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.3, pp.450-460, 1995-03-15 (Released:2008-03-31)

参考文献数

24

被引用文献数

6 7

---

Starting from recently reported nonpeptidic angiotensin II (AII) receptor antagonists, we have designed and prepared a new series of 6-arylimidazo[4, 5-c]pyridine derivatives. Variation of phenyl groups at the 4-, 6- or 7-position of imidazo[4, 5-c]pyridine showed that substitution at the 6-position resulted in receptor-binding activity almost as potent as that of DuP 753. This led to synthesis and evaluation of an extensive series of 6-aryl-imidazo[4, 5-c]pyridine derivatives. Some of them were 4-fold more potent in vitro than DuP 753, but only showed weak antihypertensive activity in vivo when given orally to rats.

著者

馬場 一彦 武市 陽一郎 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.38, no.9, pp.2542-2546, 1990-09-25 (Released:2008-03-31)

参考文献数

25

被引用文献数

2 8

---

Ground mixtures containing uracill were prepared using various additives such as celluloses, proteins, cyclodextrins, enteric coating agents and inorganic compounds in a planetary ball mill. The amorphous state of uracil was observed in the X-ray diffraction patterns of some of the ground mixtures. The results of infrared spectral analysis indicated deprotonation of uracil after 30 h of (30-h) grinding with sodium polyglutamate. All ground mixtures showed the transient supersaturation of uracil in dissolution studies. The initial amount of uracil dissolved from the 30-h ground mixtures with sodium benzoate derivatives, ethylcellulose, hydroxypropylmethylcellulose acetate succinate and proteins was 2.5 to 9-times that dissolved from intact uracil. The crystallinity and solubility of uracil in the ground mixtures were affected by the mixing ratio, grinding time and moisture content of the additive.

著者

Takao Mizumoto Tetsuya Tamura Hitoshi Kawai Atsushi Kajiyama Shigeru Itai

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.56, no.4, pp.530-535, 2008-04-01 (Released:2008-04-01)

参考文献数

12

被引用文献数

23 33

---

In this study, the taste-masking of famotidine, which could apply to any fast-disintegrating tablet, was investigated using the spray-dry method. The target characteristics of taste-masked particles were set as follows: the dissolution rate is not to be more than 30% at 1 min and not less than 85% at 15 min, and the particle size is not to be more than 150 μm in diameter to avoid a gritty feeling in the mouth. The target dissolution profiles of spray-dried particles consisting of Aquacoat ECD30 and Eudragit NE30D or triacetin was accomplished by the screening of formulas and the appropriate lab-scale manufacturing conditions. Lab-scale testing produced taste-masked particles that met the formulation targets. On the pilot scale, spray-dried particles with attributes, such as dissolution rate and particle size, of the same quality were produced, and reproducibility was also confirmed. This confirmed that the spray-dry method produced the most appropriate taste-masked particles for fast-disintegrating dosage forms.

著者

江島 明男 寺沢 弘文 杉森 正道 大薄 悟 松本 建介 川戸 康義 安岡 周美 田川 博昭

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.3, pp.683-688, 1992-03-25 (Released:2008-03-31)

参考文献数

15

被引用文献数

13 21

---

Several E-ring-modified analogues of (RS)-camptothecin were synthesized by total synthesis via Friedlander condensation and evaluated for cytotoxicity and antitumor activity against P388 mouse leukemia cells. Among them, (RS)-20-deoxyamino-7-ethyl-10-methoxycamptothecin (25c) was found to be more active than (RS)-camptothecin (1) in the in vivo assay.

著者

Yukihiro Ikeda Junko Ban Tomoyasu Ishikawa Shohei Hashiguchi Shinichi Urayama Hidetoshi Horibe

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.56, no.10, pp.1406-1411, 2008-10-01 (Released:2008-10-01)

