-
櫨本 紀夫, 原田 政信, 鈴木 重輝, 海保 房夫, 芳賀 信, 加藤 百合子
1993 年 41 巻 6 号 p.
1003-1006
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
We previously reported that liposomes composed of phosphatidylethanolamine (PE) and fatty acid exhibited pH-dependent leakage, aggregation and fusion (N. Hazemoto, M. Harada N. Komatubara, M. Haga, and Y. Kato, Chem. Pharm. Bull., 38, 748 (1990)). In this study, we have examined the effects of phosphatidylcholine (PC) and cholesterol (Chol) on the pH-sensitivity of liposomes. Contents-leakage from liposomes was always accompanied by a change in light-scattering, suggesting that aggregation or fusion of liposomes causes the leakage. The pH-sensitivity was observed only when liposomes contained less than 32 mol% of PC. The leakage vs. pH curves shifted to the more acidic regions as the PC content of the liposomes increased, but the maximum leakage (%) did not change. The effect of cholesterol on the pH-sensitivity depended on the PC/PE ratio of the liposomes. Addition of cholesterol to PC/PE/oleic acid (OA) liposomes system induced two effects, that is, aggregation of liposomes via the reduction in PC content and the stabilization of the liposomal membrane. It was shown that pH-sensitivity can be controlled by addition of the appropriate amount of PC and/or Chol to liposomal lipids.
抄録全体を表示
-
菅田 節朗
1993 年 41 巻 6 号 p.
1007-1011
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
The reaction of 3, 4-dihydroxybenzaldehyde (LH
2) and dimethyl sulfate (DMS) in forming m- and p-O-methylated products (vanillin and isovanillin, respectively) in a methanol buffer solution was studied kinetically as a chemical model of catechol-O-methyltransferase (COMT). The O-methylations, especially m-O-methylations, were catalyzed by divalent metal ions such as Cu(II), Mg(II) and Zn(II). A clear Mg(II) catalysis was observed for the first time in this medium. As Mg(II) is an important metal in the COMT catalyzed reaction in vivo, this observation is very interesting. Kinetic analyses of the present data and recalculation of a part of the previous data offered the following evidence. In Cu(II) catalysis, a 1 : 2 complex(CuL
2) was more active than the 1 : 1 complex (CuL). On the other hand, in Mg(II) catalysis and Zn(II) catalysis, ML was more active than ML
2. These facts show that ML
2 is not always more active than ML, contrary to previous reports. Methanolysis of DMS, a significant side reaction of this model reaction, and dissociation of LH
2 were studied thoroughly as bases for these kinetic analyses.
抄録全体を表示
-
鴻巣 俊之, 老田 貞夫
1993 年 41 巻 6 号 p.
1012-1018
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
Synthesis of racemic and optically active cispentacin ((-)-1) is described. Intramolecular nitrone-olefin cycloaddition of the alkenyl nitrone 7 gave cis-isoxazolidine (±)-8, which was transformed into (±)-1 by sequential reactions involving catalytic hydrogenolysis and oxidation. Similarly, the optically active nitrone (R)-22, which was derived from the ketone 15 via lipase-catalyzed hydrolysis of the acetate (±)-17, underwent intramolecular cycloaddition to give (+)-25 with high stereoselectivity (15 : 1). The cycloadduct (+)-25 was transformed in 4 steps into optically active natural cispentacin.
抄録全体を表示
-
永田 佳子, 与田 玲子, 松島 美一
1993 年 41 巻 6 号 p.
1019-1022
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
HPLC,
1H-NMR, MS and product analysis showed that pyridoxal hydrochloride was solvolyzed in methanol to form pyridoxal monomethylacetal. The reaction followed first order kinetics with the rate constant of 1.45×10
-4s
-1 at 40°C. The rate was not appreciably enhanced in the presence of an excess amount of HCl. The reaction was greatly retarded by addition of an equimolar amount of KOH. The results showed that the pyridinium-phenol species of pyridoxal hemiacetal is reactive. The reaction is responsible for the "aging" of alcoholic solutions of pyridoxal, which has caused poor reproducibility of the kinetic data for the formation of Schiff bases with amino acids.
抄録全体を表示
-
小野 政輝, 山田 扶美子, 野田 直希, 川崎 敏男, 宮原 一元
1993 年 41 巻 6 号 p.
1023-1026
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
The absolute configurations of four hydroxyfatty acids, jalapinolic acid, convolvulinolic acid, ipurolic acid and 3, 11-dihydroxyhexadecanoic acid, obtained by acid hydrolysis of various resin glycosides, have been determined to be 11S, 11S, 3S, 11S, and 3S, 11S, respectively, by Mosher's method. The R-configuration of jalapinolic acid previously defined by Horeau's method was therefore revised to S.
