Medicinal chemistry perspectives of 1,2,3,4-tetrahydroisoquinoline analogs – biological activities and SAR studies

Abstract

This review provides critical insights into the biological activities and Structure–Activity Relationship (SAR) studies of tetrahydroisoquinoline (THIQ) analogs.

Intramolecular rhodium-catalysed [2 + 2 + 2] cycloaddition of linear chiral N-bridged triynes: straightforward access to fused tetrahydroisoquinoline core

“…According to general procedure V, catalyst RhCl(PPh 3 ) 3 (10 mol%), from 54 mg (0.09 mmol) of (S, S)-6c, 34 mg of (S,S)-9c were obtained as a colourless oil (63% yield); [α] 25 D = +55.1 (c 1.0, CHCl 3 ); 1 H NMR (300 MHz, CDCl 3 ): δ ( ppm) 7.70 (d,J = 8.3 Hz,4H), 7.24 (d, J = 8.0 Hz, 4H), 6.90 (s, 2H), 4.60 (d,J = 16.7 Hz,2H),4.33 (d,J = 16.7 Hz,2H),2H),2.98 (dd,J = 15.7,5.8 Hz,2H),2.71 (d,J = 16.3 Hz,2H), 2.39 (s, 6H), 0.90-0.78 (m, 2H), 0.46-0.39 (m, 4H), 0.36-0.29 (m, 2H), 0.27-0.21 (m, 2H); 13 C NMR (75 MHz, CDCl 3 ): δ ( ppm) 143. 2,137.8,130.5,129.6 (2 × CH),128.2,127.8,127.1 (2 × CH),56.5,40.7,33.3,21.5,12.7,4.5,4.3 (3S,8S)-3,8-Di(thiophen-3-yl)-2,9-ditosyl-1,2,3,4,7,8,9,10-octahydro-2,9-phenanthroline [(S,S)-9d]. According to general procedure V, catalyst RhCl(PPh 3 ) 3 (10 mol%), from 67 mg (0.10 mmol) of (S,S)-6d, 40 mg of (S,S)-9d were obtained as a colourless oil (60% yield); [α] 25 D = +20.7 (c 1.0, CHCl 3 ); 1 H NMR (300 MHz, CDCl 3 ): δ ( ppm) 7.57 (d,J = 8.3 Hz,4H),6H),6.90 (s,2H),4H),5.47 (d,J = 5.6 Hz,2H), 4.50 (d,J = 16.8 Hz,2H),3.88 (d,J = 16.8 Hz,2H),3.16 (dd,J =...…”

“…M.p. 69-71 °C; [α] 25 D = +37.7 (c 1.0, CHCl 3 ); 1 H NMR (300 MHz, CDCl 3 ): δ ( ppm) 7.60 (d,J = 8.3 Hz,4H),7.18 (d,J = 8.0 Hz,4H),4.19 (d,J = 17.7 Hz,2H),3.97 (d,J = 17.7 Hz,2H),2H), 3.00 (d,J = 17.1 Hz,2H),2.62 (d,J = 17.1,6.4 Hz,2H), 2.37 (s, 6H), 1.60-1.52 (m, 2H), 0.92 (d, J = 6.6 Hz, 6H), 0.91 (d, J = 6.6 Hz, 6H); 13 C NMR (75 MHz, CDCl 3 ): δ ( ppm) 143.5,137.7,132.4,129.6 (2 × CH),129.1,127.3,126.9 (2 × CH),57.4,39.9,32.0,28.6,21.5,20.0,19.9 ,2,3,4,7,8,9,. According to general procedure V, catalyst [RhCl(CO 2 )] 2 (15 mol%), from 42 mg (0.06 mmol) of (S,S)-7g, 33 mg of (S,S)-9l were obtained as a white solid (79% yield).…”

“…1). 2,3 The quest for novel synthetic routes for the synthesis of nitrogen-containing polyheterocycles using atom-economical and efficient pathways still remains an active field in synthetic organic chemistry. From a synthetic point of view, it is desirable that the preparation of complex target molecules could be achieved quickly, quantitatively, and selectively by simple methodologies from readily available starting materials.…”

Chemo‐Enzymatic One‐Pot Two‐Step Functionalization of 1,2,3,4‐Tetrahydroisoquinolines by Monoamine Oxidase‐Ugi‐Joullié Reaction Sequence

“…We aimed to apply a similar amine oxidation‐imine addition sequence to functionalize 1,2,3,4‐tetrahydroisoquinolines (THIQs) which are prominent scaffolds in medicinal chemistry and in commercial drugs, e. g. quinapril, solifenacin, lifitegrast [33,34] . They are also abundant in nature.…”

Brown Seaweed‐Derived Alginic Acid: An Efficient and Reusable Catalyst for Pictet‐Spengler Reaction to Access Tetrahydro‐β‐Carboline and Tetrahydroisoquinoline Frameworks

“…Both THBCs and THIQs are appealing architectures, representing natural and synthetic products with diverse array of biological activities (Figure 1). [9][10][11][12] Besides being molecules of pharmacological interest, [13][14][15][16][17][18][19] these heterocycles have been latently explored in several synthetic transformations, such as oxidative rearrangement, ring-opening and CÀ H functionalization. [20][21] Thus, in its synthetic domain, several variations of PSR were devised to prepare THBCs and THIQs.…”