著者
武田 敬
出版者
公益社団法人日本薬学会
雑誌
藥學雜誌 = Journal of the Pharmaceutical Society of Japan (ISSN:00316903)
巻号頁・発行日
vol.117, no.6, pp.368-377, 1997-06-25
参考文献数
46
被引用文献数
2

This review describes a highly efficient [3+2] annulation based on the Brook rearrangement for functionalized cyclopentenols, which we have recently developed, and its application to the synthesis of natural products.
著者
市川 聡
出版者
公益社団法人日本薬学会
雑誌
藥學雜誌 = Journal of the Pharmaceutical Society of Japan (ISSN:00316903)
巻号頁・発行日
vol.128, no.10, pp.1403-1430, 2008-10-01
参考文献数
149
被引用文献数
4

&nbsp;&nbsp;Nucleosides and nucleotides are one of the most important elements for cells by the fact that they are components of DNAs and RNAs. In addition, they play important roles in most fundamental cellular metabolic pathways such as energy donors, second messengers, and cofactors for various enzymes. Therefore, there exists a rich source in drug discovery targeting nucleosides and nucleotides. In order to utilize nucleosides and nucleic acids on the drug development, it is very important to develop reactions and methods, by which the highly coordinating and labile nucleoside intermediates can be used. With these in mind, we have been working on synthetic nucleoside and nucleic acid chemistry. First, branched sugar nucleoside derivatives, which are potential antitumor agents, have been synthesized utilizing samarium diiodide (SmI<sub>2</sub>) mediated Reformatsky reaction or aldol reaction. 3&prime;-&beta;-Carbamoylmethylcytidine (CAMC) was found to exhibit potent cytotoxicity against various human tumor cell lines. Synthetic methodology of the caprazamycins, which are promising antibacterial nucleoside natural products, was also developed by the strategy including &beta;-selective ribosylation without using a neighboring group participation. Our synthetic route provided a range of key analogues with partial structures to define the pharmacophore. Simplification of the caprazamycins was further pursued to develop diketopiperazine analogs. Medicinal chemistry of oligodeoxynucleotides has been conducted. Thus, novel triazole-linked dumbbell oligodeoxynucleotides and modular bent oligodeoxynucleotides were synthesized. They exhibit excellent binding affinity to NF-&kappa;B or HMGB1 A-box protein, which are important therapeutic targets. Therefore, the results obtained conclusively demonstrated these oligodeoxynucleotides could be proposed as powerful decoy molecules.<br>
著者
味澤 幸義 赤羽 健司 赤羽 増夫 佐藤 和明 玉井 哲郎 斉藤 勝 田中 信之 鎌田 晃爾 小林 通洋
出版者
公益社団法人日本薬学会
雑誌
藥學雜誌 = Journal of the Pharmaceutical Society of Japan (ISSN:00316903)
巻号頁・発行日
vol.116, no.9, pp.735-747, 1996-09-25
参考文献数
13

A number of benzimidazole derivatives were synthesized and tested for cholecystokinin A (CCK-A) receptor inhibitory activity in order to study structure-activity relationships. Significant CCK-A receptor inhibitory activities were found in the compounds having carboxyl or tetrazolyl group. As the most preferred compound, 4-(5,6-dichlorobenzimidazol-2-yl)-N-(3-methoxypropyl)-N-pentylglutaramic acid (4g) was selected.
著者
内林 政夫
出版者
公益社団法人日本薬学会
雑誌
藥學雜誌 = Journal of the Pharmaceutical Society of Japan (ISSN:00316903)
巻号頁・発行日
vol.126, no.12, pp.1341-1349, 2006-12-01
参考文献数
25
被引用文献数
1 1

&nbsp;&nbsp;An overview is presented on the reports available so far on sweet potato, <i>Ipomoea batatas</i>, cultivated widely in Polynesia in the pre-Columbian era, with reference to possible ways and presumptive dates of transfer from the Americas to Polynesia, such as (1) Polynesian navigators' travel to Peru, (2) Peruvian fishermen's drift westward, (3) vessel drift, (4) seed drift, (5) root-tuber drift, and (6) transport by birds. The author supports the case (1) as most plausible. <i>Ganshu</i> or <i>Ganchu</i> described in the old Chinese herbal books is identified as <i>Dioscorea esculenta</i>. An introduction of the tuber to China and Japan is briefly mentioned.<br>
著者
永井 恒司
出版者
公益社団法人日本薬学会
雑誌
藥學雜誌 = Journal of the Pharmaceutical Society of Japan (ISSN:00316903)
巻号頁・発行日
vol.123, no.3, pp.143-150, 2003-03-01
参考文献数
11
被引用文献数
4

