Hinge-directed Selectivity

Selective inhibition of the target kinase can also be obtained by addressing binding region 11. The Banyu Tsukuba Research Institute has explored this particular strategy in their search for selective cyclin-dependent kinase 4 (CDK4) inhibitors [60, 85, 86], which are believed to suppress tumor growth by C, arrest. 

Compound CDK2 (nM) CDK 4 (nM) CDK2/CDK4 CDK4/CDK2 

---

An attractive alternative to the direct measurement of vapor pressure is the use of gas chromatographic retention to estimate p (e.g., Hinckley et al., 1990). This method is based on the evaluation of the partitioning behavior of a given compound between the gas phase (i.e., the mobile phase) and a bulk organic phase (i.e., the stationary phase) at different temperatures. The method hinges on the selection of an... 

Fig. 3.1. Experimental arrangement described by Kachi and Kon [3.33]. The CO2 pump laser cavity is formed by a mirror and a grating at the Littrow angle (autocollimation). Output coupling occurs via the zeroth order reflection from the grating. Note the hinge mount which ensures that the output beam is in a fixed direction for all wavelengths. The submillimeter laser resonator used here is of the Fabry-Perot type. A small amount of the radiation is coupled out to the detection system with a Michelson interferometer used to select the desired line when two or more lines oscillate. From [3.33]...

As was the case for XANES, here electronic structure calculations including solvent effects are used to draw conclusions on the most probable coordination isomer and from that structure the interatomic bond distances can be directly compared to the computed EXAFS spectra [150-152]. As EXAFS spectroscopy probes the structure of a statistically averaged system, the most appropriate way of comparing theoretical EXAFS data to experimental ones is to use molecular dynamics trajectories to sample the configuration space, select snapshots and finally compute a statistically average spectrum [89,153] with a direct estimate of the mean square relative disorder (MSRD, also called or the EXAFS Debye-Waller term). However, as discussed in Section 11.2.3, the relevance of MD simulations hinges on how accurate intermolecular interactions are, given that these are usually obtained at DFT level (in Car-Parinello MD simulations) or with force-fields (in classical MD simulations). 

The worst aspect of the Nation membrane is its high cost Massive R D efforts have been going on for years to develop low cost cation-selective membranes having a performance comparable to that of Nation, at a much lower price. This is a critical issue, because the commercial success or failure of the direct methanol fuel cell hinges on our ability to develop such membranes at (1-2)% of their present cost... 

Friedel-Crafts alkylation can be conducted in water without a catalyst. Cozzi and Zoh [117] described the direct nucleophilic substitution of alcohol on water, with no use of Lewis or Bronsted adds or surfactants. Selected examples can be found in Scheme 6.24. The success of these reactions hinges on the formation of relatively stable carbocation, and they can be promoted by microwave (MW) radiation [118]. 

---