Synthesis of 4-methoxybenzoylhydrazones and evaluation of their antiglycation activity.

A series of 4-methoxybenzoylhydrazones 1-30 was synthesized and the structures of the synthetic derivatives elucidated by spectroscopic methods. The compounds showed a varying degree of antiglycation activity, with IC50 values ranging between 216.52 and 748.71 µM, when compared to a rutin standard (IC50=294.46±1.50 µM). Compounds 1 (IC50=216.52±4.2 µM), 3 (IC50=289.58±2.64 µM), 6 (IC50=227.75±0.53 µM), 7 (IC50=242.53±6.1) and 11 (IC50=287.79±1.59) all showed more activity that the standard, and these compounds have the potential to serve as possible leads for drugs to inhibit protein glycation in diabetic patients. A preliminary SAR study was performed.

(E)-4-Meth-oxy-N'-(3,4,5-trihy-droxy-benzyl-idene)benzohydrazide methanol monosolvate.

The title compound, C(15)H(14)N(2)O(5)·CH(3)OH, displays an E conformation about the azomethine double bond [C=N = 1.277 (2) Å] and the benzene rings are inclined to one another by 18.28 (9)°. An intra-molecular O-H⋯O hydrogen bond occurs between the para-OH group and one of the meta-O atoms of the 3,4,5-trihy-droxy-benzyl-idene group. In the crystal, the components are linked into a three dimensional network by O-H⋯O, O-H⋯N and C-H⋯O hydrogen bonds.

Methyl (E)-3,5-dimeth-oxy-2-{[2-(4-meth-oxy-benzo-yl)hydrazin-1-yl-idene]meth-yl}benzoate.

In the title compound, C(19)H(20)N(2)O(6), the azomethine [C=N = 1.269 (2) Å] double bond adopts an E conformation and the dihedral angle between the planes of the benzene rings is 17.41 (11)°. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds generate R(2) (2)(16) loops. The dimers are connected by C-H⋯O and C-H⋯N hydrogen bonds, forming sheets lying parallel to (100).

(E)-4-Meth-oxy-N'-[(pyridin-4-yl)methyl-idene]benzohydrazide monohydrate.

In the title compound, C(14)H(13)N(3)O(2)·H(2)O, the azomethine double bond adopts an E conformation and the N-N=C-C torsion angle is 178.37 (19)°. The dihedral angle between the benzene and pyridine rings is 5.58 (12)° and the C atom of the meth-oxy group is roughly coplanar with its attached ring [deviation = 0.157 (3) Å]. In the crystal, the components are linked by O-H⋯O, O-H⋯N, N-H⋯O and C-H⋯O hydrogen bonds, forming (001) sheets. The water O atom accepts one N-H⋯O and two C-H⋯O inter-actions from the adjacent organic mol-ecule.

(E)-N'-(3,4-Dimeth-oxy-benzyl-idene)-4-meth-oxy-benzohydrazide.

In the title compound, C(17)H(18)N(2)O(4), the azomethine double bond adopts an E conformation with an N-N-C-C torsion angle of -178.3 (3)°. The benzene rings are almost coplaner, with a dihedral angle of 2.98 (14)° between their mean planes. In the crystal, the molecules are linked by N-H⋯O hydrogen bonds, resulting in chains of mol-ecules lying parallel to the b axis. The structure is further consolidated by rather weak C-H⋯O hydrogen-bonding inter-actions, resulting in six-membered rings about inversion centers linked into chains arranged parallel to the b axis.