Privileged Structures: A Useful Concept for the Rational Design of New Lead Drug Candidates

Duarte, Carolina D.; Barreiro, Eliezer J.; Fraga, Carlos A.M.

doi:10.2174/138955707782331722

Cited by 284 publications

(164 citation statements)

References 0 publications

Supporting

Mentioning

159

Contrasting

Unclassified

Order By: Relevance

“…The bioactive N-acylhydrazone (NAH) moiety has been identified in a great number of lead compounds that act on different types of molecular targets [1][2][3][4]. Because of the assemblage of amide and imine functions, NAH compounds may exist as C=N double bond stereoisomers (E/Z) (Scheme 1) and as syn/antiperiplanar conformers about the amide CO-NH bond (Scheme 1) [5].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2013

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

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

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…Alternatively, as multifunctional compounds can be conceived as molecules with improved efficacy, 50 some activities described above can be conjugated in a synergic way in order to achieve a better pharmacological profile, such as the antiviral and the immunostimulating activities of some GLA-amino acid conjugates, shown in Schemes 1 through 4. Ultimately, GL and GLA may be considered for its several pharmacological activities as privileged structures, 51 and potentially useful as scaffold for the design of new pharmacologically active compounds. …”

Section: New Pharmacological Activities Reported For Gl and Glamentioning

confidence: 99%

Glycyrrhizin and glycyrrhetic acid: scaffolds to promising new pharmacologically active compounds

Graebin¹,

Verli²,

Guimarães³

2010

J. Braz. Chem. Soc.

View full text Add to dashboard Cite

O ácido glicirrizínico (GL), também conhecido como glicirrizina, é uma saponina triterpênica, um produto natural encontrado na raiz de Glycyrrhyza glabra L. ("licquorice" ou "alcaçuz"), utilizada mundialmente como edulcorante e também na medicina tradicional do Oriente. Este artigo de revisão enfoca os novos compostos sintetizados usando GL ou sua aglicona, o ácido glicirretínico (GLA), como materiais de partida e as atividades farmacológicas descritas para os mesmos e seus derivados.Glycyrrhizinic acid (GL), also known as glycyrrhizin, is a triterpene saponin, a natural product found on the root of Glycyrrhyza glabra L. ("licquorice"), used worldwide as sweetener and in the traditional eastern medicines. This review is focused on a series of new derivatives synthesized using GL and its aglycon, glycyrrhetinic acid (GLA), as starting materials, the pharmacological activities described for those compounds, as well as new activities reported for GL and GLA themselves.

show abstract

“…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 . So, in the scope of a research program aiming to design, synthesize, and perform the pharmacological evaluation of new platelet antiaggregating lead-compound candidates, we developed new functionalized furyl 1,3-benzodioxolyl-N-acylhydrazone derivatives 9 (Figure 2), designed as isosteres of the antiplatelet thienyl-NAH derivatives 7 and 8.…”

Section: Introductionmentioning

confidence: 98%

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

View full text Add to dashboard Cite

show abstract

Privileged Structures: A Useful Concept for the Rational Design of New Lead Drug Candidates

Cited by 284 publications

References 0 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

Glycyrrhizin and glycyrrhetic acid: scaffolds to promising new pharmacologically active compounds

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

Contact Info

Product

Resources

About