The conformational properties of streptokinase (Sk) have been assessed by several spectroscopic techniques. A solvent accessibility of about 70% of the 22 Tyr residues was found by u.v. perturbation spectroscopy. Fluorescence spectroscopy indicates also the surface localization of the single Trp...

The synthesis and in vitro anti human immunodeficiency virus (HIV) and anti-hepatitis B virus (HBV) activities of some unnatural β-l-nucleoside enantiomers related to the anti-HIV compound 2′,3′-dideoxy-3′-fluoro-5-chlorouridine (β-d-3′Fdd5ClU) are reported. In contrast to β-d-3′Fdd5ClU,...

Various thiated analogues of thymine 2′,3′-dideoxy-3′-fluoronucleoside (FLT) and their 5′-monophosphates and 5′-triphosphates were prepared with the use of modified multistep procedures. The thiated analogues of FLT and FLTMP were evaluated against the wild type and drug- and multidrug-resi...

A rapid synthesis of 2′,3′-dideoxy-3′-fluoro-β-d-threo-nucleosides bearing the pyrimidine canonical bases of nucleic acids has been developed in order to discover new nucleoside derivatives as potential antiviral drugs. However, when evaluated for their antiviral activity in cell culture exp...

A new and efficient method is described for the preparation of (3S-cis)-3-fluoro-5-[(t-butyldimethylsiloxy) methyl]-2-tetrahydrofuranone (1b), a valuable intermediate for the synthesis of fluorinated nucleosides. The conversion of 1b to 1-(2,3-dideoxy-2-fluoro-β-d-threo-pentofuranosyl) thymine ...

The fluorinated furanose unit of the anti-HIV-active nucleoside (2,3-dideoxy-2-fluoro-β-d-threo-pentofuranosyl)adenine, β-FddA, has been synthesized as its 5-trityl derivative with high stereocontrol from (S)-trityl glycidol and phenylthioacetic acid.

A novel synthesis for preparing 9-(3-O-benzyl-5-O-tetrahydropyranyl-β-d-arabinofuranosyl)adenine (6) has been developed which does not require sub zero temperatures or exotic reagents. A key step in this synthesis is the selective protection of the 3′-OH of ara-A with a benzyl group. The 5′-O...

A highly efficient synthesis of (2R,3S,5S)-2-acetoxy-3-fluoro-5-(p-toluoyloxymethyl)tetrahydrofuran (2a) was developed. As a key intermediate, 2a was effectively applied to the synthesis of 9-(2,3-dideoxy-2-fluoro-β-d-threo-pentofuranosyl)adenine (FddA), thus, providing a practical synthetic ap...

A practical synthesis of 9-(2,3-dideoxy-2-fluoro-β-d-threo-pentofuranosyl)adenine (1, FddA) via a 6-chloro-9-(3-deoxy-β-d-erythro-pentofuranosyl)-9H-purine (6) is described. Fluorination at the C2′-β position of the purine 3′-deoxynucleoside was improved by the introduction of 6-chloro grou...

An improved synthesis of 9-(2,3-dideoxy-2-fluoro-β-d-threo-pentofuranosyl)adenine (1, FddA) via a fluorination of 3′-O-benzoyl-5′-O-tritylriboside (4a) using noncorrosive triethylamine trihydrofluoride (Et3N·3HF) is described. The method is suitable for large-scale synthesis. In particular, ...

The details of an NMR method of distinguishing between α- and β- anomers of 2′-deoxy-2′-fluoro-arabinofuranosyl nucleosides are presented.

Pirsidomine is a new sydnonimine compound in clinical development. As a prodrug, it is transformed into a nitric oxide-releasing metabolite in vivo. In animal tests there were no signs of tolerance with repeated administration. The short-term effects of 10, 20, and 40 mg of the drug on pulmonary...

The hemodynamic profile of pirsidomine, a new donor of NO (nitric oxide), was evaluated in dogs. In anesthetized dogs, the intravenous or intraduodenal administration of pirsidomine (0.3–10 mg/kg) decreased dose relatedly the preload and afterload of the heart, total peripheral resistance, card...

The antiischemic effect of pirsidomine (CAS 936 (3-(cis-2, 6-dimethylpiperidino)-N-(4-methoxybenzoyl))-sydnonimine), a new nitric oxide donor, was investigated in a model of myocardial infarction in the dog. Dogs were anaesthetised, thoracotomized, and the left descending coronary artery was occ...

2,7-Substituted 9-fluorenones and 9,9-disubstituted fluorene have been synthesized and their fluorescence properties analyzed. The synthesis of conjugated 2,7-bis(trimethylsilylethynyl)-(phenylethynyl)nfluoren-9-one (or the 9-(p-methoxyphenyl)-9-methyl) structures was carried out by the heteroco...

A highly efficient and green protocol has been developed for the synthesis of 4-(1-aryl-2-nitroethyl)-3-methyl-1H-pyrazol-5-ol via Michael addition of 3-methyl-2-pyrazolin-5-one with β-nitrostyrenes under catalyst free conditions on aqueous medium. A series of 4-(1-aryl-2-nitroethyl)-3-methyl-1...

The γ-alumina catalyzed synthesis of a new series of β-functionalized 5-methyl-1H-pyrazol-3-ol derivatives by the multi-component reaction of an aldehyde, ethylcyano acetate, and in situ generated 3-methyl-1H-pyrazol-5(4H)-one obtained from hydrazine monohyrade and ethyl acetoacetate in aqueou...

A simple and sensitive spectrophotometric method to the simultaneous determination of Mn2+ and Fe3+ in foods, vegetable and water sample with the aid of artificial neural networks (ANNs) is described. It relies on the complexation of analytes with recently synthesised bis pyrazol base ligand as ...

Trityl chloride (Ph3CCl) efficiently catalyzes the condensation of 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one and aromatic aldehydes under mild and solvent-free conditions, affording 4,4′-(arylmethylene)-bis(3-methyl-1-phenyl-1H-pyrazol-5-ol)s in high to excellent yields and in short reaction time....

An environmentally friendly and simple method for the synthesis of some 4,4′-(arylmethylene)bis(3-methyl-1H-pyrazol-5-ol) derivatives via a one-pot pseudo five-component reaction of hydrazine hydrate, ethyl acetoacetate and aldehydes in water using pyridine trifluoroacetate or acetic acid at 70...