845256-49-7

Basic information

• Product Name: (2S)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole-1-carbonyl chloride
• Synonyms: (2S)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole-1-carbonyl chloride
• CAS NO: 845256-49-7
• Molecular Weight: 464.027
• Mol File: 845256-49-7.mol
• Article Data: 6

Chemical Properties

• CAS DataBase Reference: (2S)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole-1-carbonyl chloride(CAS DataBase Reference)
• NIST Chemistry Reference: (2S)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole-1-carbonyl chloride(845256-49-7)
• EPA Substance Registry System: (2S)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole-1-carbonyl chloride(845256-49-7)

Safety Data

• Hazardous Substances Data: 845256-49-7(Hazardous Substances Data)

Upstream product

• 24461-61-8 phenylglycine methyl ester 
• 2835-06-5 phenylglycin 
• 144073-04-1 (RS)-2-amino-2-phenyl-4-penten-1-ol 
• 142035-33-4 ethyl N-(phenylmethylene)glycinate 
• 18162-48-6 tert-butyldimethylsilyl chloride 
• 15028-40-7 DL-2-phenylglycine methyl ester hydrochloride 
• 67627-99-0 N-benzyliden-α-phenyl-glycine methyl ester 
• 686320-24-1 C₁₂H₁₃NO₄ 
• 686320-25-2 C₁₈H₂₃NO₆ 
• 686320-28-5 4-(2,5-difluorophenyl)-2-phenyl-2-[(1,1,2,2-tetramethylpropoxy)methyl]-2,5-dihydro-1H-pyrrole 
• 686320-26-3 7a-phenyldihydro-1H-pyrrolo[1,2-c][1,3]oxazole-3,6(5H)-dione 
• 845256-51-1 6-methylene-7a-phenyltetrahydro-1H-pyrrolo[1,2-c][1,3]oxazol-3-one 
• 845256-50-0 methyl 4-methylene-2-phenylpyrrolidine-2-carboxylate 
• 686320-27-4 6-(2,5-difluorophenyl)-7a-phenyl-5,7a-dihydro-1H-pyrrolo[1,2-c][1,3]oxazole-3-one 

Downstream Products

• 845256-79-3 benzyl(3R,4S)-4-[{[(2S)-4-(2,5-difluorophenyl)-2-(hydroxymethyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]carbonyl}(methyl)amino]-3-fluoropiperidine-1-carboxylate 
• 845256-65-7 (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 
• 847041-34-3 benzyl (3R,4S)-4-[{[(2S)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]carbonyl}(methyl)amino]-3-fluoropiperidine-1-carboxylate 
• 845893-98-3 (2S)-4-(2,5-difluoro-phenyl)-N-[(2S,4S)-2-fluoromethyl-1-boc-pyrrolidin-3-yl]-2-hydroxymethyl-N-methyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide 
• 847027-69-4 (2S)-4-(2,5-difluorophenyl)-N-[(4R,6S)-6-fluoro-1-methylazepan-4-yl]-2-(hydroxymethyl)-N-methyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide 
• 847027-70-7 (2S)-4-(2,5-difluorophenyl)-N-[(4S,6R)-6-fluoro-1-methylazepan-4-yl]-2-(hydroxymethyl)-N-methyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide 
• 845256-78-2 (2S)-4-(2,5-difluorophenyl)-N-[(3R,4S)-3-fluoropiperidin-4-yl]-2-(hydroxymethyl)-N-methyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide 

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.

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.