著者

亀谷 哲治 高野 誠一 寺沢 弘文 武田 裕光

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.92, no.7, pp.868-870, 1972-07-25 (Released:2008-05-30)

参考文献数

6

被引用文献数

3 4

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In order to obtain 2, 6-dicyano-7-ethoxycarbonyl-1, 5-dioxo-1, 2, 3, 5-tetrahydroindolizine as an intermediate for the synthesis of camptothecin, Michael condensation of methyl 3-cyano-4-ethoxycarbonyl-1, 2-dihydro-2-oxopyridine-6-carboxylate (V) with acrylonitrile was carried out but failed to afford the objective substance. A similar condensation of V with t-butyl acrylate also resulted in failure. Ethyl 5-cyano-4-ethoxycarbonyl-5-oxo1, 6-dihydro-2-pyridine glyoxylate (VIII) was synthesized by the reaction of 3-cyano-4-ethoxycarbonyl-1, 2-dihydro-2-oxopyridine-6-carboxylic acid chloride with ethyl t-butylmalonate. Although cyclization of VIII to ethyl 6-cyano-1, 2, 3, 5-tetrahydro-1, 3, 5-trioxo-7-indolizine carboxylate (IX) was unsuccessful, Friedlander reaction of VIII with 2-aminobenzaldehyde gave the expected 8-cyano-7-ethoxycarbonyl-9, 11-dihydro-9, 11-dioxoindolizino[1, 2-b]quinoline (X) in one step.

著者

丹羽 弘司 引地 登 桜井 栄一 植田 公孝 福勢 元

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.100, no.11, pp.1118-1126, 1980-11-25 (Released:2008-05-30)

参考文献数

30

被引用文献数

2

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Effects of maltitol and mannitol on the gastrointestinal absorption of acetaminophen, sulfisoxazole and riboflavine in mice were investigated. When drugs were orally administered with maltitol or mannitol, and 2 hr after maltitol or mannitol was orally given in mice (in diarrhea), the blood levels of drugs became lower than that in the control, and drug absorption was inhibited. It was suggested that these results were not caused by molecular interaction between drugs and sugar alcohols, but by the action of maltitol and mannitol which accelerated small intestinal motility, secretion and vascular permeability in the intestinal membrane. These changes may be mediated by biogenic amine, serotonin, histamine and polyamines in the small intestine.

著者

藤ノ木 政勝

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.53, no.5, pp.470-470, 2017 (Released:2017-05-01)

参考文献数

5

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約20年前にDevelopment誌に掲載されたViscontiらによる報告で,精子受精能獲得に伴って様々な精子タンパク質がチロシンリン酸化を受けること,そして受精能獲得とチロシンリン酸化は重炭酸イオン(ある種のアデニル酸シクラーゼを活性化してcAMPを産生させる)およびCa2+による調節を受けることが示された.この報告をきっかけに,チロシンリン酸化は受精能獲得の唯一の生化学マーカーとして広く利用され,受精能獲得の阻害や惹起・促進に応じてリン酸化レベルが変わることから精子受精能獲得のkey eventとされるようになった.受精能獲得(capacitation)とは,狭義にはほ乳類の精子のみに認められる現象で,精液中の精子は卵子とただ共培養しても受精できないが,交尾後に雌性生殖器内より採取した精子は受精可能であるという観察結果をもとに1950年代初頭に提唱された. 重炭酸イオン刺激等により,精子の受精能獲得がin vitroで誘導可能になって以来,その具体的な責任応答が探索され,①精子頭部で起こる先体反応,②尾部で起こる超活性化,③精子細胞膜からのコレステロールの流出と流動性の増加,④精子タンパク質のチロシンリン酸化などが発見されたが,単独因子で十分なのか,全てが必要であるかについては議論がある.チロシンリン酸化は受精能獲得のkey eventであるとされながらも,これを起こす責任酵素はこれまで分かっていなかった.最近,Viscontiのグループは,本現象の責任酵素がFERとよばれる非受容体型チロシンキナーゼの精巣特異的アイソフォーム,FERTであることを発見した.なお,本稿は下記の文献に基づいて,その研究成果を紹介するものである.1) Visconti P. E. et al., Development, 121, 1129–1137(1995).2) Visconti P. E. et al., Asian J Androl., 13, 395-405(2011).3) Alvau A. et al., Development, 143, 2325–2333(2016).4) Chung J. J. et al., Cell, 157, 808-822(2014).5) Tateno H. et al., Proc. Natl. Acad. Sci. U. S. A., 110, 18543-18548(2013).

