Application of a catalyst-free Domino Mannich/Friedel-Crafts alkylation reaction for the synthesis of novel tetrahydroquinolines of potential antitumor activity

Castillo, Juan‐Carlos; Jiménez, Elio; Portilla, Jaime; Insuasty, Braulio; Quiroga, Jairo; Moreno-Fuquen, Rodolfo; Kennedy, Alan R.; Abonı́a, Rodrigo

doi:10.1016/j.tet.2017.12.049

Cited by 31 publications

(14 citation statements)

References 59 publications

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“…The predicted values are plotted versus experimental MIC results of the training set compounds against B. cereus, as given in Figure 3. Best performing QSAR model for the activity against C. albicans 38 4-Cyano-1-piperidinyl-5,6,7,8-tetrahydroisoquinoline-3(2H)-thione (2). A solution of 3-amino-1-thioxo-5,6,7,8-tetrahydro-1H-isothiochromene-4-carbonitrile (1) (5.00 g, 22 mmol) and piperidine (7.00 mL, 82 mmol) was heated on a steam bath at 100°C for 6 h under solvent-free conditions.…”

Section: ■ 2d Qsar Study Resultsmentioning

confidence: 99%

Synthesis and Antimicrobial Activity of Novel Piperidinyl Tetrahydrothieno[2,3-c]isoquinolines and Related Heterocycles

et al. 2019

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A novel series of 1-amino-2-substituted-5- piperidinyl-6,7,8,9-tertahydrothieno[2,3-c]isoquinolines (4a−e) was synthesized upon treatment of 4-cyano-1-piperidinyl-5,6,7,8-tetrahydroisoquinline-3(2H)-thione (2) with α-halo carbonyl compounds such as chloroacetone, ethyl chloroacetate, 2-bromoacetophenone, chloroacetamide, and chloroacetanilide. Construction the pyrrolyl ring associated with the thienotetrahydroisoquinoline moiety was achieved by treatment of compounds 4a, b with 2,5-dimethoxytertahydrofuran in acetic acid. 1-Pyrrolyl-2-substituted-thieno[2,3-c]isoquinolines 5a and 5b which in turn were used as multipurpose precursors for synthesis of other new heterocycles. Assignments of the chemical structures of the respectively synthesized thienotetrahydroisoquinolines and their derivatives were established on the bases of elemental and spectral techniques (Fourier transform infrared, 1 H NMR, 13 C NMR, and mass spectroscopy). Furthermore, certain compounds were screened for their antimicrobial activity which revealed promising activities against various pathogenic strains of bacteria and fungi.

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Section: ■ 2d Qsar Study Resultsmentioning

confidence: 99%

Synthesis and Antimicrobial Activity of Novel Piperidinyl Tetrahydrothieno[2,3-c]isoquinolines and Related Heterocycles

et al. 2019

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“…Some tetrahydroisoquinoline (THISQ) based compounds are of medicinal and biological importance, being used as antitumoral (Pingaew et al, 2014;Castillo et al, 2018), antifungal (Scott et al, 2002) and anti-inflammatory agents (Siegfried et al, 1989). Other tetrahydroisoquinolines were used as inhibitors including B-raf V600E or p38 kinase inhibitors (Lu et al, 2016;Rosales et al, 2007).…”

Section: Chemical Contextmentioning

confidence: 99%

Crystal structure and Hirshfeld surface analysis of 2-{[7-acetyl-4-cyano-6-hydroxy-8-(4-methoxyphenyl)-1,6-dimethyl-5,6,7,8-tetrahydroisoquinolin-3-yl]sulfanyl}acetic acid ethyl ester

Al‐Taifi¹,

Marae²,

El‐Ossaily³

et al. 2022

Acta Cryst E

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In the title molecule, C25H28N2O5S, (alternative name ethyl 2-{[7-acetyl-4-cyano-6-hydroxy-8-(4-methoxyphenyl)-1,6-dimethyl-5,6,7,8-tetrahydroisoquinolin-3-yl]sulfanyl}acetate) the 4-methoxyphenyl group is disposed on one side of the bicyclic core and the oxygen atoms of the hydroxyl and acetyl groups are disposed on the other side. In the crystal, a layered structure parallel to the ac plane is generated by O—H...O and C—H...O hydrogen bonds plus C—H...π(ring) interactions.

