Teicoplanin-based antimicrobial therapy in Staphylococcus aureus bone and joint infection: tolerance, efficacy and experience with subcutaneous administration.

Background: Staphylococci represent the first etiologic agents of bone and joint infection (BJI), leading glycopeptides use, especially in case of methicillin-resistance or betalactam intolerance. Teicoplanin may represent an alternative to vancomycin because of its acceptable bone penetration and possible subcutaneous administration.

Methods: Adults receiving teicoplanin for S.

Prospective assessment of a gene signature potentially predictive of clinical benefit in metastatic melanoma patients following MAGE-A3 immunotherapeutic (PREDICT).

Background: Genomic profiling of tumor tissue may aid in identifying predictive or prognostic gene signatures (GS) in some cancers. Retrospective gene expression profiling of melanoma and non-small-cell lung cancer led to the characterization of a GS associated with clinical benefit, including improved overall survival (OS), following immunization with the MAGE-A3 immunotherapeutic. The goal of the present study was to prospectively evaluate the predictive value of the previously characterized GS.

Solid state characterization and crystal structure from X-ray powder diffraction of two polymorphic forms of ranitidine base.

Ranitidine hydrochloride (RAN-HCl), a known anti-ulcer drug, is the product of reaction between HCl and ranitidine base (RAN-B). RAN-HCl has been extensively studied; however this is not the case of the RAN-B. The solid state characterization of RAN-B polymorphs has been carried out using different analytical techniques (microscopy, thermal analysis, Fourier transform infrared spectrometry in the attenuated total reflection mode, (13)C-CPMAS-NMR spectroscopy and X-ray powder diffraction).

Polymorphism of Alprazolam (Xanax): a review of its crystalline phases and identification, crystallographic characterization, and crystal structure of a new polymorph (form III).

A new polymorphic form of Alprazolam (Xanax), 8-chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo-[4,3-alpha][1,4]benzodiazepine, C(17)H(13)ClN(4), has been investigated by means of X-ray powder diffraction (XRPD), single crystal X-ray diffraction, and differential scanning calorimetry (DSC). This polymorphic form (form III) was obtained during DSC experiments after the exothermic recrystallization of the melt of form I. The crystal unit cell dimensions for form III were determined from diffractometer methods.

Crystal structure of carnidazole form II from synchrotron X-ray powder diffraction: structural comparison with form I, the hydrated form and the low energy conformations in vacuo.

The crystal structure of carnidazole form II, O-methyl [2-(2-methyl-5-nitro-1H-imidazole-1-yl)ethyl]thiocarbamate, has been determined using synchrotron X-ray powder diffraction in combination with simulated annealing and whole profile pattern matching, and refined by the Rietveld method. For structure solution, 12 degrees of freedom were defined: one motion group and six torsions. Form II crystallizes in space group P2(1)/n, Z=4, with unit cell parameters after Rietveld refinement: a=13.

Tribenzylphosphine oxide.

The title compound, (C(6)H(5)CH(2))(3)PO, is an organic tertiary phosphine oxide. The molecule has threefold symmetry, with the P-O bond along the threefold axis. Main dimensions include P-O 1.

p-Formamidobenzoic acid.

The title compound, C8H7NO3, is an aromatic amide that forms an extensive hydrogen-bond network within the crystal. The crystals were obtained while preparing derivatives of benzoic acid as intermediaries in the synthesis of acridones.

Ethyl methyl 1,4-dihydro-4-(3-nitrophenyl)-2, 6-bis(1-piperidylmethyl)pyridine-3,5-dicarboxylate.

In the title compound, C(28)H(38)N(4)O(6), the 4-aryl substituent occupies a pseudo-axial position approximately orthogonal to the plane of the dihydropyridine ring [88.1 (3) degrees ]. The dihydropyridine ring adopts a flattened boat conformation.

O-Isopropyl N-(2-furoyl)thiocarbamate.

The title compound, C(9)H(11)NO(3)S, has crystallographic mirror symmetry, occurs in the thiocarbamate form and is stabilized in an s-cisoid,s-transoid conformation with respect to the C-N-C group. There are two intramolecular hydrogen bonds, one between the H atom of the N-H group and the O atom of the furan ring, and the other between the H atom of the secondary carbon of the isopropyl group and the S atom. The packing of the molecules is assumed to be dictated by van der Waals interactions.

Synthesis, structural studies and pharmacological activity of novel bicyclic compounds derived from 3,4-dihydropyridones: 4-aryl-7,7-dimethyl-2,5-dioxo-1,2,3,4,5,6,7,8-octahydroquinolines.

The purpose of this research is to characterize the possible vascular selectivity of a series of novel bicyclic compounds derived from 3,4-dihydropyridones. We describe the synthesis, structural study by X-ray analysis and quantum chemical calculations at semiempirical (AMI) and ab initio (HF/321G) levels and pharmacological activity of these 4-aryl-7,7-dimethyl-2,5-dioxo-1,2,3,4,5,6,7,8-octahydroquinolines. In addition, the more favoured conformation for compounds 4a-c in solution was determined from the calculated and experimental proton coupling constants.

Novel selective kappa-opioid ligands.

The single-crystal X-ray structures of (-)-dimethyl[(2S)-1-(5,6,7,8- tetrahydro-5-oxonaphthalene-2-acetyl)piperidin-2-ylmethyl ]ammonium chloride, C20H29N2O2+.Cl-(BRL-53001A), and (-)-ethylmethyl[(2S)-1-(5,6,7,8-tetrahydro-5-oxonaphthalene- 2- acetyl)piperidin-2-ylmethyl]-ammonium chloride dihydrate, C21H31N2O2+.Cl-.

