Following the discovery of 4-[(3-bromophenyl)amino]-6,7-dimethoxyquinazoline (4; PD 153035) as an extremely potent (IC(50) 0.025 nM) inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR), several fused tricyclic quinazoline analogues have been prepared and evaluated for their ability to inhibit the enzyme. The most potent compound was the linear imidazo[4,5-g]quinazoline (8), which exhibited an IC(50) of 0.008 nM for inhibition of phosphorylation of a fragment of phospholipase C-gamma-1 as substrate. While N-methyl analogues of 8 showed similar potency, analogous N-[2-(dimethylamino)ethyl] derivatives were less effective. The next most potent compounds were the linear pyrazoloquinazolines (19 and 20) (IC(50)s 0.34 and 0.44 nM) and pyrroloquinazoline (21) (IC(50) 0.44nM), while several other linear tricyclic ring systems of similar geometry to 8 (triazolo-, thiazolo-, and pyrazinoquinazolines) were less effective. In the imidazo[4,5-g]quinazoline and pyrroloquinazoline series, the corresponding angular isomers were also much less effective than the linear ones. These results are consistent with structure-activity relationship studies previously developed for the 4-[(3-bromophenyl)amino] quinazolines, which suggested that small electron-donating substituents at the 6- and 7-positions were desirable for high potency. Cellular studies of the linear imidazoloquinazoline 8 show that it can enter cells and rapidly and very selectively shut down EGF-stimulated signal transmission by binding competitively at the ATP site of the EGFR.

Summary: A novel intelligent delivery system based on the environmental dependence of the inclusion effect of β‐cyclodextrin (β‐CD) with guest molecules, using a β‐CD polymer (CDP) microgel as carrier, is proposed. Compared with smart hydrogels, which are driven by the phase‐volume transition, controlled release from the CDP microgel is driven by “host‐guest” inclusion effects. With the pH‐dependent inclusion complexation of methyl orange (MO) with β‐CD as a model system, the behavior of the controlled release of a CDP microgel was tested by changing the pH, showing that the mechanism is reasonable.Schematic illustration of the pH‐dependent inclusion complexation of MO with β‐CD in the CDP microgel.magnified imageSchematic illustration of the pH‐dependent inclusion complexation of MO with β‐CD in the CDP microgel.

The SAFT-VRX equation of state combines the SAFT-VR equation with a crossover function that smoothly transforms the classical equation into a nonanalytical form close to the critical point. By a combinination of the accuracy of the SAFT-VR approach away from the critical region with the asymptotic scaling behavior seen at the critical point of real fluids, the SAFT-VRX equation can accurately describe the global fluid phase diagram. In previous work, we demonstrated that the SAFT-VRX equation very accurately describes the pvT and phase behavior of both nonassociating and associating pure fluids, with a minimum of fitting to experimental data. Here, we present a generalized SAFT-VRX equation of state for binary mixtures that is found to accurately predict the vapor-liquid equilibrium and pvT behavior of the systems studied. In particular, we examine binary mixtures of n-alkanes and carbon dioxide + n-alkanes. The SAFT-VRX equation accurately describes not only the gas-liquid critical locus for these systems but also the vapor-liquid equilibrium phase diagrams and thermal properties in single-phase regions.

The combination of successive substitution and the Newton method provides a robust and efficient algorithm to solve the nonlinear isofugacity and mass balance equations for two-phase split computations. The two-phase Rachford-Rice equation may sometimes introduce complexity, but the Newton and bisection methods provide a robust solution algorithm. For three-phase split calculations, the literature shows that the computed three-phase region is smaller than measured data indicate. We suggest that an improved solution algorithm for the three-phase Rachford-Rice equations can address the problem. Our proposal is to use a two-dimensional bisection method to provide good initial guesses for the Newton algorithm used to solve the three-phase RachfordRice equations. In this work, we present examples of various degree of complexity to demonstrate powerful features of the combined bisection-Newton method in threephase split calculations. To the best of our knowledge, the use of the bisection method in two variables has not been used to solve the three-phase Rachford-Rice equations in the past. V V C 2010 American Institute of Chemical Engineers AIChE J, 57: [2555][2556][2557][2558][2559][2560][2561][2562][2563][2564][2565] 2011

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