title: Synthesis and evaluation of a novel 2-azabicyclo[2.2.2]octane class of long chain fatty acid elongase 6 (ELOVL6) inhibitors.
abstract: 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.
authors: Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Co., Ltd, Okubo 3, Tsukuba, Ibaraki 300-2611, Japan.
authors: Takahide
authors: T
authors: Sasaki
authors: Tsuyoshi
authors: T
authors: Nagase
authors: Toshiyuki
authors: T
authors: Takahashi
authors: Akira
authors: A
authors: Nagumo
authors: Ken
authors: K
authors: Shimamura
authors: Yasuhisa
authors: Y
authors: Miyamoto
authors: Hidefumi
authors: H
authors: Kitazawa
authors: Maki
authors: M
authors: Kanesaka
authors: Ryo
authors: R
authors: Yoshimoto
authors: Katsumi
authors: K
authors: Aragane
authors: Shigeru
authors: S
authors: Tokita
authors: Nagaaki
authors: N
authors: Sato
mesh_terms: 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
chemical_list: D053961:Azabicyclo Compounds; C000630955:ELOVL6 protein, human; C000630968:Elovl6 protein, mouse; D005227:Fatty Acids; D009795:Octanes; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases; C026728:octane