618113-62-5Relevant academic research and scientific papers
Enzymatic resolution of 2-substituted tetrahydroquinolines. Convenient approaches to tricyclic quinoxalinediones as potent NMDA-glycine antagonists
Katayama, Seiji,Ae, Nobuyuki,Nagata, Ryu
, p. 4295 - 4299 (1998)
Two approaches leading to the enantiomerically pure tricyclic quinoxalinedione class of NMDA-glycine antagonists using enzymatic resolutions are described. An intermediate, racemic methyl 1,2,3,4- tetrahydroquinoline-2-carboxylate 3, was resolved to (S)-3
The aza-xylylene Diels-Alder approach for the synthesis of naturally occurring 2-alkyl tetrahydroquinolines
Avemaria, Frank,Vanderheiden, Sylvia,Br?se, Stefan
, p. 6785 - 6796 (2007/10/03)
The recently discovered intramolecular aza-xylylene Diels-Alder reaction, based on a 1,4-dehydrohalogenation reaction, was extended in terms of substrates and leaving groups allowing the assembly of tetrahydroquinolines in two synthetic steps. Intramolecular cleavage of a thiocarbamate using triphenylphosphine and tetrachloromethane (Appel conditions) to give chloromethyl phenylisocyanate has been presented for the first time. The synthetic feasibility of this process was demonstrated in the first total syntheses of the alkaloids rac-Angustureine and 1-methyl-2-propyltetrahydroquinoline.
Tricyclic Quinoxalinediones: 5,6-Dihydro-1H-pyrroloquinoxaline-2,3-diones and 6,7-Dihydro-1H,5H-pyridoquinoxaline-2,3-diones as Potent Antagonists for the Glycine Binding Site of the NMDA Receptor
Nagata, Ryu,Tanno, Norihiko,Kodo, Toru,Ae, Nobuyuki,Yamaguchi, Hiroshi,et al.
, p. 3956 - 3968 (2007/10/02)
A series of tricyclic quinoxalinediones, 5,6-dihydro-1H-pyrroloquinoxaline-2,3-diones and 6,7-dihydro-1H,5H-pyridoquinoxaline-2,3-diones, were synthesized and was evaluated for their affinity for the glycine binding site of the NMDA receptor using a -5,7-dichlorokynurenic acid binding assay.The six-membered ring-fused tricyclic quinoxalinedione 18g (Ki = 9.9 nM) displayed high affinity for the glycine site.The anilide derivative 20g (Ki = 2.6 nM) was 4-fold more potent than 18g and as potent as L-689,560, one of the most potent glycineantagonists so far prepared.Although the carboxylic acid derivative of the corresponding five-membered ring-fused tricyclic quinoxalinedione 18e (Ki = 7.3 nM) had affinity comparable to that of 18g, the anilide derivative 20e largely decreased in the affinity in contrast to 20g.Enantiomers 23g, 24g, 25g, and 26g were prepared and tested.Only the S enantiomer 25g (Ki = 0.96 nM) retained the affinity among the anilide derivatives, whereas both enantiomers 23g (Ki = 2.3 nM) and 24g (Ki = 9.6 nM) were active among the carboxylic acid derivatives.The origin of the high affinity of carboxylic acid derivatives such as 18e and 18g would be a charge-charge interaction between the anionic carboxylate residues of the compounds and the cationic proton-donor site in the receptor.