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア

巻号頁・発行日

vol.51, no.7, pp.640-640, 2015

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア

巻号頁・発行日

vol.48, no.2, pp.178-178_3, 2012

著者

福原 潔 大野 彰子 花尻(木倉) 瑠理

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.137, no.9, pp.1147-1154, 2017 (Released:2017-09-01)

参考文献数

14

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Considering the pharmacological effects of chiral drugs, enantiopure drugs may differ from their racemic mixture formulation in efficacy, potency, or adverse effects. Levomethorphan (LVM) and Dextromethorphan (DXM) act on the central nervous system and exhibit different pharmacological features. LVM, the l-stereoisomer of methorphan, shows many similarities to opiates such as heroin, morphine and codeine, including the potential for addiction, while the d-stereoisomer, DXM, does not have the same opioid effect. In the present study, NMR-based metabolomics were performed on the urine of rats treated with these stereoisomers, and showed significant differences in metabolic profiles. In urine within 24 h after treatment of these samples, levels of citrate, 2-oxoglutarate, creatine, and dimethylglycine were higher in LVM-treated rats than in DXM-treated rats. While urinary levels of hippurate and creatinine gradually increased over 72 h in DXM-treated rats, these metabolites were decreased in the urine by 48-72 h after treatment with LVM. The levels of these changed metabolites may provide the first evidence for different cellular responses to the metabolism of stereoisomers.

著者

須田 勝三郎 米城 善右衛門

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.1902, no.242, pp.321-326, 1902-04-26 (Released:2008-04-11)

著者

小林 力

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.47, no.3, pp.238-238, 2011 (Released:2017-03-18)

著者

市川 創作 黒岩 崇

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.5, pp.681-686, 2008 (Released:2008-05-01)

参考文献数

18

被引用文献数

2 3

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A vesicle is a compartment composed of lipid bilayer of amphiphilic molecules. The vesicle is applied to carriers of drugs, cosmetics and functional food ingredients in industries. Vesicles are also applied as a model for artificial cell membrane and expected as micro- and nano-reactors. They are generally prepared by the hydration of dry lipid film, but there is no method to prepare vesicles of a controlled size and high entrapment yield of hydrophilic materials inside them. In this article, a microchannel (MC) emulsification method was applied to prepare vesicles aimed at controlling the size and improving the entrapment yield. Firstly, monodisperse water-in-oil (W/O) emulsions were prepared by the MC emulsification method. In this process, hydrophilic materials to be entrapped were contained inside the water droplets of the emulsions. Keeping the water droplets frozen, the emulsifier was replaced by a bilayer-forming lipid mixture, and then the oil phase was evaporated. After hydration of lipid layers surrounding the water droplets, vesicles were formed. We call this preparation “lipid-coated ice droplet hydration method”. The final sizes of the prepared vesicles were comparable to the original emulsion droplet sizes. This means that the size of vesicles can be controlled by controlling the size of original water droplets of the W/O emulsions. Furthermore, calcein as a hydrophilic fluorescent marker and biopolymers, such as enzyme and polysaccharide, were entrapped into the internal water phases of vesicles. The method proposed in this study enables the formation of vesicles with a controlled size and high entrapment yields, potentially useful for expanding the application fields of vesicles as biocompatible carriers and micro- and nano-reactors for biochemical reactions.

