Lee J, Han K C, Kang J H, Pearce L L, Lewin N E, Yan S, Benzaria S, Nicklaus M C, Blumberg P M, Marquez V E
Laboratory of Medicinal Chemistry, College of Pharmacy, Seoul National University, Shinlin Dong, Kwanak-ku, Seoul 151-742, South Korea.
J Med Chem. 2001 Dec 6;44(25):4309-12. doi: 10.1021/jm0103965.
An approach to reduce the log P in a series of diacylglycerol (DAG)-lactones known for their high binding affinity for protein kinase C (PK-C) is presented. Branched alkyl groups with reduced lipophilicity were selected and combined with the replacement of the ester or lactone oxygens by NH or NOH groups. Compound 6a with an isosteric N-hydroxyl amide arm represents the most potent and least lipophilic DAG analogue known to date.
本文提出了一种降低一系列对蛋白激酶C（PK-C）具有高结合亲和力的二酰基甘油（DAG）-内酯的log P值的方法。选择了亲脂性降低的支链烷基，并将其与用NH或NOH基团取代酯或内酯氧相结合。具有等排N-羟基酰胺臂的化合物6a代表了迄今为止已知的最有效且亲脂性最低的DAG类似物。
