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

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.115, no.6, pp.446-459, 1995-06-25 (Released:2008-05-30)

参考文献数

22

被引用文献数

3 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 (IC50=0.05 μg/ml).

著者

塩入 孝之

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.113, no.11, pp.760-780, 1993-11-25 (Released:2008-05-30)

参考文献数

69

被引用文献数

1

---

Recent studies on the new methods and new reagents in organic synthesis developed by our laboratories have been reviewed. Their application to the synthesis of biologically intriguing natural products has been also described. Dolastatin 10 (1), a potent antitumor peptide of marine origin, has been efficiently synthesized by use of diethyl phosphorocyanidate (DEPC), diphenyl phosphorazidate (DPPA) and (+)-2-hydroxy-3-pinanone ((+)-HyPN). Mugineic acid (27), a typical phytosiderophore from barley, has been synthesized using a phenyl group as a carboxyl synthon. The method is quite efficient to produce mugineic acid on a large scale. Tilivalline (50), isolated from Klebsiella pneumoniae var. oxytoca, has been synthesized by use of DPPA as an +NH2 synthon and DEPC as a coupling reagent. The new Mannich type reaction has been explored to construct the pyrrolo [2.1-c] [1.4] benzodiazepine skeleton. The chiral phase transfer catalyst (65a) based on cinchonine has been utilized for the asymmetric hydroxylation of the α-tetralone derivatives (63). The first synthesis of the chiral ammonium fluoride (71) has been achieved, and its use for the silicon-based asymmetric aldol reaction has been accomplished. Trimethylsilyldiazomethane (TMSCHN2) has been developed as a stable and safe substitute for hazardous diazomethane. As a C1-unit introducing reagent, TMSCHN2 and its lithium salt mostly realize the reactions similar to those carried out with diazomethane. On the other hand, they generally behave as a [C-N-N] azole synthon in an analogous but not as the same way as diazomethane. Using the lithium salt of TMSCHN2, new methods for the preparation of alkynes and pyrroles have been developed.

著者

末宗 洋

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.112, no.7, pp.432-446, 1992-07-25 (Released:2008-05-30)

参考文献数

42

被引用文献数

4 6

---

The use of biocatalysts for the preparation of new chiral synthons has provided a novel synthetic route to the useful natural products. A method for the preparation of chiral carbocyclic alcohols has been also developed by utilizing the Pseudomonas fluorescens lipase (PFL)-catalyzed enantioselective hydrolysis. The above-mentioned alcohols have been found to be effective as chiral auxiliaries for asymmetric reactions.

著者

市川 聡

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.128, no.10, pp.1403-1430, 2008-10-01 (Released:2008-10-01)

参考文献数

149

被引用文献数

2 4

---

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 (SmI2) mediated Reformatsky reaction or aldol reaction. 3′-β-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 β-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-κB 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.

著者

黒田 耕司 横山 照由 梅田 常雄 喜多 良昭 小西 明 黒田 勤

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.99, no.7, pp.745-751, 1979-07-25 (Released:2008-05-30)

参考文献数

7

被引用文献数

2 2

---

Physicochemical properties of the polymorphs and hydrate of 6-mercaptopurine were investigated. Its crystal habits were slightly changed and form I-TX was obtained by the addition of 6-thioxanthine and/or 2, 6-dithioxanthine and subsequent recrystallization. It was found that when Form I-TX was heated at 240°, this form transformed to Form III which was found to have a solubility about 6-7 times that of Form I. The mutual transition of 6-mercaptopurine polymorphs and hydrate under various conditions of heating and suspending in water was also studied. The transition temperature and the heat of transition between Form I-TX and Form II-TXhyd were determined to be 127°and 2.15 kcal/mol, respectively, by the solubility measurement. It was expected that if the transition of Form III could be suppressed, more bioavailable preparation of 6-mercaptopurine would be obtained.

著者

木村 雄四郎 滝戸 道夫 中野 紘一 滝下 満之

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

vol.86, no.12, pp.1184-1186, 1966-12-25

被引用文献数

1

---

From the petroleum ether extracts of rhizomate of Alpinia speciosa K. SCHUMANN and A. kumatake MAKINO (A. formosana K. SCHUMANN), dihydro-5,6-dehydrokawain (I) and 5,6-dehydrokawain (II) were isolated. The latter was isolated for the first time from Zingiberaceae plants and the former, from a natural source.

