Amphoteric Drugs. I. Synthesis and Antiallergic Activity of [4-(Diphenylmethoxy)piperidino]-, [4-(Diphenylmethyl)piperazinyl]-and [4-(Diphenylmethylene)piperidino]alkanoic Acid Derivatives
スポンサーリンク
概要
- 論文の詳細を見る
A simple method of transforming classical antihistaminics into nonsedative antiallergic agents with strong effects in rat models is described. Various [4-(diphenylmethoxy)piperidino]- (series A), [4-(diphenylmethyl)piperazinyl]- (series B) and [4-(diphenylmethylene)piperidino]alkanoic acid derivatives (series C) were synthesized and examined for antiallergic activities and effects on the central nervous system (CNS), in comparison with the corresponding N-methyl derivatives (1a-c). N-Alkylcarboxylic acids (5a-c) showed stronger ingibitory effects on compound 48/80-induced lethality in rats than the corresponding N-methyl derivatives (1a-c). In particular, N-alkylcarboxylic acids (5a) in series A exhibited approximately 100-fold stronger inhibitory effects than 1a, and were the least effective in prolonging the sleeping time on hexobarbital-induced anesthesia in mice in all series. As a result of chemical modification in series A, it was found that introduction of a methyl group at the para-position on one benzene ring in the (diphenylmethoxy)piperidine system effectively reduced CNS side-effects without reducing antiallergic activityl. (+)-3-[4-[(4-Methylphenyl)phenylmethoxy]piperidino]propionic acid ((+)-5l), an optically active isomer of 5l, exhibited a stronger antiallergic effect (ED_<50>=0.17mg/kg, p.o.) than ketotifen and terfenadine in the 48h homologous passive cutaneous anaphylaxis (PCA) test, and moreover exhibited no CNS side-effects, such as prolongation of the sleeping time on hexobarbital-induced anesthesia, at an oral dose of 30mg/kg. Compound (+)-5l was thus proved to be a promising candidate as a nonsedative antiallergic agent.
- 社団法人日本薬学会の論文
- 1994-11-15
著者
-
加藤 日出男
北陸製薬株式会社
-
大橋 徹生
北陸製薬株式会社
-
小川 信男
北陸製薬株式会社中央研究所研究開発本部
-
安田 信吾
北陸製薬株式会社中央研究所研究開発本部
-
岩崎 信彦
Research and Development Division, Hokuriku Seiyaku Co., Ltd.,
-
坂口 順
Research and Development Division, Hokuriku Seiyaku Co., Ltd.,
-
大橋 徹生
Research and Development Division, Hokuriku Seiyaku Co., Ltd.,
-
小川 信男
Research and Development Division, Hokuriku Seiyaku Co., Ltd.,
-
安田 信吾
Research and Development Division, Hokuriku Seiyaku Co., Ltd.,
-
越中 栄一
Research and Development Division, Hokuriku Seiyaku Co., Ltd.,
-
加藤 日出男
Research and Development Division, Hokuriku Seiyaku Co., Ltd.,
-
伊藤 安夫
Research and Development Division, Hokuriku Seiyaku Co., Ltd.,
-
澤西 啓之
the First Division of the Research Laboratory for Development of Medicine, Hokuriku University
-
高原 栄二
Research and Development Division, Hokuriku Seiyaku Co., Ltd.,
-
岩崎 信彦
Research And Development Division Hokuriku Seiyaku Co. Ltd.
-
坂口 順
Research And Development Division Hokuriku Seiyaku Co. Ltd.
-
高原 栄二
Research And Development Division Hokuriku Seiyaku Co. Ltd.
-
澤西 啓之
北陸大・薬
-
澤西 啓之
The First Division Of The Research Laboratory For Development Of Medicine Hokuriku University
-
越中 栄一
Research And Development Division Hokuriku Seiyaku Co. Ltd.
-
伊藤 安夫
Research And Development Division Hokuriku Seiyaku Co. Ltd.
-
加藤 日出男
北陸製薬株式会社中央研究所
関連論文
- 気管支喘息治療薬ツロブテロールの経皮吸収型製剤の開発
- 232 新規TXA_2/LTD_4デュアル拮抗薬RS-601の抗喘息作用
- Benzenesulfonamide誘導体の合成とThromboxane A_2及びLeukotriene D_4に対するDual拮抗作用
- Amphoteric Drugs. II. Synthesis and Antiallergic Activity of [4-(5H-Dibenzo[a, d]cycloheptan-5-ylidene)piperidino]alkanoic Acid Derivatives and Related Compounds
- Amphoteric Drugs. I. Synthesis and Antiallergic Activity of [4-(Diphenylmethoxy)piperidino]-, [4-(Diphenylmethyl)piperazinyl]-and [4-(Diphenylmethylene)piperidino]alkanoic Acid Derivatives
- Transport Mechanism of an H_1-Antagonist at the Blood-Brain Barrier : Transport Mechanism of Mepyramine Using the Carotid Injection Technique
- 医薬品の両性イオン化(第3報)1,2,3,4,10,14b-Hexahydrodibenzo-[c, f]pyrazino[1,2-α]azepine及び2,3,4,9-Tetrahydro-1H-dibenzo[3,4 : 6,7]cyclohepta[1,2-c]pyridineのN-Alkylcarboxylic Acid誘導体の合成とその薬理作用
- Study on Zwitter-Ionization of Drugs. II. Synthesis and Pharmacological Activity of Some N-[3-(5H-Dibenzo[a, d]cyclohepten-5-ylidene)propyl]-N-methylamino- and N-[3-(6H-Dibenz[b, e]oxepin-11-ylidene)propyl]-N-methylamino-alkanoic Acid Derivatives and Rela
- INTER-INDIVIDUAL DIFFERENCES OF (+)-4-[4-(4-METHYLPHENYL)PHENYLMETHOXY-1-PIPERIDINYL]BUTYRIC ACID ((+)-MPPB) DISPOSITION IN RATS
- 医薬品の両性イオン化(第1報)4-(2-Chlorodibenz[b, f][1,4]oxazepin-11-yl)piaerazine, 4-(2-Chlorodibenzo[b, f][1,4]thiazepin-11-yl)-piperazine及び4-(11H-Dibenz[b, e]azepin-6-yl)piperazineのN-アルキルカルボン酸誘導体の合成とその薬理作用