著者

津島 忠 TADASHI TSUSHIMA

出版者

西京大学

雑誌

西京大学学術報告 理学及び家政学 (ISSN:03709310)

巻号頁・発行日

vol.2, no.5, pp.153-159, 1958-10

---

(1)本研究は道具的条件反応事態における賞罰組合せの効果を, Skinner boxタイプのCrowder-boxを使用して究明したものである。(2)第1実験に於ては, 100%の連続強化群(第1群)の消去抵抗と, 賞(70%)罰(30%)の組合せの実験群(第2群)の消去抵抗とは, 危険率1%レベルに於て, 第2群の消去抵抗が強い事が明らかにされた。(3)第2実験に於ては, 70%の部分強化群(第3群)の消去抵抗と, 70%のプラスの強化, 15%のマイナスの強化, 15%の無強化を受けた群(第4群)の消去抵抗が比較され, 両者の間に有意差を見出さなかった。(4)第2実験の両群の消去抵抗を, 第1実験の両群のそれと比較した所, 次の結果を得た。(A)第3群(70%の部分強化群)の消去抵抗は, 第1群(統制群)の消去抵抗よりも大きく, 5%レベルに於て有意差が見出された。(B)第4群(70%のプラスの強化, 15%のマイナスの強化, 15%の無強化)の消去抵抗も第1群の消去抵抗よりも大きく, 1%レベルに於て有意差が見出された。(C)第2群, 第3群, 第4群の消去抵抗の間には有意差がなかった。(5)賞罰組合わせの消去抵抗に於てみられる効果の考察から, 消去抵抗を学習或は, 習慣の強度sH_Rの評価基準とするHull流の考え方に, 決定的な疑問を投じた。(6)賞罰による消去抵抗強化の現象に就ての説明理論としては, 現在のところ(A)道具的条件反応事態における消去抵抗の中に実験神経症的な傾向を認め, 適応能力の硬さを考える筆者の立場と, (B) fearとhopeの条件づけの, 夫々の消去の仕方が異り, それらが合併し, より強く, 且つ, 不規則な消去抵抗として現われると見るであろうところのMowrer理論が挙げられる。但しこれらは何れ一つの説明理論として止揚せられるべきものであると考える。

著者

岡田 哲夫 江角 清志 山川 眞透 佐藤 久夫 辻 照二 津島 忠彦 元川 清司 小松 良英

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.41, no.1, pp.126-131, 1993-01-15 (Released:2008-03-31)

参考文献数

25

被引用文献数

19 24

---

Quantitative structure-activity relationships (QSAR) of various 7-(3-substituted-azetidin-1-yl)-1-cyclopropyl-6, 8-difluoro-1, 4-dihydro-4-oxoquinoline-3-carboxylic acids, 14-25, were studied to clarify the structural requirements for 3-substituted azetidines to potentiate antibacterial activity. A good parabolic relationship seemed to exist between the relative mean antibacterial activity indices against five representative gram-negative bacteria, GNM, and the calculated hydrophobic parameters, CLOG P, of these molecules. The CLOG P value of the most potent derivative was predicted to be around 2.3. On the other hand, against five representative gram-positive bacteria, the relative mean antibacterial activity indices, GPM, remained high and rather constant regardless of structural variation in the azetidine moiety. In order to confirm these findings, the QSAR analysis was extended with success to the quinolonecarboxylic acids, 26-34, which bear various substituted pyrrolidine, piperazine and piperidine derivatives instead of azetidines. The findings showed that the introduction of any amide substituent group to these heterocyclic amine moieties would lead to marked decrease in GNM, whereas incorporation of some amino substituent groups at a position two or three carbons remote from the N-1 position resulted in great enhancement of GNM. As azetidine quinolones exhibited somewhat low in vivo antibacterial activities, possibly reflecting their lesser bioavailability, we finally selected 3-amino-4-methoxypyrrolidine as one of the most promising C-7 substituent groups based on our QSAR analysis.

著者

岡田 哲夫 佐藤 久夫 辻 照二 津島 忠彦 中井 博 吉田 正 松浦 眞三

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.41, no.1, pp.132-138, 1993-01-15 (Released:2008-03-31)

参考文献数

12

被引用文献数

13 19

---

A new series of quinolone derivatives 3a-I bearing 3-amino-4-methoxypyrrolidines of different configurations and chirality were synthesized and their antibacterial activities as well as some of their toxicological properties were examined. As predicted by our previous quantitative structure-activity relationships (QSAR) analysis of C-7 heterocyclic amine substituted quinolonecarboxylic acid antibacterial agents, these pyrrolidine derivatives showed higher in vitro and in vivo antibacterial activities against both gram-positive and gram-negative bacteria than the analogs bearing various 3-substituted azetidines. Furthermore, the amino and methoxy substituent groups on the pyrrolidine ring exhibited strong configurational and chiral effects on the in vitro and in vivo antibacterial activities of these compounds : (1) cis compounds showed higher antibacterial activities against most of the pathogens examined : (2) N-methylation of the 3-amino group on the pyrrolidine ring lowered in vitro but not in vivo antibacterial activities, particularly leading to superior in vivo anti-pseudomonal activity; (3) the (3'S, 4'R)-derivative showed substantially higher activity that the (3'R, 4'S)-one. These findings led to the selection of compound 3k for further evaluation as it possessed the highest in vivo antibacterial activity and no cytotoxicity.