Synthesis and Pharmacological Properties of N-[4-[4-(1H-Indol-3-yl)-piperidinoalkyl]-2-thiazolyl]alkanesulfonamides as Novel Antiallergic Agents
| Autor: | Hiroshi Matsuda, Masaaki Matsuo, Jun Hiroi, Takashi Manabe, Takashi Fujii, Shinji Shigenaga |
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| Rok vydání: | 1993 |
| Předmět: |
Male
Ketotifen Indoles Ovalbumin Stereochemistry Guinea Pigs Mice Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Hypersensitivity medicine Animals Thiazole Anaphylaxis Indole test Mice Inbred ICR Sulfonamides Chemistry General Chemistry General Medicine Azelastine Thiazoles Hexobarbital Antiallergic agent Rabbits Piperidine Oxatomide medicine.drug |
| Zdroj: | Chemical and Pharmaceutical Bulletin. 41:1589-1595 |
| ISSN: | 1347-5223 0009-2363 |
| DOI: | 10.1248/cpb.41.1589 |
| Popis: | A number of N-[4-[4-(1H-indol-3-yl)piperidinoalkyl]-2- thiazolyl]alkanesulfonamides (8--21) were synthesized and evaluated for their preventive effects on systemic anaphylaxis in guinea pigs. Structure-activity analysis revealed that methane- and ethanesulfonamide derivatives having a one to three methylene tether between the piperidine and thiazole rings exhibited potent activity but the introduction of a substituent on the indole part reduced the activity. Administration (100 mg/kg p.o.) of the four compounds 8, 9, 12, 13, together with ketotifen, oxatomide, terfenadine and azelastine as reference compounds, to mice revealed that only compound 8 caused no significant increase of the sleeping time induced by hexobarbital. In addition, compound 8 (10 mg/kg i.v.) did not change the electroencephalogram in conscious rabbits. These results led to the selection of N-[4-[4-(1H-indol-3-yl)piperidinomethyl]-2-thiazolyl]methanesulfon amide (8, FK613) for further development as a novel antiallergic agent. Clinical evaluation of FK613 is now in progress. |
| Databáze: | OpenAIRE |
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