著者

MARIKO TANOGUCHI MASAO ARIMOTO HIDEYUKI SAIKA HIDEO YAMAGUCHI

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.35, no.10, pp.4162-4168, 1987-10-25 (Released:2009-10-19)

参考文献数

21

被引用文献数

17 29

---

Three kinds of lignans, including a new lignan, named hernolactone, were isolated from the seeds of Hernandia ovigera L. besides six previously reported lignans, desoxypodophyllotoxin (DPT), desoxypicropodophyllin, bursehernin, podorhizol, hernandin and dehydro-DPT. The structure of hernolactone was determined as (2R, 3R) -3- (4′-hydroxy-3′, 5′-dimethoxybenzyl) -2- (3″, 4″, 5″-trimethoxybenzyl) -γ-butyrolactone (IV) and the other two lignans were identified as (-) -yatein ((-) -deoxypodorhizon) (V) and dehydropodophyllotoxin (IX).

著者

井藤 千裕 松井 卓哉 呉 天賞 古川 宏

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.40, no.5, pp.1318-1321, 1992-05-25 (Released:2008-03-31)

参考文献数

12

被引用文献数

10 19

---

6, 7-Demethylenedesoxypodophyllotoxin (1) was isolated from the seeds of Hernandia ovigera L. (Hernandiaceae) collected in Taiwan, together with several known lignans. This is the first example of the occurrence of 1 in a natural source. The assignments of the 13C-nuclear magnetic resonance signals of several podophyllotoxin analogues isolated from this plant were also established by means of two-dimensional H-C correlation spectroscopy (COSY) and H-C long range COSY techniques.

著者

Yoshiaki Kato Kenji Niiyama Hideki Jona Shigemitsu Okada Atsushi Akao Shouichi Hiraga Yoshimi Tsuchiya Koji Tomimoto Toshiaki Mase

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.50, no.8, pp.1066-1072, 2002 (Released:2002-08-01)

参考文献数

16

被引用文献数

6 8

---

An asymmetric synthesis of a selective endothelin A receptor antagonist 1b is described. Asymmetric conjugate addition of aryllithium derived from 18 to the chiral oxazoline 17 followed by hydrolysis afforded 15 in 96% ee via purification as (S)-(−)-1-phenylethylamine salt. Pd(OAc)2/dppf (1,1′-bis(diphenylphosphino)ferrocene) catalyzed carbonylation followed by chemoselective addition of aryllithium derived from 23 which gave ketone 24. Diastereoselective reduction of the ketone with catecholborane followed by concomitant activation of the resulting alcohol and cyclization gave the late intermediate 26. Introduction of amino moiety on the pyridine ring by imidoyl rearrangement followed by deprotection and purification by crystallization furnished the enantiomerically pure target molecule 1b in 8% overall yield from 16.

著者

広田 耕作 丸橋 和夫 浅尾 哲次 千田 重男

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.30, no.9, pp.3377-3379, 1982-09-25 (Released:2008-03-31)

参考文献数

15

被引用文献数

4 8

---

Thermolysis of 6-azido-1, 3-dimethyluracil (1) in formamide gave 1, 3, 6, 8-tetramethylpyrimido [5, 4-g] pteridine-2, 4, 5, 7 (1H, 3H, 6H, 8H)-tetrone (3), while the same reaction in N, N-dimethylformamide (DMF) gave 3-(5-amino-1, 3-dimethyluracil-6-yl)-4, 6-dimethyl-[1, 2, 3] triazolo [4, 5-d] pyrimidine-5, 7 (4H, 6H)-dione (4), which was converted into 3 in refluxing formamide. Compound 4 was also obtained by the treatment of 1 with 4, 6-dimethyl [1, 2, 3] triazolo [4, 5-d] pyrimidine-5, 7 (4H, 6H)-dione (5) in refluxing DMF. The mechanism of these reactions is discussed.

