Ethyl 4-{[3-(adamantan-1-yl)-4-phenyl-5-sulfanyl­idene-4,5-dihydro-1H-1,2,4-triazol-1-yl]meth­yl}piperazine-1-carboxyl­ate

The title mol­ecule, C26H35N5O2S, displays a chair-shaped piperazine ring, as well as a planar triazole ring whose phenyl substituent is perpendicular to the mean plane of the five-membered ring [dihedral angle = 90.00 (13)°]. The methyl­ene substituent on the piperazine ring occupies an equatorial site. Weak inter­molecular C—H⋯O hydrogen bonding is present in the crystal structure. The crystal studied was a non-merohedral twin, with a 33.9 (3)% minor component

1-[(Cyclo­propyl­meth­oxy)meth­yl]-5-ethyl-6-(4-methyl­benzyl)-1,2,3,4-tetra­hydro­pyrimidine-2,4-dione

The pyrimidine ring in the title compound, C19H24N2O3, is nearly planar (r.m.s. deviation = 0.008 Å); the C atom at the 5-position deviates by 0.054 (3) Å from the mean plane and the C atom at the 6-position by 0.006 (3) Å in the opposite direction. The benzene ring is approximately perpendicular to the pyrimidine ring [dihedral angle = 83.90 (10)°]. The amino group is hydrogen-bond donor to the exocyclic O atom at the 2-position of an adjacent mol­ecule, the hydrogen bond generating an inversion dimer. The cyclo­propyl ring is disordered over two sets of sites with the major component having 71.5 (4)% occupancy

3-[(N-Methyl­anilino)meth­yl]-5-(thio­phen-2-yl)-1,3,4-oxadiazole-2(3H)-thione

In the title compound, C14H13N3OS2, the thio­phene ring is disordered over two orientations by ca 180° about the C—C bond axis linking the ring to the rest of the mol­ecule, with a site-occupancy ratio of 0.651 (5):0.349 (5). The central 1,3,4-oxadiazole-2(3H)-thione ring forms dihedral angles of 9.2 (5), 4.6 (11) and 47.70 (7)° with the major and minor parts of the disordered thio­phene ring and the terminal phenyl ring, respectively. In the crystal, no significant inter­molecular hydrogen bonds are observed. The crystal packing is stabilized by π–π inter­actions [centroid–centroid distance = 3.589 (2) Å]

Effect of valproic acid administration during pregnancy on postnatal development of cerebellar cortex and the possible protective role of folic acid

Background: Valproic acid (VPA), one of the most important antiepileptic drugs, proved to be inevitable for epileptic pregnant women to limit the hazards of convulsions on the foetuses and mothers. Periconceptional folic acid supple­mentation was investigated to protect against several birth defects. However, its role against VPA cerebellar toxicity was not properly investigated. The present study was conducted to evaluate the protective effect of folic acid against VPA cerebellar neurotoxicity. Materials and methods: Twenty-four pregnant female albino rats were divided into three groups; group I (control group, did not receive any drugs), group II (given VPA at a dose of 50 mg/kg body weight once daily) and group III (given the same dose of VPA and 400 μg/kg of body weight folic acid once daily). Ten male offspring from each group were sacrificed at two ages: at 2 and 12 weeks after birth. Samples of cerebellar cortex were taken and prepared for light, electron microscopic examination, glial fibrillary acidic protein (GFAP) immunohistochemical study and histomorphometric analysis. Results: The present study confirmed the neurotoxic effect of prenatal VPA on the cerebellar cortex, especially on Purkinje cells. The cells appeared shrunken, reduced in density, disorganised and surrounded by empty haloes. Nuclear damage and axon degeneration in the form of vacuolation, loss of organelles and absence of neurofilaments with myelin sheath depletion were detected. Concomitant supply of folic acid was shown to retain the normal architecture of Purkinje cells with their axons and nuclei. In many animals receiving folic acid, the thickness of all layers of the cortex increased up to that of the control groups, after being markedly reduced in VPA-treated groups. GFAP immunoreaction was also improved against the strong positive gliosis detected in VPA-treated groups. Conclusions: The present study confirmed the protective role of folic acid against the cerebellar neurotoxic effects of VPA prenatal exposure. It is recommended that folic acid supplements should be given to every epileptic pregnant mother treated with VPA. (Folia Morphol 2018; 77, 2: 201–209

