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181.
Noguchi T Tanaka N Nishimata T Goto R Hayakawa M Sugidachi A Ogawa T Asai F Fujimoto K 《Chemical & pharmaceutical bulletin》2008,56(6):758-770
To develop a potent and oral anticoagulant, a series of compounds with cinnamyl moiety was synthesized and their factor Xa (FXa) inhibitory activities were examined. As a result, some cinnamyl derivatives showed potent FXa inhibitory activities in vitro. Among them, compounds with substituent at the 3-position on the central benzene ring represented by (N-{4-[1-(acetimidoyl)piperidin-4-yloxy]-3-chlorophenyl}-N-[(E)-3-(3-amidinophenyl)-2-propenyl]sulfamoyl)acetic acid dihydrochloride (45b) and (N-{4-[1-(acetimidoyl)piperidin-4-yloxy]-3-carbamoylphenyl}-N-[(E)-3-(3-amidinophenyl)-2-propenyl]sulfamoyl)acetic acid dihydrochloride (45j) exhibited potent FXa inhibitory activities with IC(50) values of less than 10 nM in vitro. These compounds also showed potent anticoagulant activities both in vitro and ex vivo. Furthermore, these compounds exhibited no lethal toxicity (30 mg/kg, i.v.). 相似文献
182.
Suda M Ishii T Sootome H King AJ Shibahara M Noro N Yamashita K Noumi T 《Analytical and bioanalytical chemistry》2008,390(1):343-348
No universal approach has been reported for specific monitoring of the catalytic activity of a wide range of kinases in cells.
The present study describes an original platform for detecting the autonomous activity of serine/threonine kinases in cells
through the introduction of expression vectors encoding modified substrate kinase fusion proteins. The surrogate substrate
used consists of the p53 tumor suppressor protein fused with individual kinase domains (Chk1, DYRK3, and Cdk5) at its carboxy-terminal
through four tandem Gly-Gly-Gly-Gly-Ser repeats. After transfection into cells, phosphorylation of the p53 moiety could be
specifically induced by the catalytic activity of kinases contained in the fusion protein. Moreover, p53 phosphorylation was
significantly blocked when a kinase-inactive mutant was used as the fusion partner instead of the active kinase. Using this
system, the cell-based evaluation of several Cdk5 inhibitors was demonstrated. Thus, this approach provides a novel platform
for the specific, cell-based screening of inhibitors of a wide prospective range of protein kinases and is of tremendous potential
for drug discovery efforts. 相似文献
183.
H Aiso T Kochi H Mutsutani T Tanabe S Nishiyama F Kakiuchi 《The Journal of organic chemistry》2012,77(17):7718-7724
Palladium-catalyzed electrochemical iodination and one-pot arylation of arylpyridines are described. Ortho-selective C-H iodination proceeded via dual activation of each substrate by a palladium catalyst and an electrode. Various aryl groups were introduced at the ortho positions of arylpyridines by ON/OFF switching of two different catalytic cycles using the same palladium catalyst in a one-pot fashion. 相似文献
184.
To clarify the influence of cis-unsaturation on solid-state structures of triacylglycerols (TAGs), the crystal structures of three crystalline phases (alpha, beta' and beta) of triolein [C3H5(OCOC17H33)3] were investigated by powder X-ray diffractometry and IR and Raman spectroscopy. The influence on the structural change of the alpha phase in the course of cooling was also studied. With respect to the subcell structure and conformational order of hydrocarbon chains in the beta and beta' phases, triolein resembles saturated TAGs; trans-zigzag hydrocarbon chains are adopted in the T(parallel) subcell for the beta phase and in the O(perpendicular) subcell for the beta' phase. The influence of cis-unsaturation was most obvious in the structure of the alpha phase and its temperature dependence. The alpha phase of triolein does not form the ordinary hexagonal subcell but a rather loose distorted subcell, which hardly changes in cooling, forming a striking contrast to the hexagonal-->pseudohexagonal subcell transformation found in the alpha phase of saturated TAGs. 相似文献
185.
Iodine-mediated, oxidative desulfurization promoted cyclization of N-2-pyridylmethyl thioamides serves as an efficient and versatile method for the preparation of 2-azaindolizines (imidazo[1,5-a]pyridines) and rare 2-azaindolizine sulfur-bridged dimers. The 2-azaindolizines prepared in this manner are readily converted to a variety of fluorescent compounds by using transition-metal-catalyzed cross-coupling reactions. [reaction: see text]. 相似文献
186.
Anti-Markovnikov addition of anilines to aliphatic terminal alkynes proceeded using an 8-quinolinolato rhodium/phosphine catalyst system. The use of a strong organic base, 1,1,3,3,–tetramethylguanidine, in the catalyst system enabled the formation of the aldimine products. Substrates with various functional groups including polar groups such as a phenolic hydroxy group are applicable to the hydroamination. 相似文献
187.
Masamichi Kobayashi Tohru Kobayashi Yonghae Cho Fumitoshi Kaneko 《Macromolecular Symposia》1986,5(1):1-20
Various types of molecular assembly of long-chain compounds in solid states were investigated by means of infrared absorption, Raman and Brillouin spectroscopic methods. As for the polymorphism in even-numbered n-fatty acids, three monoclinic modifications, B, C, and E, all consisting of the orthorhombic polyethylene sublattice, give rise to their characteristic infrared and Raman spectra. A dynamical equilibrium between cis and trans conformations of the hydrogen-bonded carboxyl groups in modification C, which is related to the high-temperature stable character of this phase, is reflected to a dramatic change with temperature in the low-frequency Raman spectra. A new type of reversible solid state phase transition was found between two A-type (triclinic) modifications of myristic, palmitic, and stearic acids. The γ→α phase transition of oleic acid was found to be caused by a conformational disordering of polymethylene chains at the lamellar interfacial region. Two basic polytype structures, Mon and Orth II, of stearic acid B were investigated, and it was found that the low-frequency phonon frequencies (below 50 cm−1) were strongly influenced by the polytype structure. Based on the spectroscopic considerations, Orth II was predicted as the thermodynamically stable phase around room temperature compared with Mon, and the stability is responsible for the vibrational free energy term. Some experimental findings which support this prediction were obtained. The values of the stiffness tensor elements of Mon and Orth II, measured by Brillouin scattering, indicate that the mechanical behavior of bulk crystals is very dependent on the polytype structure. The relationship between the mobility of chain molecules and the width of the spectral bands was investigated in a quantitative manner for the case of n-alkane molecules entrapped in the urea inclusion adducts. The changes in the half-width for the polarization components of various Raman bands on the transition from the orthorhombic to the hexagonal phase are interpreted in terms of the correlation functions of the Raman tensor related to the rotational motion of the alkane molecules around the chain axes. 相似文献