著者

平塚 祥子 熊野 宏昭 片山 潤 岸川 幸生 菱沼 隆則 山内 祐一 水柿 道直

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

vol.120, no.2, pp.224-229, 2000-02-01

被引用文献数

1

---

The failure of patients to comply with treatment regimens recommended by their physicians is a significant clinical problem. Researches on the assessment of compliance have, however, been precluded by methodological difficulties such as lack of adequate measures. The purpose of this study was to develop a self-administered questionnaire to evaluate drug compliance. First, questionnaire containing a 52-items complied by two doctors, a pharmacist and a nurse, was tested on 81 outpatients, all volunteers, attending the departments of psychosomatic medicine and internal medicine. Four items were temporarily removed for later analysis because they directly inquired about drug compliance (drug compliance items). The other 48 items were analyzed and three factors consisting of 26 items were further studied : expectation on taking medicine, rejection to taking medicine and seeking knowledge of drugs. Chronback's alpha coefficients representing internal consistency of the three factors were sufficiently high (ranging from .75 to .84). Furthermore, we preformed a simplified pill count to validate the 4 drug compliance items. There was a weak to moderate correlation between the result of pill count and each of 4 drug compliance items. A new self-administered questionnaire of 30 items was thus developed and named the Drug Compliance Scale.

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

山口 秀夫 有本 正生 田之口 真理子 沼田 敦

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

vol.101, no.5, pp.485-488, 1981

被引用文献数

7

---

Two kinds of reactions were carried out on the components of the seeds of Hernandia ovigera L. The reaction of lead tetraacetate on desoxypodophyllotoxin (I) and its analogous compounds caused the cleavage of methylenedioxyl group, affording the corresponding diphenols. In the case of 3, 4-methylenedioxypropylbenzene (XII), an intermediate acetoxyl compound (XIII) was isolated. The reactions of 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone (DDQ) on I and its analogous compounds afforded smoothly aromatized compounds. By the same reaction on bursehernin (III), cyclization and aromatization occurred simultaneously affording chinensin (XVIII) which was confirmed by direct comparison with authentic speciemen. The results of the cleavage reaction on I and XII by use of borontrichloride were also described.

著者

山口 秀夫 有本 正生 山本 起巳子 沼田 敦

出版者

公益社団法人日本薬学会

雑誌

薬学雑誌 (ISSN:00316903)

巻号頁・発行日

vol.99, no.6, pp.p674-677, 1979-06

被引用文献数

1

---

Four kinds of lignans were isolated from the seeds of Hernandia ovigera L. collected in Okinawa besides the previously reported desoxypodophyllotoxin (I). Oily substance II, named bursehernin, C_<21>H_<22>O_6,was confirmed to be lignan-2 isolated from Bursera schlechtendalii. III, mp 171-173°, and IV, mp 125-126°, were determined as desoxypicropodophyllin and podorhizol obtained from Podophyllum emodi WALL. respectively. V, mp 270-275°, could not be clarified due to its small amount.

著者

大津 隆行 的場 啓子 菊地 茂行 平尾 一郎

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.75, no.4, pp.368-371, 1955-04-25 (Released:2010-02-19)

参考文献数

8

被引用文献数

3

---

Polyvinylpyrrolidone, used as the substitute plasma, is said to be effective when the molecular weight is around 30, 000 to 50, 000, and the inclusion of lower or higher molecules is thought to give adverse effect as a substitute plasma. The polymer obtained by the polymerization of vinylpyrrolidone with hydrogen peroxide and ammonia catalyst was extracted with acetone at a room temperature and fractionated by reprecipitaton from aqueous solution with acetone, obtaining a distribution curve for molecular weights.On the other hand, distribution curve of molecular weights was also obtained by the same method from the polyvinylpyrrolidone marketed by the German Bayer and the two curves were found to be very similar. These results show that the extraction of low molecular polymers with a solvent like acetone is effective in obtaining polyvinylpyrrolidone of high homogeneity. Polyvinylpyrrolidone is known to take a coiled form in a solution that its viscositic characteristics in dilute aqueous solution were also examined and it was observed that the Huggins' viscosity constant, k', markedly changes with the degree of polymerization.

