Synthesis and in vitro evaluation of 4-substituted furano[3,2-c] tetrahydroquinolines as potential anti-cancer agents

Progress in the Chemistry of Tetrahydroquinolines

“…Regarding fused tetrahydroquinoline derivatives, furo­[3,2- c ]­tetrahydroquinolines 65 were tested for their ability to inhibit cellular proliferation, finding IC 50 values in the 2.5–16.7 μM range. The most active compound of the series induced mitochondrial murine apoptosis in C6 glioma cells by up-regulating the expression of Bax and caspases 3 and 9, and by down-regulating Bcl-2 . The somewhat related, cis -fused tetrahydrochromeno­[4,3- b ]­quinolines 66 exhibited significant antiproliferative activity against MCF-7 breast cancer cell lines …”

Design, synthesis and molecular mechanisms of novel dual inhibitors of heat shock protein 90/phosphoinositide 3-kinase alpha (Hsp90/PI3Kα) against cutaneous melanoma

“…There have been some advances achieved by combining Hsp90 inhibitors and other targeted therapeutics, e.g. HER2 monoantibody trastuzumab, ALK inhibitor crizotinib, and so on [20][21][22][23][24][25][26][27][28][29] . It is therefore reasonable to discover novel inhibitors targeting Hsp90 and the chaperone protein simultaneously, we shall focus on the discovery multitarget small molecular inhibitors of Hsp90 and its oncogenic client kinase proteins.…”

The Povarov Reaction: A Versatile Method to Synthesize Tetrahydroquinolines, Quinolines and Julolidines

“…The Povarov reaction and its variants can be catalyzed by a wide variety of Brønsted and Lewis acids: BF 3 ·Et 2 O, 33 34 35 36 37 38 39 40 BiCl 3 , 41–44 CAN, 45 46 47 48 49 50 51 cerium sulfate, 52 Amberlyst 15, 53 phthalic acid, 54 p -toluenesulfonic acid 55 56 and its supramolecular analogue CX4SO 3 H, 57 ferric sulfate, 58 59 60 iodine, 61 62 63 InCl 3 , 64 65 66 67 68 69 NH 4 Br, 70 Sc(OTf) 3 , 71 72 73 74 75 and Sc(III)-loaded resin, 76 Y(OTf) 3 , 77 78 79 80 81 bistriflimide, 28 TFA 82 and zinc chloride. 83 Moreover, mixed catalytic systems may be employed, such as Ca(OTf) 2 /Bu 4 NPF 6 84 and CeCl 3 /NaI.…”

“…described by the use of bovine pancreas -chemotrypsin in aqueous acetonitrile 86 with a strong preference towards the trans diastereoisomers, whereas other enzymes such as papain, lipases, and amylases failed to provide the THQ. Concerning the reaction medium, polar solvents such as acetonitrile 34,37,41,45,47,51,54 and alcohols 53,65,87,88 were the most typical, but not a requirement since apolar solvents including dichloromethane, 35,74,89 dichloroethane 28,60,90 and toluene 78,91,92 were also well represented in the literature. Fluorinated alcohols, such as hexafluoroisopropanol (HFIP) 71 and trifluoroethanol (TFE) 50,93 can be employed to dissolve reagents that are insoluble in the most common solvents, 71 or can even act as the catalyst itself, thereby removing the requirement for the addition of acids.…”

“…Subsequent to the work of Grieco and Bahsas, in 1995, Mellor and Merriman reported the use of the Povarov reaction for the synthesis of julolidines. 25 Different julolidines were obtained by reacting 4-methylaniline (94) [or THQ (89)], formaldehyde (87), and styrene (65) [or 3,4-dihydro-…”