著者

大石 晴樹 畑山 泰道 白石 浩己 柳沢 和也 佐方 由嗣

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.105, no.3, pp.300-303, 1985-03-25 (Released:2008-05-30)

参考文献数

9

被引用文献数

8 8

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An attempt has been made to develop an automated instrument that measures the turbidity change in gelation reaction of a solution containing endotoxin and Limulus amoebocyte lysate, and quantifies endotoxin by determining gelation time of the sample. This instrument monitors the ratio R (t) of the sequential to the initial transmittance of up to 64 samples simultaneously and independently at 10 s increments. As the samples are stationarily incubated at controlled temperature of 37±0.5°C, the objective judgement of gelation is provided without any disturbance from sample vibration. Defining gelation time as the time required to obtain 5% decrease of R (t), the well correlated calibration curve was obtained for endotoxin concentration from 1 pg/ml to 100 ng/ml. The coefficients of variation of the calculated endotoxin concentration were 5.64 to 14.1%. The judgement of gelation by this method agreed well with that by the conventional gel-clot method when the proper measuring time (about a half of that by the conventional method) was selected.

著者

藤原 博 石田 説而 島崎 義男 内藤 誠之郎 土谷 正和 松浦 脩治

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.110, no.5, pp.332-340, 1990-05-25 (Released:2008-05-30)

参考文献数

17

被引用文献数

1 3

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The amounts of endotoxin in commercial blood products were measured by the turbidimetric kinetic Limulus test with an ordinary reagent (LAL-HS) and a new endotoxinspecific reagent (LAL-ES). LAL-ES contains a sufficient amount of a water-soluble (1→3)-β-D-glucan derivative as a blocker of the (1→3)-β-D-glucan-mediated coagulation pathway in the reaction of the Limulus amebocyte lysate. The amounts of endotoxin in alubumin and globulin products measured with LAL-ES agreed with pyrogenic activities in rabbits, but those measured with LAL-HS did not. Added endotoxin in the blood products was well recovered with LAL-ES, but that in some products was excessively recovered with LAL-HS. The amounts of endotoxin in diphtheria-pertussis-tetanus combined vaccines measured with LAL-HS and LAL-ES agreed with the pyrogenic activities in rabbits. The results suggested the existence of a false-positive substance like β-glucan in the blood products but not in the vaccine. LAL-ES is more suitable for the detection of endotoxin in blood products than LAL-HS.

著者

栗尾 和佐子 小西 元美 奥野 智史 中尾 晃幸 木村 朋紀 辻 琢己 山室 晶子 山本 祐実 西川 智絵 柳田 一夫 安原 智久 河野 武幸 荻田 喜代一 曽根 知道

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.134, no.11, pp.1199-1208, 2014 (Released:2014-11-01)

参考文献数

11

被引用文献数

2 1

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The Faculty of Pharmaceutical Sciences, Setsunan University, offers the Self-improvement and Participatory Career Development Education Program: Internship and Volunteer Training Experience for Pharmacy Students to third-year students. We previously reported that the training experience was effective in cultivating important attributes among students, such as a willingness to learn the aims of pharmacists, an awareness of their own role as healthcare workers, and a desire to reflect on their future careers and lives. A follow-up survey of the participants was carried out three years after the training experience. The questionnaire verified that the training experience affected attendance at subsequent lectures and course determination after graduation. We confirmed the relationship between the participants' degree of satisfaction with the training experience and increased motivation for attending subsequent lectures. Through the training experience, participants discovered future targets and subjects of study. In addition, they became more interested in subsequent classroom lessons and their future. The greater the participants' degree of satisfaction with their training experience, the more interest they took in practical training and future courses. The present study clarified that the training experience was effective in cultivating important attributes such as a willingness to learn and an interest in future courses. Moreover, the training positively affected the course determination after graduation.

