845256-50-0

Upstream product

• 153924-62-0 N-benzylidenephenylglycine methyl ester 
• 1871-57-4 2-chloromethyl-3-chloroprop-1-ene 
• 67627-99-0 N-benzyliden-α-phenyl-glycine methyl ester 
• 78-88-6 2,3-Dichloroprop-1-ene 
• 24461-61-8 phenylglycine methyl ester 
• 15028-40-7 DL-2-phenylglycine methyl ester hydrochloride 

Downstream Products

• 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 
• 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 
• 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 
• 686320-28-5 4-(2,5-difluorophenyl)-2-phenyl-2-[(1,1,2,2-tetramethylpropoxy)methyl]-2,5-dihydro-1H-pyrrole 
• 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 
• 845256-48-6 (2S)-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 
• 686321-45-9 C₂₃H₂₂F₄N₂O₂ 

Relevant academic research and scientific papers

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.

Kinesin spindle protein (KSP) inhibitors. Part V: Discovery of 2-propylamino-2,4-diaryl-2,5-dihydropyrroles as potent, water-soluble KSP inhibitors, and modulation of their basicity by β-fluorination to overcome cellular efflux by P-glycoprotein

Installation of a C2-aminopropyl side chain to the 2,4-diaryl-2,5-dihydropyrrole series of kinesin spindle protein (KSP) inhibitors results in potent, water soluble compounds, but the aminopropyl group induces susceptibility to cellular efflux by P-glycop

MITOTIC KINESIN INHIBITORS

The present invention relates to dihydropyrazole compounds that are useful for treating cellular proliferative diseases, for treating disorders associated with KSP kinesin activity, and for inhibiting KSP kinesin. The invention 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.

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 compositi