抄録全体を表示
-
片桐 信弥, 白石 拓也, 豊田 朱見, 佐藤 弘, 金子 主税, 相川 豊夫
1993 年 41 巻 6 号 p.
1027-1029
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
Deamination of an anti-human immunodeficiency virus (anti-HIV) carbocyclic adenine nucleoside, 9-[c-4, t-5-bis(hydroxymethyl)cyclopent-2-en-r-1-yl]-9H-adenine (BCA) by adenosine deaminase under a variety of pressures (1 bar-6 kbar) was investigated. It was found that, while (+)-BCA was practically unaffected, the deamination of (-)-BCA was remarkably enhanced under 4 kbar to give the corresponding (-)-hypoxanthine derivative [(-)-BCH] in nearly 100% ee.
抄録全体を表示
-
小出 隆規, 大高 章, 藤井 信孝
1993 年 41 巻 6 号 p.
1030-1034
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
Disulfide bonds of peptides were effectively established between S-protected cysteine residues as well as free cysteine residues by the action of dimethylsulfoxide in trifluoroacetic acid. Oxytocin and α-human calcitonin gene-related peptide were synthesized using this oxidation system. The feasibility of this method for the formation of two disulfide bridges of apamin was also examined.
抄録全体を表示
-
田坂 昭弘, 田村 典一, 松下 義弘, 寺西 克倫, 林 良吾, 小此木 研二, 伊藤 克己
1993 年 41 巻 6 号 p.
1035-1042
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
(2R, 3R)-2-(2, 4-Difluorophenyl)-3-mercapto-1-(1H-1, 2, 4-triazol-1-yl)-2-butanol [(2R, 3R)-7] and its stereoisomers [(2S, 3R)-, (2S, 3S)- and (2R, 3S)-7] were prepared from the optically active oxiranes 6 by a newly developed ring-opening reaction and evaluated for antifungal activity. The thiol (2R, 3R)-7 showed extremely potent antifungal activity in vitro and in vivo.The optically active oxirane (2R, 3S)-6, a useful intermediate for the synthesis of sulfur-containing antifungal azoles 5, was synthesized from methyl (R)-lactate [(R)-8] via eight steps in a stereocontrolled manner. The key step in the synthesis is the Grignard reaction of an amide derivative [(R)-12a] of (R)-lactic acid with 2, 4-difluorophenylmagnesium bromide (13).
抄録全体を表示
-
田坂 昭弘, 田村 典一, 松下 義弘, 林 良吾, 小此木 研二, 伊藤 克己
1993 年 41 巻 6 号 p.
1043-1048
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
In an effort to find potent antifungal agents, a variety of optically active triazole derivatives with a polysulfide structure, 3, 4 and 5, were prepared and evaluated for antifungal activity against Candida albicans in vitro and in vivo. The symmetrical polysulfides 3 (m=2-4) were obtained by an oxidative coupling reaction of (2R, 3R)-2-(2, 4-difluorophenyl)-3-mercapto-1-(1H-1, 2, 4-triazol-1-yl)-2-butanol (1) or by the treatment of its thiocarbonate derivative 8 with potassium tert-butoxide. The unsymmetrical disulfides 5 were synthesized by the reaction of the thiol 1 with Bunte salts 11 or the thiosulfinate 12 or by the reaction of the thiocarbonate 8 with various thiols 13. All of these polysulfides showed potent antifungal activity against candidosis in mice.
抄録全体を表示
-
小川 利寿, 中里 篤郎, 土田 勝晴, 畑山 勝男
1993 年 41 巻 6 号 p.
1049-1054
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
We have synthesized new 1, 4-dihydropyridine derivatives having nitrooxyalkylester moieties at the 3- and 5-positions in order to develop potent and long-lasting vasodilators. The antihypertensive activities of these compounds were compared with that of nifedipine. One of them, 2-nitrooxypropyl 3-nitrooxypropyl 2, 6-dimethyl-4-(3-nitrophenyl)-1, 4-dihydro-3, 5-pyridinedicarboxylate (CD-349) was selected for further development. The structure-activity relationship is discussed.
抄録全体を表示
-
伊川 篤弥, 西田 幹夫, 大久保 彰, 吉村 好之, 富田 純弘, 川田 純
1993 年 41 巻 6 号 p.