著者

藤田 直希 鍋谷 伸子 梅村 紀匡 菊池 千草 鈴木 匡

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.10, pp.1445-1448, 2016 (Released:2016-10-01)

参考文献数

7

被引用文献数

3

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In this study, we took continuous measurements of hemoglobin A1c (HbA1c) levels and conducted lifestyle checks in three cases to determine if these parameters were effective in improving overall wellness. We selected three young men with relatively high HbA1c levels. During the 12-weeks study periods, we regularly measured each participant's HbA1c levels and monitored their lifestyle habits every two weeks at the community pharmacy once every 2 weeks using specific guidelines. The first participant, a 23-year-old man, had a HbA1c level of 5.7% at his first measurement. His HbA1c level decreased to 5.2% at the last measurement. The second participant, a 19-year-old man, had an initial HbA1c level of 5.7% and a final HbA1c level of 5.4%. The third participant was a 22-year-old man with an initial HbA1c level of 5.4%. His HbA1c level had decreased to 5.1% by the last measurement. The lifestyles of all three men improved with respect to exercise and diet. Based on these results, we surmise that continuous measurements of HbA1c and regular lifestyle checks may contribute to reducing the risk of lifestyle-related disease.

著者

異島 優 丸山 徹

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.39-47, 2016 (Released:2016-01-01)

参考文献数

43

被引用文献数

1 18

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Recently, human serum albumin (HSA) has emerged as a versatile carrier for therapeutic agents against diabetes, cancer, and infectious diseases. Market-approved products include fatty acid derivatives of human insulin for diabetes and the paclitaxel-HSA nanoparticle for various cancers such as metastatic breast cancer and advanced pancreatic cancer. In this review, we focus on the next-generation approach including HSA-binding bioactive gas such as nitric oxide (NO) for treating ischemic/reperfusion injury, cancer, and bacterial infection. To date, pharmacologically active compounds that release NO within the body, such as organic nitrates, have been used as therapeutic agents, but their efficacy is significantly limited by unwanted side effects. Therefore, novel NO donors with better pharmacological and pharmacokinetic properties are highly desirable. The S-nitrosothiol fraction in plasma is largely composed of endogenous S-nitrosated HSA (SNO-HSA), which is why we are investigating whether this albumin form can be therapeutically useful. Recently, we have developed SNO-HSA analogues such as SNO-HSA with many conjugated SNO groups (poly-SNO-HSA) prepared using chemical modification. Unexpectedly, we found striking inverse effects between poly-SNO-HSA and SNO-HSA. Despite the fact that SNO-HSA inhibits apoptosis, poly-SNO-HSA possesses very strong pro-apoptotic effects against tumor cells. Furthermore, poly-SNO-HSA can reduce or even completely eliminate the multidrug resistance often developed by cancer cells. In this review, we put forward the possibility that poly-SNO-HSA can be used as a safe, effective multifunctional antitumor agent.

著者

浅井 将 川久保 昂 森 亮太郎 岩田 修永

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.137, no.7, pp.801-805, 2017 (Released:2017-07-01)

参考文献数

18

被引用文献数

12

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Down syndrome (DS) patients demonstrate the neuropathology of Alzheimer's disease (AD) characterized by the formation of senile plaques and neurofibrillary tangles by age 40-50 years. It has been considered for a number of years that 1.5-fold expression of the gene for the amyloid precursor protein (APP) located on chromosome 21 leading to overproduction of amyloid-β peptide (Aβ) results in the early onset of AD in adults with DS. However, the mean age of onset of familial AD with the Swedish mutation on APP which has high affinity for β-secretase associated with a dramatic increase in Aβ production is about 55 years. This paradox indicates that there is a poor correlation between average ages of AD onset and the theoretical amount of Aβ production and that there are factors exacerbating AD on chromosome 21. We therefore focused on dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), since overexpressing transgenic mice show AD-like brain pathology. The overexpression of DYRK1A caused suppression of the activity of neprilysin (NEP), which is a major Aβ-degrading enzyme in the brain, and phosphorylation at the NEP cytoplasmic domain. NEP activity was markedly reduced in fibroblasts derived from DS patients compared with that in fibroblasts derived from healthy controls. This impaired activity of NEP was rescued by DYRK1A inhibition. These results show that DYRK1A overexpression causes suppression of NEP activity through its phosphorylation in DS patients. Our results suggest that DYRK1A inhibitors could be effective against AD not only in adults with DS but also in sporadic AD patients.