著者

土屋 守克 長田 浩平 荒川 浩 髙橋 誠一 亀井 優徳 松井 悠子 間藤 卓

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

pp.18-00152, (Released:2019-04-04)

参考文献数

18

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The purpose of this study was to investigate the efficacy of two types of medication administration-assisting food. The subjects were 30 caregivers of children from one to eight years old hospitalized in the pediatrics unit of a university hospital, and 30 nurses caring for them. The caregivers gave medications to their children using two types of administration-assisting food, “chocolate” and “jelly.” A questionnaire was prepared to investigate the efficacy of the administration-assisting food, and the caregivers and nurses responded to the questionnaire after the medication was given. The questionnaire data included many positive responses regarding the administration-assisting food, demonstrating its efficacy. The caregivers of children aged ≥4 years responded that the “chocolate” type was more effective than the “jelly” type in administering medications. There also tended to be a positive opinion of the “chocolate” among the nurses of children aged ≥4 years. However, the opinion of the “chocolate” and “jelly” were equivalent among the nurses of children aged <4 years. The reasons for these results were thought to be that the children were at an age when their sense of taste was developing and changing, plus correlations with past experience of the food and differences in the properties of the administration-assisting food. Easiness of swallowing of administration-assisting foods may be important for children whose taste is underdeveloped. However, the taste of administration-assisting foods may be important for children with taste development. Selecting administration-assisting foods based on these factors may be useful for the smooth administration of medication.

著者

永田 実沙 岩田 加奈 曽根 知道 安原 智久

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.139, no.5, pp.817-826, 2019-05-01 (Released:2019-05-01)

参考文献数

22

被引用文献数

5

---

The use of medical supply vehicles (mobile pharmacies) as a disaster measure developed after the Great East Japan Earthquake in 2011 when a massive tsunami destroyed the medicine supply system. In the 2016 Kumamoto earthquake, mobile pharmacies were dispatched from Oita, Wakayama, and Hiroshima and contributed to medical treatment in the disaster area. In this study, we conducted an interview to structure the mental conflicts of the pharmacists supporting the disaster victims by means of the mobile pharmacies, a novel medical support tool. We conducted a semi-structured interview of 21 pharmacists. The modified grounded theory approach was used for data collection and analysis. As a result, 36 concepts and 13 categories were generated. The support pharmacists maintained mobile pharmacies as a method for cooperation among multiple occupations, and talked about further collaboration in the operation of mobile pharmacies.

著者

水谷 五郎 趙 越 Hien Thi Thu Khuat 岡島 麻衣子 金子 達雄

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.139, no.3, pp.351-362, 2019-03-01 (Released:2019-03-01)

参考文献数

42

---

Second-order nonlinear optical images of aggregates of the ampholytic megamolecular polysaccharide sacran under various stimuli were observed by optical second-harmonic generation (SHG) microscopy. SHG intensity microspots of several tens of micrometers in size are seen for sacran cotton-like lumps and fibers and they have very clear incident polarization dependence. In these microspots, the sacran molecules are oriented in concentric multilayers. We also observed SHG images of sacran prepared in a needle-ring electrode with applied voltage, where SHG was enhanced near the negatively biased needle electrode. We also observed SHG signals near the cast film edges of sacran. The appearance of the SHG image suggested a phase-separation structure in sacran aggregates. These results show that sacran molecules aggregate in several different ways.

著者

寺田 智祐

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.11, pp.1469-1476, 2016-11-01 (Released:2016-11-01)

参考文献数

47

---

After the year 2000, the treatment of cancer remarkably changed, including the development of outpatient cancer chemotherapy. Meanwhile, we have encountered many clinical problems related to cancer patient pharmacy services. To resolve these problems, I have tried to establish the individualized and optimal cancer pharmacotherapy utilizing the findings of basic research. In this review, three topics of my research will be introduced. 1) In 2005, information regarding the genetic polymorphism of UGT1A1*28 was described in the package insert of the drug irinotecan in the United States. At that time, however, there was little similar information for Japanese patients. Through clinical research, we demonstrated that UGT1A1*6 was a significant factor for neutropenia, as induced by irinotecan. 2) Tyrosine kinase inhibitors are mainly used at a fixed dose, but wide interpatient variability has been observed relative to their pharmacokinetics and/or pharmacodynamics. To overcome these variations, clinical and basic pharmacological research on erlotinib, sorafenib and sunitinib was carried out. Especially, in sunitinib therapy, we demonstrated that the breast cancer resistant protein in the intestine functions as a limiting factor for oral absorption, and that therapeutic drug monitoring could be helpful for avoiding severe toxicities, resulting in prolonged progression-free survival. 3) We quantitatively assessed side effect management by pharmacist intervention for outpatient chemotherapy. We calculated the improvement ratio between before and after pharmacist intervention, and found that 135 suggestions (50.8%) led to significant improvements, indicating that pharmacist intervention could be useful for attenuating the side effects of cancer chemotherapies.

