Polycyclic N-hetero compounds. XXXVIII. Synthesis and evaluation of antidepressive activity of [1]benzothieno[2′,3′:4,5]furo[3,2-d]primidines and their precursors

Synthesis of [1]benzothieno[2′,3′:4,5]furo[3,2-d]pyrimidines is described. Antidepressive evaluation of these compounds and their precursors were screened by inhibitory action of reserpine-induced hypothermia.     

High-performance liquid chromatographic determination of pamaquine, primaquine and carboxy primaquine in calf plasma using electrochemical detection.

A high-performance liquid chromatographic method with electrochemical detection is described for quantification of pamaquine, primaquine and carboxy primaquine in calf plasma. After the proteins had been precipitated with acetonitrile, the drugs were separated on a 5-microns C18-modified polymer gel column with an isocratic mobile phase. The detection limit was 0.01 microgram/ml in plasma for all three compounds. The applicability of the method in pharmacokinetic studies was demonstrated by determining the plasma concentrations of the three substances in calves administered a single dose of pamaquine or primaquine.     

Polycyclic N-heterocyclic compounds. 48. syntheses of furo[2,3-h]-[1,6]naphthyridine and imidazo(or pyrimido)[2,1-f]-[1,6]naphthyridines with rearrangement

The formation of a novel ring system, furo[2,3-h][1,6]naphthyridine via the Smiles rearrangement and intramolecular cyclization is described. Cyclization of 5-(ω-hydroxyalkylamino)-8-methyl-1,2-dihydrofuro[2,3-h][1,6]naphthyridines provided novel spiro compound with rearrangement.     

Locked TASC probes for homogeneous sensing of nucleic acids and imaging of fixed E. coli cells

We have designed a second-generation TASC (target-assisted self-cleavage) probe. It is based on the switching-on of incorporated cis-acting DNAzyme activity upon the target-induced conformational change of the otherwise inactive off-target probes locked in an intrastrand base-paired hairpin geometry. With E. coli 16S ribosomal RNA-relevant oligonucleotides as targets, the locked TASC probe exhibits an allosteric factor of k(on)/k(off) = 65 and the sequence selectivity is high, in terms of single nucleotide difference, when particular sequence and length of targets are chosen. Preliminary experiments with fixed E. coli cells show that the locked TASC probe with a FRET pair can be used to image fixed E. coli cells.     

An assessment of mucosal damage in vivo: effect of oral pretreatment with 5-fluorouracil on the intestinal first-pass metabolism of salicylamide in rabbits.

An assessment of 5-fluorouracil (5-FU)-induced mucosal damage in vivo by measuring the metabolism of salicylamide (SAM) was investigated in rabbit intestine. The mucosal damage in the intestine 48 h after oral administration of 5-FU (30 mg/kg) was examined using a scanning electron microscope. By the oral pretreatment with 5-FU, the morphological changes of jejunal and ileal mucosa were recognized compared with the control. The intestinal first-pass metabolism of SAM was studied using in situ intestinal sacs with complete mesenteric venous blood collection. The appearance of both SAM and its metabolites into the mesenteric venous blood was measured directly by cannulating the mesenteric vein of exposed intestine and collecting all venous blood draining from the absorbing region. Following oral pretreatment with 5-FU, the appearance of SAM glucuronide (SAMG) in the mesenteric venous blood was significantly increased. The increased blood concentration of SAMG following intraduodenal administration of SAM in vivo was observed in rabbits pretreated with 5-FU orally. However, the blood concentration of SAMG after intravenous administration of SAM was not increased compared with the control. These findings suggest that the change in intestinal first-pass metabolism of SAM may be due to the intestinal mucosal damage by oral pretreatment with 5-FU. The alteration of intestinal first-pass metabolism of a marker compound may be utilized for the assessment of intestinal mucosal damage in vivo.     

2-Oxo-1,2-ethylenedioxy group as a linker for solution-, liquid-, and solid-phase syntheses to discover drug-like small molecules

2-Oxo-1,2-ethylenedioxy (2-OED) functionality has been prepared on a soluble MPEG polymer and solid (HM resin and Lanterns) supports as platforms for discovery of drug-like small molecules. The functionality is cleaved either by Yb(OTf)₃ or TMSCHN₂ in MeOH, or by various amines to release small molecules synthesized on the platform in good yield. Application of these platforms aiming for discovery of potent agonists for growth hormone secretagogue is reported by using the Ugi four-component coupling reaction.     

The first synthesis and absolute configuration of glaucescenolide

The first synthesis of glaucescenolide (1), a cytotoxic sesquiterpene isolated from the liverwort, Schistochila glaucescens, was achieved by starting from 2,2,6-trimethylcyclohexanone (2). The absolute configuration of the naturally occurring 1 was confirmed as 5S,7S,10R.     

Photoinitiated cationic polymerization of oxetane formulated with oxirane

Photoinitiated cationic polymerization of oxetane, oxirane (epoxide), and a formulation of both was carried out and their reactivity compared. To investigate a formulated system of oxetane and oxirane in photoinitiated cationic polymerization, computational and experimental methods were used. In the computational study, we employed a semiempirical molecular orbital method (AM1). On the other hand, the reactivities of each system were evaluated and compared experimentally by a real-time FT-IR method. The computational study reveals that oxetane seems to polymerize in S_N2 mechanism, but two possibilities, of S_N1 mechanism through the α-cleavage and of S_N2 mechanism through β-cleavage, are implied for oxirane. Using the real-time FT-IR method, the formulation of oxetane and oxirane was proved to possess rather high reactivities of oxetane toward photoinitiated cationic polymerization. The formulated system exhibited slightly lower number-average molecular weight than oxetane but higher than oxirane. These experimental observations are well explained in terms of the calculated reaction paths. © 1995 John Wiley & Sons, Inc.     

High pressure-temperature Brillouin study of liquid water: evidence of the structural transition from low-density water to high-density water

The structural transformations occurring to water from low-density (LDW) to high-density (HDW) regimes have been studied by Brillouin scattering for the first time at temperatures up to 453 K and at pressures up to the solidification point. At ambient temperature (293 K) a discontinuity in pressure response of the sound velocity is observed. Furthermore, there are evident breaks in the linear behavior of log10 C11 versus log10(rho/rho0) when pressure increases up to 0.29, 0.21, and 0.19 GPa at the temperature of 293, 316, and 353 K, respectively. It is supposed to indicate the structural transition from LDW to HDW, and the possible transition boundary between LDW and HDW is in good agreement with the molecular-dynamics simulation.