579489-30-8

Upstream product

• 221024-28-8 4-chloro-1-(1-methoxymethylpropyl)-6-methyl-1H-[1,2,3]triazolo[4,5-c]pyridine 
• 2835-99-6 4-amino-3-methylphenol 
• 63897-12-1 2,4-dichloro-6-methyl-3-nitropyridine 
• 351382-63-3 2-chloro-6-methyl-3-nitropyridin-4-yl-(1-methoxymethylpropyl)amine 
• 63448-63-5 2-amino-1-methoxybutane 
• 896727-99-4 2-chloro-N₄-(1-methoxymethylpropyl)-6-methylpyridine-3,4-diamine 
• 197801-88-0 [3H]-SN₀₀₃ 

Relevant academic research and scientific papers

Synthesis and in vivo evaluation of [11C]SN003 as a PET ligand for CRF1 receptors

Synthesis and evaluation of [O-methyl-11C](4-methoxy-2-methylphenyl)[1-(1-methoxymethylpropyl)-6-methyl-1H-[1,2,3]triazolo[4,5-c]pyridin-4-yl]amine or [11C]SN003 ([11C]6), as a PET imaging agent for CRF1 recepto

Pharmacological characterization of a novel nonpeptide antagonist radioligand, (±)-N-[2-methyl-4-methoxyphenyl]-1-(1-(methoxymethyl) propyl)-6-methyl-1H-1,2,3-triazolo[4,5-c]pyridin-4-amine ([3H]SN003) for corticotropin-releasing factor receptors

The in vitro pharmacological profile of a novel small molecule corticotropin-releasing factor 1 (CRF1) receptor antagonist, (±)-N-[2-methyl-4-methoxyphenyl]-1- (1-(methoxymethyl)propyl)-6-methyl-1H-1,2,3-triazolo[4,5-c]pyridin-4-amine (SN003), and the characteristics of its radioligand ([3H]SN003) are described. SN003 has high affinity and selectivity for CRF1 receptors expressed in rat cortex, pituitary, and recombinant HEK293EBNA (HEK293e) cells with respective radiolabeled ovine CRF ([125I]oCRF) binding Ki values of 2.5, 7.9, and 6.8 nM. SN003 was shown to be a CRF1 receptor antagonist inasmuch as it inhibited CRF-induced cAMP accumulation in human CRF1HEK293e cells and CRF-stimulated adrenocorticotropin hormone release from rat pituitary cells without agonist activities. Significant decreases in the Bmax of [125I]oCRF binding by SN003 suggest that this antagonist is not simply competitive. To further explore the interaction of SN003 with the CRF1 receptors, [3H]SN003 binding to rat cortex and human CRF1HEK293e cell membranes was characterized and shown to be reversible and saturable, with KD values of 4.8 and 4.6 nM, and Bmax values of 0.142 and 7.42 pmol/mg protein, respectively. The association and dissociation rate constants of [3H]SN003 (k+1 0.292 nM-1 min-1 and k-1 0.992 × 10-2 min-1) were also assessed using human CRF1EK293e cell membranes, giving an equilibrium dissociation constant of 3.4 nM. Moreover, [3H]SN003 binding displayed a single affinity state and insensitivity to 5′-guanylylimidodiphosphate, consistent with characteristics of antagonist binding. Incomplete inhibition of [3H]SN003 binding by CRF peptides also suggests that SN003 is not simply competitive with CRF at CRF1 receptors. The distribution of [3H]SN003 binding sites was consistent with the expression pattern of CRF1 receptors in rat brain regions. Small molecule CRF1 antagonist radioligands like [3H]SN003 should enable a better understanding of small molecule interactions with the CRF1 receptor.