Synthesis, crystal structure and anti-HIV activity of 2-adamantyl/adamantylmethyl-5-aryl-1,3,4-oxadiazoles.

Two series of 2-adamantyl/adamantylmethyl-5-aryl-1,3,4-oxadiazoles (4a-l and 5a-l) were synthesized by cyclodehydration of adamantan-1-carboxylic acid/adamantylacetic acid with various aryl hydrazides (3a-l) in the presence of POCl(3). The synthesis was supported by spectroanalytical techniques and verified further by crystal structure determination of compounds 4e and 5k. The synthesized compounds were screened for their inhibitory activity against HIV-1 and HIV-2 in MT-4 cells. Compound 5b exhibited a moderate activity in vitro for the replication of both virus types, suggesting for further structural modification as a new lead in the development of an antiviral agent.

6-(1-Adamant-yl)-3-(2-chloro-phen-yl)-1,2,4-triazolo[3,4-b][1,3,4]thia-diazole.

In the title compound, C(19)H(19)ClN(4)S, the 2-chloro-phenyl and [1,2,4]triazolo[3,4-b] [1,3,4]thia-diazole fragments (r.m.s. deviations of 0.015 and 0.017 Å, respectively) are oriented at a dihedral angle of 55.76 (6)°. The adamantane group exhibits extensive rotational disorder about the single C-C bond to the thia-diazole ring, which was modelled as occupying four orientations each with 0.25 occupancy. In the crystal, the chloro-phenyl rings exhibit π-π stacking inter-actions with centroid-centroid distances of 3.9526 (18) Å.

6-(Adamantan-1-yl)-3-(3-fluoro-phen-yl)-1,2,4-triazolo[3,4-b][1,3,4]thia-diazole.

The title mol-ecule, C(19)H(19)FN(4)S, displays C(s) mol-ecular symmetry, in which the crystallographic mirror plane bis-ects the adamantan-1-yl unit while the 3-fluoro-phenyl triazole ring is located on the mirror plane. The F atom of the 3-fluoro-phenyl ring is positionally disordered [occupancy ratio 0.9:0.1]. In the crystal, π-π inter-actions between the triazole and phenyl rings occur [centroid-centroid distance = 3.5849 (7) Å] and weak C-H⋯F inter-actions form a ribbon propagating in [010].

4-Bromo-thio-benzamide.

The title compound, C(7)H(6)BrNS, crystallizes with two mol-ecules in the asymmetric unit. The dihedral angles between the aromatic ring and the thio-amide fragment are 23.6 (4) and 20.5 (3)° in the two mol-ecules. In the crystal, there are inter-molecular N-H⋯S hydrogen-bonding inter-actions between the amine group and the S atoms.

6-(1-Adamant-yl)-3-(2-fluoro-phen-yl)-1,2,4-triazolo[3,4-b][1,3,4]thia-diazole.

In the title compound, C(19)H(19)FN(4)S, the planes of the 2-fluoro-phenyl and 1,2,4-triazolo[3,4-b][1,3,4]thia-diazole ring systems are oriented at a dihedral angle of 48.98 (6)°. In the crystal, weak C-H⋯S and C-H⋯π inter-actions may help to establish the packing and π-π inter-actions between the centroids of the benzene rings at a distance of 3.8792 (13) Šoccur.

3-Methyl-thio-benzamide.

In the title compound, C(8)H(9)NS, the dihedral angle between the aromatic ring and the thio-amide fragment is 36.0 (2)°. There are π-stacking inter-actions between coplanar aryl fragments, with a centroid-centroid separation of 3.658 (2) Å. In addition, there are inter-molecular hydrogen bonds between the amino group and the S atoms.

4-Chloro-benzothio-amide.

In the title compound, C(7)H(6)ClNS, the dihedral angle between the aromatic ring and the thio-amide fragment is 28.1 (2)°. The structure features a π-stacking inter-action between the aromatic rings with a slight offset of the rings, giving a centroid-centroid separation of 3.7942 (2) Å. There are inter-molecular hydrogen-bonding inter-actions between the amino group and the S atoms.