6831-57-8Relevant articles and documents
In vitro functional evaluation of isolaureline, dicentrine and glaucine enantiomers at 5-HT2 and α1 receptors
Heng, Hui Li,Chee, Chin Fei,Thy, Chun Keng,Tee, Jia Ti,Chin, Sek Peng,Herr, Deron R.,Buckle, Michael J. C.,Paterson, Ian C.,Doughty, Stephen W.,Abd. Rahman, Noorsaadah,Chung, Lip Yong
, p. 132 - 138 (2018/10/15)
Compounds with activity at serotonin (5-hydroxytryptamine) 5-HT2 and α1 adrenergic receptors have potential for the treatment of central nervous system disorders, drug addiction or overdose. Isolaureline, dicentrine and glaucine enantiomers were synthesized, and their in vitro functional activities at human 5-HT2 and adrenergic α1 receptor subtypes were evaluated. The enantiomers of isolaureline and dicentrine acted as antagonists at 5-HT2 and α1 receptors with (R)-isolaureline showing the greatest potency (pKb?=?8.14 at the 5-HT2C receptor). Both (R)- and (S)-glaucine also antagonized α1 receptors, but they behaved very differently to the other compounds at 5-HT2 receptors: (S)-glaucine acted as a partial agonist at all three 5-HT2 receptor subtypes, whereas (R)-glaucine appeared to act as a positive allosteric modulator at the 5-HT2A receptor.
Novel Series of Dihydropyridinone P2X7 Receptor Antagonists
Lopez-Tapia, Francisco,Walker, Keith A. M.,Brotherton-Pleiss, Christine,Caroon, Joanie,Nitzan, Dov,Lowrie, Lee,Gleason, Shelley,Zhao, Shu-Hai,Berger, Jacob,Cockayne, Debra,Phippard, Deborah,Suttmann, Rebecca,Fitch, William L.,Bourdet, David,Rege, Pankaj,Huang, Xiaojun,Broadbent, Scott,Dvorak, Charles,Zhu, Jiang,Wagner, Paul,Padilla, Fernando,Loe, Brad,Jahangir, Alam,Alker, André
, p. 8413 - 8426 (2015/11/24)
Identification of singleton P2X7 inhibitor 1 from HTS gave a pharmacophore that eventually turned into potential clinical candidates 17 and 19. During development, a number of issues were successfully addressed, such as metabolic stability, plasma stability, GSH adduct formation, and aniline mutagenicity. Thus, careful modification of the molecule, such as conversion of the 1,4-dihydropyridinone to the 1,2-dihydropyridinone system, proper substitution at C-5″, and in some cases addition of fluorine atoms to the aniline ring allowed for the identification of a novel class of potent P2X7 inhibitors suitable for evaluating the role of P2X7 in inflammatory, immune, neurologic, or musculoskeletal disorders.
First total syntheses of (±)-isopiline, (±)-preocoteine, (±)-oureguattidine and (±)-3-methoxynordomesticine and the biological activities of (±)-3-methoxynordomesticine
Nimgirawath, Surachai,Udomputtimekakul, Phansuang,Taechowisan, Thongchai,Wanbanjob, Asawin,Shen, Yuemao
experimental part, p. 368 - 376 (2009/12/27)
A convenient and economical synthesis of 4-hydroxy-2,3- dimethoxybenzaldehyde has been developed. This was used as the starting material for the first total syntheses of (±)-isopiline, (±)-preocoteine, (±)-oureguattidine and (±)-3-methoxynordomesticine in