著者

松本 健次郎

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.134, no.11, pp.1165-1170, 2014-11-01 (Released:2014-11-01)

参考文献数

14

---

Primary afferent nerve fibers are highly associated with visceral hypersensitivity state of inflammatory bowel disease. Hypersensitivity of afferent fibers occurs during inflammation, and therefore to gain insight into the alteration of receptors and channels, we examined receptors such as 5-HT receptors and transient receptor potential vanilloid type 1 (TRPV1), which are expressed in primary afferent neurons. The current study was designed to investigate the time-dependent dynamic changes of 5-HT3 receptors, 5-HT4 receptors, TRPV1 channels, and 5-HT regulatory factors in DSS-induced colitis model mice. Colitis was induced by 3% dextran sulfate sodium (DSS) solution given as drinking water in C57BL/6J mice. Immunohistochemical analysis and visceromotor responses to colorectal distension were measured during induction of DSS colitis (day 0, 4 and 7). Progress of the inflammation led to down regulation of serotonin transporter immunoreactivities with concomitant increases in 5-HT and tryptophan hydroxylase-1 positive cell numbers. TRPV1-expressing nerve fibers gradually increased during DSS treatment. Abundant non-neuronal TRPV1-immunopositive cell like structure was observed on day 7 of DSS treatment, but not on day 4. The number of 5-HT3 receptor-expressing nerve fibers increased in mucosa on day 7. On the other hand, 5-HT4 receptor-expressing nerve fibers decreased on day 7. TRPV1 antagonist and 5-HT3 receptor antagonist attenuated the visceral hyperalgesia to control level in the DSS-induced colitis model. We made the novel observations of increased neuronal/non-neuronal TRPV1 channel and 5-HT3 receptor expression, and decreased 5-HT4 receptor expression in mucosa. Moreover, we show that a correlation existed between the mucosal changes and visceral hypersensitivity in experimental colitis.

著者

土釜 恭直

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.139, no.2, pp.209-219, 2019-02-01 (Released:2019-02-01)

参考文献数

41

被引用文献数

3

---

Antibody-drug conjugates (ADCs), monoclonal antibodies conjugated with highly potent drugs (payloads) through chemical linkers, are an emerging class of therapeutic agents for cancer chemotherapy. Their clinical success has been demonstrated by the 4 ADCs already approved by the U.S. Food and Drug Administration (FDA), and more than 60 promising ADCs now in clinical trials. Further advancement of this novel molecular platform could potentially revolutionize current strategies and regimens for treating cancers. The linker structure and antibody-linker conjugation modality critically contribute to ADC homogeneity, circulation stability, pharmacokinetic profiles, tolerability, and overall treatment efficacy. Despite extensive efforts to improve these parameters, most ADC linkers used to date possess linear structures, and therefore accommodate only single payloads. The clinical potential of branched ADC linkers, enabling the installation of two payload molecules, remains unexplored because of the lack of efficient conjugation methods. In addition, according to a recent report, the stability of enzymatically cleavable linkers in mouse circulation is another crucial factor for the successful evaluation of ADCs in preclinical studies. In this review, I present my research group's effort to develop both branched linkers and efficient conjugation methods for constructing dual-loading ADCs with high homogeneity and enhanced potency. I also present a novel tripeptide ADC linker with enhanced stability in mouse circulation. Multidisciplinary experience, approaches, and collaboration are key to successfully advancing our ADC research programs. I herein describe how my experience in the U.S. has helped to develop and manage complex biomedical research projects in a small academic laboratory setting.

