Yang, Shyh-Ming published the artcileDiscovery of Orally Bioavailable, Quinoline-Based Aldehyde Dehydrogenase 1A1 (ALDH1A1) Inhibitors with Potent Cellular Activity, COA of Formula: C8H16N2O, the publication is Journal of Medicinal Chemistry (2018), 61(11), 4883-4903, database is CAplus and MEDLINE.
Aldehyde dehydrogenases (ALDHs) are responsible for the metabolism of aldehydes (exogenous and endogenous) and possess vital physiol. and toxicol. functions in areas such as CNS, inflammation, metabolic disorders, and cancers. Overexpression of certain ALDHs (e.g., ALDH1A1) is an important biomarker in cancers and cancer stem cells (CSCs) indicating the potential need for the identification and development of small mol. ALDH inhibitors. Herein, a newly designed series of quinoline-based analogs of ALDH1A1 inhibitors is described. Extensive medicinal chem. optimization and biol. characterization led to the identification of analogs with significantly improved enzymic and cellular ALDH inhibition. Selected analogs, e.g., 86 (NCT-505) and 91 (NCT-506), demonstrated target engagement in a cellular thermal shift assay (CETSA), inhibited the formation of 3D spheroid cultures of OV-90 cancer cells, and potentiated the cytotoxicity of paclitaxel in SKOV-3-TR, a paclitaxel resistant ovarian cancer cell line. Lead compounds also exhibit high specificity over other ALDH isoenzymes and unrelated dehydrogenases. The in vitro ADME profiles and pharmacokinetic evaluation of selected analogs are also highlighted.
Journal of Medicinal Chemistry published new progress about 71260-16-7. 71260-16-7 belongs to piperazines, auxiliary class Piperazine, name is 2-Methyl-1-(piperazin-1-yl)propan-1-one, and the molecular formula is C5H10O2S, COA of Formula: C8H16N2O.
Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics