No abstract

meantimc the first successful crystal structure analysis of a "cobaltocenium-Angiw Ciiem. Int Ed. Engl. 1995, 34, No. 11 VCH Verlag.~gesrllsciiaft mbH, 0-6945'1 Weinheim. 1995 Oj70-0833,'95/1111-1201 B l~l.Ofl+ ..?j:(I

Inhibition of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) represents a promising strategy for the discovery of a new generation of anticancer chemotherapeutics. Our synthetic efforts, beginning from the lead compound 2, were directed at improving antiproliferative activity against cancer cells as well as various drug properties. These efforts led to the discovery of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide dimethylsulfoxide solvate (GSK1120212, JTP-74057 DMSO solvate; 1), a selective and highly potent MEK inhibitor with improved drug properties. We further confirmed that the antiproliferative activity correlates with cellular MEK inhibition and observed significant antitumor activity with daily oral dosing of 1 in a tumor xenograft model. These qualities led to the selection of 1 for clinical development.

A hydrothermal procedure is used to prepare the molecular sieve Al2 (CH3PO3)3 (1). This compound has a new three‐dimensional framework, in which one six‐coordinate and two four‐coordinate Al centers are bound to the CH3PO3 units. The channel walls of the micropores of 1 are probably not lined with O atoms but with methyl groups.

A high-quality Si−MCM-41 was prepared with the composition of SiO2, 0.2; TEAOH, 0.25; CTMABr, 35 in H2O using fumed silica as the silica source. The quality of the compounds was assessed using different analytical techniques such as XRD, N2 adsorption−desorption measurement, UV−vis absorption, FTIR, and 29Si MAS NMR. The quality of M41S mesoporous materials, synthesized using a single C16TMA+ surfactant, could be further improved by a postsynthesis hydrothermal treatment of the as-synthesized materials in water. In comparison with the ordinary preparation, the water-treated materials exhibited a higher long-distance order, a higher BET surface area, and a larger pore size. The postsynthesis water treatment method provided an easy and mild way to prepare high-quality M41S molecular sieves with the pore size controllable by altering either the treatment time or the temperature. The postsynthesis treatment also enhanced the stability, especially the hydrothermal stability, of Si−MCM-41. The 29Si MAS NMR results demonstrated that the water treatment promoted the wall polymerization or local atomic arrangement. It was suggested that the pH lowering of synthesis mixture by replacing the mother liquor with water played a crucial role in the restructuring toward a high-quality Si−MCM-41. The quality of Ti−MCM-41, Al−MCM-41, and Si−MCM-48 was also improved by a similar postsynthesis hydrothermal treatment.