1446261-57-9

Basic information

• Product Name: (R)-benzyl 2-((4-fluoro-2-(methoxycarbonyl)-6-(2,2,2-trifluoroacetamido)phenyl)ethynyl)-2-methylpyrrolidine-1-carboxylate
• Synonyms: (R)-benzyl 2-((4-fluoro-2-(methoxycarbonyl)-6-(2,2,2-trifluoroacetamido)phenyl)ethynyl)-2-methylpyrrolidine-1-carboxylate
• CAS NO: 1446261-57-9
• Molecular Weight: 506.454
• Mol File: 1446261-57-9.mol
• Article Data: 5

Chemical Properties

• CAS DataBase Reference: (R)-benzyl 2-((4-fluoro-2-(methoxycarbonyl)-6-(2,2,2-trifluoroacetamido)phenyl)ethynyl)-2-methylpyrrolidine-1-carboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-benzyl 2-((4-fluoro-2-(methoxycarbonyl)-6-(2,2,2-trifluoroacetamido)phenyl)ethynyl)-2-methylpyrrolidine-1-carboxylate(1446261-57-9)
• EPA Substance Registry System: (R)-benzyl 2-((4-fluoro-2-(methoxycarbonyl)-6-(2,2,2-trifluoroacetamido)phenyl)ethynyl)-2-methylpyrrolidine-1-carboxylate(1446261-57-9)

Safety Data

• Hazardous Substances Data: 1446261-57-9(Hazardous Substances Data)

Upstream product

• 220060-08-2 (R)-2-methylpyrrolidine-2-carboxylic acid methyl ester hydrochloride 
• 1330286-50-4 (3S,7aR)-3-(trichloromethyl)tetrahydro-1H,3H-pyrrolo[1,2-c]oxazol-1-one 
• 19734-16-8 diethyl (1-diazo-2-oxo-2-phenylethyl)phosphonate 
• 344-25-2 D-Prolin 
• 1342063-52-8 methyl 3-amino-2-bromo-5-fluorobenzoate 
• 1446261-69-3 (R)-benzyl 2-ethynyl-2-methylpyrrolidine-1-carboxylate 
• 1446261-56-8 methyl 2-bromo-5-fluoro-3-(2,2,2-trifluoroacetamido)-benzoate 

Downstream Products

• 1446261-61-5 (R)-methyl 9-fluoro-11b-methyl-6-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino[8,7-b]indole-7-carboxylate 
• 1446261-44-4 (10aR)-2-fluoro-5,8,9,10,10a,11-hexahydro-10a-methyl-5,6,7a,11-tetraazacyclohepta[def]cyclopenta[a]fluoren-4(7H)-one 

Relevant articles and documents

Discovery of Pamiparib (BGB-290), a Potent and Selective Poly (ADP-ribose) Polymerase (PARP) Inhibitor in Clinical Development

Poly (ADP-ribose) polymerase (PARP) plays a significant role in DNA repair responses; therefore, this enzyme is targeted by PARP inhibitors in cancer therapy. Here we have developed a number of fused tetra- or pentacyclic dihydrodiazepinoindolone derivatives with excellent PARP enzymatic and cellular PARylation inhibition activities. These efforts led to the identification of pamiparib (BGB-290, 139), which displays excellent PARP-1 and PARP-2 inhibition with IC50 of 1.3 and 0.9 nM, respectively. In a cellular PARylation assay, this compound inhibits PARP activity with IC50 = 0.2 nM. Cocrystal of pamiparib shows similar binding sites with PARP with other PARP inhibitors, but pamiparib is not a P-gp substrate and shows excellent drug metabolism and pharmacokinetics (DMPK) properties with significant brain penetration (17-19%, mice). The compound is currently being investigated in phase III clinical trials as a maintenance therapy in platinum-sensitive ovarian cancer and gastric cancer.

FUSED TETRACYCLIC OR FUSED PENTACYCLIC DIHYDRO DIAZEPINO CARBAZOLONE AS PARP INHIBITOR

PROBLEM TO BE SOLVED: To provide a specific fused tetracyclic or fused pentacyclic compound, and its salt, its composition, and a method for use thereof. SOLUTION: The present invention provides a compound represented by formula (I), its stereoisomer and pharmaceutically acceptable salt, where RN is H, alkyl or the like; X is C, N, O or S; m and n independently represent an integer of 0-3; t is an integer of 0-3; R1-R8 are H, an alkyl group, an alkenyl group, a heterocyclyl group and the like. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT

FUSED TETRA OR PENTA-CYCLIC DIHYDRODIAZEPINOCARBAZOLONES AS PARP INHIBITORS

Provided are certain fused tetra or penta-cyclic compounds and salts thereof, compositions thereof, and methods of use thereof.