Significance and Creation of Novel Cyclooxygenase-1 (COX-1) Selective Inhibitors
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- FUKAI Ryosuke
- Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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- ZHENG Xiaoxia
- Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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- MOTOSHIMA Kazunori
- Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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- KAKUTA Hiroki
- Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Bibliographic Information
- Other Title
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- シクロオキシゲナーゼ-1(COX-1)阻害剤の開発意義とその創出
- シクロオキシゲナーゼ 1 COX 1 ソガイザイ ノ カイハツ イギ ト ソノ ソウシュツ
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Description
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve physical and mental pain, and to improve patients' quality of life. However, stomach irritation is a major side effect. Most NSAIDs inhibit cyclooxygenases (COXs), and inhibition of COX-1 on the stomach mucous membrane is thought to be responsible for the gastric disturb- ance. Consequently, development efforts have focused on COX-2-selective inhibitors, while COX-1-selective inhibitors have been rather neglected. Subsequently, however, it was shown that inhibition of either COX-1 or COX-2 alone does not induce gastric damage. Therefore, we have developed the COX-1-selective inhibitor N-(4-aminophenyl)-4-trifluoromethylbenzamide (TFAP), which shows analgesic activity without causing gastric damage. However, metabolism of TFAP generates a colored metabolite, resulting in red-purple coloration of urine after administration. In addition, the analgesic activity of TFAP is weaker than that of indomethacin. Thus, we designed a series of new COX-1-selective inhibitors, the 5-amino-2-ethoxy-N-(substituted)benzamide (ABEX) series, in order to avoid formation of the colored metabolite by modifying the diaminopyridine skeleton. As a result of structural modification and in vitro and in vivo testing of compounds in the ABEX series, we found a novel COX-1-selective inhibitor, 5-amino-2-ethoxy-N-(3-trifluoromethylphenyl)benzamide (ABEX-3TF), which shows better analgesic activity than indomethacin, and does not cause coloration of urine.<br>
Journal
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- YAKUGAKU ZASSHI
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YAKUGAKU ZASSHI 131 (3), 347-351, 2011-03-01
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390001206128608256
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- NII Article ID
- 130000678895
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- NII Book ID
- AN00284903
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- ISSN
- 13475231
- 00316903
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- NDL BIB ID
- 11032187
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- Text Lang
- ja
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- Data Source
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- JaLC
- NDL
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed