Crystal structure of 2-[(4-bromobenzyl)thio]-5-(5-bromothiophen-2-yl)-1,3,4-oxadiazole, C₁₃H₈Br₂N₂OS₂

C13H8Br2N2OS2, monoclinic, Pc (no. 7), a = 13.4050(4) angstrom, b = 4.7716(1) angstrom, c = 11.7303(4) angstrom, beta = 105.885( 3)degrees, V = 721.66(4) angstrom(3), Z = 2, R-gt(F) = 0.0294, wR(ref) (F-2 = 0.0808, T = 160K

4-(2-Methoxyphenyl)piperazin-1-ium 6-chloro-5-isopropyl-2,4-dioxopyrimidin-1-ide

In the cation of the title salt, C11H17N2O+.C7H8ClN2O2 -, the piperazine ring adopts a distorted chair conformation and contains a positively charged N atom with quaternary character. Its mean plane makes a dihedral angle of 42.36 (8)� with the phenyl ring of its 2-methoxyphenyl substituent. The 2,4-dioxopyrimidin-1-ide anion is generated by deprotonation of the N atom at the 1-position of the pyrimidinedione ring. Intramolecular C—H...O hydrogen bonds generate S(6) ring motifs in both the cation and the anion. In the crystal, N—H...O, N—H...N and C—H...O hydrogen bonds are also observed, resulting in a twodimensional network parallel to the ab plane. The crystal stability is further consolidated by weak C—H...n interactions

3-(Adamantan-1-yl)-4-benzyl-1H-1,2,4-triazole-5(4H)-thione

The title compound, C19H23N3S, is a functionalized triazoline-3-thione derivative. The benzyl ring is almost normal to the planar 1,2,4-triazole ring (r.m.s. deviation = 0.007 A°) with a dihedral angle of 86.90 (7)°. In the crystal, molecules are linked by pairs of N—H...S hydrogen bonds, forming inversion dimers that enclose R2/2(8) loops. The crystal packing is further stabilized by weak C—H...n interactions that link adjacent dimeric units into supramolecular chains extending along the a-axis direction

Crystal structure of 3-[(4-benzylpiperazin-1-yl)methyl]-5-(thiophen-2-yl)- 2,3-dihydro-1,3,4-oxadiazole-2-thione

The title 1,3,4-oxadiazole-2-thione derivative, C18H20N4OS2, crystallized with two independent molecules (A and B) in the asymmetric unit. The 2-thienyl rings in both molecules are rotationally disordered over two orientations by approximately 180� about the single C—C bond that connects it to the oxadiazole thione ring; the ratios of site occupancies for the major and minor components were fixed in the structure refinement at 0.8:0.2 and 0.9:0.1 in molecules A and B, respectively. The 1,3,4-oxadiazole-2-thione ring forms dihedral angles of 7.71 (16), 10.0 (11) and 77.50 (12)� (molecule A), and 6.5 (3), 6.0 (9) and 55.30 (12)� (molecule B) with the major and minor parts of the disordered thiophene ring and the mean plane of the adjacent piperazine ring, respectively, resulting in approximately V-shaped conformations for the molecules. The piperazine ring in both molecules adopts a chair conformation. The terminal benzene ring is inclined towards the mean plane of the piperazine ring with N—C— C—C torsion angles of �58.2 (3) and �66.2 (3)� in molecules A and B, respectively. In the crystal, no intermolecular hydrogen bonds are observed. The crystal packing features short S� � �S contacts [3.4792 (9) A ° ] and �–� interactions [3.661 (3), 3.664 (11) and 3.5727 (10) A ° ], producing a threedimensional network

Nonclassical antifolate compounds as dihydrofolate reductase inhibitors: synthesis and biological evaluation

Submitted In Partial Fulfillment of the Requirements for Doctor of Philosophy Degree in Pharmaceutical Chemistry at the Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University 1430 H 2009 GDihydrofolate reductase (DHFR) catalyzes the reduction of folate or dihydrofolate into tetrahydrofolate, which then converted into N5, N10-methylenetetrahydrofolate. This later compound functions as the source of the methyl group to convert dUMP into dTMP. Inhibition of DHFR has long been an attractive goal for the development of chemotherapeutic agents against bacterial and parasitic infections as well as cancer. The aim of this research study is to locate a novel synthetic lead compound(s) for future development as DHFR inhibitors. A new series of quinazoline analogues is designed and fitted with functional groups believed to enhance the inhibition of the enzyme activity. Thirty seven compounds (including five unexpected products) belong to the aforementioned nucleus, have been synthesized. Structure elucidation of the new compounds was fulfilled based on 1H-, 13C-NMR and Mass spectrometry. The synthesized compounds were evaluated for their in vitro DHFR inhibition activity at the Department of Pharmacology, College of Pharmacy, King Saud University and for their in vitro antimicrobial activity at the Department of Microbiology, Faculty of Pharmacy, University of Mansoura, Egypt. Compounds 36, 47, 48-51, 53-57, and 59 proved to be the most active inhibitors of bovine liver DHFR in this investigation with IC50 values of 0.5, 1.0, 0.6, 0.7, 0.9, 0.6, 0.8, 0.4, 1.0, 0.5, 0.6, and 0.5 mM, respectively. Structure activity correlation of the obtained results revealed that, the DHFR inhibition activity is embedded in the structure core of the investigated compounds. The investigation findings indicated that the type of substituent at positions 2- and 6- of the studied quinazolines manipulate the DHFR inhibition activity. The synthesized compounds (23-59) were also tested for their in vitro antimicrobial activity against a panel of standard strains of Gram-positive bacteria, Gram-negative bacteria, and yeast-like pathogenic fungus. The antibacterial antibiotics Gentamicin, Ciprofloxacin, the DHFR inhibitor Sulphacetamide and the antifungal drug Clotrimazole were used as positive controls. The results revealed that compounds 23, 24, 28, 32, 37, 40- 42, 44, 47, 49, 51, and 56-59 showed varying degrees of inhibition against the tested microorganisms. Comparing the potency of the antibacterial active compounds and their DHFR inhibition results revealed that compounds 37, 49, and 57-59 might exert their antibacterial activity through DHFR inhibition. The other compounds 23, 24, 28, 32, 41, 42, and 44 with low DHFR inhibition might exert their activity through some other mechanism(s). The synthesized target compounds (23-59) have been comparatively evaluated in terms of their mode of binding to human dihydrofolate reductase (hDHFR) pocket. Molecular modeling has been performed for the proposed compounds to evaluate their recognition profiles at the hDHFR binding-pocket. This study concluded that, recognition with key amino acid Glu30 is essential for binding and also reflect promising biological activity. Also, the synthesized target compounds were subjected to flexible alignment, electrostatic, hydrophobic mappings, and pharmacophore prediction study. The main pharmacophore groups necessary for activity are: the 4-carbonyl fragment, the basic nitrogen atom at N-1, and the hydrophobic p-system regions, as well as of their relative distances

Interaction of some new 2-(substituted-thio)-quinazolin-4-ones with molybdenum hydroxylases: A pharmacophore prediction

Background: Molybdenum hydroxylases have been implicated as key oxidative enzymes in some diseases. Methods: Twenty 2-(substituted-thio)-quinazolin-4-one derivatives recently synthesized in our laboratory were examined for their inhibitory activity toward molybdenum hydroxylases. Results and conclusion: The tested quinazolines inhibited both xanthine oxidase and aldehyde oxidase enzymes in a competitive pattern with Ki values range of 66–753 μM. Pharmacophore prediction methodology was used to study the structure requirements of those inhibitors

Synthesis, Antimicrobial, and Anti-Proliferative Activities of Novel 4-(Adamantan-1-yl)-1-arylidene-3-thiosemicarbazides, 4-Arylmethyl N′-(Adamantan-1-yl)piperidine-1-carbothioimidates, and Related Derivatives

The reaction of 4-(adamantan-1-yl)-3-thiosemicarbazide 3 with various aromatic aldehydes yielded the corresponding thiosemicarbazones 4a–g. 1-Adamantyl isothiocyanate 2 was reacted with 1-methylpiperazine or piperidine to yield the corresponding N-(adamantan-1-yl)carbothioamides 5 and 6, respectively. The latter was reacted with benzyl or substituted benzyl bromides to yield the S-arylmethyl derivatives 7a–c. Attempted cyclization of 1,3-bis(adamantan-1-yl)thiourea 8 with chloroacetic acid via prolonged heating to the corresponding thiazolidin-4-one 9 resulted in desulfurization of 8 to yield its urea analogue 10. The thiazolidin-4-one 9 and its 5-arylidene derivatives 11a,b were obtained via microwave-assisted synthesis. The in vitro antimicrobial activity of the synthesized compounds was evaluated against a panel of Gram-positive and Gram-negative bacteria and yeast-like pathogenic fungus Candida albicans. Compounds 7a–c displayed marked broad spectrum antibacterial activities (minimal inhibitory concentration (MIC), 0.5–32 μg/mL) and compounds 4a and 4g showed good activity against Candida albicans. Nine representative compounds were evaluated for anti-proliferative activity towards three human tumor cell lines. Compounds 7a–c displayed significant generalized anti-proliferative activity against all the tested cell lines with IC50 < 10 μM

Crystal structure of 5-(adamantan-1-yl)-3-[(4-trifluoromethylanilino)methyl]-2,3-dihydro-1,3,4-oxadiazole-2-thione, C20H22F3N3OS

C20H22F3N3OS, triclinic, P1 (no. 1), a = 6.9678(8) Å, b = 10.7614(14) Å, c = 13.0503(14) Å, α = 76.870(3)°, β = 88.004(4)°, γ = 87.275(4)°, V = 951.60(19) Å3 , Z = 2, Rgt(F) = 0.0629, wRref(F2 ) = 0.1626, T = 100 K

Crystal structure of 2-[(4-bromobenzyl)thio]-5-(5-bromothiophen-2-yl)-1,3,4-oxadiazole, C13H8Br2N2OS2

C13H8Br2N2OS2, monoclinic, Pc (no. 7), a = 13.4050(4) Å, b = 4.7716(1) Å, c = 11.7303(4) Å, β = 105.885(3)∘, V = 721.66(4) Å3, Z = 2, Rgt(F) = 0.0294, wRref(F2 = 0.0808, T = 160 K. CCDC no.: 2271238 Table 1 contains crystallographic data and Table 2 contains the list of the atoms including atomic coordinates and displacement parameters

Crystal structure of 2-[(4-bromobenzyl)thio]-5-(5-bromothiophen-2-yl)-1,3,4-oxadiazole, C13H8Br2N2OS2

C13H8Br2N2OS2, monoclinic, Pc (no. 7), a = 13.4050(4) Å, b = 4.7716(1) Å, c = 11.7303(4) Å, β = 105.885(3)∘$105.885{(3)}^{\circ }$, V = 721.66(4) Å3, Z = 2, Rgt${R}_{gt}$(F) = 0.0294, wRref$w{R}_{ref}$(F2 = 0.0808, T = 160 K