著者

川口 実希 木村 美智男 宇佐美 英績 川地 志緒里 郷 真貴子 池田 義明 吉村 知哲

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.139, no.3, pp.483-490, 2019-03-01 (Released:2019-03-01)

参考文献数

22

---

This study aimed to clarify the situation of use of health foods by patients and the level of satisfaction of patients in order to make use of information on cases where patients undergoing cancer medication therapy use health foods. Between May 7, 2018 and June 29, 2018, we conducted a questionnaire survey of patients with progressive cancer who were undergoing cancer chemotherapy at Ogaki Municipal Hospital. In addition, we conducted a multivariate analysis of patients who were using health foods and those who were not. The questionnaire items included the objectives of use, product effectiveness and satisfaction, and QOL. The rate of health food use was 81/281 (29.5%). The primary objectives of use were, “to maintain health” (29.8%) and “to alleviate symptoms” (24.0%). The primary sources of information about health foods were “a friend” (50.6%) and “TV” (13.5%). The satisfaction level was 0-3 points in 8.3% of patients, 4-6 points in 38.1% of patients, and 7-10 points in 53.6% of patients. For “stage of illness (recurrence),” the odds ratio was 1.810 (95% CI, 1.040-3.150; p=0.035), and for “QOL value,” the odds ratio was 2.210 (95% CI, 1.220-4.020; p=0.009), indicating that these factors had a significant influence on health food use. Health foods tended to be used in patients who had recurring cancer with low QOL and various symptoms, and friends and other people close to the patient had a large influence on the patient's decision. It was clear that the patients' satisfaction level was high.

著者

萩庭 丈寿 坂井 進一郎 相見 則郎 山中 悦二 新間 信夫

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.93, no.4, pp.448-452, 1973-04-25 (Released:2008-05-30)

参考文献数

12

被引用文献数

21 33

---

In the reinvestigation of the constituents of Uncaria rhynchophylla MIQ. (Japanese name "kagikazura"), the presence of two oxindole alkaloids, corynoxeine and isocorynoxeine, was demonstrated, besides the reported rhynchophylline and isorhynchophylline.3) Furthermore, four indole alkaloids were newly isolated ; hirsutine, hirsuteine, dihydrocorynantheine, and corynantheine. A chemical structural evidence of hirsutine was obtained from its epimerization to dihydrocorynantheine with acetic acid catalysis.

著者

山中 悦二 君塚 ゆみ子 相見 則郎 坂井 進一郎 萩庭 丈寿

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.103, no.10, pp.1028-1033, 1983-10-25 (Released:2008-05-30)

参考文献数

8

被引用文献数

12 27

---

Quantitative analysis of the tertiary alkaloids in various parts of Uncaria rhynchophylla MIQ. was made by use of high performance liquid chromatography (HPLC). The best result was obtained in the following conditions : column ; Radial Pak C8 and mobile phase ; CH3CN-0.05M AcONH4 buffer (pH 4.0) [90 : 10]. The result revealed that the constitution of the alkaloids varied markedly depending on the botanical parts examined. While oxindole alkaloids (1, 2, 3 and 6) occupy ca. 97% of total alkaloids in hook, small stem and leaf, respectively, content of indole alkaloids (mainly 8 and 10) is almost exclusive (ca. 96%) in the bark of underground part. In the bark of aerial part both oxindole and indole alkaloids were found to be contained in nearly equal amounts. The alkaloidal content is very low in the wood (aerial or underground part) but the content ratios of rare alkaloids (4 and 7) to the total alkaloids are higher than the other parts.

著者

小林 義郎

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.100, no.8, pp.779-791, 1980-08-25 (Released:2008-05-30)

参考文献数

18

被引用文献数

1

---

Studies on organic fluorine compounds in our laboratory are summarized. New methods for the synthesis of fluorine compound are as follows ; 1) fluorination of alcohols with fluorophosphoranes, 2) trifluoromethylation of aromatic and aliphatic halides with trifluoromethyl halides and copper powder, and 3) cycloaddition reaction with novel fluorine reagents like hexafluorobutyne. Reactions of trifluoromethyl aromatic compounds were investigated thoroughly, and some interesting characters of fluorine compounds were revealed. Trifluoromethylated valence bond isomers of aromatic compounds were synthesized, and some novel reactions of these highly strained compounds were shown. The characteristics that a fluorine atom is a small substituent and that a carbon-fluorine bond is very strong were used to study the metabolism of vitamin D3. Some interesting reactions by use of fluorine compounds as synthetic reagents are also discussed.

