17019-04-4

Basic information

• Product Name: 9H-Pyrido[3,4-b]indole, 7-methoxy-1-methyl-9-(phenylmethyl)-
• CAS NO: 17019-04-4
• Molecular Formula: C20H18N2O
• Molecular Weight: 302.376
• Mol File: 17019-04-4.mol
• Article Data: 8

Chemical Properties

• CAS DataBase Reference: 9H-Pyrido[3,4-b]indole, 7-methoxy-1-methyl-9-(phenylmethyl)-(CAS DataBase Reference)
• NIST Chemistry Reference: 9H-Pyrido[3,4-b]indole, 7-methoxy-1-methyl-9-(phenylmethyl)-(17019-04-4)
• EPA Substance Registry System: 9H-Pyrido[3,4-b]indole, 7-methoxy-1-methyl-9-(phenylmethyl)-(17019-04-4)

Safety Data

• Hazardous Substances Data: 17019-04-4(Hazardous Substances Data)

Upstream product

• 442-51-3 harmine 
• 100-39-0 benzyl bromide 
• 3610-36-4 2-(6-methoxy-1H-indol-3-yl)ethanamine 
• 100-44-7 benzyl chloride 
• 486-93-1 tetrahydroharmine 
• 2016-04-8 N,N-dimethylformamide dibenzyl acetal 

Downstream Products

• 103033-52-9 1-(9-benzyl-7-methoxy-9H-β-carbolin-1-ylmethyl)-2-methyl-cyclohexanol 

Relevant articles and documents

Structure-Based Design and Synthesis of Harmine Derivatives with Different Selectivity Profiles in Kinase versus Monoamine Oxidase Inhibition

Dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) is an emerging biological target with implications in diverse therapeutic areas such as neurological disorders (Down syndrome, in particular), metabolism, and oncology. Harmine, a natural product that selectively inhibits DYRK1A amongst kinases, could serve as a tool compound to better understand the biological processes that arise from DYRK1A inhibition. On the other hand, harmine is also a potent inhibitor of monoamine oxidase A (MAO-A). Using structure-based design, we synthesized a collection of harmine analogues with tunable selectivity toward these two enzymes. Modifications at the 7-position typically decreased affinity for DYRK1A, whereas substitution at the 9-position had a similar effect on MAO-A inhibition but DYRK1A inhibition was maintained. The resulting collection of compounds can help to understand the biological role of DYRK1A and also to assess the interference in the biological effect originating in MAO-A inhibition.

Synthesis and serum protein binding of novel ring-substituted harmine derivatives

A series of new derivatives of the natural β-carboline alkaloid harmine, introducing hydrophobic substituents into positions 7 and 9 were synthesized as potential anticancer agents. Their binding affinities for human serum albumin (HSA) and α1-acid glycoprotein (AAG) were investigated by affinity chromatography combined with fluorescence, circular dichroism (CD) and UV absorption spectroscopy. The weak binding of harmine to both proteins (Ka ～ 3 × 104 M-1) was highly increased by aromatic substitutions (Ka ～ 105-106 M-1). Derivatives having a substituted benzyl group in the N9-position of the β-carboline nucleus showed about tenfold and hundredfold affinity enhancement for HSA and AAG, respectively. Such a strong plasma protein interaction would be of pharmacokinetic relevance for these potential drug candidates. Induced CD spectra indicated the variant selective, dimeric binding of the 7-pyridylethoxy derivative to AAG. Absorbance and fluorescence spectra refer to the binding preference of the neutral form of the studied β-carbolines for both proteins.

KINASE INHIBITOR COMPOUNDS AND COMPOSITIONS AND METHODS OF USE

Described herein are compounds having the following structure: formula (I) or a stereoisomer, pharmaceutically acceptable salt, oxide, or solvate thereof. Also disclosed are compositions containing the compounds, methods of inhibiting activity of DYRKl A in a cell, methods of increasing cell proliferation in a population of pancreatic beta cells, methods of treating a subject for a condition associated with insufficient insulin secretion, and methods of treating a subject for a neurological disorder.