著者

加納 日出夫 足達 郁夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.16, no.1, pp.117-125, 1968-01-25 (Released:2008-03-31)

被引用文献数

6 12

---

Nine bicyclic isoxazolines (IVa-g and Va-b) were prepared by 1, 3-dipolar cycloaddition of nitrile oxides to the following heterocyclic olefins : 2, 3-and 2, 5-dihydrofurans, 5-methyl-2, 3-dihydrofuran, 2, 3-dihydropyran, and N-acetyl-2-piperidein. Acid-catalized cleavage of IVa-d gave the corresponding 4-substituted 3-phenylisoxazoles (VIa-c and IIIg). Nine 4-aminoalkyl-3-phenylisoxazoles (IIIa-i) were prepared for pharmacological testings in comparison with those of 3- and 5-aminoalkyl analogs (I and II). Base-catalized cleavage of the adducts (IVa-c and Va) was also investigated and in some cases the lactones (XIIa and XIIb) were obtained besides the isoxazoles (VIa and VIb). In this connection the Hofmann reactions of the bicyclic isoxazoline-3-carbon-amides (IVe'and IVf') were studied.

著者

足達 郁夫 加納 日出夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.17, no.11, pp.2201-2208, 1969-11-25 (Released:2008-03-31)

被引用文献数

5 12

---

Ring opening reactions with some bases were examined in the following quaternary salts : 2-ethyl-3, 4-diphenylisoxazolium chloroferrate (V), and 2, 4-dimethyl-3-phenyl-, 3, 4-diphenyl-2-methyl- and 2-methyl-3-phenylisoxazolium perchlorate (IXa, b and c). Treatments of V and IX with sodium alcoholate in alcohol gave the corresponding alkyl cinnamates (VIIa-e). By the use of aqueous sodium hydroxide, V and IXb gave the respective cinnamic anhydrides (Xa and b) contrary to the report of Kohler, et al., and IXa gave an unexpected product, 2, 5-diphenyl-1, 3, 4-trimethylpyrrole (XIa) along with usual ring cleaved products, XIIa and XIIIa. Reactions of IXa, b with several amines gave β-keto acid amides (XIIc-h), the ketones (XIIIa, b) and the pyrrole (XIa) (only from IXa), respectively. Reactions of IXa with Grignard reagents gave 5-substituted △3-isoxazolines (XIVa, b). Similar 5-amino-△3-isoxazolines (XVa-c) were obtained by cautious treatment of IXa, b with piperidine or morpholine. Solvolysis of X, XIV and XV were also investigated, and a tentative mechanism for the formation of the various products are presented.

著者

足達 郁夫 宮崎 理慧 加納 日出夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.22, no.1, pp.70-77, 1974-01-25 (Released:2008-03-31)

被引用文献数

16 29

---

Synthesis and thermal-reaction of 4-isoxazolines were investigated. Reaction of 3-unsubstituted isoxazolium salts with sodium borohydride yielded the corresponding 4-isoxazolines and their borane complexes together with β-hydroxyaminopropiophenone derivatives. Analogous reaction of 5-unsubstituted isoxazolium salt yielded two isomeric products, 4- and 3-isoxazoline derivatives. The 3-isoxazoline derivative underwent further reduction to give isoxazolidine derivatives. Thermal-conversion of some 4-isoxazolines and their borane complexes into 2-acylaziridine derivatives is also reported.

著者

Kazutaka Tachibana Ikuhiro Imaoka Takuya Shiraishi Hitoshi Yoshino Mitsuaki Nakamura Masateru Ohta Hiromitsu Kawata Kenji Taniguchi Nobuyuki Ishikura Toshiaki Tsunenari Hidemi Saito Masahiro Nagamuta Toshito Nakagawa Kenji Takanashi Etsuro Onuma Haruhiko Sato

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.57, no.10, pp.1178, 2009-10-01 (Released:2009-10-03)

著者

Takuya Shiraishi Shojiro Kadono Masayuki Haramura Hirofumi Kodama Yoshiyuki Ono Hitoshi Iikura Tohru Esaki Takaki Koga Kunihiro Hattori Yoshiaki Watanabe Akihisa Sakamoto Kazutaka Yoshihashi Takehisa Kitazawa Keiko Esaki Masateru Ohta Haruhiko Sato Toshiro Kozono

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.58, no.1, pp.38-44, 2010-01-01 (Released:2010-01-01)

参考文献数

29

被引用文献数

1

---

Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is regarded as a promising target for developing new anticoagulant drugs. In previous reports, we described a S3 subsite found in the X-ray crystal structure of compound 2 that bound to FVIIa/soluble tissue factor (sTF). Based on the X-ray crystal structure information and with the aim of improving the inhibition activity for FVIIa/TF and selectivity against other serine proteases, we synthesized derivatives by introducing substituents at position 5 of the indole ring of compound 2. Among them, compound 16 showed high selectivity against other serine proteases. Contrary to our expectations, compound 16 did not occupy the S3-subsite; X-ray structure analysis revealed that compound 16 improved selectivity by forming hydrogen bonds with Gln217, Thr99 and Asn100.

