117659-52-6

Upstream product

• 100-46-9 benzylamine 
• 4042-36-8 D-pyrrolidone-5-carboxylic acid 
• 178327-71-4 (R)-5-oxopyrrolidine-2-carboxylic acid benzylamide 

Downstream Products

• 1266228-97-0 methyl (3S,8aR)-2-benzyloctahydropyrrolo[1,2-a]pyrazine-3-carboxylate 
• 1421527-56-1 methyl (3R,8aR)-2-benzyloctahydropyrrolo[1,2-a]pyrazine-3-carboxylate 
• 1266230-14-1 C₃₄H₄₉F₂N₅O₆ 
• 1266229-74-6 tert-butyl [(1S)-2-({(1S)-2-[(3S,8aR)-[(4R)-3,4-dihydro-2H-chromen-4-ylcarbamoyl]hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl]-2-oxo-1-phenylethyl}amino)-1-methyl-2-oxoethyl]methylcarbamate 
• 1266230-13-0 (3S,8aR)-2-[(2S)-2-amino-2-(4,4-difluorocyclohexyl)acetyl]-N-[(4R)-3,4-dihydro-2H-chromen-4-yl]octahydropyrrolo[1,2-a]pyrazine-3-carboxamide 
• 1266229-75-7 (3S,8aR)-2-[(2S)-2-amino-2-phenylacetyl]-N-[(4R)-3,4-dihydro-2H-chromen-4-yl]octahydropyrrolo[1,2-a]pyrazine-3-carboxamide 
• 1266230-03-8 benzyl [(1S)-2-[(3S,8aR)-3-[(4R)-3,4-dihydro-2H-chromen-4-ylcarbamoyl]hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl]-2-oxo-1-(tetrahydro-2H-pyran-4-yl)ethyl]carbamate 
• 1266230-12-9 benzyl {(1S)-1-(4,4-difluorocyclohexyl)-2-[(3S,8aR)-3-[(4R)-3,4-dihydro-2H-chromen-4-ylcarbamoyl]hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl]-2-oxoethyl}carbamate 
• 1266229-67-7 benzyl {(1S)-2-[(3S,8aR)-3-[(4R)-3,4-dihydro-2H-chromen-4-ylcarbamoyl]hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl]-2-oxo-1-phenylethyl}carbamate 
• 1266232-21-6 C₃₅H₅₁N₅O₆ 
• 1266231-92-8 C₃₅H₅₁F₂N₅O₅ 
• 1266230-01-6 tert-butyl [(1S)-2-({(1S)-1-cyclohexyl-2-[(3S,8aR)-3-[(4R)-3,4-dihydro-2H-cromen-4-ylcarbamoyl] hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl]-2-oxoethyl}amino)-1-methyl-2-oxoethyl]methylcarbamate 
• 1266229-12-2 tert-buty l[(1S)-2-({(1S)-1-cyclohexyl-2-oxo-2-[(3S,8aR)-3-[(1R)-1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl]hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl]ethyl}amino)-1-methyl-2-oxoethyl]methylcarbamate 
• 1266231-73-5 C₃₃H₅₁N₅O₅ 

Relevant academic research and scientific papers

HETEROCYCLIC COMPOUND

Provided is a compound useful for the prophylaxis or treatment of cancer. The present invention relates to a compound represented by formula (I): wherein each symbol in the formula is as defined in the specification, or a salt thereof or a prodrug thereof, which is useful for the prophylaxis or treatment of cancer.

Design and synthesis of potent inhibitor of apoptosis (IAP) proteins antagonists bearing an octahydropyrrolo[1,2-a]pyrazine scaffold as a novel proline mimetic

To develop novel inhibitor of apoptosis (IAP) proteins antagonists, we designed a bicyclic octahydropyrrolo[1,2-a]pyrazine scaffold as a novel proline bioisostere. This design was based on the X-ray co-crystal structure of four N-terminal amino acid residues (AVPI) of the second mitochondria-derived activator of caspase (Smac) with the X-chromosome-linked IAP (XIAP) protein. Lead optimization of this scaffold to improve oral absorption yielded compound 45, which showed potent cellular IAP1 (cIAP1 IC50: 1.3 nM) and XIAP (IC50: 200 nM) inhibitory activity, in addition to potent tumor growth inhibitory activity (GI50: 1.8 nM) in MDA-MB-231 breast cancer cells. X-ray crystallographic analysis of compound 45 bound to XIAP and to cIAP1 was achieved, revealing the various key interactions that contribute to the higher cIAPI affinity of compound 45 over XIAP. Because of its potent IAP inhibitory activities, compound 45 (T-3256336) caused tumor regression in a MDA-MB-231 tumor xenograft model (T/C: -53% at 30 mg/kg).

Heterocyclic Compound

The present invention provides a compound represented by the formula wherein each symbol is as defined in the specification, or a salt thereof. The compound of the present invention shows a strong IAP antagonistic activity.

Synthesis of chiral diamines using novel 2-trichloromethyloxazolidin-4-one precursors derived from 5-oxo-proline and proline

Efficient syntheses of chiral vicinal diamines derived from (S)-oxo-proline and (S)-proline are described. The novel diastereomerically pure precursor (2R,5S)-2-trichloromethyl-1-aza-3-oxabicyclo-[3.3.0]-octan-4,8-dione 3 and its enantiomer are readily available by reaction of the inexpensive enantiomers of 5-oxo-proline with chloral. Compound 3 reacts with primary and secondary amines to afford the 5-oxo-prolylamides 4 in quantitative yield. In contrast, the (S)-proline-derived precursor (2R,5S)-2-trichloromethyl-1-aza-3-oxabicyclo[3.3.0]octan-4-one 6 gave (S)-N-formylprolylamides 9 and/or (S)-prolylamides 8 depending on the reaction conditions. Upon reduction with LiAlH4, amides 4 and 9 afforded the proline-derived (S)-2-(alkylaminomethyl)pyrrolidines 1 and (S)-N-methyl-2-(alkylaminomethyl)-pyrrolidines 5 in 70-90% yields.