参考文献数

29

被引用文献数

20 32

---

TAK-599 (known as ceftaroline fosamil) is a novel N-phosphono type prodrug of a cephalosporin compound, T-91825, that exhibits strong activity against methicillin resistant Staphylococcus aureus (MRSA). The stability and stabilization of TAK-599 were investigated by kinetic analysis focused on crystallinity and moisture content. Initially it was planned to develop TAK-599 as an injectable formulation using the amorphous solid powder prepared by lyophilization. However, amorphous of TAK-599 free form was found to be chemically unstable even when stored at 8 °C, and thus development was focused on the crystalline material. After exhaustive screening of crystallization condition, the monoacetic acid solvate was found to yield TAK-599 in a crystalline form. Physicochemical properties were studied to identify the key factors affecting the stabilization of TAK-599 in order to improve long-term stability, and the results indicated that the crystallinity of TAK-599 correlated with stability. Furthermore, moisture content was also identified in our studies as an important factor in stabilizing TAK-599. TAK-599 containing about 3% moisture was found to be the most stable form. It was concluded that both sufficient crystallinity and strict moisture control of TAK-599 were essential to maintain long-term stability at 25 °C.

著者

Yifan Zhong Xiaoyan Han Shengbin Li Hui Qi Yali Song Xiaoqiang Qiao

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.904-910, 2017-10-01 (Released:2017-10-01)

参考文献数

30

被引用文献数

12

---

N-Myristoyltransferase (NMT) has been validated pre-clinically as a target for treatment of fungal infections. Various substituted thiochroman-4-one derivatives have been synthesized by an efficient method. The synthesized compounds 7a–y and 8a–t were evaluated for their in vitro antifungal activity against the Canidia albicans, Cryptococcus neoformans, Epidermophyton floccosum, Mucor racemosus, Microsporum gypseum and Aspergillus nigerstrain. A series of compounds exhibited significant activity (minimal inhibitory concentrotion (MIC)=0.5–16 µg/mL) against Canidia albicans and Cryptococcus neoformans. The antifungal activity of compound 7b was reached to that of fluconazole, which can serve as a good starting point for further studies of structural diversity of the NMT inhibitors. The molecular docking studies revealed an interesting binding profile with very high receptor affinity for NMT of Canidia albicans.

著者

Tarek Fathy El-Moselhy Peter Ayoub Sidhom Eman Ahmed Esmat Nageh Ahmed El-Mahdy

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.893-903, 2017-10-01 (Released:2017-10-01)

参考文献数

47

被引用文献数

7

---

Resurgence to target L-type voltage-dependent calcium channels has been applied by the synthesis of two series of nifedipine analogues where the ortho- or a meta-nitrophenyl ring is retained. A pre-synthetic molecular docking study with a receptor model followed by molecular alignment has been performed on 47 compounds to predict the most active member. The IC50 values revealed that some of the compounds are similar to or more active than nifedipine. Substitution of groups at the 3- and 5-positions of the dihydropyridine (DHP) ring gave 3k, which is more active than nifedipine. Our valid three-dimensional quantitative structure–activity relationship (3D-QSAR) model prefigures the influence of lipophilicity, bulkiness and chelating effects of the C3 and C5 substituents. Bulky groups interfere with ring-to-ring hydrophobic interaction with tyrosine (Tyr)4311 and limit the efficiency of increasing the length of the hydrocarbon chain of esters at the 3- and 5-positions of the DHP ring as an approach to increasing the activity. The presence of a chelating substituent on the phenyl ring at the 4-position of the DHP ring ensures strong binding to the receptor and hence stabilization of the closed-channel conformation. The validation of 3D-QSAR model indicated its proficiency in predicting activity of newly compounds belonging to the same chemical class.

著者

Yu-Shi Tian Yi Zhou Tatsuya Takagi Masanori Kameoka Norihito Kawashita

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.3, pp.191-206, 2018-03-01 (Released:2018-03-01)

参考文献数

103

被引用文献数

42

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The global occurrence of viral infectious diseases poses a significant threat to human health. Dengue virus (DENV) infection is one of the most noteworthy of these infections. According to a WHO survey, approximately 400 million people are infected annually; symptoms deteriorate in approximately one percent of cases. Numerous foundational and clinical investigations on viral epidemiology, structure and function analysis, infection source and route, therapeutic targets, vaccines, and therapeutic drugs have been conducted by both academic and industrial researchers. At present, CYD-TDV or Dengvaxia® is the only approved vaccine, but potent inhibitors are currently under development. In this review, an overview of the viral life circle and the history of DENVs is presented, and the most recently reported antiviral candidates and newly discovered promising targets are focused and summarized. We believe that these successes and failures have enabled progress in anti-DENV drug discovery and hope that our review will stimulate further innovation in this area.