著者

吉武 毅人 大澤 友二

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.137, no.8, pp.927-928, 2017 (Released:2017-08-01)

被引用文献数

1

著者

漆崎 文男 山口 洋 水町 浩

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.106, no.6, pp.491-497, 1986-06-25 (Released:2011-01-31)

参考文献数

9

被引用文献数

1 7

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Polyvinyl alcohol (PVA) aqueous solutions with high water content were repeatedly frozen and defrosted to obtain PVA hydrogels with high elasticity.Tack and viscoelasticities such as storage modulus and loss tangent of the PVA hydrogels were determined as a function of molecular weight, saponification value of PVA, number of cycles of freezing-defrosting procedure or temperature of defrosting, in order to obtain an information on utilities of the materials as prepared poultices and transdermal therapeutic system.Correlation matrix method of multiregression analysis was applied to our data on tack and viscoelasticities of gels, and it was found that there was a significant correlation between tack and storage modulus as well as loss tangent of the materials.Tack, which is one of the most essential properties of pressure sensitive adhesives as prepared poultices and drug delivery system, can easily be predicted, if we measure viscoelasticities of the materials.

著者

谷野 哲也 市川 聡 魚谷 幸一 大山 洋 松田 彰

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.131, no.3, pp.335-346, 2011 (Released:2011-03-01)

参考文献数

34

被引用文献数

2 2

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This review describes the synthesis and structure-activity relationship (SAR) study of muraymycins (MRYs), which are potent antibacterial nucleoside antibiotics. The key elements of our synthetic approach include the preparation of L-epi-capreomycidine via a C-H amination reaction and a convergent assemblage to construct of the framework of MRYs using Ugi four component reaction. With this approach the first total synthesis of MRY D2 and its epimer, epi-MRY D2, which does not have lipophilic substituents, has been accomplished. The fact that MRY D2 and it's epimer did not show any antibacterial activity indicated the lipophilic substituents of MRYs plays an important role in membrane-permeability. Hence, MRY analogues with lipophilic substituents were designed and synthesized simply by altering the aldehyde component in Ugi four-component assemblage. The MRY analogues with lipophilic substituents exhibited improved antibacterial activity against anti drug-resistant bacteria. It was also suggested that the accessory urea-dipeptide motif might contribute to MraY inhibitory and antibacterial activity. Our synthetic approach would effectively provide a variety of MRY analogues and resultant SAR information brings us directions to create further MRY analogues.

著者

今戸 佐太郎

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.81, no.6, pp.828-832, 1961-06-25 (Released:2010-02-19)

参考文献数

2

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trans-Bis (N-ethylidene-DL-threoninato) copper (II) dihydrate comes in α- and β-form crystals, both melting at 202-203° with decomposition. The α-form crystal is a monoclinic holohedral class and the β-form crystal belongs to the triclinic holohedral class, the α-form crystal having C2h-2/m and β-form, Ci-1. These crystals were proved to be polymorphic forms by their comparative examination through X-ray powder and chemical methods.

著者

稲垣 昌宣

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.8, pp.1187-1194, 2008-08-01 (Released:2008-08-01)

参考文献数

29

被引用文献数

2 7

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Glycosphingolipids (GSLs) are contained in a various cell membranes and have recently been implicated in many physiologic functions. They are classified based on their sugar moieties into ceramides, cerebrosides, sulfatides, ceramide-oligohexosides, globosides, and gangliosides. A number of GSLs have been obtained from marine invertebrates such as echinoderms, poriferans, and mollusks and have unique biological activities. During the course of our search for biologically active GSLs from echinoderms, we conducted the isolation and structural elucidation of GSLs from starfish and feather stars and found numerous GSLs, some of which have unique structures. In particular, gangliosides from feather stars were unique in that the sialic acids bind to inositol-phosphoceramide. We also found that the GSLs from starfish and feather stars possess neuritogenic activity toward the rat pheochromocytoma cell line PC12, antihyperglycemic effects against type 2 diabetic BKS. Cg-m+/+Leprdb/J (db/db) mice, and antiosteoporosis effects toward the osteoporosis model mice (OVX mice). These biological activities are thought to be related to dementia, osteoporosis, and diabetes, which are becoming social problems, and are expected to become the seeds of preventive or therapeutic drugs for these illness.

