Synthesis, crystal structure and local anti-inflammatory activity of L-phenylalanine methyl ester derivative of dexamethasone-derived cortienic acid

Abstract

L-phenylalanine methyl ester derivative of dexamethasone – derived cortienic acid (DF) was synthesized and its crystal structure was characterized by X-ray diffraction method. The crystal system is orthorhombic with space group P2₁2₁2₁ and cell constants a = 8.2969 (3) Å, b = 18.9358 (8) Å, c = 20.0904 (6) Å, V = 3156.4 (2) ų and Z = 4.  Ring A of the steroid nucleus and phenyl ring in the 17β-side chain are almost planar. Rings B and C have a slightly distorted chair conformation, whereas ring D has an envelope conformation. The packing of DF is characterized by a network of intermolecular hydrogen bonds involving the O4 atom from one side of the steroid nucleus and O1 and F1 atoms from the other side as hydrogen bond acceptors. Apart from the intermolecular hydrogen bonds in the crystal packing, there are also numerous intramolecular hydrogen bonds of the N–H...O, C–H...O and C–H...F type. Local anti-inflammatory activity of DF was evaluated by use of croton oil-induced ear edema test. This derivative achieved maximal inhibition of ear edema at significantly lower concentration in comparison with dexamethasone.