N6-cyclopentyl-3'-substituted-xylofuranosyladenosines: a new class of non-xanthine adenosine A1 receptor antagonists.

The present study explores the C-3' site of the 3-deoxy-3-xylofuranosyl ring of nucleoside analogues with an adenine or N6-cyclopentyladenine (CPA) base moiety and evaluates the effect on adenosine receptor affinity. Two series of sugar-modified adenosines, i.e.

Synthesis and Conformational Study of 3-Hydroxy-4-(Hydroxymethyl)-1-Cyclohexanyl Purines and Pyrimidines.

The cyclohexane nucleosides with a 1,4-relationship between nucleoside base and hydroxymethyl moiety were synthesized using a conjugated addition reaction of the nucleobases to ethyl 1,3-cyclohexadiene-1-carboxylate and hydroboration of the cyclohexenyl precursor. The lack of antiviral activity of the compounds was correlated with the conformation of these nucleosides as deduced from NMR and X-ray analysis.

Synthesis and structure-activity relationships of analogs of 2'-deoxy-2'-(3-methoxybenzamido)adenosine, a selective inhibitor of trypanosomal glycosomal glyceraldehyde-3-phosphate dehydrogenase.

In continuation of a project aimed at the structure-based design of drugs against sleeping sickness, analogs of 2'-deoxy-2'-(3-methoxybenzamido)adenosine (1) were synthesized and tested to establish structure-activity relationships for inhibiting glycosomal glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Compound 1 was recently designed using the NAD:GAPDH complexes of the human enzyme and that of Trypanosoma brucei, the causative agent of sleeping sickness. In an effort to exploit an extra hydrophobic domain due to Val 207 of the parasite enzyme, several new 2'-amido-2'-deoxyadenosines were synthesized.

A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma.

Human melanoma MZ2-MEL expresses several distinct antigens that are recognized by autologous cytolytic T lymphocytes (CTL). Some of these antigens are encoded by genes MAGE-1, MAGE-3, and BAGE, which are expressed in a large fraction of tumors of various histological types but are silent in normal adult tissues with the exception of testis. We report here the identification of the gene coding for MZ2-F, another antigen recognized by autologous CTL on MZ2-MEL cells.

1-(2,3-Dideoxy-erythro-beta-D-hexopyranosyl)cytosine: an example of the conformational and stacking properties of pyranosyl pyrimidine nucleosides. A crystallographic and computational approach.

C10H15N3O4, Mr = 241.25, orthorhombic, P2(1)2(1)2(1), a = 7.4013 (4), b = 8.

2'-Azido-2',3'-dideoxythymidine: synthesis and crystal structure of a 2'-substituted dideoxynucleoside.

1-(2-Azido-2,3-dideoxy-beta-D-erythro-pentofuranosyl)thymine (2'-N3ddThd) was synthesized from 1-(5-O-trityl-2,3-anhydro-beta-D-lyxofuranosyl)thymine by two different procedures. Method A prepared the title compound by opening of the oxirane ring with LiEt3BH followed by mesylation of the 2'-hydroxyl function, introduction of the 2'-azido substituent and deblocking of the 5'-function. In method B nucleophilic opening of 3'-deoxy-5'-O-(tert-butyldimethylsilyl)-5-methyl-2,2'-anhydrouridine+ ++ was carried out with sodium azide in hexamethylphosphoramide in the presence of benzoic acid.

Structure of a nucleoside analogue, 3'-deoxy-3'-fluorothymidine.

1-(2,3-Dideoxy-3-fluoro-beta-D-erythro-pentofuranosyl)thymine, C10H13FN2O4, Mr = 244.22, monoclinic, P21, a = 6.408 (14), b = 18.

Synthesis and anti-HIV evaluation of 2',3'-dideoxyribo-5-chloropyrimidine analogues: reduced toxicity of 5-chlorinated 2',3'-dideoxynucleosides.

In view of the selective anti-HIV activity of 2',3'-dideoxy-3'-fluoro-5-chlorouridine (11), a series of eight 2',3'-dideoxy-5-chloropyrimidines were synthesized and evaluated for their inhibitory activity against human immunodeficiency virus type 1 (HIV-1) replication in MT-4 cells. A marked improvement in selectivity was noted for the 5-chlorouracil derivatives of 2,3-dideoxyribofuranose, 3-azido-2,3-dideoxyribofuranose, and 3-fluoro-2,3-dideoxyribofuranose, mainly due to decreased toxicity of the compounds for the host cells. While chlorination of 2',3'-dideoxycytidine removed the anti-HIV activity, introduction of a chlorine at the C-5 position of 3'-fluoro-, 3'-azido- or 2',3'-didehydro-2',3'-dideoxycytidine led to reduced cytotoxicity with only slightly reduced anti-HIV activity.

Structure of the neuroleptic drug 4-amino-N-1-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(ethylsulfonyl)-2- methoxybenzamide (amisulpride).

C17H27N3O4S, Mr = 369.48, monoclinic, P2(1)/c, a = 13.333 (7), b = 7.

Structure and absolute configuration of two stereoisomers of alpha,alpha'-[iminobis-(methylene)]bis(3,4-dihydro-2H-1-benzopyran-2- methanol) hydrobromide.

alpha,alpha'-1,1'-Bis(3,4-dihydro-2H-benzopyran-2-yl)-2,2'-iminodieth anol hydrobromide. (I) C22H28NO4+.Br-, Mr = 450.

Structure and conformational analysis of the opioid antagonist (-)-(1R,5R,9R)-5,9-diethyl-2-(3-furylmethyl)-2'-hydroxy-6,7-benzomorpha n (Mr2266).

C21H27NO2, Mr = 325.449, monoclinic, P2(1), a = 16.3916 (7), b = 12.