1055-1059
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
Aluminum hydroxide gel (ALG), which is currently used as a phosphate-adsorbent, dissolves in gastric juice and the eluted aluminum ion has been suggested to be a causative agent of osteomalacia and encephalopathy. A new type of microcrystalline boehmite compound of aluminum oxide hydroxide with high acid resistance (named PT-A), has been developed by the author's group as a possible replacement for ALG.In the present study, the characteristic behaviors of PT-A and ALG toward various food components were compared at different pH's to get information on possible interference with phosphate adsorption onto the adsorbents by food components. The order of adsorption of food components per unit mass of PT-A was : proteins>nucleotides>lipids>carbohydrates. The order with ALG, with a minor exception, was the same as that with PT-A. However, the amounts of materials adsorbed on PT-A were generally much less than those on ALG. When phosphate was mixed with a synthetic milk as a model standard meal and exposed to the two adsorbents, phosphate-adsorption was entirely unaffected; however, the phosphate adsorption capacity of ALG was much less than that of PT-A. In conclusion, PT-A has a higher capacity for adsorbing phosphate, and adsorbs food components to a lesser extent than ALG. Phosphate-adsorption onto PT-A was not subject to interference by food components.
抄録全体を表示
-
川島 豊, 小川 利寿, 加藤 美幸, 中里 篤郎, 土田 勝晴, 畑山 勝男, 広野 修一, 森口 郁生
1993 年 41 巻 6 号 p.
1060-1065
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
1, 4-Dihydropyridine derivatives having two nitrooxyalkyl moieties as esters at the 3 and 5 positions possess antihypertensive activity. To understand how substituents affect the biological activity, the quantitative structure-activity relationship (QSAR) of 27 compounds was analyzed using the Fuzzy adaptive least-squares (FALS 91) method. The QSAR models suggested that the hydrophobicity and electronic effect at the 4 position of the 1, 4-dihydropyridine along with the special structures of the nitrooxyalkylester components are important for antihypertensive activity.
抄録全体を表示
-
伊藤 研, 太田 淳稔, 須原 寛, 田橋 圭三, 河嶋 洋一
1993 年 41 巻 6 号 p.
1066-1073
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
In order to search for anti-hepatitis drugs, we synthesized a series of eight- and nine-membered cyclic disulfides (1) and six- and seven-membered cyclic sulfides (2) and evaluated them for ability to reduce mortality in the model of acute hepatic failure induced by Propionibacterium acnes-lipopolysaccharide in mice. Compounds 1 were synthesized by oxidative cyclization of the corresponding dithiol derivatives (3) with diethyl bromomalonate or iodine. Compounds 2 were prepared from the methyl esters of 1 by desulfurization with tris(diethylamino)phosphine followed by deprotection. Compounds 1 were generally found to be more active than compounds 2. Compound 1b (SA3443) was found to exhibit potent protective activity. The synthesis and structure-activity relationships are discussed.
抄録全体を表示
-
Syntheses and Biological Activities of Optical Isomers of 3-Chloro-5-[3-(2-oxo-1, 2, 3, 5, 6, 7, 8, 8a-octahydroimidazo[1, 2-a]pyridine-3-spiro-4'-piperidino)propyl]-10, 11-dihydro-5H-dibenz[b, f]azepine (Mosapramine) Dihydrochloride
田代 千秋, 瀬戸口 信郎, 福田 武美, 丸林 信洋
1993 年 41 巻 6 号 p.
1074-1078
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
Mosapramine (1) is a new neuroleptic drug with an asymmetric carbon atom (8a) in its imidazopyridine ring. The enantiomers of this agent were synthesized to compare their biological activities, such as antiapomorphine activity, affinity for dopamine D
2 receptor and acute toxicity. The key intermediates, (R)-(-)- and (S)-(+)-2-oxo-1, 2, 3, 5, 6, 7, 8, 8a-octahydromidazo[1, 2-a]pyridine-3-spiro-4'-piperidines, were prepared by optical resolution of the corresponding (±)-compound and were treated with 3-chloro-5-(3-methanesulfonyloxypropyl)-10, 11-dihydro-5H-dibenz[b, f]azepine to afford (R)-(-)-1 and (S)-(+)-1, respectively. There were few differences in the examined biological activities of the two enantiomers as thier dihydrochlorides.
抄録全体を表示
-
手納 直規, 和中 敬子, 岡田 芳男, 田口 博明, 岡本 歌子, 奥宮 明子, 岡本 彰祐
1993 年 41 巻 6 号 p.