In Japanese pharmaceutical community, there seems to be a lack of “Science of Science” and “Research on Research” which are to utilize unit sciences and research for the benefit of human being. In other words, pharmaceutical people in Japan should have much more pharmaceutical philosophy. The late Professor Komei Miyaki, founder Editor-in-Chief of FARUMASHIA, the monthly membership magazine of Pharmaceutical Society of Japan, under whom I worked as one of editorial board members, taught me that scientists should have their own philosophy of their sciences. Such a pharmaceutical philosophy as mentioned above should be established on the basis of complete separation of medical profession between doctors and pharmacists, which form the most important and necessary issue in safety assurance for patients with the complete zero defect (ZD action), as there is a long history for that in Europe since the separation was completed by King Friedrich II in 1240. Therefore, we have to learn the social status of European/American pharmacist practitioners who are the great No. 1 among all the professions. European pharmacists guarantee the safety of every chemical used for human body and pets, such as medicines, cosmetics, foods, tooth stuffs and so on. Regarding the pharmaceutical sciences in Japan also there seems to be a lack of pharmaceutical philosophy, as pharmaceutical scientists have no identity in research object that may be similar to basic scientists who are non-pharmacy graduates. Japanese sciences generally have developed along the lines of the Western model, reaching the current high level. We now not only should receive profits from the outside but also should embark on a mission to support pharmaceutical sciences throughout the world, especially Asian courtiers. At the present, we do not seem to be fulfilling our mission to do that, even though general activity includes significant international exchange. We have to make much more effort for international contribution/participation. For that, the most important and necessary issue is to make change in fundamental sense in Japanese pharmaceutical community, though an internationalization of technological issues is usually taken into consideration. In this connection, regarding the new drug development, we must have a change in the sense to establish pharmaceutical philosophy and jump up in conception from the existing one. Based on the above mentioned pharmaceutical philosophy, seven star pharmacists should be educated as described in 2000 FIP Statement of Policy: Good Pharmacy Education Practice, who could be a (1) care giver; (2) decision maker; (3) communicator; (4)leader; (5) manager; (6) life-long learner; (7)teacher.<br>
著者
飯塚 幸澄 櫻井 栄一 田中 頼久
出版者
公益社団法人日本薬学会
雑誌
藥學雜誌 = Journal of the Pharmaceutical Society of Japan (ISSN:00316903)
巻号頁・発行日
vol.121, no.5, pp.365-369, 2001-05-01
参考文献数
12
被引用文献数
7 10

The antidiabetic effect of hot water extracts from Folium Mori was investigated in GK rat; one of the animal models of non-insulin dependent diabetic mellitus types. Folium Mori extracts (150 mg/kg) significantly reduced the blood glucose of GK rat from 203.8&plusmn;29.8 to 138.5&plusmn;21.2 mg/dl at 14 days after oral administration. However, in normal rats, blood glucose and insulin levels were not changed by treatment with Folium Mori. The Folium Mori also decreased blood glucose and improved glucose tolerance at 14 days after repeated administration in GK rats. The Folium Mori treatment significantly increased glucose metabolism in the glucose clamp test for GK rats. These results suggest that Folium Mori has quite unique properties such as raising insulin sensitivity and improving insulin resistance.
著者
本間 克明 酒井 律子 武島 晶子 島森 美光 早瀬 幸俊
出版者
公益社団法人日本薬学会
雑誌
藥學雜誌 = Journal of the Pharmaceutical Society of Japan (ISSN:00316903)
巻号頁・発行日
vol.124, no.10, pp.693-697, 2004-10-01
参考文献数
5
被引用文献数
1

