Chiral tetrahydroquinoline derivatives as potent anti-hyperalgesic agents in animal models of sustained inflammation and chronic neuropathic pain

Fabio, Romano Di; Alvaro, Giuseppe; Bertani, Barbara; Donati, Daniele; Pizzi, Domenica Maria; Gentile, Gabriella; Pentassuglia, Giorgio; Giacobbe, Simone; Spada, Simone; Ratti, Emiliangelo; Corsi, Mauro; Quartaroli, M.; Barnaby, Robert J.; Vitulli, Giovanni

doi:10.1016/j.bmcl.2006.12.022

Cited by 21 publications

(14 citation statements)

References 25 publications

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“…292,301−303 The Wittig reaction was also used instead of the Knoevenagel condensation (Scheme 42). 304 Horner-Wadsworth-Emmons reaction was used to prepare the marine alkaloid parazoanthine B and its analogues. 305 Another strategy consisted in synthesizing the 3-substituted hydantoin via the cyclization of an ureido intermediate and then to perform Knoevenagel condensation to afford the desired hydantoins.…”

Section: -Substituted 5-alkyl/arylidene Hydantoinsmentioning

confidence: 99%

Recent Advances in the Synthesis of Hydantoins: The State of the Art of a Valuable Scaffold

et al. 2017

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The review highlights the hydantoin syntheses presented from the point of view of the preparation methods. Novel synthetic routes to various hydantoin structures, the advances brought to the classical methods in the aim of producing more sustainable and environmentally friendly procedures for the preparation of these biomolecules, and a critical comparison of the different synthetic approaches developed in the last twelve years are also described. The review is composed of 95 schemes, 8 figures and 528 references for the last 12 years and includes the description of the hydantoin-based marketed drugs and clinical candidates.

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Section: -Substituted 5-alkyl/arylidene Hydantoinsmentioning

confidence: 99%

Recent Advances in the Synthesis of Hydantoins: The State of the Art of a Valuable Scaffold

et al. 2017

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“…Fabio et al employed metal triflate mediated asymmetric Mannich-type condensation reaction to synthesize orally bioavailable antihyperalgesic tetrahydroquinoline derivative 77 (figure 7). 62…”

Section: Synthesis Of Antiinflammatory Moleculesmentioning

confidence: 99%

Mannich reaction: A versatile and convenient approach to bioactive skeletons

Ganesan

2013

J Chem Sci

112

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This review gives an insight into the recent applications of Mannich reaction and its variants in the construction of bioactive molecules. Emphasis is given to the Mannich reaction that provides bioactive molecules and/or modifies the property of an existing bioactive molecule. The role of Mannich reaction in the construction of antimalarial, antitumour, antimicrobial, antitubercular, antiinflammatory and anticonvulsant molecules and also the significance of aminoalkyl Mannich side chain on the biological property of molecules is discussed here.

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“…Notably, the substrate 2-methyl-1, 2, 3, 4-tetrahydroquinoline ( 10 ) was deracemized by a CHAO triple mutant (T198F/L199S/M226F) leading to the production of ( R )-2-methyl-1, 2, 3, 4-tetrahydroquinoline (THQ) with 76% yield and 98% ee. This R -enantiomer is a valuable building block for the synthesis of a variety of THQ derivatives of pharmaceutical or clinical importance 17 18 19 20 21 22 .…”

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confidence: 99%

New recombinant cyclohexylamine oxidase variants for deracemization of secondary amines by orthogonally assaying designed mutants with structurally diverse substrates

Yao

Cong

et al. 2016

Sci Rep

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To further expand the substrate range of the cyclohexylamine oxidase (CHAO) from Brevibacterium oxydans, a library of diverse mutants was created and assayed toward a group of structurally diverse substrates. Among them, mutants T198A and M226A exhibited enhanced activity relative to wt CHAO for most (S)-enantiomers of primary amines and some secondary amines. While mutants T198I, L199I, L199F, M226I and M226T were more active than wt CHAO toward the primary amines, mutants T198F, L199T, Y321A, Y321T, Y321I and Y321F enhanced the enzyme activity toward the secondary amines. In particular, mutant Y321I displayed an enhanced catalytic efficiency toward 1-(4-methoxybenzyl)-1, 2, 3, 4, 5, 6, 7, 8-octahydroisoquinoline (13). Whereas a double mutant, Y321I/M226T, acted on (S)-N-(prop-2-yn-1-yl)-2, 3-dihydro-1H-inden-1-amine [(S)-8]. Since (R)-8 is an irreversible inhibitor of monoamine oxidase and (S)-13 is an intermediate of dextromethorphan, a cough suppressant drug, deracemizations of 8 and 13 were carried out with crude enzyme extracts of the respective mutants. This resulted in 51% and 78% isolated yields of (R)-8 and (S)-13, respectively, each with high enantiomeric excess (93% and 99% ee). The results demonstrated the application potential of the evolved CHAO mutants in drug synthesis requiring chiral secondary amines.

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Chiral tetrahydroquinoline derivatives as potent anti-hyperalgesic agents in animal models of sustained inflammation and chronic neuropathic pain

Cited by 21 publications

References 25 publications

Recent Advances in the Synthesis of Hydantoins: The State of the Art of a Valuable Scaffold

Recent Advances in the Synthesis of Hydantoins: The State of the Art of a Valuable Scaffold

Mannich reaction: A versatile and convenient approach to bioactive skeletons

New recombinant cyclohexylamine oxidase variants for deracemization of secondary amines by orthogonally assaying designed mutants with structurally diverse substrates

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