845256-65-7

Basic information

• Product Name: ALR-3456
• Synonyms: ALR-3456;1H-Pyrrole-1-carboxamide, 4-(2,5-difluorophenyl)-N-[(3R,4S)-3-fluoro-1-methyl-4-piperidinyl]-2,5-dihydro-2-(hydroxymethyl)-N-methyl-2-phenyl-, (2S)-;MK0731;(R)-2-aMino-2-cyclopropyl-1-((S)-4-(2,5-difluorophenyl)-2-phenyl-2H-pyrrol-1(5H)-yl)ethanone;(S)-4-(2,5-difluorophenyl)-N-((3R,4S)-3-fluoro-1-Methylpiperidin-4-yl)-2-(hydroxyMethyl)-N-Methyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxaMide;ALR-3456 , MK-0731;(2S)-4-(2,5-Difluorophenyl)-N-[(3R,4S)-3-fluoro-1-methyl-4-piperidinyl]-2,5-dihydro-2-(hydroxymethyl)-N-methyl-2-phenyl-1H-pyrrole-1-carboxamide;(5S)-3-(2,5-difluorophenyl)-N-[(3R,4S)-3-fluoro-1-methylpiperidin-4-yl]-5-(hydroxymethyl)-N-methyl-5-phenyl-2H-pyrrole-1-carboxamide
• CAS NO: 845256-65-7
• Molecular Formula: C25H28F3N3O2
• Molecular Weight: 459.509
• Mol File: 845256-65-7.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 590.5±50.0 °C(Predicted)
• Appearance: /
• Density: 1.32±0.1 g/cm3(Predicted)
• PKA: 14.57±0.10(Predicted)
• CAS DataBase Reference: ALR-3456(CAS DataBase Reference)
• NIST Chemistry Reference: ALR-3456(845256-65-7)
• EPA Substance Registry System: ALR-3456(845256-65-7)

Safety Data

• Hazardous Substances Data: 845256-65-7(Hazardous Substances Data)

Usage

General Description

ALR-3456 is a chemical compound designed to inhibit the activity of a specific enzyme called aldose reductase, which is involved in the development of diabetic complications. By blocking the function of this enzyme, ALR-3456 aims to reduce the accumulation of sorbitol, a sugar alcohol that can lead to tissue damage and inflammation in people with diabetes. ALR-3456 has shown promise in preclinical studies for its potential to prevent or slow the progression of diabetic retinopathy, neuropathy, and nephropathy, making it a potential candidate for the development of new medications for diabetic patients. Further research and clinical trials are needed to fully evaluate the effectiveness and safety of ALR-3456 for treating diabetic complications.

Upstream product

• 845256-63-5 (3R,4S)-3-fluoro-N,1-dimethylpiperidin-4-amine 
• 845256-49-7 (2S)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole-1-carbonyl chloride 

Relevant articles and documents

Kinesin Spindle Protein (KSP) inhibitors. 9. Discovery of (2S)-4-(2,5-difluorophenyl)-N-[(3R,4S)-3-fluoro-1-methylpiperidin-4-yl] -2-(hydroxymethyl)-N-methyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide (MK-0731) for the treatment of taxane-refractory cancer

Inhibition of kinesin spindle protein (KSP) is a novel mechanism for treatment of cancer with the potential to overcome limitations associated with currently employed cytotoxic agents. Herein, we describe a C2-hydroxymethyl dihydropyrrole KSP inhibitor (11) that circumvents hERG channel binding and poor in vivo potency, issues that limited earlier compounds from our program. However, introduction of the C2-hydroxymethyl group caused 11 to be a substrate for cellular efflux by P-glycoprotein (Pgp). Utilizing knowledge garnered from previous KSP inhibitors, we found that β-fluorination modulated the pK a of the piperidine nitrogen and reduced Pgp efflux, but the resulting compound (14) generated a toxic metabolite in vivo. Incorporation of fluorine in a strategic, metabolically benign position by synthesis of an N-methyl-3-fluoro-4-(aminomethyl)piperidine urea led to compound 30 that has an optimal in vitro and metabolic profile. Compound 30 (MK-0731) was recently studied in a phase I clinical trial in patients with taxane-refractory solid tumors.

Mitotic kinesin inhibitors

The present invention relates to dihydropyrrole compounds that are useful for treating cellular proliferative diseases, for treating disorders associated with KSP kinesin activity, and for inhibiting KSP kinesin. The invention is also related to compositions which comprise these compounds, and methods of using them to treat cancer in mammals.