生活環境の改善や医学の進歩等により, わが国の平均寿命は平成13年では男性78.07年, 女性84.93年となり, 1)世界有数の長寿国となっている. そして, 65歳以上の高齢者人口は平成12年でおよそ2200万人と総人口の17.4%を占めており, 平成27年には26%台となり, さらに平成42年には29.6%, 平成62年には35.7%に達すると推計されている. 2)このような急速な高齢化の進展や疾病構造の変化等によりわが国の医療をとりまく環境は大きく変化しており, それに伴い国民医療費は年々増大し, 平成11年度には約30兆円に到達した. 年齢階級別国民医療費を平成12年度で見ると, 65歳以上の医療費が約12兆円で, 実に50%を占めるに至っており, これを1人当たりの医療費で見ると, 15歳から44歳が約7万円, 45歳から64歳が約19万円であるのに対して, 65歳以上では約54万円, 70歳以上では約63万円, 75歳以上では約70万円と15歳から44歳及び45歳から64歳の医療費に比べて, それぞれ約3倍から10倍高くなっている. 3)この原因としては高齢者は受診率が高く, また重症化し易く, かつ治療には長期間かかることなどが考えられている.
著者
渡部 恵 杉浦 宗敏 清野 敏一 光永 義治 中村 均 山田 安彦 土屋 文人 大江 和彦 伊賀 立二
出版者
公益社団法人日本薬学会
雑誌
藥學雜誌 = Journal of the Pharmaceutical Society of Japan (ISSN:00316903)
巻号頁・発行日
vol.122, no.10, pp.841-847, 2002-10-01
参考文献数
4
被引用文献数
4 4

In the computerized prescription order entry system, it has been pointed out that a physician's input mischoice for medicine is one of the causes of medication errors. We therefore investigated the input mischoices by physicians at the time of writing prescriptions. Subsequently, the number of input characters in a prescription order was changed to three characters from two characters. Furthermore, 105 items of high-alert medications, which are likely to result in injury if errors occur, were established. A warning screen display system that requests reconfirmation of the effect, name, usage, and dosage of those medicines was also built. It was found that 70% of input mistakes were caused by choosing the medicine displayed immediately above or below the desired drug. By changing the number of input characters of a prescription order to three characters from two characters, the rate of specification of a trademark improved sharply from 36% to 85%. Consequently, the rate of choice of a drug with another trademark decreased significantly from 0.028% to 0.0047%. In 5% of cases when the warning screen was displayed for a high-alert medicine, the prescription was stopped, and 25% were changed to other medicines. The above results show that the system that requires the input of three or more characters for the physician order entry and displays a warning screen for high-alert medicines is useful in preventing mischoices at the time of prescription input.<br>
著者
小村 弘 茂本 友貴枝 河原 亥一郎 松田 健一 阿野 理恵子 村山 洋子 森脇 俊哉 吉田 長弘
出版者
公益社団法人日本薬学会
雑誌
藥學雜誌 = Journal of the Pharmaceutical Society of Japan (ISSN:00316903)
巻号頁・発行日
vol.125, no.1, pp.141-147, 2005-01-01
参考文献数
27
被引用文献数
1 2

コンビナトリアルケミストリーの発展により化合物ライブラリーの数は百万を越え, 週に何十万もの化合物が多くの生物学的ターゲットに対してスクリーニングされている. これに伴い多くのリード化合物が見出されている. さらに開発候補品のディベロッパビリティにおいて動態代謝特性が重要な要因の1つであるとの認識が深まり,優れた薬物動態プロファイルを伴った開発候補品を見出すため探索動態グループに対する要求が年々高まってきている.このような状況下において, 溶解性, Caco-2膜透過性及び代謝安定性試験などについてハイスループットスクリーニング(HTS)への取り組みが行われてきた. しかしながら, 探索動態試験におけるHTSは時間と労力を必要とし, 評価できる化合物の数は最大でも生物学的ターゲットに対するHTSの1/100から1/10000と限られている. 近年, 合成化合物の体内動態特性を予測するためのin silicoモデルが検討されている.特にpolar surface area(PSA), molecular weight(MW), 脂溶性(logP)及びhydrogen bonding(HB)の数などの種々のパラメータが用いられ, 薬物の膜透過性又は経口吸収性の予測が試みられている.
著者
小村 弘 松田 健一 茂本 友貴枝 河原 亥一郎 阿野 理恵子 村山 洋子 森脇 俊哉 吉田 長弘
出版者
公益社団法人日本薬学会
雑誌
藥學雜誌 = Journal of the Pharmaceutical Society of Japan (ISSN:00316903)
巻号頁・発行日
vol.125, no.1, pp.131-139, 2005-01-01
参考文献数
25
被引用文献数
1 3

