A synthesis of 2-endo-amino-2-exo-hydroxymethylnorbornenes having inhibitory activity against protein kinase C.
2-endo-Hexadecylamino-2-exo-hydroxymethylnorbornene (1a) was synthesized from 2-acetamidonorbornene-2-carboxylic acid methyl ester (2) in a good overall yield. 2-endo-Hexadecylamino-2,3-exo-bis(hydroxymethyl)norbornene (1b) was synthesized starting from dimethyl acetamidofumarate based on Diels-Alder strategy. 1a and 1b inhibited protein kinase C at the IC51 values of 2 x 10(-5) and 1 x 10(-5) M, respectively, but not protein kinase A at a concentration of 1 x 10(-3) M. The structure-activity relationships are discussed.
Iwasaki
T
T
Research Laboratory of Applied Biochemistry, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
Yamazaki
H
H
Nishitani
T
T
Sato
T
T
D009636:Norbornanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D009636:Norbornanes; C069422:2-hexadecylamino-2-hydroxymethylnorbornene; C069423:2-hexadecylamino-2,3-bis(hydroxymethyl)norbornene; D011493:Protein Kinase C