著者

伊藤 豊 矢野 真吾 渡辺 和夫 山中 悦二 相見 則郎 坂井 進一郎

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.38, no.6, pp.1702-1706, 1990-06-25 (Released:2008-03-31)

参考文献数

16

被引用文献数

10 19

---

We investigated the selectivities and structure requirements for alpha-1 and alpha-2 adrenoceptor blocking activities of yohimbine (YO) and its 12 related analogs, such as β-yohimbine (β-YO), dihydrocorynantheine (DHC) and (-)indoloquinolizidine ((-)IQ). The affinity of YO analogs to alpha-adrenoceptor was assessed by measuring their blockade of pressor responses to epinephrine in pithed rats. Among YO structure groups, the potency order was YO>DHC=β-YO>geissoschizine methylether>14β-hydroxy YO>14β-benzoyloxy YO (inactive). (-)IQ was slightly less potent than YO, but much stronger than (+)IQ. Among (±)IQ structure groups, the potency order was (±)IQ>(±)1, 12b-trans-1-hydroxy IQ»(±)1, 12b-cis-1-hydroxy IQ (imactive). (±)Borrerine was active, but (±)desmethylborrerine was inactive. The alpha-1 blocking activities of the four compounds YO, β-YO, DHC and (-)IQ, were assessed in experiments of pressor responses to methoxamine in pithed rats and contractile responses to methoxamine in the rat vas deferens. The potency order was (-)IQ>YO>DHC>β-YO. Furthermore, the alpha-2 blocking activities of the four analogs were assessed in experiments of pressor responses to clonidine and inhibition of electrically driven cardioacceleration by clonidine, in pithed rats. The potency order was YO>β-YO>(-)IQ>DHC. Based on the potency ratio between alpha-1 and alpha-2 blocking activities, DHC or YO was most selective for alpha-1 or alpha-2 subtype, respectively, among the four YO analogs. These results suggest that the A, B, C and D rings of YO analogs and their planarity are necessary for the affinity to alpha-adrenoceptors and that the predominant conformation of the carboxymethyl or hydroxy group on the E ring of YO structure determines the selectivity for alpha-1 and alpha-2 blocking activities.

著者

山中 悦二 成嶋 真弓 犬飼 邦江(旧姓長島) 坂井 進一郎

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.34, no.1, pp.77-81, 1986-01-25 (Released:2008-03-31)

参考文献数

12

被引用文献数

7 13

---

Convenient syntheses of 1, 2, 3, 4, 6, 7, 12, 12b-octahydroindolo[2, 3-α]quinolizine derivatives (4a, b) and a relatd unsaturated lactam (14) are described. The condensation of tryptamine (1) with 8a, b (prepared from 7a, b by decarboethoxylation), followed by treatment with alkali gave the lactams (4a, b), respectively. The stereochemistry of 4b was determined by conversion to the known cis- and trans-compounds (5b). The condensation of 1 with the sulfenylated ester (10), which was prepared in two ways, followed by treatment with alkali gave the lactams (12a, b). Oxidation of 12a, b with m-chloroperbenzoic acid gave the sulfoxides (13) which were heated at 50°C to give the lactams (14, 15) and the pyridone (16).

著者

山中 悦二 丸田 悦子 笠松 里江 相見 則郎 坂井 進一郎 / / TANOMJIT SUPAVITA J. DAVID PHILLIPSON

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.3713-3721, 1986-09-25 (Released:2008-03-31)

参考文献数

21

被引用文献数

4 6

---

Oxidation of the enamine (6) with dibenzoyl peroxide followed by reduction with NaBH4 gave the benzoate (8), which was converted to the cis-hydroxyl compound (9), while hydroboration-oxidation of 6 gave the trans-isomer (11). Treatment of a mixture of the enamines (13 and 14) with dibenzoyl peroxide/NaBH4 gave the benzoates (15 and 16), which were converted to 14α-hydroxy-3-isorauniticine (17) and the acetal (18), respectively. Hydroboration-oxidation of 13 gave 14α-hydroxyrauniticine (2), which was found to be identical with the natural alkaloid whose structure had erroneously been proposed as 14β-hydroxy-3-isorauniticine (4).

