- Pyrroloquinoline scaffold-based 5-HT6R ligands: Synthesis, quantum chemical and molecular dynamic studies, and influence of nitrogen atom position in the scaffold on affinity
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Based on pyrroloquinoline scaffold bearing 5-HT2C agonists, a series of arylsulfonamide derivatives of 1H-pyrrolo[2,3-f]quinoline and 1H-pyrrolo[3,2-h]quinoline, substituted at position 3 with tetrahydropyridine, were synthesized and evaluated in vitro for their affinity for 5-HT6 receptors. A structure–activity relationship study showed that the 1H-pyrrolo[3,2-h]quinoline scaffold was more favorable for 5-HT6R binding than the 1H-pyrrolo[2,3-f]quinoline one, suggesting dependence upon the type of condensation of the pyrrole and quinoline rings. As revealed by quantum-chemical calculations and molecular dynamic studies, position of the quinoline nitrogen atom in the planar pyrroloquinoline skeleton might affect the spatial orientation of the arylsulfonyl fragment, as a result of structure stabilization by internal hydrogen bonds.
- Grychowska, Katarzyna,Kurczab, Rafa?,?liwa, Pawe?,Sata?a, Grzegorz,Dubiel, Krzysztof,Mat?oka, Miko?aj,Moszczyński-P?tkowski, Rafa?,Pieczykolan, Jerzy,Bojarski, Andrzej J.,Zajdel, Pawe?
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p. 3588 - 3595
(2018/05/31)
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- A new ring-forming methodology for the synthesis of bioactive pyrroloquinoline derivatives
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A new, efficient, two-step method for the synthesis of bioactive pyrroloquinolines is described. Readily available nitroquinolines, bearing the nitro moiety in the carbocyclic ring, are treated with 4-chlorophenoxyacetonitrile in the presence of potassium tert-butoxide/THF to give the analogous vicarious nucleophilic substitution products (5, 8 and 11). These, in turn, are subjected to catalytic hydrogenation to produce 1H-pyrrolo[2,3-f]quinoline (6), 3H-pyrrolo[3,2-f]quinoline (9) and 1H-pyrrolo[3,2-h]quinoline (12) in good yields and relatively short reaction times. The differential activity of two N-alkylated 1H-pyrrolo[2,3-f]quinolines (1) in cisplatin resistant cell lines compared to the corresponding parent lines suggests that these might be useful leads for developing agents for use in drug resistant diseases.
- Vlachou, Margarita,Tsotinis, Andrew,Kelland, Lloyd R.,Thurston, David E.
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p. 129 - 133
(2007/10/03)
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- Vicarious Nucleophilic Substitution in Nitroquinolines
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5-Nitro-, 6-nitro-, and 8-nitroquinoline react with the carbanions of chloromethyl phenyl sulfone, chloro-N,N-dimethylmethanesulfonamide and substituted acetonitriles XCH2CN (X=OPh, SPh, Cl) giving products of the vicarious nucleophilic substitution of hy
- Makosza, Mieczyslaw,Kinowski, Andrzej,Danikiewicz, Witold,Mudryk, Boguslaw
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