Mahmood-ul-Hassan Khan

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 POCl3. 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.

Synthesis, anti-HIV activity and molecular modeling study of 3-aryl-6-adamantylmethyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives

Abstract A series of novel 3-aryl-6-adamantylmethyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 6a–l were synthesized by a simple method with the aim of developing novel HIV non-nucleoside reverse transcriptase inhibitors. All the synthesized compounds were structurally confirmed by spectral analyses. The structure of 6a was unambiguously verified by X-ray structure determination. The synthesized compounds were evaluated for their anti-HIV activity and four analogs displayed moderate inhibitory activity with EC50 values ranging from 10.10 to 12.40 μg mL–1. Molecular docking of 6g with HIV-1 reverse transcriptase was studied to rationalize some structure-activity relationships (SARs).

Synthesis, crystal structure, anti-HIV, and antiproliferative activity of new oxadiazole and thiazole analogs

A series of 2-adamantyl-5-arylthiazolyl-1,3,4-oxadiazoles 7a–x together with thiazoles 13 and 14 were synthesized. Compounds 7a–l, 13, and 14 were tested in vitro with the aim of identifying novel lead compounds active against human immunodeficiency virus type-1 and human immunodeficiency virus type-2 activity in MT-4 cells. Title compounds were also tested against representatives of Gram-positive and Gram-negative bacteria (Staphylococcus aureus, Salmonella spp.), various mycobacterial strains (Mycobacterium fortuitum and Mycobacterium smegmatis), yeast (Candida albicans), and mold (Aspergillus fumigatus). None of the compounds showed antiviral or antimicrobial activity, except compounds 13 and 14 exhibited anti-human immunodeficiency virus-1 activity with EC50 values of 1.79 and 2.39 μM with Selectivity index = 18 and 4, respectively. On the other hand, compounds 7a and 7j showed a marked cytotoxicity against the human CD4+ lymphocytes (MT-4). Therefore, 7a and 7j were evaluated for their antiproliferative activity against two solid tumor-derived cell lines, which exhibited IC50 values of 8.1 ± 0.10 µM and 4.8 ± 0.08 µM against Hep-G2 cell lines, respectively.

6-(1-Adamant­yl)-3-(2-fluoro­phen­yl)-1,2,4-triazolo[3,4-b][1,3,4]thia­diazole

In the title compound, C19H19FN4S, the planes of the 2-fluorophenyl and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole ring systems are oriented at a dihedral angle of 48.98 (6)°. In the crystal, weak C—H⋯S and C—H⋯π interactions may help to establish the packing and π–π interactions between the centroids of the benzene rings at a distance of 3.8792 (13) Å occur.

4-Bromo­thio­benzamide

The title compound, C7H6BrNS, crystallizes with two molecules in the asymmetric unit. The dihedral angles between the aromatic ring and the thioamide fragment are 23.6 (4) and 20.5 (3)° in the two molecules. In the crystal, there are intermolecular N—H⋯S hydrogen-bonding interactions between the amine group and the S atoms.

3-Methyl-thio-benzamide.

In the title compound, C8H9NS, the dihedral angle between the aromatic ring and the thioamide fragment is 36.0 (2)°. There are π-stacking interactions between coplanar aryl fragments, with a centroid–centroid separation of 3.658 (2) Å. In addition, there are intermolecular hydrogen bonds between the amino group and the S atoms.

4-Chloro-benzothio-amide.

In the title compound, C7H6ClNS, the dihedral angle between the aromatic ring and the thioamide fragment is 28.1 (2)°. The structure features a π-stacking interaction between the aromatic rings with a slight offset of the rings, giving a centroid–centroid separation of 3.7942 (2) Å. There are intermolecular hydrogen-bonding interactions between the amino group and the S atoms.

Synthesis, Crystal Structure and Antiproliferative Activity of 6-Adamantyl-3-aryl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles

A series of 3,6-disubstituted [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 5a - l bearing an adamantyl moiety were synthesized by condensation of 4-amino-5-aryl-2H-1,2,4-triazole-3(4H)-thiones 4a -l with adamantyl-1-carboxylic acid in the presence of POCl3. The structures of the newly synthesized compounds were established using spectroanalytical techniques and verified further by the crystal structure determination of compounds 5a and 5j. The compounds were screened for their antiproliferative activity against a large panel of human cell lines. Graphical Abstract Synthesis, Crystal Structure and Antiproliferative Activity of 6-Adamantyl-3-aryl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles

6-(Adamantan-1-yl)-3-(3-fluoro­phen­yl)-1,2,4-triazolo[3,4-b][1,3,4]thia­diazole

The title molecule, C19H19FN4S, displays C s molecular symmetry, in which the crystallographic mirror plane bisects the adamantan-1-yl unit while the 3-fluorophenyl triazole ring is located on the mirror plane. The F atom of the 3-fluorophenyl ring is positionally disordered [occupancy ratio 0.9:0.1]. In the crystal, π–π interactions between the triazole and phenyl rings occur [centroid–centroid distance = 3.5849 (7) Å] and weak C—H⋯F interactions form a ribbon propagating in [010].