406233-70-3

Upstream product

• 25437-95-0 4-(4-Oxo-1-piperidinyl)benzoic acid ethyl ester 
• 1779-49-3 Methyltriphenylphosphonium bromide 
• 2065-66-9 methyl-triphenylphosphonium iodide 

Downstream Products

• 1246085-65-3 ethyl 4-(4-((2-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)methyl)piperidin-1-yl)benzoate 
• 926933-92-8 (R)-N-(4-(4-(dimethylamino)-1-(phenylthio)butan-2-ylamino)-3-nitrophenylsulfonyl)-4-(4-methylenepiperidin-1-yl)benzamide 
• 926933-91-7 4-(4-methylenepiperidin-1-yl)benzoic acid 

Relevant academic research and scientific papers

Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL

Overexpression of the antiapototic proteins Bcl-2 and Bcl-xL provides a common mechanism through which cancer cells gain a survival advantage and become resistant to conventional chemotherapy. Inhibition of these prosurvival proteins is an attractive strategy for cancer therapy. We recently described the discovery of a selective Bcl-xL antagonist that potentiates the antitumor activity of chemotherapy and radiation. Here we describe the use of structure-guided design to exploit a deep hydrophobic binding pocket on the surface of these proteins to develop the first dual, subnanomolar inhibitors of Bcl-xL and Bcl-2. This study culminated in the identification of 2, which exhibited EC50 values of 8 nM and 30 nM in Bcl-2 and Bcl-xL dependent cells, respectively. Compound 2 demonstrated single agent efficacy against human follicular lymphoma cell lines that overexpress Bcl-2, and efficacy in a murine xenograft model of lymphoma when given both as a single agent and in combination with etoposide.

N-acylsulfonamide apoptosis promoters

N-Benzoyl arylsulfonamides having the formula are BCL-Xl inhibitors and are useful for promoting apoptosis. Also disclosed are BCL-Xl inhibiting compositions and methods of promoting apoptosis in a mammal.

N-Acylsulfonamide apoptosis promoters

N-Benzoyl arylsulfonamides having the formula Are BCL-X1 inhibitors and are useful for promoting apoptosis. Also disclosed are BCL-X1 inhibiting compositions and methods of promoting apoptosis in a mammal.