著者

王子田 彰夫 高嶋 一平

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.136, no.1, pp.3-7, 2016 (Released:2016-01-01)

参考文献数

7

---

Fluorescence probes are now widely used as indispensable tools in many cell functional analyses. At present, the design of fluorescent probes largely depends on the limited numbers of established sensing mechanisms such as photo-induced electron transfer (PET), photo-induced charge transfer (PCT), and fluorescence resonance energy transfer (FRET). Although these mechanisms are versatile in metal ion sensing, introduction of a new sensing mechanism is highly desirable not only to design a more sophisticated probe with high selectivity and sensitivity but also to expand the diversity of the sensing targets to unveil biological phenomena. In this article, we report the design of dual emission fluorescent probes for metal ions based on a unique fluorescence-sensing mechanism. The fluorescent probes incorporating this sensing mechanism displayed a large emission red-shift on complexation with metal ions such as CdII and AgI. X-ray crystallography and theoretical computational calculations of the CdII and AgI complexes revealed that the emission shift was induced by non-coordination contact between the aromatic ring of fluorophore and the metal ion (arene-metal ion contact; AM-contact), which modulates the energy levels of molecular orbitals. The fluorescent probe was successfully applied to in cell ratiometric bioimaging of bioactive hydrogen sulfide (H2S). These successful applications highlight the usefulness of this sensing mechanism in biological fluorescence analysis.

著者

玉木 啓文 佐藤 宏樹 堀 里子 澤田 康文

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.132, no.4, pp.525-529, 2012 (Released:2012-04-01)

参考文献数

4

被引用文献数

1 2

---

Confusion of drug names is one of the most common causes of drug-related medical errors. A similarity measure of drug names, “vwhtfrag”, was developed to discriminate whether drug name pairs are likely to cause confusion errors, and to provide information that would be helpful to avoid errors. The aim of the present study was to evaluate and improve vwhtfrag. Firstly, we evaluated the correlation of vwhtfrag with subjective similarity or error rate of drug name pairs in psychological experiments. Vwhtfrag showed a higher correlation to subjective similarity (college students: r=0.84) or error rate than did other conventional similarity measures (htco, cos1, edit). Moreover, name pairs that showed coincidences of the initial character strings had a higher subjective similarity than those which had coincidences of the end character strings and had the same vwhtfrag. Therefore, we developed a new similarity measure (vwhtfrag+), in which coincidence of initial character strings in name pairs is weighted by 1.53 times over coincidence of end character strings. Vwhtfrag+ showed a higher correlation to subjective similarity than did unmodified vwhtfrag. Further studies appear warranted to examine in detail whether vwhtfrag+ has superior ability to discriminate drug name pairs likely to cause confusion errors.

著者

安永 峻五 下村 脩

出版者

日本薬学会

雑誌

薬学雑誌 (ISSN:00316903)

巻号頁・発行日

vol.74, no.7, pp.778-780, 1954-07

---

In electrochromatography, five kinds of different filter paper holders were used and the velocity of migration, area of colored band, and migration distance of each position on the filter paper were measured under identical conditions so as to examine the separatory ability and equality of rate of each apparatus. It was thereby found that the best separation is effected by placing the paper in a convex form, with the middle higher, while for uniform mobility, the filter paper should be cooled directly by closely adhering the lower surface on a cooling vat.

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

北 潔 山田 陽城

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.136, no.2, pp.203-204, 2016 (Released:2016-02-01)

参考文献数

5

著者

窪田 正彦 新井 清 頼光 彰子 島岡 真佐子 星野 響 林 一之 伊田 泰康 南 典昭 山本 博文 田中 恵一 高田 三千人 西原 正勝 藤谷 幸治 神田 博史

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

vol.113, no.11, pp.810-817, 1993-11-25

---

The cultivation of Papaver bracteatum, having thebaine as a major alkaloid, needs permission by the law of the narcotic regulation in Japan. Therefore, the flowergrowing of P. bracteatum as garden plants is prohibited by law. Chemical, morphological and cytological analyses of gardening 18 plants of the section Oxytona of the genus Papaver collected in western Hiroshima prefecture were carried out as a preliminary study. On inquiry, thebaine was identified as an only alkaloid from one of the gardening plants. The amounts of thebaine contained in this sample was 0.68%. Petals of this plant are scarlet with black spots at their bases which are surrounded by bracts. These results indicated that one of the investigated plants was identified to be P. bracteatum.