1079-1090
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
The molecule of trans-4-aminomethylcyclohexanecarbonylphenylalanine 4-carboxymethylanilide (8), which is a potent and selective inhibitor of plasma kallikrein, can be devided into three parts (P
1, P
1' and P
2'), each of which contains one of the rings. In order to study the role of each part in the manifestation of potent and selective inhibitory activity and the relationship between the structure and inhibitory activities toward plasmin, plasma kallikrein, urokinase and thrombin, each part was substituted with various other moieties to give many kinds of analogs and their inhibitory activities against the above enzymes were examined. Among them, trans-4-aminomethylcyclohexanecarbonyl-O-2-bromobenzyloxycarbonyltyrosine 4-acetylanilide (12) inhibited plasmin and plasma kallikrein with IC
50 values of 2.3×10
-7 M and 3.7×10
-7 M, and K
i values of 1.2×10
-7 M and 1.3×10
-7 M, respectively.
抄録全体を表示
-
林 裕晃, 池田 淳一, 黒田 武志, 久保 和博, 佐野 智行, 鈴木 文夫
1993 年 41 巻 6 号 p.
1091-1099
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
A series of 5-deoxy-5-(4-substituted piperazin-1-yl)-1, 4 : 3, 6-dianhydro-L-iditol 2-nitrates was prepared and evaluated for oral anti-ischemic activities. Inhibition of lysine-vasopressin-induced T-wave elevation in the electrocardiogram (ECG) of rats (angina pectoris model) served as a primary assay. Optimum activity was observed for the compounds with the aryl-heteroatom (O, S, or N)-propyl group. Among them, the phenylthiopropyl-substituted compound 13 exhibited the most potent activity. Furthermore, intraduodenal administration (i.d.) of 13 tended to decrease left ventricular end-diastolic pressure (LVEDP) in a propranolol-induced heart failure model (dogs) and showed a potent protective effect against reperfusion arrhythmia in rats. Thus, 13 (KF 14124) is under further study as an orally active nitrate.
抄録全体を表示
-
林 裕晃, 池田 淳一, 久保 和博, 森山 孝広, 唐沢 啓, 鈴木 文夫
1993 年 41 巻 6 号 p.
1100-1110
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
A series of 5-(4-aryl- or 4-arylcarbonylpiperazin-1-yl)-5-deoxy-1, 4 : 3, 6-dianhydro-L-iditol 2-nitrates was prepared in order to obtain orally active, nitrate-type vasodilators with reduced side effects. Our drug design was based on a small reduction in the lipophilicity compared to that of 5-deoxy-5-[4-(3-phenylthiopropyl)piperazin-1-yl]-1, 4 : 3, 6-dianhydro-L-iditol 2-nitrate (1, KF14124). Compounds 4h(aryl=benzimidazol-2-yl), 4i(arylcarbonyl=nicotinoyl), and 4w(arylcarbonyl=3-furoyl) showed potent anti-ischemic activity in a lysine-vasopressin-induced angina pectoris model (rats), and their structure-activity relationships are discussed. Compound 4i exhibited potent vasodilation of the coronary artery in anesthetized dogs and also exhibited potent preload reducion in a heart failure model (dogs) as compared with isosorbide dinitrate (2), nicorandil (3), and KF14124 (1). Furthermore, 4i showed much weaker acute lethal toxicity and less central nervous system depression than 1 in mice. Thus, 4i (KW-3196) is under development as a vasodilator and a drug for treating angina pectoris.
抄録全体を表示
-
宮本 勝仁, 村山 栄五郎, 越智 清成, 渡邊 博義, 久保寺 登
1993 年 41 巻 6 号 p.
1111-1113
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
Four vitamin D
3 analogues (7a, 7b, 7c and 7d) bearing a hydroxyalkoxy group at the 2β-position were synthesized from the α-epoxide (5). The C-3 analogue (7b) showed the highest potency for elevating plasma calcium levels in rats. Furthermore, the 25-hydroxylated C-3 analogue (ED-71) (3), prepared from the 25-hydroxylated α-epoxide (9), significantly increased plasma calcium to levels much higher than those in rats administered 1α, 25-(OH)
2-D
3 (1).
抄録全体を表示
-
堀 学, 大高 博
1993 年 41 巻 6 号 p.
1114-1117
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
Alkylation of 4(3H)-quinazolinones with 1-iodopentane in the presence of sodium hydride gave a mixture of 3-pentyl-4(3H)-quinazolinones (2) and 4-pentyloxyquinazolines (3). The ratio of O-alkyl/N-alkyl products varied according to the 2-substituents of the quinazoline ring. Multiple regression analyses revealed that the ratio was determined by a steric factor (width parameter of B) and an electronic factor (in terms of Hammett's σ
p) of the 2-substituent. It was found to be the case in the reported alkylation of 4(3H)-quinazolinones with propargyl bromide.