著者

Kazutaka Tachibana Ikuhiro Imaoka Takuya Shiraishi Hitoshi Yoshino Mitsuaki Nakamura Masateru Ohta Hiromitsu Kawata Kenji Taniguchi Nobuyuki Ishikura Toshiaki Tsunenari Hidemi Saito Masahiro Nagamuta Toshito Nakagawa Kenji Takanashi Etsuro Onuma Haruhiko Sato

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.56, no.11, pp.1555-1561, 2008-11-01 (Released:2008-11-01)

参考文献数

21

被引用文献数

14 20

---

The 3-(4-cyano-3-trifluoromethylphenyl)-5,5-dimethylthiohydantoin derivatives which have carboxy-terminal side chains were synthesized and their agonistic/antagonistic activities against androgen receptor (AR) measured. Among them, compound 13b showed antagonistic activity (IC50=130 nM) with no agonistic activity even at 10000 nM. This compound exhibited significant metabolic stability and oral antiandrogenic activity (ED50=7 mg/kg).

著者

樫原 宏 篠木 浩 末宗 洋 酒井 浄

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.34, no.11, pp.4527-4532, 1986-11-25 (Released:2008-03-31)

参考文献数

16

被引用文献数

6 11

---

During the course of synthetic studies on the 5, 6-disubsituted 4-oxo-tetrahydro-2-pyroneskeleton in connection with biologically active compounds, we have found a convenient procedure for the regioselective introduction of a double bond in methyl alkyl ketones and a novel synthetic method for indan derivatives.

著者

藤井 郁雄 阿部 昌之 早川 謙二 兼松 顕

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.32, no.11, pp.4670-4673, 1984-11-25 (Released:2008-03-31)

参考文献数

5

被引用文献数

2 4

---

3, 4-Dimethoxy trans-6-morphinanone (1) and its cis isomer (2) were prepared stereoselectively from thebaine (3) and dihydrocodeinone (9), respectively. A general way of spectrally differentiating between these two stereoisomers is discussed.

著者

本田 昌徳 上田 義隆 杉山 重夫 古森 徹哉

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.39, no.6, pp.1385-1391, 1991-06-25 (Released:2008-03-31)

参考文献数

24

被引用文献数

12 20

---

A cerebroside, 1-O-(β-D-galactopyranosyloxy)-(2S, 3S, 4R, 6E)-2-[(R)-2-hydroxytetracosanoylamino]-17-methyl-6-octadecene-3, 4-diol (2), was asymmetrically synthesized from isobutyraldehyde. On the basis of a comparison of the physical data, the absolute structure of a new cerebroside 1b from a Chondropsis sp. sponge is thought to be the same at that of 2.

著者

宮内 正雄 笹原 邦宏 藤本 光一 川本 勲 井手 純也 中尾 英雄

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.37, no.9, pp.2369-2374, 1989-09-25 (Released:2008-03-31)

参考文献数

21

被引用文献数

10 9

---

The degradation kinetics of pivaloyloxymethyl (POM) esters of cephalosporins in phosphate buffer solution (pH6-8) were investigated. The degradation of the starting Δ3 cephalosporin ester proceeded mainly via isomerization to the Δ2 ester and subsequent hydrolysis to the Δ2 acid. Hydrolysis to the Δ3 acid (the parent acid) was very slow. Analysis of the rate constants indicated that the isomerization rate k12 was approximately equal to the apparent degradation rate of the Δ3 ester kdeg, and slower than the hydrolysis rate of the Δ2 ester k24. The isomerization process to the Δ2 ester was found to be the rate-determining step in the degradation of cephalosporin esters. The substituent at the C-3 position of the cephalosporins affected the degradation kinetics. The degradation was accelerated by increase of pH, buffer concentartion and added protein.

著者

宮内 正雄 栗原 英志 藤本 光一 川本 勲 井手 純也 中尾 英雄

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.37, no.9, pp.2375-2378, 1989-09-25 (Released:2008-03-31)

参考文献数

17

被引用文献数

1 2

---

The effect of substituents at the C-3 position on the degradation kinetics of the pivaloyloxymethyl (POM) ester of Δ3 cephalosporin in phosphate buffer solution (pH6-8) was investigated. In the degradation, the isomerization process to the Δ2 ester was the rate-determining step. In this study, the logarithm of the isomerization rate to the Δ2 ester (log k12) correlated with the carbon-13 unclear magnetic resonance chemical shift difference value at C-3 and C-4 of the Δ3 ester (Δδ(4-3)). The energy level of the lowest unoccupied molecular orbital (LUMO) of the Δ3 esters also correlated with log k12. The electronic properties at the C-2 position had no effect on the isomerization reaction. On the other hand, the logarithm of the isomerization rate back to the Δ3 ester (log k21) correlated with the van der Waals volume (MV) of the 3-substituent. These results show that the substituent at the C-3 position influences mainly the electronic structure of the conjugated π-bond system (C3=C4-C4=O) and consequently affects the feasibility of isomerization to the Δ2 ester, i.e., the stability to degradation.

