1229705-59-2Relevant academic research and scientific papers
LSD1 INHIBITORS AND USES THEREOF
-
Paragraph 00183-00184, (2016/11/17)
Provided are novel compounds of Formula (I) and pharmaceutically acceptable salts thereof, which are useful for treating a variety of diseases, disorders or conditions, associated with LSDl. Also provided are pharmaceutical compositions comprising the novel compounds of Formula (I), pharmaceutically acceptable salts thereof, and methods for their use in treating one or more diseases, disorders or conditions, associated with LSDl.
Azetidine derivatives as novel γ-aminobutyric acid uptake inhibitors: Synthesis, biological evaluation, and structure-activity relationship
Faust, Mark R.,H?fner, Georg,Pabel, J?rg,Wanner, Klaus T.
experimental part, p. 2453 - 2466 (2010/07/08)
In this study azetidine derivatives representing conformationally constrained GABA or β-alanine analogs were evaluated for their potency as GABA-uptake inhibitors. The study comprised derivatives substituted in 2- as well as in 3-position with either an acetic acid moiety or a carboxylic acid function. In addition, azetidine derivatives bearing a tetrazole ring as a bioisosteric substitute for a carboxylic acid group were included. 3-Hydroxy-3-(4-methoxyphenyl)azetidine derivatives were explored as analogs of the known GABA-uptake inhibitor NNC-05-2045 exhibiting an azetidine ring instead of a piperidine ring present in the latter. Both, N-unsubstituted compounds as well as their N-alkylated lipophilic derivatives, were biologically evaluated for their affinity to the GAT-1 and GAT-3 transporters. Azetidin-2-ylacetic acid derivatives provided with a 4,4-diphenylbutenyl or 4,4-bis(3-methyl-2-thienyl)butenyl moiety as lipophilic residue were found to exhibit the highest potency at GAT-1 with IC50 values of 2.83 ± 0.67 μM and 2.01 ± 0.77 μM, respectively. The most potent GAT-3 inhibitor among these compounds appeared to be the β-alanine analog 1-{2-[tris(4-methoxyphenyl)methoxy]ethyl}azetidine-3-carboxylic acid (12d) displaying an IC50 value of 15.3 ± 4.5 μM. Whereas the tetrazole derivatives showed no potency as GABA-uptake inhibitors, the 3-hydroxy-3-(4-methoxyphenyl)azetidine derivatives exhibited moderate affinity to GAT-1 (compound 18b: IC50 = 26.6 ± 3.3 μM) and to GAT-3 (compound 18e: IC50 = 31.0 ± 4.7 μM).