抄録全体を表示
-
石山 宗孝, 志賀 匡宣, 佐々本 一美, 溝口 誠, 何 品剛
1993 年 41 巻 6 号 p.
1118-1122
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
A new tetrazolium compound, sodium salt of 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1, 3-benzene disulfonate (1a), which produces a highly water-soluble formazan dye, due to the presence of two sulfonate groups, was synthesized and its potential utility evaluated in assays of NADH and cell proliferation. The compound proved to have a similar sensitivity to 2, 3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide (XTT) in the assay of NADH and was also useful as an indicator of cell viability, with less cytotoxicity than XTT, in the proliferation assay using P388 cell lines.
抄録全体を表示
-
鈴木 博文, 中川 寛, 御舩 正樹, 斎藤 寛
1993 年 41 巻 6 号 p.
1123-1126
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
A plastic membrane ion-selective electrode applicable to many basic drugs has been developed. The electrode developed was constructed with tricresyl phosphate and a poly(vinyl chloride) matrix on a polytetrafluoroethylene film. The electrode showed a near-Nernstian response to chlorpromazine, trihexyphenidyl, imipramine, dibucaine, papaverine, propranolol, tetracaine, trazodone, quinidine and cinnarizine. The determination of 50 to 3000 μg/ml of trazodone hydrochloride in a pH 4.0 acetate buffer solution showed an average recovery of 99.4% (mean standard deviation 0.7%) by direct potentiometry. Inorganic cations and pharmaceutical excipients did not interfere with the determination. Trazodone hydrochloride and trihexyphenidyl hydrochloride in tablets were determined, and the results compared favorably with those obtained by conventional methods.
抄録全体を表示
-
斉藤 英樹, 宮瀬 敏男, 上野 明
1993 年 41 巻 6 号 p.
1127-1131
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
From the roots of Polygala senega var. latifolia TORR. et GRAY five new oligosaccharides, called senegoses A-E, were isolated and their structures were elucidated by spectroscopic and chemical means. These oligosaccharides were esterified with acetic, benzoic, trans-ferulic and cis-ferulic acids.
抄録全体を表示
-
市川 秀喜, 情野 香, 徳満 宏之, 福田 友昭, 福森 義信
1993 年 41 巻 6 号 p.
1132-1136
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
The latices of copoly(ethyl acrylate-methyl methacrylate-2-hydroxyethyl methacrylate) exhibited a very low degree of agglomeration in the Wurster coating process, when the softening temperatures of their films were higher than inlet air temperature. This low agglomeration was due to their poor film-formability and, consequently, their low binding strength. Although this led to a low fixing efficiency of cosuspended solid particles, the coating efficiency of polymer itself remained high (about 90%). This low tendency of agglomeration was confirmed even in a coating of as fine a powder as 32-44 μm.
抄録全体を表示
-
高畑 英夫, 大沢 孝, 小林 征雄
1993 年 41 巻 6 号 p.
1137-1143
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
The effect of drug and polymer properties on microencapsulation of acidic drugs with enteric polymers by the surface neutralization method was studied using eight benzoic acid derivatives and three enteric polymers (carboxymethylethylcellulose (CMEC), hydroxypropylmethylcellulose acetate succinate-H (AS-H) and hydroxypropylmethylcellulose acetate succinate-L (AS-L)). Each core material containing a drug was granulated to beads from 500 to 710 μm in diameter to remove the effect of drug crystal morphology. Microcapsules (MCs) were prepared by suspending the beads in an enteric polymer solution, followed by filtration and drying. Then, the properties of the MCs produced were evaluated. The polymer content in MCs (PC) and recovery percent of the drugs in MCs were in the order AS-H>AS-L>CMEC, but the percent of recovered single-nuclear MCs was in the order CMEC>AS-L>AS-H. The PCs did not correlate with the solubilities of drugs, but showed an obvious dependency on the pH of the saturated solution of the drug. That is, as the pH decreased, the PCs increased. To estimate the PCs on the basis of drug and polymer properties, a mathematical model was established on the basis of an acid-base equilibrium equation, and the ratio of polymer acidic groups associated with hydrogen ion (FS) was calculated. A linear relationship was obtained between √((FS-α
p)) values (α
p : equivalency ratio of hydrogen ion to acidic groups of polymer at which the polymer begins to precipitate) and the experimental PCs. Thus, microencapsulation efficiency seemed to be predictable by using this relationship.