著者

田中 喜秀 鳴石 奈穂子

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.128, no.11, pp.1595-1604, 2008 (Released:2008-11-01)

参考文献数

15

被引用文献数

5 5 1

---

Psychological stress is of major importance to all age groups in recent years, and may lead to mental disorder and various diseases. An objective and quantitative method for measuring salivary stress-related substances is highly desired because saliva collection is easy, stress free and noninvasive. We have developed a rapid and easy-to-use analytical tool for the measurement of cortisol and secretory immunoglobulin A (sIgA) based on microchip technology, immunoselectivity and electrophoretic separation technique. Performing immunoreaction and capillary electrophoresis (CE) separation on microchips is a promising technique for on-site determination of biogenic substances, and has a few advantages over conventional immunoassay methods: reduced sample size, shortening analysis times, high separation efficiency, reduced cost, and downsizing of analytical system. At this stage of our research, some preliminary prototypes of a high-sensitive microchip CE instrument were constructed to determine the stress-related substances in real saliva samples. However, there is not enough detection sensitivity for cortisol analysis. On the other hand, sIgA was successfully analyzed using a laboratory-built microchip CE system and optimal analytical conditions. The sIgA determination is rapid compared with a conventional immunoassay method, and provides an acceptable degree of repeatability and recovery. In the future, microchip technologies will enable total automation and integration of sample preparation. This research has widespread future potential for monitoring multiple stress-related markers within minutes from a trace of saliva, and can contribute to disease prevention and overall good health.

著者

嶋根 卓也

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.136, no.1, pp.79-87, 2016 (Released:2016-01-01)

参考文献数

16

被引用文献数

6

---

The non-medical use or abuse of prescription drugs, including benzodiazepines, is a growing health problem in Japan. An association between prescription drug overdose and suicide risk has also been reported. The Japanese Ministry of Health, Labour and Welfare has expected pharmacists to act as “gatekeepers”, facilitating early identification of individuals at high risk of prescription drug abuse including overdose, supplying medication counseling to patients, and helping to introduce these patients to appropriate medical care. Prescription drugs such as benzodiazepines are widely used in psychiatry. However, these drugs are prescribed not only by psychiatrists but also by other healthcare professionals including primary care physicians. Moreover, in recent years, the dispensing of prescriptions has moved rapidly from inside to outside hospitals, with prescription drugs being dispensed mainly at community pharmacies. Although all healthcare professionals including hospital pharmacists can play a role in preventing prescription drug abuse, the role of the community pharmacist is vital in addressing this problem. Formerly, community pharmacists were recognized as “community scientists”, low-threshold accessible healthcare advisors. Now, community pharmacists should return to the role of community scientists to prevent prescription drug abuse. This article begins by reviewing the current situation of prescription drug abuse and dependence in Japan. The role of pharmacists as gatekeepers in preventing prescription drug abuse is then examined. Finally, this article discusses the effect of intervention in the form of gatekeeper training for community pharmacists.

著者

野村 渉

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.135, no.3, pp.405-414, 2015 (Released:2015-03-01)

参考文献数

79

---

Artificial zinc finger proteins (ZFPs) consist of Cys2-His2-type modules composed of approximately 30 amino acids that adopt a ββα structure and coordinate a zinc ion. ZFPs recognizing specific DNA target sequences can substitute for the binding domains of various DNA-modifying enzymes to create designer nucleases, recombinases, and methylases with programmable sequence specificity. Enzymatic genome editing and modification can be applied to many fields of basic research and medicine. The recent development of new platforms using transcription activator-like effector (TALE) proteins or the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) system has expanded the range of possibilities for genome-editing technologies. These technologies empower investigators with the ability to efficiently knockout or regulate the functions of genes of interest. In this review, we discuss historical advancements in artificial ZFP applications and important issues that may influence the future of genome editing and engineering technologies. The development of artificial ZFPs has greatly increased the feasibility of manipulating endogenous gene functions through transcriptional control and gene modification. Advances in the ZFP, TALE, and CRISPR/Cas platforms have paved the way for the next generation of genome engineering approaches. Perspectives for the future of genome engineering are also discussed, including applications of targeting specific genomic alleles and studies in synthetic biology.