Publications by authors named "Craig R Woods"

9 Publications

  • Page 1 of 1

Discovery of the first known small-molecule inhibitors of heme-regulated eukaryotic initiation factor 2alpha (HRI) kinase.

Bioorg Med Chem Lett 2009 Dec 13;19(23):6548-51. Epub 2009 Oct 13.

Johnson & Johnson Pharmaceutical Research and Development, LLC, San Diego, CA 92121, United States.

A series of indeno[1,2-c]pyrazoles were discovered to be the first known inhibitors of heme-regulated eukaryotic initiation factor 2alpha (HRI) kinase. The synthesis, structure-activity relationship profile, and in-vitro pharmacological characterization of this inaugural series of HRI kinase inhibitors are detailed.
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http://dx.doi.org/10.1016/j.bmcl.2009.10.033DOI Listing
December 2009

Discovery of potent cholecystokinin-2 receptor antagonists: elucidation of key pharmacophore elements by X-ray crystallographic and NMR conformational analysis.

Bioorg Med Chem 2008 Apr 5;16(7):3917-25. Epub 2008 Feb 5.

Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Drug Discover, 3210 Merryfield Row, San Diego, CA 92121, USA.

A novel series of cholecystokinin-2 receptor (CCK-2R) antagonists has been identified, as exemplified by anthranilic sulfonamide 1 (pK(i)=7.6). Pharmacokinetic and stability studies indicated that this series of compounds suffered from metabolic degradation, and that both the benzothiadiazole and piperidine rings were rapidly oxidized by liver enzymes. A combination of synthesis, computational methods, (1)H NMR conformational studies, and X-ray crystallographic analyses were applied to elucidate key pharmacophore elements, and to discover analogs with improved pharmacokinetic profiles, and high receptor binding affinity and selectivity.
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http://dx.doi.org/10.1016/j.bmc.2008.01.059DOI Listing
April 2008

Synthesis and solid-phase purification of anthranilic sulfonamides as CCK-2 ligands.

Bioorg Med Chem Lett 2007 Dec 29;17(24):6905-9. Epub 2007 Sep 29.

Johnson & Johnson Pharmaceutical Research and Development, 3210 Merryfield Row, San Diego, CA 92121, USA.

A novel strategy for the synthesis of cholecystokinin-2 receptor ligands was developed. The route employs a solution-phase synthesis of a series of anthranilic sulfonamides followed by a resin capture purification strategy to produce multi-milligram quantities of compounds for bioassay. The synthesis was used to produce >100 compounds containing various functional groups, highlighting the general applicability of this strategy and to address specific metabolism issues in our CCK-2 program.
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http://dx.doi.org/10.1016/j.bmcl.2007.09.087DOI Listing
December 2007

Synthesis and DNA binding properties of iminodiacetic acid-linked polyamides: characterization of cooperative extended 2:1 side-by-side parallel binding.

J Am Chem Soc 2002 Sep;124(36):10676-82

Department of Chemistry, Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

A series of iminodiacetic acid (IDA)-linked polyamides (DpPyPyPy-IDA-PyPyPyDp) were prepared and constitute polyamides joined head-to-head by a functionalizable five-atom linker. It was found that the IDA linker exerts a unique influence over the DNA binding conformation differing from both the beta-alanine (extended) or gamma-aminobutyric acid (hairpin) linkers, resulting in cooperative parallel side-by-side 2:1 binding in an extended conformation most likely with a staggered versus stacked alignment. A generalized variant of a fluorescent intercalator displacement (FID) assay conducted on a series of hairpin deoxyoligonucleotides containing a systematically varied A/T-rich binding-site size was used to distinguish between the binding modes of the IDA-linked polyamides.
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http://dx.doi.org/10.1021/ja026588mDOI Listing
September 2002

Synthesis and DNA binding properties of saturated distamycin analogues.

Bioorg Med Chem Lett 2002 Sep;12(18):2647-50

Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550North Torrey Pines Road, CA 92037, La Jolla, USA.

A series of saturated heterocyclic analogues of distamycin were prepared and examined. A fluorescent intercalator displacement (FID) assay conducted on p[dA]-p[dT] DNA to obtain C(50) values and a hairpin deoxyoligonucleotide containing an A/T-rich binding site was used to evaluate DNA binding affinity. It is observed that saturated heterocycles greatly reduce the DNA binding relative to distamycin.
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http://dx.doi.org/10.1016/s0960-894x(02)00467-5DOI Listing
September 2002

Hairpin versus extended DNA binding of a substituted beta-alanine linked polyamide.

J Am Chem Soc 2002 Mar;124(10):2148-52

Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.

A series of alpha-substituted beta-alanine (beta) linked polyamides (DbaPyPyPy-beta*-PyPyPy) were prepared and examined. This resulted in the observation that while most substituents disrupt DNA binding, (R)-alpha-methoxy-beta-alanine (beta((R)-OMe)) maintains strong binding affinity and preferentially adopts a hairpin versus extended binding mode, providing an alternative hairpin linker to gamma-aminobutyric acid (gamma). A generalized variant of a fluorescent intercalator displacement assay conducted on a series of hairpin deoxyoligonucleotides containing a systematically varied A/T-rich binding site size was developed to distinguish between the extended binding of the parent beta-alanine 1 (DbaPyPyPy-beta-PyPyPy) and the hairpin binding of 3 (DbaPyPyPy-beta((R)-OMe)-PyPyPy).
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http://dx.doi.org/10.1021/ja0122039DOI Listing
March 2002
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