Discovery of Benzylpiperazine Derivatives as CNS-Penetrant and Selective Histone Deacetylase 6 Inhibitors

• Published in: ACS medicinal chemistry letters Vol. 13; no. 7; pp. 1077 - 1082
• Main Authors: Hashimoto, Kosuke, Ide, Soichiro, Arata, Mayumi, Nakata, Akiko, Ito, Akihiro, Ito, Takashi K., Kudo, Norio, Lin, Bangzhong, Nunomura, Kazuto, Tsuganezawa, Keiko, Yoshida, Minoru, Nagaoka, Yasuo, Sumiyoshi, Takaaki
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 14.07.2022; Amer Chemical Soc
• Subjects: Chemistry, Medicinal; Letter; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Science & Technology; selective inhibitor; HDAC6; phenylhydroxamate; brain penetration; antidepressant; DESIGN; ACETYLATION; TAU; AXONAL-TRANSPORT; MOUSE MODEL; IN-VIVO; DISEASE; HDAC6 INHIBITORS; STRESS; COGNITIVE DEFICITS

Inhibition of histone deacetylase 6 (HDAC6) in the brain is a highly attractive therapeutic target for the treatment of neurodegenerative diseases. The low blood–brain barrier permeability of most known HDAC6 inhibitors, however, prevents their application as central nervous system (CNS) drugs. To o...