Synthesis, crystal structure and biological evaluation of some novel 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles and 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines.

Nitrogen-containing heterocycles are of particular interest and significant importance for the discovery of potent bioactive agents in pharmaceutical industry. The present study reports the synthesis of a library of new conjugated heterocycles including 3,6-disubstituted-1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazoles (4a-g and 5a-e) and 3,6-disubstituted-1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazines (6a-h), by cyclocondensation reaction of 4-amino-5-(pyridin-4-yl)-4H-1,2,4-triazole-3-thiol 3 with various substituted aromatic acids and phenacyl bromides, respectively. The structures of newly synthesized compounds were characterized by elemental analysis, IR, (1)H and (13)C NMR spectroscopy and in case of 4c by X-ray crystallographic analysis.

Synthesis, urease inhibition, antioxidant, antibacterial, and molecular docking studies of 1,3,4-oxadiazole derivatives.

A series of eighteen 1,3,4-oxadiazole derivatives have been synthesized by treating aromatic acid hydrazides with carbon disulfide in ethanolic potassium hydroxide yielding potassium salts of 1,3,4-oxadiazoles. Upon neutralization with 1 N hydrochloric acid yielded crude crystals of 1,3,4-oxadiazoles, which were purified by recrystallization in boiling methanol. The synthesized 1,3,4-oxadiazoles derivatives were evaluated in vitro for their urease inhibitory activities, most of the investigated compounds were potent inhibitors of Jack bean urease.

Synthesis, antioxidant activities and urease inhibition of some new 1,2,4-triazole and 1,3,4-thiadiazole derivatives.

New series of 4,5-disubstituted-2,4-dihydro-3H-1,2,4-triazole-3-thiones (8a-j) and 2,5-disubstituted-1,3,4-thiadiazoles (9a-h) were synthesized by dehydrative cyclization of hydrazinecarbothioamide derivatives (7a-k) by refluxing in 4N aqueous sodium hydroxide and by overnight stirring with polyphosphoric acid, respectively. The structures of the newly synthesized compounds were characterized by IR, (1)H NMR, (13)C NMR, elemental analysis and mass spectroscopic studies and the synthesized compounds were screened for their antioxidant and urease inhibition activities. N-(2,4-Dimethylphenyl)-5-(4-nitrophenyl)-1,3,4-thiadiazol-2-amine (9h) showed excellent antioxidant activity more than the standard drug whereas 4-(2,4-dimethylphenyl)-5-(3-nitrophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (8d) and 4-(2,3-dimethylphenyl)-5-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (8e) exhibited potent urease inhibitory activities.

Identification of novel urease inhibitors by high-throughput virtual and in vitro screening.

Ureases are important in both agriculture and human health. Bacterial ureases are directly involved in many farm-field problems and pathological conditions. Here, we report a structure-based virtual screening of an in-house compound bank of about 6000 molecular entities by computational docking and binding free energy calculations followed by in vitro screening.

2-(2-Fluoro-biphenyl-4-yl)-N'-(propan-2-yl-idene)propanohydrazide.

In the title compound, C(18)H(19)FN(2)O, the hydrazide side chain is approximately perpendicular to the central ring [dihedral angle = 76.80 (5)°]. The F atom is disordered over two positions with occupancies of 0.

3-(4-Fluoro-benz-yl)-1H-isochromene-1-thione.

In the mol-ecule of the title compound, C(16)H(11)FOS, the benzene ring is oriented at a dihedral angle of 89.68 (3)° with respect to the planar [maximum deviation 0.009 (2) Å] isocoumarin ring system.

3-Benzyl-isochroman-1-one.

In the mol-ecule of the title compound, C(16)H(14)O(2), the aromatic rings are oriented at a dihedral angle of 78.49 (3)°. The heterocyclic ring adopts a twist conformation.

4-(4-Methoxy-phen-yl)-3-[2-(2-methoxy-phen-yl)eth-yl]-1H-1,2,4-triazol-5(4H)-one.

The title compound, C(18)H(19)N(3)O(3), is a biologically active triazole derivative. The five-membered ring is oriented with respect to the six-membered rings at dihedral angles of 51.59 (4) and 61.

3-(3-Fluoro-benz-yl)isochroman-1-one.

In the mol-ecule of the title compound, C(16)H(13)FO(2), the aromatic rings are oriented at a dihedral angle of 74.46 (4)°. The heterocyclic ring adopts a twisted conformation.

4-(3-Methoxy-phen-yl)-3-[2-(4-methoxy-phen-yl)eth-yl]-1H-1,2,4-triazol-5(4H)-one.

The asymmetric unit of the title compound, C(18)H(19)N(3)O(3), contains two crystallographically independent but similar mol-ecules. The triazole ring is oriented with respect to the benzene rings to form dihedral angles of 57.96 (6) and 7.