著者

Takashi Mano Rodney W. Stevens Kazuo Ando Makoto Kawai Kiyoshi Kawamura Kazunari Nakao Yoshiyuki Okumura Takako Okumura Minoru Sakakibara Kimitaka Miyamoto Tetsuya Tamura

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.53, no.8, pp.965-973, 2005 (Released:2005-08-01)

参考文献数

25

被引用文献数

15 20

---

Structural modification of imidazole 5-lipoxygenase (5-LO) inhibitors for optimizing inhibitory potency, pharmacokinetic behavior and toxicity (ocular) profile led to 4-{3-[4-(2-methyl-1H-imidazol-1-yl)phenylthio]}phenyl-3,4,5,6-tetrahydro-2H-pyran-4-carboxamide (6) with no observable ocular toxicity. The orally active and safe imidazole 5-LO inhibitor 6 was selected as a clinical candidate and advanced to clinical studies. An improved synthesis of 6 is also discussed.

著者

Yoshinori Hashimoto Masato Kono Shingo Harada Tetsuhiro Nemoto

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.66, no.11, pp.1041-1047, 2018-11-01 (Released:2018-11-01)

参考文献数

43

被引用文献数

8

---

We developed the first carbenoid insertion reaction into the urea C−N bond. The urea insertion reaction proceeded smoothly using Rh2(NHPiv)4, a rhodium catalyst previously designed by our group, to construct a diazabicyclic system. Highly functionalized bridged molecules with three adjacent stereocenters were diastereoselectively synthesized via the urea insertion reaction followed by hydride reduction or nucleophilic addition sequences in one-pot.

著者

工藤 恵子 宮原 一元 丸林 信洋 川崎 敏男

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.10, pp.4229-4232, 1984-10-25 (Released:2008-03-31)

参考文献数

16

被引用文献数

6 21

---

The structure of one of the minor compounds, which coexists only with a 25β (S)-spirostanol glycoside (a steroid saponin) such as I, II, XI and XV, was determined to be the corresponding 22β (S)-0, 25α (S) analog Ia, IIa, XIa and XVa, respectively. Since it was believed that all the natural spirostanol glycosides have the 22α (R)-O configuration, these compounds are worthy of note as the first glycosides of 22β (S)-O-spirostanol so far isolated.

著者

阿部 フミ子 長尾 常敦 岡部 光 山内 辰郎 丸林 信洋 上田 幾彦

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.8, pp.2127-2129, 1990-08-25 (Released:2008-03-31)

参考文献数

5

被引用文献数

7 10

---

Parsonsianine, a 14-membered macrocyclic pyrrolizidine alkaloid, composed of retronecine, (2S, 3R)-2, 3-dihydroxy-2-ethylbutanoic acid and (2R, 3S)-2, 3-dihydroxy-2-isopropylbutanedioic acid, was isolated from the leaves of Parsonsia laevigata and the structure was determined by means of nuclear magnetic resonance and X-ray analysis.

著者

新宮 一司 古澤 世理子 丸林 信洋 上田 幾彦 矢原 正治 野原 稔弘

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.10, pp.2866-2867, 1990-10-25 (Released:2008-03-31)

参考文献数

9

被引用文献数

4 7

---

The structure of a new withanolide, (17R, 20R, 22R, 25R)-21, 24R-epoxy-27-methoxy-1-oxowitha-2, 5-dienolide, isolated from the methanolic extract of the fresh aerial parts of Datura metel L. (Solanaceae), was established by X-ray analysis.

