Aldehydes and ketones are two of the most important functional groups in organic chemistry. Their synthetic and mechanistic chemistry has been studied in detail (1). It has also been known for some time that aldehydes and ketones can serve as ligands in transition metal complexes (2-33). However, this area has not received a great deal of systematic study. Indeed, the frequent use of acetone as a reaction or recrystallization solvent has likely led to the occasional serendipitous synthesis of acetone complexes-or at least it has once in the authors' laboratory.There are numerous transition metal catalyzed reactions that involve aldehyde or ketone starting materials or intermediates (34-37). Two industrially important examples are given in Figure 1. Clearly, the systematic study of stable aldehyde and ketone complexes is necesary to provide in-Volume 65 Number 4
Quantitative dopant profile measurements are performed on a nanometer scale by scanning capacitance microscopy (SCM). An atomic force microscope is used to position a nanometer scale tip at a semiconductor surface, and local capacitance change is measured as a function of sample bias. A new feedback method has been demonstrated in which the magnitude of the ac bias voltage applied to the sample is adjusted to maintain a constant capacitance change as the tip is scanned across the sample surface. A quasi-1D model is used to extract dopant density profiles from the SCM measurements. The inverted SCM dopant profiles are compared with profiles obtained by process simulation and secondary ion mass spectroscopy measurement. Good agreement was found between the SCM measured profile and the lateral profile predicted by SUPREM 4 over the concentration range from 1017 to 1020 cm−3.
The MTD of sorafenib plus temsirolimus in HCC was lower than in other tumor types. HCC-specific phase I studies are necessary. The observed efficacy warrants further study.
The present studies represent the first published report of a dopamine D1 positive allosteric modulator (PAM). D1 receptors have been proposed as a therapeutic target for the treatment of cognitive deficits associated with schizophrenia. However, the clinical utility of orthosteric agonist compounds is limited by cardiovascular side effects, poor pharmacokinetics, lack of D1 selectivity, and an inverted dose response. A number of these challenges may be overcome by utilization of a selective D1 PAM. The current studies describe two chemically distinct selective for human and nonhuman primate D1 receptors, but lacks activity at the rodent (rat and mouse) D1 receptors. Using molecular biology techniques, a single amino acid was identified at position 130, which mediates the species selectivity of Compound B. These data represent the first described D1-selective PAMs and define critical amino acids that regulate species selectivity.
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