Synthesis and evaluation of a novel 2-azabicyclo[2.2.2]octane class of long chain fatty acid elongase 6 (ELOVL6) inhibitors.
A series of novel 2-azabicyclo[2.2.2]octane derivatives was synthesized and evaluated as long chain fatty acid elongase 6 (ELOVL6) inhibitors. Screening of our corporate chemical collections against ELOVL6 resulted in the identification of lead 1. Exploratory chemistry efforts were applied to lead 1 to identify the orally available, potent, and selective ELOVL6 inhibitor 28a.
Sasaki
Takahide
T
Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Co., Ltd, Okubo 3, Tsukuba, Ibaraki 300-2611, Japan.
Nagase
Tsuyoshi
T
Takahashi
Toshiyuki
T
Nagumo
Akira
A
Shimamura
Ken
K
Miyamoto
Yasuhisa
Y
Kitazawa
Hidefumi
H
Kanesaka
Maki
M
Yoshimoto
Ryo
R
Aragane
Katsumi
K
Tokita
Shigeru
S
Sato
Nagaaki
N
D000123:Acetyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000818:Animals; D053961:Azabicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000081031:Fatty Acid Elongases; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009795:Octanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D053961:Azabicyclo Compounds; C000630955:ELOVL6 protein, human; C000630968:Elovl6 protein, mouse; D005227:Fatty Acids; D009795:Octanes; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases; C026728:octane