5-(2-Methoxy-benz-yl)-4-(2-methoxy-phen-yl)-4H-1,2,4-triazol-3-ol.

In the mol-ecule of the title compound, C(17)H(17)N(3)O(3), the triazole ring is oriented at dihedral angles of 88.09 (3) and 83.72 (3)° with respect to the 2-methoxy-benzyl and 2-methoxy-phenyl rings, respectively.

3-(3-Bromo-benz-yl)isoquinolin-1(2H)-one.

In the title compound, C(16)H(12)BrNO, the ring systems subtend an inter-planar dihedral angle of 75.95 (3)°. In the crystal packing, mol-ecules are linked to form centrosymmetric pairs by pairs of classical N-H⋯O hydrogen bonds.

3-(3-Bromo-benz-yl)-1H-isochromen-1-one.

In the title compound, C(16)H(11)BrO(2), the isocoumarin ring system is planar (r.m.s.

Methyl 3-(4-methoxy-benzo-yl)propionate.

The asymmetric unit of the title compound, C(12)H(14)O(3), contains two independent mol-ecules, in which the benzene rings are oriented at a dihedral angle of 72.08 (3)°. In the crystal structure, inter-molecular C-H⋯O hydrogen bonds link the mol-ecules into centrosymmetric dimers.

3-(3-Methoxy-benz-yl)-4-(2-methoxy-phen-yl)-1H-1,2,4-triazole-5(4H)-thione.

In the title compound, C(17)H(17)N(3)O(2)S, the five-membered ring forms dihedral angles of 53.02 (3) and 78.57 (3)° with the 3-meth-oxy-substituted and 2-meth-oxy-substituted benzene rings, respectively.

2-(2-Fluoro-benzoyl-meth-yl)benzoic acid.

In the title compound, C(15)H(11)FO(3), the aromatic rings are oriented at a dihedral angle of 69.26 (3)°. In the crystal structure, inversion dimers arise from pairs of inter-molecular O-H⋯O hydrogen bonds, and C-H⋯O hydrogen bonds further consolidate the packing.

1-(3-Chloro-benz-yl)-5-iodo-indoline-2,3-dione.

In the title compound, C(15)H(9)ClINO(2), which possesses anticonvulsant activity, the iodo-indoline ring system is essentially planar (maximum deviation 1.245 Å) and is oriented with respect to the 3-chloro-benzyl ring at a dihedral angle of 76.59 (3)°.

3-(4-Ethoxy-benzo-yl)propionic acid.

The title compound, C(12)H(14)O(4), is an important inter-mediate in the synthesis of biologically active heterocyclic compounds. In the crystal structure, inter-molecular O-H⋯O and C-H⋯O hydrogen bonds link the mol-ecules. There are also C-H⋯π contacts between the benzene ring and the methyl-ene groups.

2-[(4-Chloro-benz-yl)carbonyl-meth-yl]benzoic acid.

The title compound, C(16)H(13)ClO(3), is an important inter-mediate in the conversion of isocoumarin to 3,4-dihydro-isocoumarin. The two aromatic rings are oriented at a dihedral angle of 67.18 (3)°.

5-(3-Methoxy-pheneth-yl)-4-(2-methoxy-phen-yl)-4H-1,2,4-triazol-3-ol.

In the mol-ecule of the title compound, C(18)H(19)N(3)O(3), the triazole ring is oriented with respect to the 3-methoxy-phenyl and 2-methoxy-phenyl rings at dihedral angles of 11.79 (3) and 89.22 (3)°, respectively.

3-(3-Chloro-benz-yl)-1H-isochromen-1-one.

The asymmetric unit of the title compound, C(16)H(11)ClO(2), a chemically synthesized isocoumarin, contains three independent mol-ecules. The benzopyran and benzene rings are approximately perpendicular to each other, forming dihedral angles ranging from 83.08 (14) to 87.

Methyl 2,5-dichloro-benzoate.

In the mol-ecule of the title compound, C(8)H(6)Cl(2)O(2), the benzene ring is oriented with respect to the planar ester group at a dihedral angle of 39.22 (3)°.

(E)-3-(3,5-Dimethoxy-phen-yl)acrylo-hydrazide.

In the title compound, C(11)H(14)N(2)O(3), the planar hydrazide group is oriented with respect to the benzene ring at a dihedral angle of 48.00 (3)°. In the crystal structure, inter-molecular N-H⋯O hydrogen bonds link the mol-ecules.

4-(2-Methoxy-phenyl)-3-(3,4,5-tri-methoxy-phen-ethyl)-2H-1,2,4-triazole-5(4H)-thione.

The title compound, C(20)H(23)N(3)O(4)S, is an important biologically active heterocyclic compound. The five-membered ring is oriented with respect to the six-membered rings at dihedral angles of 78.60 (3) (trimethoxyphenyl ring) and 71.