A new method for the synthesis of 3-aryl-5-fluoroisoxazoles via the reaction of nitrosonium chlorosulfate with 2-aryl-1-bromo-1-fluorocyclopropanes containing acceptor substituents in the aromatic ring has been developed. The reaction proceeds highly regioselectively thus providing 3-aryl-5-fluo...

A series of 4-substituted 3-aryl-5-trifluoromethyl-4,5-dihydroisoxazole derivatives was synthesized by selective reduction of the corresponding 3-aryl-5-trifluoromethyl-4-isoxazole with NaBH4 under various reaction conditions. It was found that the reduction selectivity of endocyclic carbon-carb...

The fomazan compounds 3-(p-isopropylphenyl)-5-(o,m,p-nitrophenyl)-5-phenylformazans (1–3) have been synthesized and characterized by FTIR, UV–Vis and 1H NMR spectroscopic techniques and elemental analysis. Quantum chemical calculations of the molecular structures, vibrational frequencies, gaug...

A number of 6-(2-furyl)-9-(p-methoxybenzyl)purines carrying a variety of substituents in the 2- or 8-position have been synthesized and their ability to inhibit growth of Mycobacterium tuberculosis in vitro has been determined. It is demonstrated that sterical hindrance in the purine 8-position ...

A core building block 3 for (2 S,3 R,4 S,5 S,6 S,11 E)-3-amino-6-methyl-12-(4-methoxyphenyl)-2,4,5-trihydroxydodec- 11-enoic acid (2, AMMTD) has been efficiently synthesized using the Sharpless asymmetric dihydroxylation and the Dondoni's furan addition to a nitrone derivative as key steps....

On the treatment of 1-aryl-2-(2-furyl)-5-(2-thienyl)pyrroles with tetracyanoethylene, 1-aryl-2-(2-thienyl)-5-(5-tricyanoethenyl-2-furyl)pyrroles were produced. These compounds formed crystals with greenish metallic luster. In their solid-state UV–vis–NIR diffuse reflection–absorption spectra,...

The two potent rodent bladder carcinogens o-anisidine and p-cresidine, and the structurally related non-carcinogen 2,4-dimethoxyaniline, have been extensively evaluated for genotoxicity to rodents and found to be inactive. Most data were generated on o-anisidine, an agent that is also only margi...

As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative International Validation Study of an in vivo rat alkaline comet assay, we examined 1,2-dibromoethane (DBE), p-anisidine (ASD), and o-anthranilic acid (ANT) to investigate the effectiveness of the comet a...

We have previously described a significant decrease in the positive cooperativity level and affinity of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] binding to its chick intestinal chromatin receptor induced in vitro by a physiological 10-fold molar excess of (24R)-25-dihydroxyvitamin D 3 [24R,25(OH)2...

1α,25-(OH)2D3 regulates protein kinase C (PKC) activity in growth zone chondrocytes by stimulating increased phosphatidylinositol-specific phospholipase C (PI-PLC) activity and subsequent production of diacylglycerol (DAG). In contrast, 24R,25-(OH)2D3 regulates PKC activity in resting zone (RC)...

Gas chromatography/mass spectrometric (GC/MS) analysis of 24R,25-dihydroxyvitamin D3 (24,25-(OH)2D3, 1a) in rat serum is examined using 6,19,19-trideuterated derivative (24,25-(OH)2[6,19,19-2H]D3, 1c) as an internal standard. Pyro- and isopyro-24,25-(OH)2D3 (2a and 3a) are synthesized and the st...

1α,25-(OH)2D3 exerts its effects on chondrocytes and enterocytes via nuclear receptors (1,25-nVDR) and a separate membrane receptor (1,25-mVDR) that activates protein kinase C (PKC). 24R,25-(OH)2D3 also stimulates PKC in chondrocytes, but through other membrane mechanisms. This study examined t...

The effect(s) of 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] on fracture healing was studied in a vitamin D-depleted chick model. 24R,25(OH)2D3, together with another hormonally active vitamin D metabolite, 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], improved bone mechanical strength parameters (...

The kidney is the major source of the circulating dihydroxylated metabolites of vitamin D, 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] and 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3]. The enzymes which catalyze the production of these two dihydroxylated vitamin D metabolites are the 25(OH)D3-1α-h...

Maintenance of the pool of chondrocytes in the resting zone of the growth plate in the presence of the physiological apoptogen inorganic phosphate (Pi) is crucial for skeletal development. Costochondral resting zone chondrocytes are regulated by the vitamin D metabolite 24R,25-dihydroxyvitamin D...

Measurement of serum 25-hydroxyvitamin D [25(OH)D] is considered the best indicator of vitamin D status. Two minor vitamin D metabolites are common interferences encountered in 25(OH)D assays. The first is 3-epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3], which if not chromatographically resolved fro...

Previously we showed that costochondral growth plate resting zone (RC) chondrocytes response primarily to 24R,25(OH)2D3 whereas prehypertrophic and hypertrophic (GC) cells respond to 1α,25(OH)2D3. 24R,25(OH)2D3 increases RC cell proliferation and inhibits activity of matrix processing enzymes, ...

BackgroundEpidemiological studies indicate high serum 25(OH)D3 is associated with increased survival in breast cancer patients. Pre-clinical studies attributed this to anti-tumorigenic properties of its metabolite 1α,25(OH)2D3. However, 1α,25(OH)2D3 is highly calcemic and thus has a narrow the...

Based on a previously identified antileishmanial 6,8-dibromo-3-nitroimidazo[1,2-a]pyridine derivative, a Suzuki-Miyaura coupling reaction at position 8 of the scaffold was studied and optimized from a 8-bromo-6-chloro-3-nitroimidazo[1,2-a]pyridine substrate. Twenty-one original derivatives were ...

Human 15-lipoxygenase-1 (15-LOX-1) is a mammalian lipoxygenase which plays an important regulatory role in several CNS and inflammatory lung diseases. To further explore the role of this enzyme in drug discovery, novel potent inhibitors with favorable physicochemical properties are required. In ...