RESUMEN

The overall mol-ecular geometry of the title compound, C(11)H(12)N(4)O(3)S, is bent, with a dihedral angle of 89.24 (5)° between the best planes through the two aromatic rings. Each mol-ecule behaves as a hydrogen-bond donor toward three different mol-ecules, through its amidic and the two aminic H atoms, and it behaves as a hydrogen-bond acceptor from two other mol-ecules via one of its sulfonamidic O atoms. In the crystal, mol-ecules linked by N-H⋯N and N-H⋯O hydrogen bonds form kinked layers parallel to (001), adjacent layers being connected by van der Waals inter-actions.

RESUMEN

In the title compound, C(13)H(15)N(2) (+)·Cl(-)·H(2)O, the ions and water mol-ecules are -connected by N-H⋯Cl, O-H⋯Cl, NH⋯Cl⋯HO, NH⋯Cl⋯HN and OH⋯Cl⋯HO inter-actions, forming discrete D(2) and D(2) (1)(3) chains, C(2) (1)(6) chains and R(4) (2)(8) rings, leading to a neutral two-dimensional network. The crystal structure is further stabilized by π-π stacking inter-actions [centroid-centroid distance = 3.652 (11) Å].

RESUMEN

Novel analogues of cis-N,N,N-trimethyl-(6-methyl-1,4-dioxan-2-yl)methanaminium iodide (2a) were synthesized by inserting methyl groups alternatively or simultaneously in positions 5 and 6 of the 1,4-dioxane nucleus in all combinations. Their biological profile was assessed by receptor binding assays at human muscarinic M(1)-M(5) receptors stably expressed in CHO cells and by functional studies performed on classical isolated organ preparations, namely, rabbit electrically stimulated vas deferens, and guinea pig electrically stimulated left atrium, ileum, and lung strips. The results showed that the simultaneous presence of one methyl group in both positions 5 and 6 with a trans stereochemical relationship with each other (diastereomers 4 and 5) or the geminal dimethylation in position 6 (compound 8) favour the selective activation of M(3) receptors. Compounds 4, 5, and 8 might be valuable tools in the characterization of the M(3) receptor, as well as provide useful information for the design and development of novel selective M(3) antagonists.

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The physico-chemical and structural characterization of diacerhein, an anthraquinone with antiinflammatory activity, employed in the symptomatic treatment of inflammatory osteoarthritis, is reported. The combined use of FT-IR, DSC, X-ray powder and single-crystal diffraction has provided a valuable tool to fully characterize the title compound. The X-ray diffraction study has revealed the existence of hydrogen-bond assisted tight packing of the quasi-planar molecules in the solid. The collected results are intended to implement the information required for the compilation of drug master files.

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The use of adenovirus (Ad) as vaccine vectors is hindered by pre-existing immunity to human Ads in most of the human population. In order to overcome this limitation, uncommon alternative Ad serotypes need to be utilized. In this study, an E1-E3 deleted recombinant Ad based on the chimpanzee serotype 3 (ChAd3) was engineered to express human carcinoembryonic antigen (CEA) protein or rat neu extracellular/transmembrane domains (ECD.TM). ChAd3 vectors were tested in CEA transgenic (CEA.Tg) and BALB/NeuT mice, which show immunologic tolerance to these antigens. ChAd3 is capable of inducing an immune response comparable to that of hAd5 serotype-based vectors, thus breaking tolerance to tumor associated antigens (TAAs) and achieving anti-tumor effects. Of importance is that ChAd3 can overcome hAd5 pre-existing immunity and work in conjunction with DNA electroporation (DNA-EP) and other Ad vaccines based on common human serotypes.

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Metoprolol, a widely used adrenoreceptor blocking drug, is commonly administered as the succinate or tartrate salt. The structure of metoprolol succinate, C(15)H(26)NO(3) (+)·0.5C(4)H(4)O(4) (2-), is characterized by the presence of ribbons in which cations, generated by N-protonation of the metoprolol mol-ecules, are hydrogen bonded to succinate anions. The dicarboxylic acid transfers its H atoms to two metoprolol mol-ecules; the asymmetric unit contains one cation and half an anion, the latter possessing twofold rotational symmetry. There are localized nets of O-H⋯O and N-H⋯O hydrogen bonds along a ribbon, within centrosymmetric arrangements formed by pairs of metoprolol cations and pairs of anions, each of the latter contributing with one of its carboxyl groups to the localized net. This arrangement is repeated along the ribbon by the operation of the twofold axis bis-ecting the anion, as well as by the lattice translation.

