Gomes Ligia Rebelo, Low John Nicolson, Cagide Fernando, Gaspar Alexandra, Reis Joana, Borges Fernanda
REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua Campo Alegre, 687, P-4169-007, Porto P-4200-150, Portugal.
Acta Crystallogr B Struct Sci Cryst Eng Mater. 2013 Jun;69(Pt 3):294-309. doi: 10.1107/S2052519213009676. Epub 2013 May 8.
N-phenyl-4-oxo-4H-2-chromone carboxamides were found to be inactive as MAO inhibitors in contrast with their N-phenyl-4-oxo-4H-3-chromone carboxamide isomers. In order to obtain a close insight into the docking mechanism for this family of compounds, the molecular and supramolecular structures of nine N-phenyl-4-oxo-4H-2-chromone carboxamides were determined. It was found that, in most of the secondary structures, the N(amido) and the O(carboxyl) of the carboxamide residue participate in strong intramolecular interactions, with the O atom of the chromene ring and with the H(ortho)-C (phenyl), respectively. When the phenyl ring had accessible acceptors as substituents a third intramolecular hydrogen bond was also observed. As a consequence, rotations of the chromone and phenyl rings around the N-C(alpha) and C(alpha')-C=O are constrained and the compounds were found to be more planar than would otherwise be expected. The deviation from planarity of the whole molecule can be quantified by the dihedral angles between mean planes of the aromatic rings and it was found that they were mainly affected by the degree of torsion of the phenyl ring with respect to the amide residue. The molecular conformations assumed by the secondary amides clearly contrast with that of a related tertiary amide that was also determined in this study. The unavailability of the N in this compound as a donor strongly influences the molecular isomerism and conformation. This analysis demonstrates that the molecules can be classified into four groups depending on the types of interactions formed as described above. If the secondary N(amido) of the carboximide is involved in two intramolecular interactions then this atom does not form any intermolecular contacts. In all other cases it does and the supramolecular structure formed is in most cases supplemented by weak C-H···O interactions.
与N-苯基-4-氧代-4H-3-色酮羧酰胺异构体形成对比的是，N-苯基-4-氧代-4H-2-色酮羧酰胺被发现作为单胺氧化酶（MAO）抑制剂没有活性。为了深入了解这类化合物的对接机制，测定了9种N-苯基-4-氧代-4H-2-色酮羧酰胺的分子和超分子结构。结果发现，在大多数二级结构中，羧酰胺残基的N（酰胺基）和O（羧基）分别与色烯环的O原子和H（邻位）-C（苯基）参与强烈的分子内相互作用。当苯环有可及的受体作为取代基时，还观察到第三个分子内氢键。因此，色酮环和苯环围绕N-C（α）和C（α'）-C=O的旋转受到限制，并且发现这些化合物比预期的更具平面性。整个分子的平面度偏差可以通过芳香环平均平面之间的二面角来量化，并且发现它们主要受苯环相对于酰胺残基的扭转程度影响。仲酰胺所呈现的分子构象与本研究中也测定的相关叔酰胺的构象形成明显对比。该化合物中N作为供体不可用强烈影响分子异构性和构象。该分析表明，根据上述形成的相互作用类型，分子可分为四类。如果羧酰亚胺的仲N（酰胺基）参与两个分子内相互作用，那么该原子不形成任何分子间接触。在所有其他情况下它会形成，并且在大多数情况下形成的超分子结构由弱C-H···O相互作用补充。