著者

Takanobu KUROITA Masamitsu SAKAMORI Takeshi KAWAKITA

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.44, no.4, pp.756-764, 1996-04-15 (Released:2008-03-31)

参考文献数

24

被引用文献数

25 31

---

Several 3-substituted 5-chloro-2-methoxybenzamides were synthesized and evaluated for serotonin-3 (5-HT-3) receptor binding affinity. The 5-HT3 receptor antagonistic activity of zacopride, a representative 5-HT3 receptor antagonist, was unchanged by the replacement of the 4-amino substituent on the aromaitc moiety by a 3-dimethyl-amino substituent. This finding prompted a structural modification of azasetron, another 5-HT3 receptor antagonist. Consequently, a new series of 3, 4-dihydro-2H-1, 4-benzoxazine-8-carboxamides was obtaiend and these compounds were found to be more potent than 3, 4-dihydro-3-oxo-2H-1, 4-bvenzoxazine-8-carboxamids. In particular, (S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-6-chloro-3, 4-dihydro-4-methyl-2H-1, 4-benzoxazine-8-carboxaminde showed a high affinity for 5-HT3 receptors (Ki=0.051 nM) and especially potent antagonistic activity against the von Bezold-Jarisch reflex (ED50=0.089 μg/kg i.v.) in rats.

著者

川北 武志 黒板 孝信 安本 光由 佐野 光春 稲葉 賢一 福田 武美 田原 哲治

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.40, no.3, pp.624-630, 1992-03-25 (Released:2008-03-31)

参考文献数

31

被引用文献数

11 13

---

A series of 3, 4-dihydro-3-oxo-1, 4-benzoxazine-8-carboxamide derivatives was synthesized and evaluated for serotonin-3 (5-HT3) receptor antagonistic activity assessed by their ability to antagonize the von Bezold-Jarish (BJ) effect in rats. Derivatives bearing 1-azabicyclo[2.2.2]oct-3-yl moiety as a basic function attached to the carboxamide at position 8 showed more potent antagonistic activity than those bearing the other three basic moieties. Structure-activity relationships of this series showed that methyl and chloro groups were more effective as substituents at positions 4 and 6, respectively. The representative compound 15 (Y-25130) in this series showed potent antagonistic activity on the BJ effect (ED50=1.3μg/kg i.v.), high affinity for 5-HT3 receptor (Ki=2.9nM) and complete protection against cisplatin-induced emesis in dogs at a dose of 0.1mg/kg i.v.

著者

Takanobu KUROITA Nobuhiro MARUBAYASHI Mitsuharu SANO Kouji KANZAKI Kenichi INABA Takeshi KAWAKITA

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.44, no.11, pp.2051-2060, 1996-11-15 (Released:2008-03-31)

参考文献数

29

被引用文献数

21 29

---

A series of 3, 4-dihydro-2H-1, 4-benzoxazine-8-carboxamide derivatives was synthesized and evaluated for serotonin-3 (5-HT3) receptor antagonistic activities by means of assays of 5-HT3 receptor binding and the ability to antagonize the von Bezold-Jarisch reflex in rats. Replacement of the 1, 4-benzoxazine ring with a 1, 4-benzthiazine ring or seven-membered ring (i.e., 1, 5-benzoxepine or 1, 5-benzthiepine) resulted in decreased affinity for 5-HT3 receptor. Introduction of substituents at the 2 position of the 1, 4-benzoxazine ring increased the antagonistic activities (dimethyl>methyl>dihydro>phenyl). The compounds bearing a 9-methyl-9-azabicyclo[3.3.1]non-3-yl moiety as the basic part of 3, 4-dihydro-2H-1, 4-benzoxazine-8-carboxamide derivatives were equipotent to those bearing 1-azabicyclo[2.2.2]oct-3-yl moiety. The 9-methyl-9-azabicyclo[3.3.1]non-3-yl moiety was confirmed to adopt a boat-chair conformation on the basis of both NMR studies and X-ray analysis. In this series, endo-6-chloro-3, 4-dihydro-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-2, 2, 4-trimethyl-2H-1, 4-benzoxazine-8-carboxamide showed the highest affinity for 5-HT3 receptors (Ki=0.019 nM), and a long-lasting 5-HT3 receptor antagonistic activity as evidenced by antagonism to the von Bezold-Jarisch reflex in rats. Such a long-lasting 5-HT3 receptor antagonism would be attributed to the introduction of both two methyl groups at the 2 position of the benzoxazine ring and the 9-methyl-9-azabicyclo[3.3.1]non-3-yl moiety, which adopts the boat-chair conformation.

