57841-56-2

Upstream product

• 2942-59-8 2-chloronicotinic acid 
• 49609-84-9 2-Chloronicotinoyl chloride 
• 108-42-9 3-chloro-aniline 

Downstream Products

• 1346265-80-2 2-[(1-benzylpiperidin-4-yl)amino]-N-(3-chlorophenyl)nicotinamide 
• 1420999-18-3 2-[(1-benzylpiperidin-4-yl)sulfanyl]-N-(3-chlorophenyl)nicotinamide 
• 1420999-17-2 2-(1-benzylpiperidin-4-yloxy)-N-(3-chlorophenyl)nicotinamide 
• 1420998-69-1 C₂₂H₂₇ClN₄O₃ 
• 1428533-11-2 BRN-137 
• 1420998-50-0 N-(3-chlorophenyl)-2-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]nicotinamide 
• 1420998-53-3 C₂₂H₂₇ClN₄O₃ 
• 1420999-05-8 2-{1-[1-(6-chloro-5-fluoropyrimidin-4-yl)ethyl]piperidin-4-ylamino}-N-(3-chlorophenyl)pyridine-3-carboxamide 
• 1420998-99-7 N-(3-chlorophenyl)-2-({1-[2-(N,N-diethylamino)ethyl]piperidin-4-yl}amino)nicotinamide 
• 1420998-90-8 N-(3-chlorophenyl)-2-(4-piperidylamino)nicotinamide 
• 1420999-12-7 (R)-2-(1-benzylpiperidin-3-ylamino)-N-(3-chlorophenyl)nicotinamide 
• 1420998-92-0 (R)-N-(3-chlorophenyl)-2-(3-piperidylamino)nicotinamide 

Relevant academic research and scientific papers

NOVEL COMPOUND HAVING ANGIOGENESIS INHIBITORY ACTIVITY, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION COMPRISING SAME

Disclosed are an anti-angiogenic compound, represented by Chemical Formula I, or a pharmaceutically acceptable salt thereof, a preparation method thereof, and a pharmaceutically acceptable composition including the same. Because the compound of Chemical Formular I potently suppresses the angiogenesis, the compound of Chemical Formula I is applicable to the prevention and treatment of diseases caused by aberrant activity of vascular endothelial growth factor, and available as an anti-angiogenic agent.

Novel Compound Having Angiogenesis Inhibitory Activity, Method for Preparing Same, and Pharmaceutical Composition Comprising Same

Disclosed are an anti-angiogenic compound, represented by Chemical Formula I, or a pharmaceutically acceptable salt thereof, a preparation method thereof, and a pharmaceutically acceptable composition including the same. Because the compound of Chemical Formula I potently suppresses the angiogenesis, the compound of Chemical Formula I is applicable to the prevention and treatment of diseases caused by aberrant activity of vascular endothelial growth factor, and available as an anti-angiogenic agent.

Synthesis and evaluation of nicotinamide derivative as anti-angiogenic agents

Previously, we have found that BRN-103, a nicotinamide derivative, inhibits vascular endothelial growth factor (VEGF)-mediated angiogenesis signaling in human endothelial cells. During our continuous efforts to identify more potent anti-angiogenic agents, we synthesized various nicotinamide derivatives and evaluated their anti-angiogenic effects. We found that 2-{1-[1-(6-chloro-5- fluoropyrimidin-4-yl)ethyl]piperidin-4-ylamino}-N-(3-chlorophenyl) pyridine-3-carboxamide (BRN-250) significantly inhibited human umbilical vascular endothelial cells (HUVECs) proliferation, migration, tube formation, and microvessel growth in a concentration range of 10-100 nM. Furthermore, BRN-250 inhibited the VEGF-induced phosphorylation and intracellular tyrosine kinase activity of VEGF receptor 2 (VEGFR2) and the activation of its downstream AKT pathway. Taken together, these findings suggest that BRN-250 be considered a potential lead compound for cancer therapy.

BRN-103, a novel nicotinamide derivative, inhibits VEGF-induced angiogenesis and proliferation in human umbilical vein endothelial cells

Anti-angiogenesis is regarded as an effective strategy for cancer treatment, and vascular endothelial growth factor (VEGF) plays a key role in the regulations of angiogenesis and vasculogenesis. In the present study, the authors synthesized five novel nicotinamide derivatives which structurally mimic the receptor tyrosine kinase inhibitor sunitinib and evaluated their anti-angiogenic effects. Transwell migration assays revealed that 2-(1-benzylpiperidin-4-yl) amino-N-(3-chlorophenyl) nicotinamide (BRN-103), among the five derivatives most potently inhibited VEGF-induced human umbilical vein endothelial cells (HUVECs). In addition, BRN-103 dose-dependently inhibited VEGF-induced migration, proliferation, and capillary-like tube formation of HUVECs and vessel sprouting from mouse aortic rings. To understand the molecular mechanisms responsible for these activities, the authors examined the effect of BRN-103 on VEGF signaling pathways in HUVECs. BRN-103 was found to suppress the VEGF-induced phosphorylation of VEGF receptor 2 (VEGR2) and the activations of AKT and eNOS. Taken together, these results suggest that BRN-103 inhibits VEGF-mediated angiogenesis signaling in human endothelial cells.