著者

熊懐 稜丸

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.105, no.8, pp.713-723, 1985-08-25 (Released:2008-05-30)

参考文献数

26

被引用文献数

4 3

---

New reactions developed for the synthesis of medicinally useful trifluoromethyl compounds are discussed. First, the trifluoromethylation of aromatic halogen compounds with CF3I and Cu powder is presented. This method is applicable to a wide range of aromatic halides, while aliphatic halides cannot be converted to trifluoromethyl compounds. This difficulty was removed by two-step procedure. CF3I and Cu powder were shaken in a stainless steel tube, and the excess of Cu powder was removed by filtration. The solution of [CF3-Cu] was treated with halogen compounds to give trifluoromethyl compounds. Next, the Friedel-Crafts reaction of trifluoropropene was presented, which gave trifluoropropyl compounds. It was very difficult to obtain these products by other routes. Attempted application of the trifluoropropyl compounds are included. Finally, some reactions useful for the synthesis of special types of trifluoromethyl compounds were summarized, where photoreaction, 1, 3-dipolar reaction, and ene reaction of trifluoromethyl compounds are included.

著者

熊懐 稜丸

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.126, no.11, pp.1059-1085, 2006-11-01 (Released:2006-11-01)

参考文献数

66

被引用文献数

2 2

---

This review describes new syntheses of organofluorine compounds taking advantage of the special properties of fluorine compounds as synthones. The main reactions presented are as follows: 1) Trifluoromethylation of aryl or alkyl halides. Application of this reaction for the synthesis of fluorine analogues of nucleic acid bases is discussed. 2) Some syntheses of trifluoromethyl compounds using the Diels-Alder or the 1,3-dipolar reaction, trifluoromethylated carbene, and photoreaction. 3) The Friedel-Crafts reaction of 3,3,3-trifluoropropene, where linear alkylation occurs due to electronic effect of the trifluoromethyl group in good contrast with the Friedel-Crafts reaction of propene. 4) The ene reaction of trifluoromethylated carbonyl compounds, which work as good enophiles. Application of this reaction to the synthesis of trifluoro analogues of terpenes is discussed. 5) The ene reaction of trifluoromethylated imines. 6) Reaction of halothane, which has a highly acidic hydrogen and two halogens adjacent to the trifluoromethyl group and shows interesting reactivities with various bases and metals to give products with unexpected structures. 7) Reaction of 2-bromo-2,2-difluoroacetate with Cu, where the cross-coupling reaction, Michael-type reaction, and radical reaction for different types of difluoroacetates are presented. 8) Reaction of 2-bromo-2,2-difluoroacetate in the presence of Rh catalyst. This reaction provided a new methodology for the introduction of fluoroalkyl substituents to the α-position of α,β-unsaturated ketones. The Rh catalyst solved some difficulties in the introduction of difluoroacetate to carbonyl compounds (Reformatsky reaction). Application of this reaction to imines provided easy access to β,β-difluoro-β-lactams.

著者

佐藤 和之

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.126, no.8, pp.597-605, 2006-08-01 (Released:2006-08-01)

参考文献数

30

被引用文献数

2 2

---

Novel fluoroalkylated products where a CF2COOEt group was introduced at the α-position of α,β-unsaturated ketones or the Reformatsky-type products have been obtained selectively by the reaction of BrCF2COOEt and α,β-unsaturated ketones with Et2Zn in the presence of RhCl(PPh3)3 depending on the solvents. Furthermore, the novel α-fluoroalkylated products could synthesize by using various halofluoroalkyl compounds (Rf-X) instead of BrCF2COOEt. On the other hand, this Reformatsky-type reaction by imines gave difluoro-β-lactams or 3-amino-2,2-difluorocalboxylic esters without or with MgSO4•7H2O, selectively.

