Patent Watch

January 14, 2013

These insulin-like growth factor 1 receptor inhibitors may help fight cancer. S. Balachandran and co-inventors disclose sulfonylindole derivatives represented by structure 1 that can inhibit, modulate, and/or regulate insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF-1R). These inhibitors may be useful for treating cancer.

Protein kinase (PK) activities affect all aspects of cell life, including growth, differentiation, and proliferation. Abnormal PK activities are implicated in many diseases, ranging from psoriasis to glioblastoma (brain cancer).

Receptor tyrosine kinases (RTKs) are growth factor receptors that exhibit PK activity and perform diverse biological functions. At least 19 RTK classes are known; one class includes IR, IGF-1R, and insulin receptor–related receptor (IRR). Abnormal levels of IGF-1R and its ligands, IGF-1 and IGF-2, are expressed in many cancer tumors, such as breast, prostate, thyroid, lung, hepatoma, colon, brain, and neuroendocrine. Inhibiting IGF-1R is thus a promising therapeutic target in cancer treatment.

Known inhibitors of IGF-1R, such as the experimental drug BMS-754807, inhibit cancer growth in vitro, in vivo, and in clinical trials. Compounds represented by 1 that have similar activities also are potential cancer treatments.

The inventors describe 29 examples of 1, including compounds 24 in the figure. All 29 compounds have the (S)-configuration. The table shows the compounds’ antiproliferation IC50 values in μM for the MCF7 colon cancer and HT29 breast cancer cell lines.

(Merck Sharp & Dohme [Rahway, NJ]. WIPO Publication 2012145471, Oct. 26, 2012; Ahmed F. Abdel-Magid)

This patent was originally reviewed in ACS Medicinal Chemistry Letters.

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