1155013-89-0

Upstream product

• 41979-39-9 4-piperidone hydrochloride 
• 76283-09-5 4-bromo-2-fluorobenzyl bromide 

Downstream Products

• 1604731-70-5 1-(4-bromo-2-fluoro-benzyl)-3,5-bis(3,4,5-methoxybenzenemethylene)piperidin-4-one 
• 1604731-68-1 1-(4-bromo-2-fluoro-benzyl)-3,5-bis(2,3,4-methoxybenzenemethylene)piperidin-4-one 
• 1604731-66-9 1-(4-bromo-2-fluoro-benzyl)-3,5-bis(3,4-methoxybenzenemethylene)piperidin-4-one 
• 1604731-64-7 1-(4-bromo-2-fluoro-benzyl)-3,5-bis(4-methoxybenzenemethylene)piperidin-4-one 

Relevant academic research and scientific papers

1-BENZYLSPIRO[PIPERIDINE-4,1′-PYRIDO[3,4-b]indole] ‘co-potentiators’ for minimal function CFTR mutants

We previously identified a spiro [piperidine-4,1-pyrido [3,4-b]indole] class of co-potentiators that function in synergy with existing CFTR potentiators such as VX-770 or GLGP1837 to restore channel activity of a defined subset of minimal function cystic fibrosis transmembrane conductance regulator (CFTR) mutants. Here, structure-activity studies were conducted to improve their potency over the previously identified compound, 20 (originally termed CP-A01). Targeted synthesis of 37 spiro [piperidine-4,1-pyrido [3,4-b]indoles] was generally accomplished using versatile two or three step reaction protocols with each step having high efficiency. Structure-activity relationship studies established that analog 2i, with 6′-methoxyindole and 2,4,5-trifluorobenzyl substituents, had the greatest potency for activation of N1303K-CFTR, with EC50 ～600 nM representing an ～17-fold improvement over the original compound identified in a small molecule screen.