肝臓での代謝安定性は経口吸収性とともに生体内利用率に影響する重要な因子であり, その最適化は多くのプロジェクトにおける最重要課題の1つである. 一般に代謝試験には肝ミクロソーム系又は単離肝細胞系が用いられている. 肝細胞系はphaseI及びII代謝活性, さらに肝取り込みや胆汁排泄に関与する膜輸送系を有しており, 開発候補品を初め薬物の詳細な代謝検討に使用されている.しかし非凍結及び凍結ヒト肝細胞の場合コストが高く付くこと, またロット間の代謝活性の個体差が大きいこと, そしてロボットへの適応が難しいことから, 創薬の初期スクリーニングには適していないものと考えられる. 一方, 肝ミクロソーム系では細胞質の酵素によるphaseI及び硫酸抱合活性などのphaseII代謝を測定することができないが, 主代謝酵素であるcytochromeP450(CYP)活性が存在し,いずれの種についてもミクロソームを容易に入手できる. 特にヒトではハイスループットスクリーニング用として多くのドナーから調製されたミクロソームが市販されている.
著者
小村 弘 河原 亥一郎 茂本 友貴枝 松田 健一 阿野 理恵子 村山 洋子 森脇 俊哉 吉田 長弘
出版者
公益社団法人日本薬学会
雑誌
藥學雜誌 = Journal of the Pharmaceutical Society of Japan (ISSN:00316903)
巻号頁・発行日
vol.125, no.1, pp.121-130, 2005-01-01
参考文献数
27
被引用文献数
2 5

経口吸収性は生体内利用率に影響する重要なファクターの1つであり, ヒトでの低い吸収率さらにはその個体間の大きなバラツキは, 開発候補品のディベロッパビリティーを大きく低下させる. 近年コンビナトリアルケミストリー及びハイスループットスクリーニング(HTS)の導入は幅広い生物学的ターゲットに対して効率的にリード化合物の創出を可能にしてきたが, リード化合物の経口吸収性を初め体内動態に関わる物性を悪化させた. したがって, 創薬において吸収性に優れた開発候補品を創製するためにはリード化合物の最適化が必要となる. 吸収性は主に水に対する溶解性と膜透過性が大きく関わっており, これらのスクリーニング系が開発されてきた.近年その処理能力を上げるため, より簡便な比濁分析法や溶液沈殿法を用いた溶解性試験, さらにはCaco-2細胞の短期間培養法, N in one 及び96 well formatを用いた透過性試験系が採用されている.
著者
山田 耕史
出版者
公益社団法人日本薬学会
雑誌
藥學雜誌 = Journal of the Pharmaceutical Society of Japan (ISSN:00316903)
巻号頁・発行日
vol.122, no.12, pp.1133-1143, 2002-12-01
参考文献数
67
被引用文献数
4 17

Glycosphingolipids (GSLs), together with glycopeptides, are typical constituents of various cell membranes in a wide variety of organisms. In particular, it is known that GSLs have numerous physiological functions due to variations in the sugar chain, in spite of the very small quantity of constituents. Those are classified into cerebrosides, sulfatides, ceramide oligohexosides, globosides, and gangliosides based on the constituent sugars. Gangliosides, sialic acid-containing GSLs, are especially enriched in the brain and nervous tissues and are involved in the regulation of many cellular events. Recently, a number of GSLs have been isolated from marine invertebrates such as echinoderms, poriferans, and mollusks. We have also been researching biologically active GSLs from echinoderms to elucidate the structure-function relationships of GSLs and to develop novel medicinal resources. This review summarizes the structures and biological activities of GSLs from sea cucumbers. This study showed that the characteristics of GSLs and structure-activity relationships had neuritogenic activity toward the rat pheochromocytoma cell line PC12. That is, most of the cerebroside constituents of the sea cucumber are same glucocerebrosides as in other animals, except for some constituents, while the ganglioside constituents were unique in that a sialic acid directly binds to the glucose of cerebroside, they are mutually connected in tandem, and some are located in the internal parts of the sugar chain. It also became apparent that sialic acid is indispensable for the neuritogenic activities.<br>
著者
青山 豊彦 塩入 孝之
出版者
公益社団法人日本薬学会
雑誌
藥學雜誌 = Journal of the Pharmaceutical Society of Japan (ISSN:00316903)
巻号頁・発行日
vol.115, no.6, pp.446-459, 1995-06-25
参考文献数
22
被引用文献数
5