著者

中尾 英雄 荒川 順生 中村 隆洋 福島 正美

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.20, no.9, pp.1968-1979, 1972-09-25 (Released:2008-03-31)

被引用文献数

24 31

---

A series of 2, 5-bis (1-aziridinyl)-p-benzoquinone derivatives were synthesized and evaluated as antileukemic agents. The most active compounds against lymphoid leukemia L-1210 in BDF1 mice were 2, 5-bis (1-aziridinyl)-3-(2-carbamoyloxyethyl-1-methoxy)-6-methyl-p-benzoquinone, carbazilquinone (7), and related compounds (8, 23 and 24). Structure-activity relationships were discussed.

著者

中尾 英雄 荒川 順生

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.20, no.9, pp.1962-1967, 1972-09-25 (Released:2008-03-31)

被引用文献数

8 13

---

A series of p-benzoquinone derivatives having one or two carbamoyloxyalkyl groups in the 2 and/or 5-positions were synthesized and evaluated as antileukemic agents. Among these compounds 2, 5-bis (1-aziridinyl)-3-(2-carbamoyloxyethyl)-6-methyl-p-benzoquinone (21) showed high activity against lymphoid leukemia L-1210 in BDF1 mice.

著者

斉藤 仁 好川 博 西村 吉雄 近藤 信一 竹内 富雄 梅澤 濱夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.34, no.9, pp.3741-3746, 1986-09-25 (Released:2008-03-31)

参考文献数

11

被引用文献数

17 25

---

D-(and L-)2, 6-Dideoxy-2-aminoglycosidic variants of 4'-O-demethyl-1-epipodophyllotoxin were synthesized by glycosidation of 4'-O-benzyloxycarbonyl- or 4'-O-chloroacetyl-4'-O-demethyl-1-epipodophyllotoxin (6 or 14) with the corresponding aminosugar derivatives. 1-O-(2-Amino-2-deoxy-4 : 6-O-ethylidene-β-D-glucopyranosyl)-4'-O-demethyl-1-epipodophyllotoxin (18) reacted with aldehydes in the presence of sodium cyanoborohydride, or reacted with α, β-unsaturated esters, or with α, β-unsaturated nitriles to yield the corresponding N-alkyl analogs. A number of the 4'-O-demethyl-1-epipodopyllotoxin β-D-aminoglycoside derivatives gave significant survival time increases in mice with leukemia L-1210. In particular, 1-O-(2-dimethylamino-2-deoxy-4 : 6-O-ethylidene-β-D-glucopyranosyl)-4'-O-demethyl-1-epipodophyllotoxin (19) showed superior activity to VP-16-213 (etoposide, 1).

著者

AKIO NISHIURA TERUO MURAKAMI YUTAKA HIGASHI NOBORU YATA

出版者

The Pharmaceutical Society of Japan

雑誌

Journal of Pharmacobio-Dynamics (ISSN:0386846X)

巻号頁・発行日

vol.10, no.3, pp.135-141, 1987 (Released:2008-02-19)

参考文献数

22

被引用文献数

10 12

---

The mechanism of interorgan variation in tissue distribution of quinidine was investigated from a viewpoint of binding characteristics to phospholipids and the composition of phospholipids in various tissues. The order of binding of quinidine to an individual standard phospholipid, expressed as a product of the association constant (K) and the number of binding sites (n), was : phosphatidyl ethanolamine (PhE)<dipalmitoyl phosphatidyl choline (saturated PhC)≥phosphatidyl choline (unsaturated PhC)<phosphatidyl inositol (PhI)<phosphatidyl glycerol (PhG)<phosphatidic acid (PhA)<phosphatidyl serine (PhS). Thus, quinidine was found to bind preferentially to acid phospholipids such as PhS, PhA, PhG, and PhI. The greatest binding was obtained in PhS among the various phospholipids and was more than 300-fold that of neutral phospholipids such as PhC and PhE. The concentration of individual components of phospholipids in the lung, kidney, liver and heart was determined using a two dimensional thin-layer chromatography. The concentration of PhS, highly responsible for the quinidine binding to phospholipids in each tissue, was ranked in the following order : heart<liver<kidney<lung. The contribution of PhS to quinidine binding was more than 86% in all tissues. A good correlation between the concentration of PhS in each tissue and the Ct/Cp ratio in vivo was obtained (r=0.984). Thus, it was concluded that the tissue distribution of quinidine in vivo depended on the composition of phospholipids in tissues and that a determinant of interorgan variation in the tissue distribution of quinidine was the concentration of PhS in the tissues.