著者

豊田 正夫

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.120, no.12, pp.1359-1372, 2000-12-01 (Released:2008-05-30)

参考文献数

37

被引用文献数

1 8

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Four hundred samples of Conocephalum conicum, collected in various places have been analyzed by GC-MS. This resulted in the presence of three chemo-types of C. conicum. One of them elaborate (-)-sabinene (type-I) as a major compound. The other two types characteristically contained (+)-bornyl acetate (type-II) and methyl cinnamate (type-III) as major constituent respectively. The structures of three new monoterpenic esters, isolated from the ether extract of C. conicum (type-I and/or II) have been established by chemical and spectral means. They were shown to be monoterpenic esters of (+)-borneol and p-coumaric acid derivatives. The ether extract of the liverwort Chiloscyphus polyanthos afforded sesquiterpenoids which are enantiomeric to those found in another liverwort Lepidozia vitrea. The absolute configurations of the sesquiterpenoids found in the C. polyanthos were determined by spectroscopic evidence, chemical derivatization and/or x-ray crystallographic analysis. The ether extract of the liverwort Porella perrottetiana afforded (-)-α-eudesmol, which showed an opposite sign of the optical rotation to that found in higher plants. Present work on the absolute configuration and an optical purity of (-)-α-eudesmol strongly suggested that the positive values (e.g.+28.5°) described in many previous papers should be revised. Since the absolute configuration of (-)-α-eudesmol was identical to that (+)-β-eudesmol found in the higher plants, it was apparent that the expression of the positive sign might be revised to (-)-α-eudesmol. The optical purity, reconfirmation of the absolute configuration and synthesis of (-)-α-eudesmol will be discussed.

著者

Zheng Zhihui Yang Yi Shao Huayi Liu Zongying Lu Xinhua Xu Yanni He Xiaobo Jiang Wei Jiang Qin Zhao Baohua Zhang Hua Li Zhuorong Si Shuyi

出版者

公益社団法人 日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.34, no.10, pp.1631-1634, 2011

被引用文献数

6

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In our previous study, two synthetic thiophenes such as IMB-05 and IMB-15 were found as peroxisome proliferator-activated receptor gamma (PPARγ) agonists and exhibited beneficial effects on glucose tolerance of diabetic mice <i>in vivo</i>. In the present study, their effect on the transactivity of other nuclear receptors was further investigated. IMB-05 and IMB-15 could not only activated PPARγ but also efficiently activate PPARα in GAL4-hPPARα/γ (ligand binding domain (LBD)) chimeric receptor assay and PPAR response element (PPRE)-luc reporter gene assay with EC₅₀ values of 1.8—5.2 μ<small>M</small>, whereas no activity was observed in other nuclear receptor assays. In addition, the maximal efficacy of IMB-05 and IMB-15 in activating PPARα/γ was approximately 30% of that observed with Wy14643 and rosiglitazone. These data indicate that the two thiophene derivatives are novel class of partial PPARα/γ dual agonists, which may be the mechanism underlying their regulatory effects on glucose homeostasis.

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

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.125, no.1, pp.131-139, 2005-01-01 (Released:2005-01-01)

参考文献数

25

被引用文献数

2 3

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Metabolic screening using liver microsomes of rats and humans is an indispensable tool to optimize a lead structure and to select compounds for in vivo study. Elucidating the relationship between in vitro intrinsic clearance (CLint, app) and in vivo clearance (CLb) is a prerequisite for screening. We investigated the relationship between CLint, app in rat liver microsomes and CLb after intravenous administration in rats in eight projects. No relationship between these two parameters was found across all of the projects examined. However, there was a certain relationship in the same core structure of six projects, but not in the other two projects. The poor correlation in the projects was improved by considering serum protein binding or microsomal binding in the estimation of in vitro clearances. Although the binding assay was labor intensive, unlike metabolic screening, the introduction of the equilibrium dialysis method using a 96-well format increased the throughput. Optimization of metabolic stability was conducted on the basis of the structure-metabolic stability relationship (SMR) in one of the projects, showing a good correlation without the binding factors. The replacement of the piperazine with a homopiperazine moiety improved metabolic stability in the rat and human liver microsomes. The compound also showed a desirable in vivo pharmacokinetic profile in rats, suggesting that the SMR study on the confirmed in vitro and in vivo correlation is essential to the optimization.