著者

小林 和弘 織田 範一 伊藤 磯雄

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.101, no.9, pp.806-813, 1981-09-25 (Released:2008-05-30)

参考文献数

14

被引用文献数

1 1

---

As the initial study of variations of skeletons of antitumor antibiotics, simple synthesis of naphtho [2, 3-g] quinolines (IIIa, b, VIII) and naphtho [2, 3-g] quinoxalines (XIIIa, b), which are novel heterocyclic ring systems, was carried out by Diels-Alder reaction of 1, 2-dimethylenecyclohexane with quinoline-5, 8-diones (Ia-c) or quinoxaline-5, 8-diones (IIa, b). Air oxidation of these Diels-Alder adducts gave tetrahydro naphtho [2, 3-g] quinolines (IVa, b, IX) and tetrahydronaphtho [2, 3-g] quinoxalines (XVa, b). The Diels-Alder adducts and aromatized compounds were converted into the corresponding diacetoxynaphtho [2, 3-g] quinolines (VI, VII, X) and diacetoxynaphtho [2, 3-g] quinoxalines (XVII, XVIII).

著者

小林 和弘 織田 範一 榊原 仁作

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.103, no.2, pp.165-172, 1983-02-25 (Released:2008-05-30)

参考文献数

16

被引用文献数

1 1

---

Ethyl 5-hydroxybenzo [α] phenazine-6-carboxylates (IIa, b) were prepared by the condensation of ethyl 1, 4-dihydro-1, 4-dioxo-3-methoxy-2-naphthoate (I) with o-phenylene-diamines. Acylations and alkylations of IIa, b gave the corresponding o-acyl and alkyl compounds (IIIa-k). The reaction of IIa, b with ethanolamine gave β-hydroxyethyl-carboxamides (Va, b). Compound Va was converted into β-chlorinated compound (VIa), whose chlorine was substituted by dialkylamines to give ethylenediamine-type amides (VIIa, b, c). Compounds VIId and VIIe were obtained by the reaction of IIb with dialkylalkylenediamines. Oxidation of IIa, b afforded N-oxides (IXa, b). The antimicrobial activities of all synthetic compounds were tested by paper discagar diffusion assay. Compounds IIId, e, g, VIIa and IXa showed inhibitory activities to T. interdigitale and IXa to C. albicans.

著者

小林 和弘 織田 範一 榊原 仁作

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.103, no.4, pp.473-479, 1983-04-25 (Released:2008-05-30)

参考文献数

8

被引用文献数

1 1

---

Ethyl 1, 4-dihydro-1, 4-dioxo-3-methoxy-2-naphthoate (I) is condensed with amidines, 2-aminopyridines and 3-aminopyrazole, to give new tetracyclic quinones (IIIa-c and VI) containing nitrogen atom and hydrogenation of IIIa and IIIb over Pd-C or Raney-Ni afforded 1, 2, 3, 4-tetrahydro (IXa, b) or 1, 2, 3, 4, 7, 8, 9, 10-octahydrobenzo[g]pyrido[2, 1-b]quinazoline (Xa), respectively. Benzo[g]pyrido[2, 1-b]quinazoline derivatives except for Xa showed inhibitory activities to S. aureus and T. interdigitale.

著者

小松 俊哉 矢野 雅士 稲田 治明 岩本 光男 岡田 一男 鈴木 健一

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.12, pp.1016-1021, 1995-12-25 (Released:2008-05-30)

参考文献数

9

被引用文献数

3 3

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The two mono-hydroxylated metabolites of 9-amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopenta [b] quinoline monohydrochloride monohydrate (NIK-247), which is a new drug for the treatment of dementia, were synthesized to determine their chemical structures. Reduction of two tricyclic ketones, 9-amino-1, 2, 3, 5, 6, 7-hexahydro-8H-cyclopenta [b] quinolin-8-one and 9-amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopenta [b]-quinolin-1-one, with NaBH4 afforded the corresponding racemic alcohols. The optically active mono-hydroxylated metabolites, (+)-9-amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopenta [b] quinolin-8-ol and (+)-9-amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopenta [b] quinolin-1-ol, were obtained by optical resolution of each racemic alcohol using (+)-di-p-toluoyl-D-tartaric acid.