Studies on the synthesis of condensed pyridazine derivatives. IV. Synthesis and anxiolytic activity of 2-aryl-5,6-dihydro-(1)benzothiepino[5,4- c]pyridazin-3(2H)-ones and related compound.

A series of 2-aryl-5,6-dihydro-(1)benzothiepino[5,4-c]pyridazin-3(2H)- ones and related compounds were synthesized and evaluated for their ability to displace 3H-diazepam from rat brain membranes in vitro, and to prevent bicuculline induced convulsions in mice in vivo. Compounds with a 4'-methoxyphenyl (36) or 4'-chlorophenyl group (37, 39--42) as 2-aryl substituents showed prominent activities in both the in vitro and in vivo tests. Among them, 2-(4'-chlorophenyl)-5,6-dihydro- (37) and 2-(4'-chlorophenyl)-5,6-dihydro-10-fluoro-(1)benzothiepino[5,4-c]+ ++pyridazin- 3(2H)-one 7-oxides (41) showed activity twice as potent as diazepam in an anticonflict test (Vogel type, rats) while exhibiting less muscle relaxation (rotarod test, mice) and augmentation of gamma-aminobutyric acid-induced chloride current (Icl) in isolated frog sensory neurones than diazepam. Compound 37 (Y-23684) was selected from this series as a candidate for further development. The structure-activity relationships are discussed.     

Isolation of o-xylylene (o-quinodimethane) dirivatives. A strong through-bond interaction in 2,3-benzobicyclo[2.2.0]hexane system

Some o-xylylene (o-quinodimethane) derivatives were isolated as stable cyrstalline materials. A strong through-bond interaction in tetracyanoethylene addition product of tetraphenylbenzodicyclobutadiene ($\text{21}$ is suggested.     

First thermally responsive supramolecular polymer based on glycosylated amino acid

In materials science, a dynamic property sensitive to an environmental change (heat, light, electric current, pH, and other chemical or physical changes) is indispensable for intelligent materials. Such organic materials, however, are very limited even in conventional polymers. This paper clearly demonstrates that, regardless of the low molecular weight, a glycosylated amino acid derivative newly screened by a combinatorial method forms a macroscopic supramolecular hydrogel that reversibly swells or shrinks in response to the external temperature. Using the unique thermal response of the present hydrogel, we carried out the controlled release of DNA and the perfect removal of bisphenol A from the polluted water. Recently, advanced supramolecular polymers, in which monomers are noncovalently connected, are expected to be highly advantageous over traditional polymers because of their tunable and recyclable characteristics. The present result newly confers a dynamic feature on the supramolecular polymers, which is desirable for the sophisticated application in many fields.     

Preparation and thermal analysis of synthetic malachite CuCO3·Cu(OH)2

The synthesis of malachite CuCO₃·Cu(OH)₂ or Cu₂CO₃(OH)₂ was studied through titrations of copper(II) salt solutions with a solution of sodium carbonate at different temperatures. The precipitates were characterized by TG, IR and chemical analysis. The composition varies depending on thepH of the solution and the temperature. Purer malachite was synthesized by simple mixing of a solution of copper(II) nitrate or sulfate with a solution of sodium carbonate at 50°C.The kinetics of the thermal decomposition of synthetic malachite was described by eitherR ₃ orA _m(m=1.2–1.4) law, according to TG analysis, both isothermal and nonisothermal. The Arrhenius parameters determined using three different integral methods showed the kinetic compensation effect, which is correlated to the working temperature interval analyzed.The authors thank Mr. H. Takemoto for analyzing kinetics of the thermal decomposition of synthetic malachite.     

Solubility of α-amino acids in water under high pressure: glycine, -alanine, -valine, -leucine, and -isoleucine

The solubility of glycine, -alanine, -valine, -leucine, and -isoleucine in water was measured at 298.15 K and pressures up to 400 MPa. The standard deviation of the logarithm of the solubility is 0.001–0.003, equal to or better than the accuracy of atmospheric pressure measurement in the literature (0.001–0.05). A variety of solubility phenomena were observed. The solubility of glycine decreased with increasing pressure, whereas that of -alanine increased. The -valine and -isoleucine have a solubility maximum at around 100 MPa, and -leucine seems to exhibit a solid-phase phase transition at around 200 MPa. Pressure coefficient of the solubilities at 0.10 MPa is compared with that thermodynamically estimated in reference to aqueous density measurements of glycine and -alanine at 298.15 K and 0.10 MPa, supporting a reliability of our high-pressure measurements.