Studies on cardiotonic agents. V. Synthesis of 1-(6,7-dimethoxy-4-quinazolinyl)piperidine derivatives carrying various 5-membered heterocyclic rings at the 4-position

A series of 1-(6,7-dimethoxy-4-quinazolinyl)piperidines carrying various 5-membered heterocycles at the 4-position was synthesized and examined for cardiotonic activity in anesthesized dogs. The (4-oxo-2-thioxo-3-imidazolindinyl)amino derivatives showed the most potent inotropic activity. Marked loss of activity was observed in the 2,4-dihydro-3-thioxo-3H-1,2,4-triazolyl, the 2,4-dihydro-3-oxo-3H-pyrazolyl and the (2,3-dihydro-2-thioxo-3H-1,3,4-thiadiazol-5-yl)amino derivatives. The synthesis and structure-activity relationships are discussed.     

Regioselective 2 A -2 D -Disulfonylations of Cyclodextrins for Practical Bifunctionalization on the Secondary Hydroxyl Face

A useful technique to bifunctionalize the secondary hydroxyl faces of cyclodextrins is described. Regioselective2^A,2^D-disulfonylations ofcyclodextrins were achieved by reacting cyclodextrins with a combinationof a novel disulfonyl imidazole reagent and molecular sieves inN,N-dimethylformamide. The resulting disulfonates were convertedto 2^A,3^A,2^D,3^D-dimannoepoxy-cyclodextrins and3^A,3^D-diamino-3^A,3^D-dideoxy-(2^AS,3^AS),(2^DS,3^DS)-cyclodextrins, which contain twofunctional groups on the periphery of the molecules.     

Phototriggered self-assembly of hydrogen-bonded rosette

Azobenzene-appended melamine M2 and barbiturate B2, both possessing bulky tridodecyloxyphenyl (TDP) wedge(s), were designed and synthesized to establish a photoresponsive hydrogen-bonded supramolecular assembly. The geometrical isomer EE-M2 bearing two E-azobenzene moieties easily complexed with B2, affording a remarkably stable cyclic hexamer EE-M2(3).B2(3) (rosette) in chloroform, toluene, and methylcyclohexane, as confirmed by size exclusion chromatography, dynamic light scattering, (1)H NMR, and UV-vis studies. The E --> Z photoisomerization of the azobenzene moieties upon irradiation with UV light was significantly suppressed in the rosette because of the steric crowding of the TDP wedges (total of nine TDP wedges in a rosette), whereas irradiation of the monomeric EE-M2 resulted in facile transformation into ZZ-M2 bearing two Z-azobenzene moieties. (1)H NMR studies of the complexation of the initially photogenerated ZZ-M2 with B2 revealed that it is hard for ZZ-M2 to form a rosette with B2 because of the intermolecular steric interaction between the TDP wedges. The photoregulatable complexation efficiency of M2 allowed us to accomplish the phototriggered formation of the rosette by irradiation of a monomeric mixture of ZZ-M2 and B2 using visible light.     

Total synthesis of (+)-cylindricine C

A stereoselective total synthesis of (+)-cylindricine C has been achieved starting with (S)-N-Boc-2-pyrrolidinone. The key elements of this synthesis involve the sequence of reactions including BF₃-mediated addition of the allyl Grignard reagent to the cyclic imine, spirocyclization via enamine formation, and intramolecular Michael addition to form the tricyclic core.     

Studies on cardiotonic agents. I. Synthesis of some quinazoline derivatives

A series of quinazoline derivatives with various 4-heterocyclylpiperidino groups at the 4-position was synthesized and tested for cardiotonic activity in anesthetized dogs. Among them, several 6,7-dimethoxyquinazoline derivatives showed potent cardiotonic activity.     

Studies on cardiotonic agents. II. Synthesis of novel phthalazine and 1,2,3-benzotriazine derivatives

A series of phthalazine and 1,2,3-benzotriazine derivatives which have heterocyclylpiperidino groups was synthesized and tested for cardiotonic activity in anesthetized dogs. Several 6,7-dimethoxyphthalazine derivatives showed relatively potent cardiotonic activity comparable to that of amrinone.     

Gas permeation of porous organic/inorganic hybrid membranes

Selective gas permeation of porous organic/inorganic hybrid membranes via sol-gel route and its thermal stability are described. Separation performance of the hybrid membrane was improved compared with porous membranes governed by the Knudsen flow, and gas permeability was still much higher than that through nonporous membranes. Additionally, it was shown that these membranes were applicable at higher temperatures than organic membranes.SEM observation demonstrated that the thin membrane was crack-free. Nitrogen physisorption isotherms showed the pore size was in the range of nanometers. Gas permeability through this membrane including phenyl group was in the range of 10^–8 [cc(STP) cm/(cm² s cmHg)] at 25°C. The ratios of O₂/N₂ and CO₂/N₂ were 1.5 and 6.0, respectively, showing the permeation was not governed by the Knudsen flow. The permeability decreased as the temperature increased. Furthermore, the specific affinity between gas molecules and surface was observed not only in the permeation data of the hybrid membranes but in the physisorption data. These results suggested that the gas permeation through the hybrid membrane was governed by the surface flow mechanism.Thermal analysis indicated that these functional groups were still stable at higher temperatures. The phenyl group especially remained undamaged even at 400°C.     

Preparation and characterization of polypropylene/mesoporous silica nanocomposites with confined polypropylene

Polypropylene (PP)/Ti-MCM-41 nanocomposites were prepared by isospecific propylene polymerization with Ti-MCM-41/Al(i-C₄H₉)₃ catalyst. The cross polarization/magic angle spinning (CP/MAS) ¹³C NMR spectrum of the composite was similar to that of the conventional isotactic PP, and the decrease in the pore volume of Ti-MCM-41 in the nanocomposites, as measured by N₂ adsorption, was consistent with the value calculated from the weight loss in the thermogravimetric analysis (TGA) curve; both these facts attest to propylene polymerization within the mesopores of Ti-MCM-41. Alkali treatment followed by extraction with o-dichlorobenzene allows us to extract the confined PP out of the Ti-MCM-41 mesopores. Although the PP/Ti-MCM-41 nanocomposites do not exhibit a crystalline melting point, the same PP when extracted from the mesopores showed a clear melting point at 154.7 °C; this indicates that the crystallization of PP confined in mesopores is strongly hindered. For the PP polymerized within the confinement, the molecular weight (M_w) and molecular weight distribution (M_w/M_n) were 84,000 and 4.3, respectively; these values were considerably smaller than those of the PP polymerized concurrently outside the Ti-MCM-41 mesopores (M_w = 200,000–450,000, M_w/M_n = 40–75). Therefore, the confinement also has a marked effect on the molecular weight of the PP. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 3324–3332, 2003