著者

堀 耕造 野村 敬一 数野 秀樹 吉井 英一

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.38, no.6, pp.1778-1780, 1990-06-25 (Released:2008-03-31)

参考文献数

15

被引用文献数

3 4

---

L-Rhamnal has been transformed into the tetrahydrofuran subunits (14 and 21) of tetronasin (ICI-139603) (1) and tetronomycin (2), in which the three chiral centers at the 2- and 5-positions and the methoxy-bearing carbon are of mirror image.

著者

渡辺 淳 岡部 博 溝尻 顕爾 中島 善次 菅野 浩一 山本 隆一

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.27, no.5, pp.1075-1084, 1979-05-25 (Released:2008-03-31)

被引用文献数

1

---

The drug was well absorbed from the intestinal tract, and the bulk of it was excreted in the urine and feces. Biliary excretion was significant, and the existence of enterohepatic circulation was considered likely. After intravenous injection, elimination of radioactivity from the blood and various tissues, except for fat, was rapid for 2 hr, then became slower. Elimination of unchanged drug from the blood was very fast. Repeated oral doses did not changed the excretion and distribution features as compared to a single oral dose. Significant accumulation of radioactivity was not caused by repeated doses of 14C-labeled perisoxal. Three oxidized metabolites, p-hydroxyperisoxal, m-hydroxyperisoxal and 4-hydroxyperisoxal, were identified. Excretion of hydroxyperisoxals in the urine (free and conjugates) was greater than that of perisoxal itself.

著者

Maya Fujita Takaki Yagi Umi Okura Jun’ichi Tanaka Naohide Hirashima Masahiko Tanaka

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.41, no.5, pp.786-796, 2018-05-01 (Released:2018-05-01)

参考文献数

49

被引用文献数

9

---

Although calcineurin is abundantly expressed in the nervous system and involved in neurite extension and synaptic plasticity in neurons, little is known about its roles in glial cells. To investigate the roles of calcineurin in glial cells, we generated glial calcineurin B1-conditional knockout (CKO) mice and analyzed the abnormalities in the small intestine. The CKO mice were generated by crossing floxed calcineurin B1 mice with glial fibrillary acidic protein (GFAP)-Cre mice. The CKO mice exhibited growth retardation approximately from the third postnatal week and died mostly within the fourth postnatal week. The small intestine of the CKO mice was thin and hemorrhagic. The mucosal layer was degenerated and GFAP expression was reduced in the CKO small intestine. These pathological changes were associated with inflammation and increased intestinal permeability. In contrast, no apparent abnormalities were observed in the large intestine of the CKO mice. Nuclear factor of activated T cells failed to translocate into the nucleus after stimulation in enteric glial cells of the CKO small intestine. In conclusion, the calcineurin B1 deficiency in glial cells impairs the small intestine and leads to malnutrition and eventual death in mice, suggesting that calcineurin plays a novel and important role in enteric glial cells.

著者

山下 純一 安本 三治 橋本 貞夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.31, no.11, pp.3872-3877, 1983-11-25 (Released:2008-03-31)

参考文献数

19

被引用文献数

3 4

---

The mechanism of the condensation of 5-fluorouracil and 2-acetoxytetrahydrofuran (3), giving 1-(tetrahydro-2-furyl)-5-fluorouracil, was studied. An equilibrium between 2-acetoxytetrahydrofuran (3) and 2, 3-dihydrofuran (4) was observed at 120-170°C in dimethylformamide. It was found by the use of 1, 3-dideuterio-5-fluorouracil that the condensation of 5-fluorouracil with 3 occurred both by direct substitution and by the formation of 4 from 3 followed by addition of the uracil to it. The contribution of the latter path increased with increase of the reaction temperature.

著者

岩波 勝 前田 哲哉 藤本 正治 長野 嘉信 長野 憲昭 山崎 敦城 柴沼 忠夫 玉沢 一晴 矢野 邦一郎

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.28, no.9, pp.2629-2636, 1980-09-25 (Released:2008-03-31)

参考文献数

14

被引用文献数

11 16

---

A novel intramolecular rearrangement of isothiazolethioacetamides into 1, 3-dithietanecarboxamides is described, together with the synthesis of a new cephamycin derivative (YM-09330) having a 1, 3-dithietane structure at the 7β-position. This compound showed strong antibacterial activity, especially against gram-negative organisms.