1447911-05-8

Basic information

• Product Name: 6-bromo-2-(cyclopropylmethyl)-1-methyl-1H-benzimidazole
• Synonyms: 6-bromo-2-(cyclopropylmethyl)-1-methyl-1H-benzimidazole
• CAS NO: 1447911-05-8
• Molecular Weight: 265.153
• Mol File: 1447911-05-8.mol
• Article Data: 2

Chemical Properties

• CAS DataBase Reference: 6-bromo-2-(cyclopropylmethyl)-1-methyl-1H-benzimidazole(CAS DataBase Reference)
• NIST Chemistry Reference: 6-bromo-2-(cyclopropylmethyl)-1-methyl-1H-benzimidazole(1447911-05-8)
• EPA Substance Registry System: 6-bromo-2-(cyclopropylmethyl)-1-methyl-1H-benzimidazole(1447911-05-8)

Safety Data

• Hazardous Substances Data: 1447911-05-8(Hazardous Substances Data)

Upstream product

• 321-23-3 4-bromo-2-fluoronitrobenzene 

Downstream Products

• 1447911-04-7 1-(2-(cyclopropylmethyl)-1-methyl-1H-benzimidazol-6-yl)-4-((4-fluorobenzyl)oxy)pyridin-2(1H)-one 

Relevant articles and documents

Amine-free melanin-concentrating hormone receptor 1 antagonists: Novel 1-(1H-benzimidazol-6-yl)pyridin-2(1H)-one derivatives and design to avoid CYP3A4 time-dependent inhibition

Melanin-concentrating hormone (MCH) is an attractive target for antiobesity agents, and numerous drug discovery programs are dedicated to finding small-molecule MCH receptor 1 (MCHR1) antagonists. We recently reported novel pyridine-2(1H)-ones as aliphatic amine-free MCHR1 antagonists that structurally featured an imidazo[1,2-a]pyridine-based bicyclic motif. To investigate imidazopyridine variants with lower basicity and less potential to inhibit cytochrome P450 3A4 (CYP3A4), we designed pyridine-2(1H)-ones bearing various less basic bicyclic motifs. Among these, a lead compound 6a bearing a 1H-benzimidazole motif showed comparable binding affinity to MCHR1 to the corresponding imidazopyridine derivative 1. Optimization of 6a afforded a series of potent thiophene derivatives (6q-u); however, most of these were found to cause time-dependent inhibition (TDI) of CYP3A4. As bioactivation of thiophenes to form sulfoxide or epoxide species was considered to be a major cause of CYP3A4 TDI, we introduced electron withdrawing groups on the thiophene and found that a CF3 group on the ring or a Cl adjacent to the sulfur atom helped prevent CYP3A4 TDI. Consequently, 4-[(5-chlorothiophen-2-yl)methoxy]-1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one (6s) was identified as a potent MCHR1 antagonist without the risk of CYP3A4 TDI, which exhibited a promising safety profile including low CYP3A4 inhibition and exerted significant antiobesity effects in diet-induced obese F344 rats.