Tilivalline (1a), a metabolite isolated from Klebsiella pneumoniae var. oxytoca, belongs to a group of pyrrolo [2, 1-c] [1, 4] benzodiazepines, a characteristic skeleton of anthramycin-type antitumor antibiotics. We have accomplished a completely stereoselective, efficient and convenient synthesis of 1a utilizing a new Mannich type intramolecular cyclization as a key step. Further, a computational chemical analysis clarified the effect of zinc chloride on the high stereoselectivity in the tilivalline synthesis. To aim both the extension of the scope of the new Mannich type intramolecular cyclization and the studies on the structure-biological activity relationship, we further extended the method to the synthesis of tilivalline derivatives and 2-(3'-indolyl)-1, 4-benzodiazepines (50). Investigation on the cytotoxicity of 1a and its analogs has revealed that 1a shows the strong cytotoxicity toward mouse leukemia L 1210 cells and the replacement of the indole function of 1a with cyano one increases the cytotoxicity of 1a about 100 times (IC<SUB>50</SUB>=0.05 &mu;g/ml).
著者
生塩 孝則 遠藤 寛二 山本 恵司
出版者
公益社団法人日本薬学会
雑誌
藥學雜誌 = Journal of the Pharmaceutical Society of Japan (ISSN:00316903)
巻号頁・発行日
vol.116, no.11, pp.866-875, 1996-11-25
参考文献数
20
被引用文献数
4

The physicochemical properties of the enantiomer and racemates of suplatast tosilate (ST) were investigated by means of infrared spectroscopy, solid-state <SUP>13</SUP>C CP/MAS NMR spectroscopy, thermal analysis, and X-ray diffraction analysis, and by measuring the solubility and hygroscopy. The infrared and NMR spectra and X-ray diffraction pattern of the enantiomer were distinctly different from those of the racemate. The melting point of the enantiomer was lower than that of the racemate by 5&deg;C, while the solubility of the enantiomer was 1.3 times higher than that of the racemate. The hygroscopic rate of the enantiomer was greater than that of the racemate. These results suggested that ST was classified into a racemic compound crystal. Furthermore, by comparing the relative peak intensity ratios on X-ray diffraction patterns of crystals with various optical purities prepared by recrystallization, it was found that a mixture of racemic compound crystals and either of racemic mixture crystals or racemic solid solutions was obtained by recrystallization of ST in the content of 0 to 64%ee, while the recrystallization of ST in the content of more than 64%ee led to the formation of racemic mixture crystals or racemic solid solutions.
著者
住谷 賢治 馬場 泰行 猪股 伸一 豊岡 秀訓 幸田 幸直
出版者
公益社団法人日本薬学会
雑誌
藥學雜誌 = Journal of the Pharmaceutical Society of Japan (ISSN:00316903)
巻号頁・発行日
vol.120, no.7, pp.652-656, 2000-07-01
参考文献数
17
被引用文献数
8

Orally-disintegrating tablets of clonidine hydrochloride, an α_2-adrenergic agonist, were prepared by the method of drying an aqueous suspension. The suspension was prepared using powdered lactose, and the composition ratio was 2 : 1 (powdered lactose : 0.048% clonidine hydrochloride solution). The suspension was dried under 4±1℃(72±15% R.H.). We obtained tablets containing clonidine hydrochloride (40μg/tablet). Physical properties of the tablets were as follows : hardness was 4.0 kgf, and disintegration time was 41.7 s (in vitro). In the clinical use, 8 patients, aged 1-2 year and weighing 9-11 kg, received approximately 4μg/kg body weight as clonidine hydrochloride. The tablet was administered 90 min before entering the operating room. All patients were willing to accept the tablet. The quality of separation from parents, sedation and a mask acceptance were excellent on all patients. These results suggest that the orally-disintegrating tablet of clonidine hydrochloride was useful in a clinical situation for the preanesthetic medication of pediatric patients aged 1-2 year.
著者
和田 浩二
出版者
公益社団法人 日本薬学会
雑誌
藥學雜誌 = Journal of the Pharmaceutical Society of Japan (ISSN:00316903)
巻号頁・発行日
vol.122, no.11, pp.929-956, 2002-11-01
被引用文献数
13