抄録全体を表示
-
福森 義信, 市川 秀喜, 徳満 宏之, 宮本 雅仁, 情野 香, 金森 隆一, 秋根 康之, 時田 信彦
1993 年 41 巻 6 号 p.
1144-1148
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
Microcapsules of hygroscopic, hyghly water-soluble gadopentetate dimeglumine (Gd-DTPA-DM) for use in preliminary in vivo experiments for neutron-capture therapy were designed. They were prepared with such properties as a particle size small enough to be suspended and injected through a syringe, a negligible release of Gd-DTPA-DM, and a high drug content by means of the Wurster process, a spray coating method using a spouted bed with a draft tube. They were composed of lactose cores of 53-63 μm, an undercoat of ethyl cellulose (EC) and polyvinylpyrrolidone (PVP), a drug-layer of Gd-DTPA-DM, EC and PVP, a waterproof coat and a release-sustaining overcoat of EC and cholesterol (1 : 1), and a surface treated with hydrogenated egg lecithin. By curing at 110°C for 30 min after mixing with 20% pulverized mannitol powder, the 20% overcoating suppressed the release of Gd-DTPA-DM from 75-106 μm microcapsules to less than 10% for the first 20 min, which was the period required to prepare a suspension, inject it and irradiate the neutron. The microcapsules could be used to confirm that the intracellular presence of Gd is not critical in gadolinium neutron-capture therapy.
抄録全体を表示
-
森本 俊明, 千葉 三男, 阿知波 一雄
1993 年 41 巻 6 号 p.
1149-1156
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
Modified DIOPs, (4R, 5R)-4-(diaryl- or dialkylphosphino)methyl-5-(diarylphosphino)methyl-2, 2-dimethyl-1, 3-dioxolanes, were prepared on the basis of our design concept, and used as ligands for the rhodium(I)-catalyzed asymmetric hydrogenations of ketopantolactone, itaconic acid, demethyl itaconate, and β-aryl-substituted itaconic acid derivatives. A neutral rhodium(I)-complex of (4R-trans)-dicyclohexyl[[5-[(diphenylphosphino)methyl]-2, 2-dimethyl-1, 3-dioxolan-4-yl]methyl]phosphine (DIOCP) bearing both a dicyclohexylphosphino group and a diphenylphosphino group was found to be a more efficient catalyst than the original DIOP in the asymmetric hydrogenation of ketopantolactone. Modified DIOPs bearing electron-donating groups at their para positions were efficient ligands for the rhodium(I)-catalyzed asymmetric hydrogenations of itaconic acid and its derivatives; in particular, (4R-trans)-[(2, 2-dimethyl-1, 3-dioxolane-4, 5-diyl)bis(metylene)]bis[bis(4'-methoxy-3', 5'-dimethylphenyl)phosphine] (MOD-DIOP) bearing both a p-methoxy group and two m, m'-methyl groups on each phenyl group showed much higher enantioselectivity and catalytic activity than DIOP.
抄録全体を表示
-
大石 宏文, 小川 雅史
1993 年 41 巻 6 号 p.
1157-1159
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
3, 3'-Dihydroxy-α, β-diethyldiphenylethane (I), 3, 3'-dihydroxy-α, β-diethylstilbene (II), hexestrol (III) and diethylstilbestrol (IV) have already been reported to show hypotensive effects on rats and exhibit phytogrowth-inhibitory activities. We have proposed that two phenolic hydroxyl groups in these compounds are necessary for the biological activities, and a structure-activity relationship for I-related compounds was accomplished using molecular-mechanics (MM) calculations. As a result, the following three findings were obtained; 1) the minimized conformational energy obtained from MM calculatinos, which is a parameter expressing the molecular stability, showed a relatively high correlation with the biological activities, 2) as results of quantitative structure-activity relationship (QSAR) analyses, the combination of the distance between two phenolic hydroxyl oxygens led to the regression equations with high correlation values, and 3) the idealized molecular model of the most active compound (I) showed the highest stability and had a particular conformation which differed from the other compounds (II-IV).
抄録全体を表示
-
吉松 三博, 藤本 三千代, 清水 洋, 堀 幹夫, 片岡 貞
1993 年 41 巻 6 号 p.
1160-1162
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
Generation of α-lithio-Se, O-heteroacetals was accomplished by direct deprotonation of O-methoxyethylselenoacetals with lithium 2, 2, 6, 6-tetramethylpiperidide. Alkylation of the α-lithioheteroacetals smoothly proceeded to give the products 6 and 7. Olefinic Se, O-heteroacetals 6c and 6d were cyclized via α-seleno carbenium ions generated by selective C-O bond cleavage with titanium tetrachloride to provide the cyclohexane derivatives 8a and 8b, respectively.
