Studies towards the identification of putative bioactive conformation of potent vasodilator arylidene N-acylhydrazone derivatives

Kümmerle, Arthur Eugen; Raimundo, Juliana Montani; Leal, Carla Moreira; Silva, Givanildo S. da; Balliano, Tatiane Luciano; Pereira, Μ. A.; Simone, C. A. De; Sudo, Roberto T.; Zapata‐Sudo, Gisele; Fraga, Carlos A.M.; Barreiro, Eliezer J.

doi:10.1016/j.ejmech.2009.04.044

Cited by 73 publications

(82 citation statements)

References 20 publications

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“…N-Methylation of NAH 1, which results in N-methyl-NAH 3a, causes conformational restriction of the amide bond, thus preventing its rotation, as previously described by our group [17,26]. In fact, this modification abolished the duplication of the signals in the NMR spectra.…”

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confidence: 59%

“…For this simulation, more stable E (A/B) and Z (C) stereoisomers, obtained through a process of geometric optimization by molecular mechanics followed by conformational analysis using the semi-empirical method AM1 in the PC Spartan Pro 1.0.5 software [19], were selected (Table 2). Although the B conformer was not as stable as A, the choice was based on observations from other NAH compounds in X-ray diffraction studies (Table 2) [17]. The theoretical results for amide NH irradiation showed that this effect should be observed mainly in H 6 and N=CH for both E (A and B) conformers and be more pronounced at N=CH in the B conformer ( Table 2).…”

Section: Determination Of the Relative Configuration Of The Imine Doumentioning

confidence: 99%

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Characterization of Amide Bond Conformers for a Novel Heterocyclic Template of N-acylhydrazone Derivatives

et al. 2013

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Herein we describe NMR experiments and structural modifications of 4-methyl-2-phenylpyrimidine-N-acylhydrazone compounds (aryl-NAH) in order to discover if duplication of some signals in their 1 H-and 13 C-NMR spectra was related to a mixture of imine double bond stereoisomers (E/Z) or CO-NH bond conformers (syn and anti-periplanar). NMR data from NOEdiff, 2D-NOESY and 1 H-NMR spectra at different temperatures, and also the synthesis of isopropylidene hydrazone revealed the nature of duplicated signals of a 4-methyl-2-phenylpyrimidine-N-acylhydrazone derivative as a mixture of two conformers in solution. Further we investigated the stereoelectronic influence of substituents at the ortho position on the pyrimidine ring with respect to the carbonyl group, as well as the OPEN ACCESSMolecules 2013, 18 11684 electronic effects of pyrimidine by changing it to phenyl. The conformer equilibrium was attributed to the decoplanarization of the aromatic ring and carbonyl group (generated by an ortho-alkyl group) and/or the electron withdrawing character of the pyrimidine ring. Both effects increased the rotational barrier of the C-N amide bond, as verified by the ΔG ≠ values calculated from dynamic NMR. As far as we know, it is the first description of aryl-NAH compounds presenting two CO-NH bond-related conformations.

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mentioning

confidence: 59%

Section: Determination Of the Relative Configuration Of The Imine Doumentioning

confidence: 99%

Characterization of Amide Bond Conformers for a Novel Heterocyclic Template of N-acylhydrazone Derivatives

et al. 2013

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“…Recently, a number of hydrazones have been prepared and structurally characterized (Wardell et al, 2006;Kummerle et al, 2009). As an extension of work on the structural characterization of hydrazones, the title compound, Fig.…”

Section: Data Collectionmentioning

confidence: 99%

“…For the crystal structures of hydrazones, see : Wardell et al (2006); Kummerle et al (2009). For bond-length data, see: Allen et al (1987).…”

Section: Related Literaturementioning

confidence: 99%

N′-(2-Chlorobenzylidene)-4-methylbenzohydrazide

Wang

Hai

2012

Acta Cryst E

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Key indicators: single-crystal X-ray study; T = 298 K; mean (C-C) = 0.003 Å; R factor = 0.037; wR factor = 0.104; data-to-parameter ratio = 11.9.In the title compound, C 15 H 13 ClN 2 O, the molecule displays a trans conformation with respect to the C N bond. The two aromatic rings form a dihedral angle of 12.0 (3) . In the crystal, molecules are connected via N-HÁ Á ÁO hydrogen bonds into chains propagating along the c-axis direction. Related literature

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“…In this context, we have described previously the platelet antiaggregating profile of a series of 2-pyridynylhydrazones 5 6 and N-acylhydrazone (NAH) derivatives from phenothiazine 6 7 and 1,3-benzodioxolyl series, for example LASSBio-294 7 and LASSBio-785 8 have also potent inotropic 9 and vasodilator properties 10,11 ( Figure 2). The NAH subunit has been described as the pharmacophoric framework of several bioactive substances from different therapeutic classes 12,13 , indicating the privileged status of this moiety, as has been recently reviewed 14 .…”

Section: Introductionmentioning

confidence: 99%

Novel furfurylidene N-acylhydrazones derived from natural safrole: discovery of LASSBio-1215, a new potent antiplatelet prototype

Rodrigues

Costa

Santos

et al. 2011

Journal of Enzyme Inhibition and Medicinal Chemistry

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Studies towards the identification of putative bioactive conformation of potent vasodilator arylidene N-acylhydrazone derivatives

Cited by 73 publications

References 20 publications

Characterization of Amide Bond Conformers for a Novel Heterocyclic Template of N-acylhydrazone Derivatives

Characterization of Amide Bond Conformers for a Novel Heterocyclic Template of N-acylhydrazone Derivatives

N′-(2-Chlorobenzylidene)-4-methylbenzohydrazide

Novel furfurylidene N-acylhydrazones derived from natural safrole: discovery of LASSBio-1215, a new potent antiplatelet prototype

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