Abstract:
:We have developed a new series of progesterone receptor modulators based upon the 4-aryl-phenylsulfonamide. Initial work in the series afforded potent compounds with good properties, however an advanced intermediate proved to be genotoxic in a non-GLP Ames assay following metabolic activation. We subsequently solved this problem and identified advanced leads which demonstrated oral efficacy in rhesus monkey pharmacodynamic and kinetics models.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
McComas C,Cohen J,Huselton C,Marella M,Melenski E,Mugford C,Slayden O,Winneker R,Wrobel J,Yudt MR,Fensome Adoi
10.1016/j.bmcl.2012.09.077subject
Has Abstractpub_date
2012-12-01 00:00:00pages
7119-22issue
23eissn
0960-894Xissn
1464-3405pii
S0960-894X(12)01232-2journal_volume
22pub_type
杂志文章abstract::Insulin-like growth factor receptor (IGF-1R) is a growth factor receptor tyrosine kinase that acts as a critical mediator of cell proliferation and survival. Inhibitors of this receptor are believed to provide a new target in cancer therapy. We previously reported an isoquinolinedione series of IGF-1R inhibitors. Now ...
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abstract::We herein report the discovery of a new γ-secretase modulator class with an aminothiazole core starting from a HTS hit (3). Synthesis and SAR of this series are discussed. These novel compounds demonstrate moderate to good in vitro potency in inhibiting amyloid beta (Aβ) peptide production. Overall γ-secretase is not ...
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
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doi:10.1016/j.bmcl.2003.11.002
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
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doi:10.1016/j.bmcl.2009.10.006
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
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doi:10.1016/j.bmcl.2009.06.023
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.04.070
更新日期:2011-06-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
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