Quinazoline-containing Hydrazydes of Dicarboxylic Acids and Products of Their Structural Modification: A Novel Class of Anti-inflammatory Agents

The synthesis of hydrazides formed by quinazolin-4(3H)-ylidenehydrazine and dicarboxylic acids, as well as their further modification are described in the present manuscript. It was shown that above-mentioned hydrazides may be obtained via acylation of initial quinazolin-4(3H)-ylidenehydrazine by corresponding acylhalides, cyclic anhydrides and imidazolides of dicarboxylic acids monoesters. Obtained hydrazides were converted into [1,2,4]triazolo[1,5-с]quinazolines that were used as initial compounds for chemical modification aimed to the introduction of amide fragment to the molecule. The IR, 1H NMR and chromato-mass spectral data of obtained compounds were studied and discussed. Obtained substances were studied for anti-inflammatory activity using carrageenan-induced paw inflammation model. Amides of ([1,2,4]triazolo[1,5-с]quinazoline-2-yl)alkyl carboxylic acids were detected as promising class of anti-inflammatory agents for further purposeful synthesis and profound study of anti-inflammatory activity.

The solvent nature influence on the self-assembly of monosubstituted pillar[5]arenes containing N-(aminoalkyl)amide fragment

Chemistry of macrocyclic compounds is one of the rapidly developing areas of modern organic chemistry. These macrocycles have become widespread due to the high availability of parents compounds, the possibility of synthesis of ligands based on them for highly selective recognition, ion-selective membranes, electrodes, sensors and nanocontainers for targeted drug delivery. Moreover, in the past few years, attention of researchers has again been riveted on mechanically interlocked molecules (rotaxanes and pseudorotaxans) and supramolecular polymers, which can be explained by their potential application as molecular machines and materials. Mechanically interlocked molecules are molecular architectures consisting from two or more components which mechanically bind due to their own topology. Supramolecular polymers are comprise ordered monomer units combined via non-covalent bonds (hydrogen bonds or electrostatic interactions). Thus, this manuscript presents an approach to the synthesis of monosubstituted pillar[5]arenes containing N-(aminoalkyl)amide fragments with various substituent lengths. The formation of self-inclusion complexes by synthesized macrocycles was established by one- and two-dimensional NMR spectroscopy. According to NMR data, only four carbon atoms of the alkyl fragment were included in the macrocyclic cavity regardless of the alkyl chain length. Formation of self-inclusion complexes becomes possible due to the intramolecular hydrogen bond between the NH protons and the oxygen atom of methoxyl fragment, which is confirmed by IR spectroscopy. It was shown by dynamic light scattering that the synthesized pillar[5]arenes in chloroform form aggregates with an average hydrodynamic diameter of 316-640 nm and polydispersity index from 0.18 to 0.20, while polydisperse systems are formed in dimethyl sulfoxide.

Crystal structure of 4-[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl] 2-methyl (2S,4S,5R)-1-[(2S,3R,5R)-5-methoxycarbonyl-2-(2-methylphenyl)pyrrolidine-3-carbonyl]-5-(2-methylphenyl)pyrrolidine-2,4-dicarboxylate

The title compound, C38H50N2O7, represents a chiral β-proline dipeptide. Corresponding stereogenic centres of constituting pyrrolidine units have opposite absolute configurations. The central amide fragment is planar within 0.1 Å and adopts a Z configuration along the N—CO bond. In the crystal, the hydrogen atoms of the methylene groups form several short intermolecular C—H...O contacts with the carbonyl oxygen atoms of an adjacent molecule. The only active amino hydrogen atom is not involved in hydrogen bonding.

2,4-Dichloro-N-(2,5-dioxopyrrolidin-1-yl)benzamide

In the title compound, C11H8Cl2N2O3, the plane of the pyrrolidine ring (r.m.s. deviation = 0.065 Å) makes a dihedral angle of 52.9 (2)° with the plane of the benzene ring. The least-squares plane of the central amide fragment makes dihedral angles of 49.3 (7) and 77.9 (7)° with those of the benzene and pyrrolidine rings, respectively. In the crystal, molecules are linked via N—H...O hydrogen bonds, forming chains along the b-axis direction. π–π interactions link these chains into a two-dimensional network parallel to (100).

Supramolecular motifs for the self-assembly of monosubstituted pillar[5]arenes with an amide fragment: from nanoparticles to supramolecular polymers

The effects of solvents on the aggregation properties of novel monosubstituted pillar[5]arenes containing an N-alkylamide fragment have been investigated.

Crystal structure ofN-(2-hydroxy-5-methylphenyl)benzamide

In the title compound, C14H13NO2, the mean plane of the non-H atoms of the central amide fragment C—N—C(=O)—C (r.m.s. deviation = 0.029 Å) forms dihedral angles of 5.63 (6) and 10.20 (5)° with the phenyl and hydroxyphenyl rings, respectively. A short intramolecular N—H...O contact is present. In the crystal, the molecules are linked by O—H...O hydrogen bonds to generateC(7) chains along [100]. The chains are reinforced by weak C—H...O contacts, which together with the O—H...O bonds lead toR22(7) loops. Very weak N—H...O interactions link the molecules into inversion dimers.

Crystal structure of 2-fluoro-N-(1,3-thiazol-2-yl)benzamide

In the title compound, C10H7FN2OS, the mean plane of the central amide fragment (r.m.s. deviation = 0.048 Å) makes dihedral angles of 35.28 (8) and 10.14 (12)° with those of the fluorobenzene and thiazole rings, respectively. The thiazole S and amide O atoms lie to the same side of the molecule. In the crystal, pairs of N—H...N hydrogen bonds connect the molecules into inversion dimers withR22(8) motifs, and weak C—H...O interactions connect the molecules intoC(6) [001] chains. Together, the N—H...N and C—H...O hydrogen bonds generate (100) sheets.

Crystal structure of 3-chloro-N-(2-nitrophenyl)benzamide

In the title compound, C13H9ClN2O3, the mean plane of the central amide fragment (r.m.s. deviation = 0.016 Å) subtends dihedral angles of 15.2 (2) and 8.2 (2)° with the chloro- and nitro-substituted benzene rings, respectively. An intramolecular N—H...O hydrogen bond generates anS(6) ring. In the crystal, molecules are linked by weak C—H...O hydrogen bonds, formingC(7) chains which propagate along [010], but no Cl...Cl short contacts are observed.

Crystal structure of 2-nitro-N-(2-nitrophenyl)benzamide

In the title compound, C13H9N3O5, the mean plane of the non-H atoms of the central amide fragment C—N—C(=O)—C [r.m.s. deviation = 0.0442 Å] forms dihedral angles of 71.76 (6) and 24.29 (10)° with the C-bonded and N-bonded benzene rings, respectively. In the crystal, molecules are linked by N—H...O hydrogen bonds formingC(4) chains along [100]. Weak C—H...O contacts link the molecules into (100) sheets containing edge-fusedR44(30) rings. Together, the N—H...O and C—H...O hydrogen bonds generate a three-dimensional network.