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

In the title compound, C14H21N3S, the 1,2,4-triazole ring is nearly planar, with a maximum deviation of 0.003 (4) Å. In the crystal, mol­ecules are linked into inversion dimers by pairs of N—H⋯S hydrogen bonds

3-(1-Adamant­yl)-4-amino-1-(2-benzoyl-1-phenyl­eth­yl)-1H-1,2,4-triazol-5(4H)-thione

In the title compound, C27H30N4OS, the 3-(adamantan-1-yl)-4-amino-1H-1,2,4-triazole-5(4H)-thione unit and the O atom are each disordered over two sets of sites with refined site-occupancies of 0.7630 (13) and 0.2370 (13). The 1,2,4-triazole ring of the major component forms dihedral angles of 62.61 (17) and 61.93 (16)° with the benzene rings, while that of the minor component makes corresponding angles of 86.3 (4) and 79.1 (4)°. The dihedral angle between the benzene rings is 39.21 (16)°. The mol­ecular structure is stabilized by an intra­molecular C—H⋯N hydrogen bond, which generates an S(6) ring motif. In the crystal, mol­ecules are linked into inversion dimers by pairs of N—H⋯S hydrogen bonds

2-{[(2-Methyl­prop-2-en-1-yl)­oxy]meth­yl}-6-phenyl-2,3,4,5-tetra­hydro-1,2,4-triazine-3,5-dione

The 1,2,4-triazine ring in the title compound, C14H15N3O3, is approximately planar (r.m.s. deviation = 0.019 Å); the C atom at the 6-position deviates by 0.026 (2) Å from the mean plane whereas the C atom at the 2-position deviates by 0.166 (4) Å in the opposite direction. The triazine ring is oriented at 8.60 (13)° with respect to the phenyl ring. The imino group is hydrogen-bond donor to the exocyclic O atom at the 3-position of an adjacent mol­ecule, the hydrogen bond generating an inversion dimer

6-(3,5-Dimethyl­benz­yl)-5-ethyl-1-[(3-phenyl­prop­oxy)meth­yl]-1,2,3,4-tetra­hydro­pyrimidine-2,4-dione

The pyrimidine ring of the title compound, C25H30N2O3, is approximately planar (r.m.s. deviation = 0.003 Å); the C atom at the 5-position deviates by 0.012 (3) Å from the mean plane and the C atom at the 6-position by 0.038 (3) Å. In the mol­ecule, the pyrimidine ring is oriented at 86.72 (9) and 59.75 (9)° with respect to the two benzene rings, and the two benzene rings are inclined to each other at 58.35 (9)°. In the crystal, the amino group is hydrogen-bond donor to the exocyclic O atom at the 4-position of an adjacent mol­ecule, the hydrogen bond generating an inversion dimer

6-(3,5-Dimethyl­benz­yl)-5-ethyl-1-[(2-phen­oxy­eth­oxy)meth­yl]-1,2,3,4-tetra­hydro­pyrimidine-2,4-dione

The six-membered ring of the uracil part of the title compound, C24H28N2O4, is nearly planar (r.m.s. deviation = 0.013 Å); the aromatic ring of the 3,5-dimethyl­benzyl substitutent is aligned at 85.4 (1)° with respect to this mean plane. The phenyl ring of the substituent at the 1-position takes up two orientations in a 1:1 ratio. In the crystal, two mol­ecules are liked by a pair of N—H⋯O hydrogen bonds, generating a centrosymmetric hydrogen-bonded dimer

2-Eth­oxy­methyl-6-ethyl-2,3,4,5-tetra­hydro-1,2,4-triazine-3,5-dione

The 1,2,4-triazine ring of the title compound, C8H13N3O3, is nearly planar (r.m.s. deviation = 0.019 Å). The imino group is hydrogen-bond donor to the exocyclic O atom at the 5-position of an adjacent mol­ecule, the N—H⋯O hydrogen bond generating a chain parallel to the b axis