抄録全体を表示
-
藤原 英俊, 岡林 一蔵
1993 年 41 巻 6 号 p.
1163-1165
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
Pyrido[3', 2' : 5, 6]pyrano[4, 3, 2-de]quinoline (1), which can be regarded as a combined structure of a xanthene analog and quinoline, was synthesized starting from 6-amino-5H-[1]benzopyrano[2, 3-b]pyridin-5-one (2).
抄録全体を表示
-
石井 永, 太田 修治, 西岡 弘美, 林田 直美, 原山 尚
1993 年 41 巻 6 号 p.
1166-1168
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
A convenient and effective transformation of 2-methylbenzofuran (B) to salicylaldehyde (C) was achieved by ozonolysis of B in CH
2Cl
2 at -78°C followed by alkaline hydrolysis.
抄録全体を表示
-
関 宏子, 橋本 彰宏, 日野 亨
1993 年 41 巻 6 号 p.
1169-1172
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
The
1H- and
13C-NMR spectra of harman (2) and N-methylharman (3) have been reinvestigated, and definitive assignments of all the protons and carbons of 2 in CDCl
3, DMSO-d
6, and CD
3OD were obtained by the use of DEPT, HC-COSY (or HMQC), COLOC (or HMBC), and CNOEDIF techniques.
抄録全体を表示
-
関 宏子, 中川 昌子, 橋本 彰宏, 日野 亨
1993 年 41 巻 6 号 p.
1173-1176
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
The
1H- and
13C-NMR spectra of manzamine C (1) and its analogs (2-8) have been analyzed by applying HC-COSY (or HMQC) and COLOC (or HMBC) methods. The slow ring-inversion of the piperidine part in 6 was observed at room temperature. The free energy of activation for interconversion of rotamers in the amide analog (8) was evaluated.
抄録全体を表示
-
村上 啓寿, 白橋 秀明, 永津 明人, 榊原 仁作
1993 年 41 巻 6 号 p.
1177-1179
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
Two unprecedented acyl-distributed glyceroglycolipids have been isolated from the nitrogen-fixing cyanobacterium Anabaena flos-aquae f. flos-aquae. The structures were determined as (2'S)-3', 6-O-diacyl-glyceryl β-D-galactopyranoside (1) and (2'R)-2', 6-O-diacyl-glyceryl β-D-galactopyranoside (2) on the basis of physicochemical evidence. The positional distribution of fatty acid residues was elucidated by enzymatic hydrolysis using Rhizopus arrhizus lipase.
抄録全体を表示
-
木村 敏行, 渡辺 和人, 舘岡 裕二, 近藤 繁美, / 山本 郁男, Ikuo YAMAMOTO
1993 年 41 巻 6 号 p.
1180-1182
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
Central depressant effects in mice of N
3-substituted thymidines (Td) (1) were examined by intracerebroventricular (i.c.v.) injection. Nine derivatives including the methyl, ethyl, propyl, allyl, benzyl, xylyl and α-phenylethyl derivatives at the N
3-position of 1 were synthesized and their pharmacological effects were evaluated by using hypnotic activity, pentobarbital-induced sleep prolongation and locomotor activity as indices for central depressant effects. At a dose of 2.0 μmol/mouse, the values of mean sleeping time induced by N
3-benzylthymidine (6), N
3-o-xylylthymidine (7), N
3-m-xylylthymidine (8), N
3-p-xylylthymidine (9), and N
3-α-phenylethylthymidine (10) were 61, 30, 48, 45 and 23 min, respectively. These derivatives (2.0 μmol/mouse) prolonged pentobarbital-induced (40 mg/kg, i.p.) sleeping time. None of the alkyl (2-4) or allyl (5) derivatives exerted hypnotic activity, although the derivatives tested (2-10) significantly prolonged the pentobarbital-induced sleeping time. Compound 1 and its xylyl derivatives tested (0.25 μmol/mouse, i.c.v.) decreased locomotor activity. These results indicate that thymidine derivatives have central depressant activity, and the benzyl derivatives but not alkyl derivatives possess a hypnotic activity.
抄録全体を表示
-
糸川 秀治, 益山 光一, 森田 博史, 竹谷 孝一
1993 年 41 巻 6 号 p.
1183-1184
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
Five cytostatic sesquiterpenes, desoxo-narchinol-A (1), nardosinone (2), debilon (3), nardosinonediol (4) and kanshone A (5), were isolated from the roots and rhizomes of Nardostachys chinensis (Valerianaceae). The steric structure of 1 was determined by nuclear Overhauser effects (NOEs) and the exciton chirality method. All five showed cytotoxic activity against P-388 cells and the structure-activity relationship of 1 was also discussed.