The chemical constituents of <i>Aconitum yesoense</i> var. <i>macroyesoense</i> and <i>Aconitum japonicum</i> were examined using high-resolution spectral analysis. Twelve novel alkaloids were isolated from <i>A. yesoense</i> var. <i>macroyesoense</i> together with 20 known alkaloids. Eight novel alkaloids were isolated from <i>A. japonicum</i> together with 15 known alkaloids. An HPLC-atmospheric pressure chemical ionization-mass spectrometry (HPLC-APCI-MS) method was useful for the simultaneous determination of 21 <i>Aconitum</i> alkaloids found in <i>A. yesoense</i> var. <i>macroyesoense</i> and A. <i>japonicum</i>. These compounds were fairly stable under the conditions used, and the protonated molecules or fragment ions characteristic of the molecule appeared as base peaks in the mass spectra and were used for selected ion monitoring. HPLC-APCI-MS is a very promising approach for structural investigations of positional isomers and stereoisomers. This method was applied successfully to stereoisomeric <i>Aconitum</i> alkaloids differing in configuration at C-1, -6, or -12. Comparison of the APCI spectra showed that the abundance of fragment ions was significantly higher for the C-1, -6, or -12 β-form alkaloid than for C-1, -6, or -12 α-form alkaloid. The main alkaloid constituents in the root of <i>A. yesoense</i> var. <i>macroyesoense</i>, <i>Aconitum</i> alkaloids of the C<sub>20</sub>-diterpenoid type, kobusine and pseudokobusine, and their acyl derivatives were examined for their peripheral vasoactivities by measuring laser-flowmetrically the cutaneous blood flow in the hind foot of mice after intravenous administration. It is thought that the hydroxyl groups of alkaloids, especially a free OH group of pseudokobusine at C-6, were important for action on the peripheral vasculature leading to dilatation, and the results indicated that esterification of the hydroxyl group at C-15 with either anisoate, veratroate, or <i>p</i>-nitrobenzoate may contribute to enhancement of the activity of the parent alkaloids.<br>
著者
小磯 邦子 中島 修 松村 大輔 藤本 康之 橋本 祐一
出版者
公益社団法人日本薬学会
雑誌
藥學雜誌 = Journal of the Pharmaceutical Society of Japan (ISSN:00316903)
巻号頁・発行日
vol.120, no.1, pp.104-112, 2000-01-01

Human myeloid leukemia K562 cells can be induced to differentiate to mature cells bidirectionary, i.e., hemin induces erythroid differentiation, while 12-O-tetradecanoylphorbol 13-acetate (TPA) induces differentiation to monocytes. The differentiation-inducing activity of various hemin-related compounds suggested certain structural requirements for the activity : 1) the iron moiety of hemin is not essential, and 2) the propionic acid side chains of hemin play an important role in the differntiation and induction. In addition, we have examined the influence of some bioresponsemodifying factors on hemin/protoporphyrin IX-induced differentiation of K562 cell line. Retinoids and tubulindisruptors, themselves did not induce differentiation, enhanced hemin/protoporphyrin IX-induced differentiation of K562 cells. We also examined the possible involvement of peripheral-type benzodiazepine receptor (PBR) in hemin/protoporphyrin IX-induced differentiation on K562 cell lines. The PBR specific ligands modified hemin-induced differentiation. These results suggest a requirement for retinoids (or retinoids-like cofactors) for hemin/protoporphyrin IX-induced differentiation of K562 cells and the involvement of PBR in erythroid differentiation of K562 cell line. Further we showed that TPA suppresses hemin-induduced erythroid differentiation of K562 cells, while retinoids augment it. TPA is a potent inducer of heme oxygenase (HO), which catabolizes heme to biliverdin. An HO inhibitor, tin protoporphyrin (SnPP), suppresses TPA-induced K562 cell differentiation to monocytes. It was also found that cotreatment of K562 cells with SnPP and TPA induces erythroid differentiation of K562 cells, though SnPP alone or TPA alone does not induce erythroid differentiation, suggesting a role of HO in the directional switch of differentiation.