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“…Notably, compound 106c (R = 4-FC 6 H 4 , R 1 = 4-F) with an IC 50 value of 0.08 µM showed excellent activity against the A549 cell line, while 1,2,3,4-tetrahydroquinolinylphosphine sulfide 107f (R = 4-FC 6 H 4 , R 1 = 4-F) with an IC 50 value of 0.03 µM was the most active against the A549 cell line. In 2018, Castillo et al, described a catalyst-free method to construct diversely substituted 1,2,3,4-tetrahydroquinolines 110 through a Domino Mannich/Friedel-Crafts alkylation reaction of N-arylamines 108, paraformaldehyde (109) and electron-rich olefins 105 in ACN at room temperature [98]. This work showed that the choice of solvent was crucial and could greatly influence the reaction course: for example, γ-aminoethers were observed when methanol, ethanol, n-propanol or n-butanol were used as solvent [99].…”

Section: Quinoline Derivativesmentioning

confidence: 99%

Synthesis of Biologically Active Molecules through Multicomponent Reactions

et al. 2020

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Focusing on the literature progress since 2002, the present review explores the highly significant role that multicomponent reactions (MCRs) have played as a very important tool for expedite synthesis of a vast number of organic molecules, but also, highlights the fact that many of such molecules are biologically active or at least have been submitted to any biological screen. The selected papers covered in this review must meet two mandatory requirements: (1) the reported products should be obtained via a multicomponent reaction; (2) the reported products should be biologically actives or at least tested for any biological property. Given the diversity of synthetic approaches utilized in MCRs, the highly diverse nature of the biological activities evaluated for the synthesized compounds, and considering their huge structural variability, much of the reported data are organized into concise schemes and tables to facilitate comparison, and to underscore the key points of this review.Molecules 2020, 25, 505 2 of 71 acetylcholinesterase inhibitors, anti-HIV, antimicrobial, antioxidant, anti-mycobacterial and anticancer activities ( Figure 1). It is noteworthy that 64% and 16% of the supporting literature found for this review correspond to heterocyclic structures with anticancer and antimicrobial activities, respectively. Scheme 2. Three-component synthesis of 3,4-dihydropyrimidinones/thiones type 7 under microwave irradiation, for anti-inflammatory activity.Patil et al., reported a one-pot pseudo-five-component synthesis of highly functionalized tetrahydropyridines 9 using Cu(OTf) 2 as catalyst, Scheme 3. In vitro anti-inflammatory activity of the obtained compounds 9 was determined against matrix metalloproteinases (MMPs) as MMP-2 and MMP-9 by using gelatin zymography [29]. Scheme 3. Multicomponent Cu(OTf) 2 catalyzed synthesis of substituted tetrahydropyridines 9 for anti-inflammatory activity.A highly diastereoselective synthesis (exclusively the cis isomer is formed), of chromeno β-lactam hybrids 13/14 was also achieved by an efficient one-pot three-component reaction between either 5,5-dimethylcyclohexane-1,3-dione (10a) or 4-hydroxycoumarin (10b), diverse benzaldehydes 11 and malononitrile (12), in the presence of DABCO under reflux conditions (Scheme 4). Scheme 4. Three-component synthesis of β-lactam hybrids 13/14 for anti-inflammatory activity.The synthesized compounds (13 in 80-95% yield) and (14 in 82-95% yield) were screened for anti-inflammatory activity (as well as for anticancer activity, please see Section 3.13.13. Compound 13b (Ar = 4-ClC 6 H 4 , Ar 1 = 4-MeC 6 H 4 ) was the most active of all the chromeno β-lactam hybrids 13/14 tested, with a 19.8 anti-inflammatory ratio, although, it resulted less active than the reference drug dexamethasone corticosteroid used for the treatment of rheumatoid and skin inflammation [30].

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Application of a catalyst-free Domino Mannich/Friedel-Crafts alkylation reaction for the synthesis of novel tetrahydroquinolines of potential antitumor activity

Cited by 31 publications

References 59 publications

Synthesis and Antimicrobial Activity of Novel Piperidinyl Tetrahydrothieno[2,3-c]isoquinolines and Related Heterocycles

Synthesis and Antimicrobial Activity of Novel Piperidinyl Tetrahydrothieno[2,3-c]isoquinolines and Related Heterocycles

Crystal structure and Hirshfeld surface analysis of 2-{[7-acetyl-4-cyano-6-hydroxy-8-(4-methoxyphenyl)-1,6-dimethyl-5,6,7,8-tetrahydroisoquinolin-3-yl]sulfanyl}acetic acid ethyl ester

Synthesis of Biologically Active Molecules through Multicomponent Reactions

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