RESUMEN

The structure [Danilovski et al. (2001 ▶). Croat. Chim. Acta74, 103-120] of the T-N (non-solvated) polymorph of torasemide, C(16)H(20)N(4)O(3)S, a diuretic drug used in the treatment of hypertension, has been redetermined at low temperature. The zwitterionic form of the mol-ecule is confirmed, although GAUSSIAN03 calculations suggest that this form is less stable in the gas phase. The unit-cell contraction between 298 and 100 K is approximately isotropic and the largest structual change is in a C-N-C-C torsion angle, which differs by 11.4 (3)° between the room-temperature and low-temperature structures. There are two mol-ecules in the asymmetric unit, both of which contain an intra-molecular N-H⋯N hydrogen bond. In the crystal structure, both mol-ecules form inversion dimers linked by pairs of N-H⋯N hydrogen bonds. Further N-H⋯N and N-H⋯O hydrogen bonds lead to a three-dimensional network. The different hydrogen-bond arrangements and packing motifs in the polymorphs of torasemide are discussed in detail.

RESUMEN

The title compound, C(16)H(20)N(4)O(3)S·0.25CH(4)O·0.25H(2)O, is a hydrate/methanol solvate of torasemide, a diuretic drug used in the treatment of hypertension. The asymmetric unit contains two torasemide mol-ecules and half-occupied methanol and water mol-ecules. It is isomorphous with the previously reported nonsolvated T-II form of torasemide. The water mol-ecules contribute to the stability of the structure by participating in an extensive system of O-H⋯O hydrogen bonds; N-H⋯N and N-H⋯O hydrogen bonds are also present. Both asymmetric mol-ecules of torasemide form inversion dimers in the crystal.

RESUMEN

The crystal structure of the title compound, C(18)H(13)NO(4), the oxidized form of the drug aminaftone used in venous disease therapy, is characterized by the presence of ribbons of hydrogen-bonded mol-ecules parallel to the [111] crystallographic direction and by stacking inter-actions between rings [centroid-centroid distance between quinone rings = 3.684 (3) Šand between amino-benzoate rings = 4.157 (3) Å] along the ribbons.

RESUMEN

The structure of the title compound, C(14)H(28)N(3)O(2) (+)·HSO(4) (-), a nootropic drug (pramiracetam) investigated for cognition-enhancing properties, is closely similar to that of the previously determined acetonitrile solvate, both structures being characterized by the presence of ribbons of hydrogen-bonded ions. The pyrrolidine ring adopts an envelope conformation.

RESUMEN

To assess the stereochemical requirements for efficient alpha2C-adrenoreceptor activation, the enantiomeric forms of m-nitrobiphenyline [(+/-)-5] were prepared and tested on cells expressing the human alpha2-adrenoreceptor subtypes. The importance of chirality was confirmed, since the enantiomer (R)-(+)-5 was much more efficient than (S)-(-)-5 in producing alpha2C-activation. Surprising reversal of enantioselectivity was observed with respect to structurally similar biphenyline [(+/-)-1] whose (S)-(-)-form proved the preferred alpha2C-configuration.

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Muscarinic agonists, bearing 1,4-dioxane and 1,4-oxathiane nuclei, were synthesized and tested to evaluate their potency at M(1)-M(4) muscarinic receptor subtypes. The stereochemical relationship between the 2-side chain and the 6-methyl group plays an important role in drug-receptor interaction, since the cis isomers are more potent than the corresponding trans isomers. However, the latter are able to discriminate between the muscarinic receptor subtypes. Among them compound 5b proves particularly interesting, since it selectively activates the ileal M(3) receptor subtype and is devoid of agonist activity at the others.

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Clioquinol, a 8-hydroxyquinoline derivative, is producing very encouraging results in the treatment of Alzheimer's disease (AD). Its biological effects are most likely ascribed to complexation of specific metal ions, such as copper(II) and zinc(II), critically associated with protein aggregation and degeneration processes in the brain. We report here, for the first time, a structural characterization of the zinc(II) and copper(II) complexes of clioquinol. A ligand to metal stoichiometry of 2:1 is found in both cases, though in the presence of quite different coordination polyhedra. The present findings are discussed in the frame of modern approaches to AD treatment.

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The crystal structure of a complex of terbium(III) with quinizarine 2-sulfonate has been solved by single-crystal X-ray diffraction methods. The metal cation is coordinated by two adjacent phenolate and quinone oxygens of the anthraquinone moiety of a quinizarine sulfonate anion and by six water molecules. To our knowledge, this is the first structure of a metal complex of the 1,4-dihydroxy anthraquinone ligand. On the basis of strict similarities in the spectroscopic features of the terbium adducts with either doxorubicin or quinizarine 2-sulfonate, the present structure is proposed as a model for the metal complexes of anthracyclines.

RESUMEN

Slow decomposition of L-ascorbic acid, carried out under aerobic conditions and in the presence of cadmium ions, results in formation of a crystalline product that is highly insoluble in water. This compound has been identified as a cadmium oxalate polymeric species with formula Cd(C(2)O(4)).3H(2)O. The crystal structure of this compound is described. Relevant crystal data are the following: C(4)H(12)O(14)Cd(2), fw = 508.94; triclinic; space group P1 (No. 1); a = 6.010(1) A, b = 6.668(1) A, c = 8.498(1) A; alpha = 74.64(1) degrees, beta = 74.25(1) degrees, gamma = 80.91(1) degrees; V = 314.7(5) A(3); Z = 1.

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