抄録全体を表示
-
関根 利一, 新井 寧夫, 池上 文雄, 藤井 祐一, 進藤 省一郎, 柳澤 利彦, 石田 優子, / 村越 勇, Isamu MURAKO ...
1993 年 41 巻 6 号 p.
1185-1187
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
A new flavonol glycoside, camelliaside C, was isolated from "tea seed cake" prepared from the defatted seeds of Camellia sinensis O. KUNTZE. The structure was determined as kaempferol 3-O-β-D-galactopyranosyl-(1→2)-β-D-glucopyranoside by spectroscopic methods (FAB-MS, UV, IR,
1H- and
13C-NMR) and the enzymatic transformation of camelliaside C to astragalin. Camelliaside C showed an inhibitory effect on the arachidonate 5-lipoxygenase of RBL-1 cells (IC
50 : 1.4×10
-4 M) as did camelliaside A and B isolated from the same product.
抄録全体を表示
-
太田 俊作, 鎌田 靖弘, 稲垣 貴代, 桝田 縁, 山本 智史, 山下 正行, 川崎 郁勇
1993 年 41 巻 6 号 p.
1188-1190
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
Several N, N-diethyl-2-acylmethylbenzamides (6) were prepared from N, N-diethyl-2-toluamides (4), and the ketoamides (6) were easily cyclized to the corresponding 3-substituted isocoumarins (8) by heating in acetic acid or xylene. This simple procedure was applied to the synthesis of thunberginol A (1), thunberginol B (2), thunberginol F (14), and a key-intermediate (8j) for achlisocoumarin I (3).
抄録全体を表示
-
佃 拓夫, 梅田 勲, 増渕 一直, 白井 道朗, 新間 信夫
1993 年 41 巻 6 号 p.
1191-1193
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
Restrictinol 2 and 9, 10, 11, 12-tetrahydro-7-desmethylrestricticin (Ro 09-1571) have been synthesized from L-glucose. Ro 09-1571 showed improved in vitro antifungal activity and chemical stability as compared with Restricticin 1.
抄録全体を表示
-
吉川 雅之, 福田 陽一, 畠山 祥子, 田中 宣充, 松田 久司, 山原 條二, 村上 啓寿
1993 年 41 巻 6 号 p.
1194-1196
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
Four new sesquiterpenes, sulfoorientalols a, b, c, and d, having a sulfonic acid function were isolated from Chinese Alismatis Rhizoma. Their structures were determined on the basis of chemical and physicochemical evidence. Sulfoorientalols inhibited the contraction of isolated bladder smooth muscle induced by carbachol.
抄録全体を表示
-
吉川 雅之, 村上 啓寿, 井上 泰尚, 黒田 泰行, 北川 勲
1993 年 41 巻 6 号 p.
1197-1199
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
Using a stereoselective nitromethane addition and a reductive elimination of an ethoxyethoxyl moiety with NaBH
4 as key steps, two optically active pseudo-sugars, pseudo-α-D-glucopyranose and pseudo-β-D-glucopyranose, were synthesized from D-glucuronolactone in favorable overall yield. Furthermore, a biologically active pseudo-aminosugar, validamine, was synthesized via a substitution reaction for an acetoxyl group at the β-position of the nitro group in the nitrocyclitol derivative which was prepared from a synthetic intermediate of pseudo-D-glucopyranose.
抄録全体を表示
-
山田 実穂, 板井 昭子
1993 年 41 巻 6 号 p.
1200-1202
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
An efficient automated method of searching for stable docking structures of protein-ligand complex has been developed. The method outputs several promising docking models in which protein and ligand interact favorably, covering all possible binding modes and ligand conformations. Our search method is excellent in terms of not only ease of use and speed of calculation, but also reliability and reproducibility of the docking results. It should become an indispensable tool for investigating biochemical reaction processes and designing new drug structures based on receptor structure.
抄録全体を表示
-
山田 実穂, 板井 昭子
1993 年 41 巻 6 号 p.
1203-1205
発行日: 1993/06/15
公開日: 2008/03/31
ジャーナル
フリー
The method of automated searching for stable docking structures of protein-ligand complex, which is reported in the preceding paper, was applied to a dihydrofolate reductase-inhibitor system. The usefulness of the method was confirmed by the fact that the most stable docking models accurately reproduced the crystal structures of two enzyme-inhibitor complexes.
抄録全体を表示