1613722-69-2

Upstream product

• 3230-65-7 3,4-dihydroisoquinoline 
• 58662-78-5 2-amino-5-(benzyloxy)benzoic acid 
• 1196-38-9 3,4-dihydroisoquinolin-1(2H)-one 
• 125299-60-7 6-(benzyloxy)isatoic anhydride 
• 91-21-4 1,2,3,4-tetrahydroisoquinoline 
• 68423-36-9 (5-(benzyloxy)-2-nitrophenyl)methanol 

Relevant academic research and scientific papers

Amine substitution of quinazolinones leads to selective nanomolar AChE inhibitors with 'inverted' binding mode

Selective and nanomolar acetylcholinesterase inhibitors were obtained by connecting tri- and tetracyclic quinazolinones - previously described as moderately active and unselective cholinesterase (ChE) inhibitors - via a hydroxyl group in para position to an anilinic nitrogen with different amines linked via a three carbon atom spacer. These tri- and tetracyclic quinazolinones containing different alicyclic ring sizes and connected to tertiary amines were docked to a high-resolution hAChE crystal structure to investigate the preferred binding mode in relation to results obtained by experimental structure-activity relationships. While the 'classical orientation' locating the heterocycle in the active site was rarely found, an alternative binding mode with the basic aliphatic amine in the active center ('inverted' orientation) was obtained for most compounds. Analyses of extended SARs based on this inverted binding mode are able to explain the compounds' binding affinities at AChE.

Metal-Free Annulation of 2-Nitrobenzyl Alcohols and Tetrahydroisoquinolines toward the Divergent Synthesis of Quinazolinones and Quinazolinethiones

A simple metal-free method for the synthesis of quinazolinones from commercially available 2-nitrobenzyl alcohols and tetrahydroisoquinolines is developed. The reaction conditions were tolerant of an array of functionalities such as halogen, tertiary amine, protected alcohol, and ester groups. Under nearly identical conditions, quinazolinethiones were obtained in the presence of elemental sulfur and suitable mediators.

Copper-catalyzed synthesis of pyrido-fused quinazolinones from 2-aminoarylmethanols and isoquinolines or tetrahydroisoquinolines

Pyrido-fused quinazolinones were synthesizedviacopper-catalyzed cascade C(sp2)-H amination and annulation of 2-aminoarylmethanols with isoquinolines or pyridines. The transformation proceeded readily in the presence of a commercially available CuCl2catalyst with molecular oxygen as a green oxidant. Moreover, the dehydrogenative cross-coupling of 2-aminoarylmethanols with tetrahydroisoquinolines was explored, in which CuBr exhibited higher catalytic activity than CuCl2. Broad substrate scope with good tolerance of functionalities was observed under the optimized reaction conditions. The bioactive naturally occurring alkaloid rutaecarpine could be obtained by this strategy. The remarkable feature of this protocol is that complicated heterocyclic structures are readily achieved in a single synthetic step from easily accessible reactants and catalysts. This pathway to pyrido-fused quinazolinones would be complementary to existing protocols.

A simple heterocyclic fusion reaction and its application for expeditious syntheses of rutaecarpine and its analogs

In the search for new inhibitors of cholinesterases, a simple heterocyclic fusion reaction of isatoic anhydride 8 and 3,4-dihydroisoquinoline 22 was discovered which involves a spontaneous dehydrogenation upon heating. Applying the reaction, the bioactive natural alkaloid rutaecarpine and several substituted derivatives out of tryptamines and anthranilic acids or isatoic anhydrides, respectively, can be synthesized without tedious chromatographic purification. This provides simple and fast access to larger amounts of compounds with this privileged structure in medicinal chemistry.