To provide a covalently linked complex which is hydrolyzed by carboxylesterase within the cell to perform enzyme or receptor modification which is enhanced or more extended relative to an inhibitor which is accumulated in a target cell and is not conjugated.
In a covalently linked complex of alpha amino acid ester and an aurora kinase inhibitor or p38 kinase inhibitor, the alpha amino acid ester is combined with the inhibitor as represented by radicals in a formula (IA) or a formula (IB). [In the formula, R1 denotes cyclopentyloxy carbonyl or the like, R2 denotes benzyl or phenyl, R4 denotes a hydrogen atom or the like, Y and Y1 denote bonds, L denotes alkylene or the like, X denotes a bond or -C(=O), (z) denotes 0 or 1, (s) denotes 0 or 1, and Alk3 denotes alkylene of straight 1-6C chains].
DRUMMOND ALAN HASTINGS
NEEDHAM LINDSEY ANN
JPN5008005790; ＣＡＨＡＲＤ，Ｄ． ｅｔ ａｌ．: 'Ａｒｙｌｏｘｙ ｐｈｏｓｐｈｏｒａｍｉｄａｔｅ ｔｒｉｅｓｔｅｒｓ ａｓ ｐｒｏｔｉｄｅｓ' ＭＩＮＩ-ＲＥＶＩＥＷＳ ＩＮ ＭＥＤＩＣＩＮＡＬ ＣＨＥＭＩＳＴＲＹ Ｖ４ Ｎ４, 2004, Ｐ３７１-３８１
JPN6011068763; ＴＨＯＲＮＡＬＬＥＹ，Ｐ．Ｊ． ｅｔ ａｌ．: 'Ａｎｔｉｔｕｍｏｒ Ａｃｔｉｖｉｔｙ ｏｆ Ｓ-（ｐ-Ｂｒｏｍｏｂｅｎｚｙｌ）ｇｌｕｔａｔｈｉｏｎｅ Ｄｉｅｓｔｅｒｓ ｉｎ Ｖｉｔｒｏ： Ａ Ｓｔｒｕｃｔｕｒｅ-Ａｃｔｉｖｉｔｙ Ｓｔｕｄｙ' Ｊｏｕｒｎａｌ ｏｆ Ｍｅｄｉｃｉｎａｌ Ｃｈｅｍｉｓｔｒｙ Ｖ３９， Ｎ１７, 1996, Ｐ３４０９-３４１１
Shinji Kai
Yusuke Kaneko
Kiyoshi Inamoto
Masami Tomita