@article {1117, title = {A divergent approach to the synthesis of 3-substituted-2-pyrazolines: Suzuki cross-coupling of 3-sulfonyloxy-2-pyrazolines.}, journal = {The Journal of Organic Chemistry}, volume = {74}, year = {2009}, month = {2009 Aug 21}, pages = {6390-3}, abstract = {

The efficient Suzuki cross-coupling of pyrazoline nonaflates with organoboron reagents was achieved to afford diverse 3-substituted-2-pyrazolines in excellent yield. The nonaflates displayed improved reactivity over the corresponding triflates and smoothly coupled to a variety of aryl- and heteroarylboronic acids. This process and its broad scope constitute a rapid, divergent strategy for the synthesis of elaborated 2-pyrazolines that are not readily obtained via conventional methods.

}, keywords = {Kinetics, Pyrazoles, Sulfonic Acids}, issn = {1520-6904}, doi = {10.1021/jo9011859}, author = {Grimm, Jonathan B and Wilson, Kevin J and Witter, David J} } @article {1116, title = {Exploring the pharmacokinetic properties of phosphorus-containing selective HDAC 1 and 2 inhibitors (SHI-1:2).}, journal = {Bioorganic \& Medicinal Chemistry Letters}, volume = {19}, year = {2009}, month = {2009 Apr 1}, pages = {2053-8}, abstract = {

We report the preparation and structure-activity relationships of phosphorus-containing histone deacetylase inhibitors. A strong trend between decreasing phosphorus functional group size and superior mouse pharmacokinetic properties was identified. In addition, optimized candidates showed tumor growth inhibition in xenograft studies.

}, keywords = {Administration, Animals, Antineoplastic Agents, Enzyme Inhibitors, Heterologous, Histone Deacetylase 1, Histone Deacetylase 2, Histone Deacetylase Inhibitors, Histone Deacetylases, Mice, Nude, Oral, Phosphonic Acids, Repressor Proteins, Transplantation}, issn = {1464-3405}, doi = {10.1016/j.bmcl.2009.02.009}, author = {Heidebrecht, Richard W and Chenard, Melissa and Close, Joshua and Dahlberg, William K and Fleming, Judith and Grimm, Jonathan B and Hamill, Julie E and Harsch, Andreas and Haines, Brian B and Hughes, Bethany and Kral, Astrid M and Middleton, Richard E and Mushti, Chandrasekhar and Ozerova, Nicole and Szewczak, Alexander A and Wang, Hongmei and Wilson, Kevin and Witter, David J and Secrist, J Paul and Miller, Thomas A} } @article {1115, title = {Phenylglycine and phenylalanine derivatives as potent and selective HDAC1 inhibitors (SHI-1).}, journal = {Bioorganic \& Medicinal Chemistry Letters}, volume = {18}, year = {2008}, month = {2008 Mar 15}, pages = {1859-63}, abstract = {

An HTS screening campaign identified a series of low molecular weight phenols that showed excellent selectivity (\>100-fold) for HDAC1/HDAC2 over other Class I and Class II HDACs. Evolution and optimization of this HTS hit series provided HDAC1-selective (SHI-1) compounds with excellent anti-proliferative activity and improved physical properties. Dose-dependent efficacy in a mouse HCT116 xenograft model was demonstrated with a phenylglycine SHI-1 analog.

}, keywords = {Acetylation, Amides, Animals, Cell Proliferation, Colonic Neoplasms, Cultured, Dogs, Enzyme Inhibitors, Ether-A-Go-Go Potassium Channels, Glycine, Histone Deacetylase 1, Histone Deacetylase Inhibitors, Humans, Macaca mulatta, Mice, Molecular Structure, Phenylalanine, Structure-Activity Relationship, Tumor Cells, Xenograft Model Antitumor Assays}, issn = {1464-3405}, doi = {10.1016/j.bmcl.2008.02.012}, author = {Wilson, Kevin J and Witter, David J and Grimm, Jonathan B and Siliphaivanh, Phieng and Otte, Karin M and Kral, Astrid M and Fleming, Judith C and Harsch, Andreas and Hamill, Julie E and Cruz, Jonathan C and Chenard, Melissa and Szewczak, Alexander A and Middleton, Richard E and Hughes, Bethany L and Dahlberg, William K and Secrist, J Paul and Miller, Thomas A} } @article {1112, title = {A new strategy for the synthesis of benzylic sulfonamides: palladium-catalyzed arylation and sulfonamide metathesis.}, journal = {The Journal of Organic Chemistry}, volume = {72}, year = {2007}, month = {2007 Oct 12}, pages = {8135-8}, abstract = {

An efficient two-step strategy has been developed to access diversely functionalized benzylic sulfonamides. Execution of this strategy required the development of two reaction methods: the palladium-catalyzed cross-coupling of aryl halides with CH-acidic methanesulfonamides and a metathesis reaction between the resulting alpha-arylated sulfonamides and diverse amines. The broad scope of the cross-coupling process combined with a versatile sulfonamide metathesis constitutes an efficient strategy for the synthesis of various benzylic sulfonamides.

}, keywords = {Benzyl Compounds, Catalysis, Molecular Structure, Palladium, Sulfonamides}, issn = {0022-3263}, doi = {10.1021/jo701431j}, author = {Grimm, Jonathan B and Katcher, Matthew H and Witter, David J and Northrup, Alan B} }