Thioureas from 3-aminoquinazolin-4(3H)-one. 2. Unusual alkaline recyclization of 3-(N",N",S-trialkylisothioureido)quinazolin-4(3H)-ones into new 1,3,4-oxadiazoles

3-(N",N",S-trialkylisothioureido)quinazolin-4(3H)-ones obtained by the reactions of 3-(N",N"-dialkylthioureido)quinazolin-4(3H)-ones with alkyl halides undergo unusual recyclization into 5-(2-aminophenyl)-2-dialkylamino-1,3,4-oxadiazoles under the action of aqueous solutions of alkali, hydrazine, and primary aliphatic amines. A plausible mechanism of the recyclization was proposed.     

Condensed Thienopyrimidines. 14. Synthesis of 10H-Thiopyrano[4',3':4',5']thieno[2',3':4,5]pyrimido[2,3-c]-1,2,4-triazines

Reaction of a substituted 2-aminothienothiopyran with methyl(phenyl) isothiocyanate, intramolecular cyclization of the obtained N'-methyl(phenyl) thioureido derivatives, and work up of the cyclization products with hydrazine hydrate gave 2-hydrazinodihydrothiopyranothienopyrimidines. Treatment of the latter with pyruvic acid gave the novel 10H-thiopyrano[4',3':4',5']thieno[2',3':4,5]pyrimido[2,3-c]-1,2,4-triazines.     

Bromination of Substituted 5H-Imidazo[1,2-b]-1,2,4-triazepin-4-ones and -thiones

The reactions of substituted 5H-imidazo[1,2-b]-1,2,4-triazepin-4-ones and -thiones with bromine and N-bromosuccinimide have been studied. Derivatives of 3- and 8-bromo-, 3,8-dibromoimidazo[1,2-b]-1,2,4-triazepine and 5H-2-bromomethyl-3-methyl-7,8-diphenylimidazo[1,2-b]-1,2,4-triazepin-4-one are formed, depending on the degree of substitution, the nature of the brominating agent, and the reaction conditions.     

Synthesis and Characterization of Tetraosmium Carbonyl Complexes Containing a Bridging CO2 Ligand

Treatment of (thd)H (thd=2,2,6,6-tetramethyl-3,5-heptandionate) with excess Os₃(CO)₁₂ in an autoclave at 180°C gives the formation of a brown metal chain complex [Os₂(CO)₅(thd)₂]₂ (1) and a yellow CO₂ cluster complex [Os₄(-H)(-CO₂)(thd)(CO)₁₃] (2) in low yields. Complex 2 was fully identified by a combination of spectroscopic methods and X-ray diffraction study, showing a unique CO₂ ligand bridging a triosmium metal fragment, Os₃(-H)(CO)₁₀ and a monometallic osmium fragment, Os(CO)₃(thd). Upon treatment of 1 with Me₃NO at an elevated temperature, oxidation of the CO ligand occurred at the position trans to the unique CO₂ ligand on the Os(CO)₃(thd) fragment, giving the formation of a second CO₂ cluster [Os₄(-H)(-CO₂)(thd)(CO)₁₂(NCMe)] (3), which is stabilized by a weakly coordinated acetonitrile molecule.     

Synthesis of D-Glucose-based Azacrown Ethers with Phosphinoxidoalkyl Side Chains and Their Application to an Enantioselective Reaction

Five chiral -D-glucose-based monoaza-15-crown-5 ethers with phosphinoxidoalkyl side chains of one to five carbon atoms (5a–e)have been synthesised. The cation binding ability of the new lariat ethers was evaluated bythe picrate extraction method. The substituents at the nitrogen atom were not a major influenceon the cation extraction ability of the azacrown ether; the compounds showed, however, a significant asymmetric induction as phase transfer catalysts in the Michael addition of2-nitropropane to chalcone (95% ee).     