著者

富岡 清 河崎 久 古賀 憲司

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.7, pp.1898-1901, 1990-07-25 (Released:2008-03-31)

参考文献数

14

被引用文献数

3 4

---

Demethyl derivatives of steganes and deoxypodorhizon, 3, 4, 6, 7, 9, 10, 12, 13, 18, 23, were prepared by the selective demethylation of the methoxy group of steganes and deoxypodorhizon, 2, 5, 8, 11, 22. The cytotoxicity of these derivatives was evaluated against KB cell and was found not to exceed that of the parent steganes. 4-Demethyldexypodorhizon (18) was found to show more potent cytotoxicity than deoxypodorhizon (22).

著者

岡野 耕二 水原 由加子 末宗 洋 秋田 弘幸 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.36, no.4, pp.1358-1365, 1988-04-25 (Released:2008-03-31)

参考文献数

9

被引用文献数

5 10

---

During a detailed examination on the cyclization of 1, 4-diketones to cyclopentenones, we have found that two oxygenated products (4 and 5) are formed when the purification by column chromatography on silica gel takes a long time. The highly functionalized cyclopentenone (4a) obtained as the major product in this manner seems to be an attractive synthon for the synthesis of natural products. For eaxmple, the chiral synthon (1S, 4S)-4-benzyloxycarbonyl-1, 4-dihydroxy-2-methoxycarbonyl-3-methyl-2-cyclopentene ((+)-7) with high optical purity was obtained by microbial reduction with Rhodotorula rubra CCY 20-7-1, and the absolute stereochemistry was established independently by using the exciton chirality method and the chemical method.

著者

HIROSHI SUEMUNE YUKAKO MIZUHARA HIROYUKI AKITA TAKESHI OISHI KIYOSHI SAKAI

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.35, no.8, pp.3112-3118, 1987-08-25 (Released:2009-10-19)

参考文献数

16

被引用文献数

9 15

---

Asymmetric synthesis of platelet-activating factor (PAF) and its enantiomer by using biocatalysts was studied. Microbial reduction of the pro-chiral α-ketoester (3) afforded (+) -4 (> 99% ee), which could be converted to (+) -and (-) -batyl alcohol (12), a key synthetic intermediate for PAF. Compound (-) -4 (96% ee), with the requisite configuration for the synthesis of natural PAF, could also be obtained by enzyme-catalyzed enantioselective hydrolysis of (±) -15.

著者

末宗 洋 水原 由加子 秋田 弘幸 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.8, pp.3440-3444, 1986-08-25 (Released:2008-03-31)

参考文献数

12

被引用文献数

24 44

---

An enzymatic synthesis of 2, 3-O-isopropylidene-sn-glycerol (10), the synthetic key intermediate for platelet-activating factor, was achieved. Several 1, 3-di-O-acyl-2-benzylglycerols (5a-d) were synthesized from dihydroxyacetone dimer (2), and subjected to enzyme-catalyzed asymmetric hydrolysis. The optical purities of the mono-hydrolyzed products (6) were determined from the 400 MHz proton nuclear magnetic resonance spectra after conversion of 6 to the esters of (-)α-methoxy-α-trifluoromethylphenylacetic acid. Upon hydrogenolysis of the benzyl ether, followed by protection of diol and hydrolysis of the acetate, (-)-6a afforded 10.

著者

上野 貢嗣 末宗 洋 佐伯 清太郎 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.33, no.9, pp.4021-4025, 1985-09-25 (Released:2008-03-31)

参考文献数

13

被引用文献数

10 15

---

The conversion of naturally abundant (+)-limonen-10-ol (2) into the synthetic intermediate (3) for brefeldin A is described. The cis-3, 4-disubstituted cyclopentanone (4), which was easily obtained from 2 by Rh (I)-catalyzed cyclization reaction via the 4-pentenal derivative, could be converted to the target compound 3 via the appropriate modification of substituents on the five-membered ring.