Design and synthesis of new orally active inhibitors of human neutrophil elastase

…, T Sekioka, K Kitagawa, S Yamamoto, K Tanaka…

Index: Ohmoto, Kazuyuki; Okuma, Motohiro; Yamamoto, Tetsuya; Kijima, Hideomi; Sekioka, Tomohiko; Kitagawa, Kanji; Yamamoto, Shigeki; Tanaka, Kenji; Kawabata, Kazuhito; Sakata, Atsushi; Imawaka, Haruo; Nakai, Hisao; Toda, Masaaki Bioorganic and Medicinal Chemistry, 2001 , vol. 9, # 5 p. 1307 - 1323

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Citation Number: 17

Abstract

To identify new orally active inhibitors, further modification of 1 (ONO-6818) was performed. Peptidic derivatives 4b, 4c and 4n showed more potent inhibitory activity than nonpeptidic derivatives 3a–c. As a result, a series of peptidic inhibitors, 4a–s and 5a–v, were discovered. Among these N-aryl derivatives 5a–g, 5i, 5m and 5o–v showed oral activity. Their oral activity showed good correlation with their metabolic stability. Compounds 5h and 5j–l, ...