Synthesis of 4-Benzylsulfonyl-5-polyfluoroalkyl-ν-triazoles from 1,1-Dihydropolyfluoroalkyl Benzyl Sulfones

The reaction of 1,1-dihydropolyfluoroalkyl benzyl sulfones with sodium azide or trimethylsilyl azide in the presence of tertiary amines gives ammonium salts of 4-benzylsulfonyl-5-polyfluoroalkyl--triazoles. The proposed reaction scheme includes the participation of catalytic amounts of azide ion in the cyclization of the formed intermediate vinyl azides to triazoles. X-ray analysis of 1,4-diazabicyclo[2.2.2]octane salt of 4-benzylsulfonyl-5-(-H-hexafluoropropyl)--triazole has been carried out.     

Transition Metal Complexes with Pyrazole-based Ligands. Part 12. Characterisation and thermal decomposition of CuCl2 complexes with di- and trisubstituted pyrazoles

The synthesis of copper(II) chloride complexes with 3,5-dimethylpyrazole, 1-carboxamidine-3,5-dimethylpyrazole, 5-amino-4-carboxamide-1-phenylpyrazole and 4-acetyl-3-amino-5-methylpyrazole is described. The compounds are characterized by elemental analysis, FT-IR spectroscopy, thermal methods, magnetic moment and molar conductivity measurements. Thermal decomposition of the dichloro-(3,5-dimethylpyrazole)-copper(II) complex results in an unstable intermediate with a stochiometric composition. The decomposition of the other compounds is continuous. This revised version was published online in August 2006 with corrections to the Cover Date.     

Lipophilicity in PK design: methyl, ethyl, futile

Lipophilicity, often expressed as distribution coefficients (log D) in octanol/water, is an important physicochemical parameter influencing processes such as oral absorption, brain uptake and various pharmacokinetic (PK) properties. Increasing log D values increases oral absorption, plasma protein binding and volume of distribution. However, more lipophilic compounds also become more vulnerable to P450 metabolism, leading to higher clearance. Molecular size and hydrogen bonding capacity are two other properties often considered as important for membrane permeation and pharmacokinetics. Interrelationships among these physicochemical properties are discussed. Increasing size (molecular weight) often gives higher potency, but inevitably also leads to either higher lipophilicity, and hence poorer dissolution/solubility, or to more hydrogen bonding capacity, which limits oral absorption. Differences in optimal properties between gastrointestinal absorption and uptake into the brain are addressed. Special attention is given to the desired lipophilicity of CNS drugs. In examples using -blockers, Ca channel antagonists and peptidic renin inhibitors we will demonstrate how potency and pharmacokinetic properties need to be balanced.     

新型共轭高分子聚[吡咯2,5-二(3-甲氧基-4-羟基苯甲烯)]的合成与表征

本文采用两步法合成了一种新型共轭高分子聚 [吡咯 2 ,5 二 (3 甲氧基 4 羟基苯甲烯 ) ],其前聚物聚 [吡咯 2 ,5 二 (3 甲氧基 4 羟基苯甲烷 ) ]可溶于一般的极性有机溶剂 .通过红外、核磁、紫外光谱分析鉴定了产物及其前聚物的结构 .利用DSC与TGA测试分析了所合成聚合物的热学性质 .紫外光谱表明在聚合物链中引入醌式吡咯环结构有利于降低产物的能隙 ,其能隙为 1 14eV ,属窄能隙类共轭聚合物 .经碘掺杂后产物的电导率在半导体的范围内     

冠醚富集原子吸收光谱法测定水样中痕量镉

报道了用装有涂布了聚苯并15－冠－5（A型）的分子筛的玻璃分离柱可用于水中痕量镉的预富集,此分离方法是基于CdI4^2-络阴离子与冠醚的络合反应,取水样750ml调其酸度至pH3左右,加入KI 15g,溶解后,以2－3ml.min^-1的流速通过交换柱,用0．5mol.L^-1 HCl作为洗脱剂,以0．3－0．5ml.min^-1的流速将Cd^2 从络合物中解脱淋洗下,淋也液定容为25ml后用FAAS法测定其含镉量。