905273-87-2

Usage

Physical properties

Crystalline solid, white to off-white color

Common uses

Intermediate in synthesis of pharmaceuticals and agrochemicals

Chemical properties

Derivative of nicotinamide, chelating agent for metal ions, corrosion inhibitor, reagent in production of organic compounds

Medicinal properties

Potential as an anti-inflammatory agent, studied for potential medicinal properties

Upstream product

• 5326-23-8 6-Chloro-3-pyridinecarboxylic acid 
• 58757-38-3 6-Chloronicotinoyl chloride 
• 108-18-9 diisopropylamine 

Downstream Products

• 1450723-16-6 6-amino-N-[[4-(benzenesulfonyl)phenyl]methyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide 
• 1352893-24-3 6-chloro-1H,3H-furo[3,4-c]pyridin-3-one 
• 1450723-54-2 6-chloro-2-[(2,4-dimethoxyphenyl)methyl]-1H,2H,3H-pyrrolo[3.4-c]pyridine 
• 1450723-55-3 N,2-bis[(2.4-dimethoxyphenyl)methyl]-1H,2H,3H-pyrrolo[3,4-c]pyridin-6-amine 
• 905273-88-3 6-chloro-4-formyl-N,N-bis(propan-2-yl)pyridine-3-carboxamide 
• 1453272-30-4 2-chloro-4,5-bis(chloromethyl)pyridine hydrochloride 

Relevant academic research and scientific papers

TYK2 INHIBITORS AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of TYK2, and the treatment of TYK2-mediated disorders.

Minimizing CYP2C9 Inhibition of Exposed-Pyridine NAMPT (Nicotinamide Phosphoribosyltransferase) Inhibitors

NAMPT inhibitors may show potential as therapeutics for oncology. Throughout our NAMPT inhibitor program, we found that exposed pyridines or related heterocyclic systems in the left-hand portion of the inhibitors are necessary pharmacophores for potent cellular NAMPT inhibition. However, when combined with a benzyl group in the center of the inhibitors, such pyridine-like moieties also led to consistent and potent inhibition of CYP2C9. In an attempt to reduce CYP2C9 inhibition, a parallel synthesis approach was used to identify central benzyl group replacements with increased Fsp3. A spirocyclic central motif was thus discovered that was combined with left-hand pyridines (or pyridine-like systems) to provide cellularly potent NAMPT inhibitors with minimal CYP2C9 inhibition. Further optimization of potency and ADME properties led to the discovery of compound 68, a highly potent NAMPT inhibitor with outstanding efficacy in a mouse tumor xenograft model and lacking measurable CYP2C9 inhibition at the concentrations tested.

Identification of 2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-derived ureas as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT)

Potent nicotinamide phosphoribosyltransferase (NAMPT) inhibitors containing 2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-derived ureas were identified using structure-based design techniques. The new compounds displayed improved aqueous solubilities, determined using a high-throughput solubility assessment, relative to previously disclosed urea and amide-containing NAMPT inhibitors. An optimized 2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-derived compound exhibited potent anti-NAMPT activity (18; BC NAMPT IC50 = 11 nM; PC-3 antiproliferative IC50 = 36 nM), satisfactory mouse PK properties, and was efficacious in a PC-3 mouse xenograft model. The crystal structure of another optimized compound (29; NAMPT IC50 = 10 nM; A2780 antiproliferative IC50 = 7 nM) in complex with the NAMPT protein was also determined.

AMIDO-BENZYL SULFONE AND SULFONAMIDE DERIVATIVES

Disclosed are certain amido-benzyl sulfone and sulfonamide compounds, pharmaceutical compositions comprising such compounds, land methods of treatment using such compounds.