Synthesis and antitumor activity of novel pyrimidinyl pyrazole derivatives. II. Optimization of the phenylpiperazine moiety of 1-[5-methyl-1-(2-pyrimidinyl)-4-pyrazolyl]-3-phenylpiperazinyl-1-trans-propenes

A series of novel 3-substituted-1-[5-methyl-1-(2-pyrimidinyl)-4-pyrazolyl]-1-trans-propenes in order to improve the in vitro and in vivo activity of our prototype 3-[4-(3-chlorophenyl)-1-piperazinyl]-1-[5-methyl-1-(2-pyrimidinyl)-4-pyrazolyl]-1-trans-propene (2) were synthesized and evaluated by assays of growth inhibition against several tumor cell lines in vitro and antitumor activity against some tumor models when dosed both intraperitoneally and orally in vivo. Compounds 7a and 7e, the 3,5-difluorophenyl and 3,5-dichlorophenyl analogues of 2, respectively, showed significantly more potent cytotoxicity than 2 in vitro and potent antitumor activities without causing decrease of body temperature related to side effects.     

Selective preparation of pyridines, pyridones, and iminopyridines from two different alkynes via azazirconacycles

Selective preparation of pyridine derivatives from two different alkynes and a nitrile was achieved by a novel procedure in which an alkyne and a nitrile couple first to give an azazirconacyclopentadiene followed by reaction with the second alkyne in the presence of 1 equiv of NiCl(2)(PPh(3))(2). This procedure gives only single products of pyridine derivatives from two different symmetrical alkynes and a nitrile. Our novel procedure can be used even with two similar alkyl-substituted alkynes such as 3-hexyne and 4-octyne. Two possible pyridine isomers from 3-hexyne, 4-octyne, and acetonitrile could be completely and independently prepared as single products by this method. The origin of the selectivity comes from the addition order of two different alkynes. This method was applied for the formation of pyridones and iminopyridines using isocyanate and carbodiimide derivatives instead of nitriles, respectively. Reaction of an alkyne with Cp(2)ZrEt(2) and an isocyanate or a carbodiimide gives an azazirconacycle. Treatment of the azazirconacycle with the second alkyne in the presence of 1 equiv of NiCl(2)(PPh(3))(2) gave a pyridone or an iminopyridine derivative. The use of two different unsymmetrical alkynes afforded the pyridine with five different substituents when the first alkyne has a trialkylsilyl group and the second alkyne has a phenyl group as functional groups. On the other hand, azazirconacyclopentadienes reacted with propargyl bromide in the presence of CuCl with excellent regioselectivity to give tetrasubstituted pyridine derivatives as single products. With the assistance of the trialkylsilyl groups, pyridines with all different substituents including H were also prepared.     

A few comments on the internal rotations in DNA

Comments are given on the internal rotation angles in DNA molecules, their variations, and their oscillatory motions.     

Chromatographic preconcentration of copper in environmental and biological samples using 2,4,6-tri(2-pyridyl)-1,3,5-triazine-tetraphenylborate-naphthalene adsorbent

A method was established for the determination of trace amounts of copper using chromatographic preconcentration of copper(I) with 2,4,6-tri(2-pyridyl)-1,3,5-triazine and tetraphenylborate. Copper is quantitatively adsorbed on this adsorbent in the pH range 1.8–10.5 and at flow-rates of 0.2–10 ml/min. The solid mass consisting of copper complex along with naphthalene is dissolved from the column with 5 ml of dimethylformamide. A calibration curve is obeyed over the concentration range 0.2–10.0 g of copper in 5 ml of dimethylformamide. Eight replicate determinations of 3 g of copper gave a mean absorbance of 0.185 with a relative standard deviation of 1.4%. The characteristic concentration for 1% absorption is 0.0143 g/ml (0.103 gmg/ml for direct AAS in aqueous medium). The interference of various ion and salts has been studied and the proposed method has been employed to the determination of copper in biological and water samples.     

Stereocontrol in the free‐radical polymerization of methacrylates with fluoroalcohols

The free‐radical polymerization of methyl methacrylate (MMA), ethyl methacrylate (EMA), isopropyl methacrylate (IPMA), and tert‐butyl methacrylate (t‐BuMA) was carried out under various conditions to achieve stereoregulation. In the MMA polymerization, syndiotactic specificity was enhanced by the use of fluoroalcohols, including (CF₃)₃COH as a solvent or an additive. The polymerization of MMA in (CF₃)₃COH at −98 °C achieved the highest syndiotacticity (rr = 93%) for the radical polymerization of methacrylates. Similar effects of fluoroalcohols enhancing syndiotactic specificity were also observed in the polymerization of EMA, whereas the effect was negligible in the IPMA polymerization. In contrast to the polymerizations of MMA and EMA, syndiotactic specificity was decreased by the use of (CF₃)₃COH in the t‐BuMA polymerization. The stereoeffects of fluoroalcohols seemed to be due to the hydrogen‐bonding interaction of the alcohols with monomers and growing species. The interaction was confirmed by NMR measurements. In addition, in the bulk polymerization of MMA at −78 °C, syndiotactic specificity and polymer yield increased even in the presence of a small amount {[(CF₃)₃COH]/[MMA]_o < 1} of (CF₃)₃COH. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 4693–4703, 2000     

Optically active antifungal azoles. XI. An alternative synthetic route for 1

New routes for the synthesis of the optically active antifungal triazoles 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone (1b) and the 3-14-(1H-1,2,3-triazol-1-yl)phenyl]-2-imidazolidinone analog (1a) that possess an imidazolidine nucleus were established. The key synthetic intermediates, (2R,3R)-3-(2,2-diethoxvethyl)amino-2-(2,4-difluorophenyl)-1-(1H1,2,4-triazol-1-yl)-2-butanol (8) and (2R,3R)-2-(2,4-difiuorophenyl)-3-(2-h ydroxyethyl)amino-1-(1H-1,2,4-triazol-1-yl)-2-butanol (14), were prepared by the ring-opening reaction of the oxirane (2) with the corresponding 2-substituted ethylamines. The acetal (8) was converted to the imidazolidinones (1a, b) by condensation with the carbamates (10a, b) followed by treatment with hydrochloric acid and subsequent catalytic hydrogenation. The candidate selected for the clinical trials, 1b (TAK-456), was alternatively prepared from the hydroxyethylamino intermediate (14) via two reaction steps: condensation with the carbamate (10b) to the urea (15) and subsequent cyclization to the imidazolidinones. This newly developed synthetic route could be applied to a large scale preparation of 1b.     

Photoacoust1C Studies on Very Thin Poly(Methyl Methacrylate) Films Prepared by a Cast1Ng-On-Water Method

Photoacoustic (PA) responses from very-thin poly(methyl methacrylate) (PMMA) films were investigated at various lamination conditions. The PA signal increased when the dye-doped films were laminated up to five layers, but tended to saturate beyond five layers. When the blank films were superimposed on the dye-doped film, the signal became smaller. The signal was larger when the dye-doped film was arranged outermost in the laminated film assembly of dye-doped and blank films. The results imply the effect of film vibration on the PA response.     

Application of Infrared Spectroscopy to Structure Studies of Nucleic Acids

Abstract

The purpose of this review is to show the extent to which infrared spectroscopy has been and will be useful for elucidating the molecular structures of nucleic acids.