著者

Makoto OTSUKA Hitoshi HASEGAWA Yoshihisa MATSUDA

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.45, no.5, pp.894-898, 1997-05-15 (Released:2008-03-31)

参考文献数

19

被引用文献数

35 50

---

The effects of a solvent system on the pharmaceutical properties of carbamazepine (CBZ) granules containing a polymorphic form of bulk powder were investigated by X-ray diffraction analysis, thermal analysis, mercury porosimetry and Brunauer-Emmett-Teller (BET) surface area measurement. A powder mixture consisting of 20% CBZ form I, as a bulk powder, 56% crystalline α-lactose monohydrate and 24% corn starch was used as a pharmaceutical powder, with the three kinds of binder solutions (distilled water, 50% aqueous ethanol and ethanol) containing 5% hydroxypropylcellulose (HPC). After kneading with a binder solution, the granules were obtained using an extruding granulator. The X-ray diffraction and differential scanning calorimetry (DSC) results of the granules indicated that form I with 50% ethanol solution transformed into a dihydrate form during extruding granulation, but this did not occur with the distilled water or ethanol solutions. The order of hardness and specific surface area (Sw) of the granules was distilled water>50% ethanol>ethanol and 50% ethanol>ethanol>distilled water. The stress-thickness profiles of the tabletting compression processes of CBZ granules obtained using various binder solution systems were measured, and the initial compression process due to particle rearrangement was affected by the characteristics in the granules. The total pore volume of tablets obtained from 50% ethanol was the lowest, and their order was ethanol>distilled water>50% ethanol. Their order of tablet hardness reflected the total pore volume of the tablet, and was 50% ethanol>distilled water>ethanol. All pharmaceutical properties of the granules and/or tablets containing CBZ were affected by the characteristics of the solvent systems in binder solution.

著者

Takashi Kojima Fumie Kato Reiko Teraoka Yoshihisa Matsuda Shuji Kitagawa Mitsutomo Tsuhako

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.55, no.3, pp.407-411, 2007 (Released:2007-03-01)

参考文献数

25

被引用文献数

9 11

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Two novel pseudopolymorphs, methanolate and ethanolate of tamoxifen [(Z)-2-[4-(1,2-diphenyl-1-butenyl)phenoxy]-N,N-dimethylethylamine]citrate, were prepared in addition to forms A and B reported previously. Their crystalline forms were identified and characterized by powder and single crystal X-ray diffractometry, differential scanning calorimetry, thermogravimetric analysis, hot-stage microscopy, scanning electron microscopy and diffuse reflectance infrared Fourier-transform spectroscopy, and their physicochemical stability was also evaluated. The results of single crystal X-ray analysis and thermogravimetric analysis of methanolate and ethanolate suggested that the stoichiometry of tamoxifen citrate : methanol and tamoxifen citrate : ethanol could be composed of a 1 : 1 molecular ratio for both solvates. The results of physicochemical stability evaluations at 75 and 97% RH at 40 and 60 °C indicated that the metastable form A was quite stable for at least 2 months even under severe storage conditions, whereas methanolate immediately transformed to a crystalline mixture of forms A and B, and subsequently changed to the stable form B.

著者

Kimura Masahiro Shindo Mitsuno Moriizumi Toshiyuki Tagawa Noriko Fujinami Aya Kato Ikuo Uchida Yoshiki

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.62, no.6, pp.586-590, 2014

被引用文献数

6

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Salusin-β has been detected in numerous mammalian tissues and has been shown to have various effects on the cardiovascular system. In this study, we showed that salusin-β exhibited potent antibacterial activity against Gram-positive microorganisms such as Bacillus subtilis NBRC 3513, Bacillus megaterium ATCC 19213, Staphylococcus aureus NBRC 12732, and Staphylococcus epidermidis NBRC 12933. A cytoplasmic membrane-depolarizing assay using the DiSC3(5) dye revealed that the addition of 4 nmol/mL of salusin-β caused the leakage of fluorescence dye from Staphylococcus aureus NBRC 12732. The antimicrobial potency and circular dichroism (CD) spectroscopy of five analogs related to salusin-β were examined to determine structure-function relationships in its N- and C-terminal regions. The results obtained suggest that the N-terminal sequences of the salusin-β molecule are important for the expression of the potent antimicrobial activity of this peptide. A profile corresponding to that of the α-helix conformation was observed in the salusin-β solution.