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

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

Uses

Used in Pharmaceutical Industry:
ALR-3456 is used as a potential therapeutic agent for the management of diabetic complications due to its ability to inhibit aldose reductase, thereby reducing the accumulation of sorbitol and its associated tissue damage and inflammation.
Used in Diabetic Retinopathy Treatment:
ALR-3456 is used as a preventative or treatment agent for diabetic retinopathy, aiming to slow the progression of this vision-threatening complication of diabetes.
Used in Diabetic Neuropathy Treatment:
ALR-3456 is used as a preventative or treatment agent for diabetic neuropathy, potentially reducing nerve damage and associated pain and dysfunction in diabetic patients.
Used in Diabetic Nephropathy Treatment:
ALR-3456 is used as a preventative or treatment agent for diabetic nephropathy, working to protect the kidneys from the harmful effects of diabetes and slow the progression of kidney disease.

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.

A PROCESS FOR THE PREPARATION OF 2,2-DISUBSTITUTED PYRROLES

The present invention relates to the stereoselective preparation of 2,2-disubstituted-4-carbonatepyrroles from readily available chiral starting materials. Such pyrroles are useful as intermediates in the preparation of 2,2,4-trisubstituted 2,5-dihydropyrroles, that are inhibitors of mitotic kinesins and are useful for treating cellular proliferative diseases, for treating disorders associated with KSP kinesin activity, and for inhibiting KSP kinesin. The product of the process of the invention may be illustrated by the Formula (I).

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.