b-Annulated 1,4-dihydropyridines as Notch Inhibitors

Jorge E Gómez-Galeno, Cecilia Hurtado, Jiongjia Cheng, Ceren Yardimci, Mark Mercola, John R Cashman

Bioorg Med Chem Lett. 2018 Nov 1;28(20):3363-3367.

PMID: 30201292

Abstract:

The Notch signaling pathway is involved in cell proliferation and differentiation, and has been recognized as an active pathway in regenerating tissue and cancerous cells. Notch signaling inhibition is considered a viable approach to the treatment of a variety of conditions including colorectal cancer, pancreatic cancer, breast cancer and metastatic melanoma. The discovery that the b-annulated dihydropyridine FLI-06 (1) is an inhibitor of the Notch pathway with an EC50 ≈ 2.5 μM prompted us to screen a library of related analogs. After structure activity studies were conducted, racemic compound 7 was identified with an EC50 = 0.36 μM. Synthesis of individual enantiomers provided (+)-7 enantiomer with an EC50 = 0.13 μM, or about 20-fold the potency of 1.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP313967189	FLI-06		313967-18-9	Price