1033713-91-5

Upstream product

• 1199792-95-4 1-benzyl 2-tert-butyl (2S,5R)-5-ethylpyrrolidine-1,2-dicarboxylate 
• 1033713-89-1 1-benzyl 2-tert-butyl (2S)-5-methoxypyrrolidine-1,2-dicarboxylate 
• 81470-51-1 tert-butyl N-benzyloxycarbonyl-L-pyroglutamate 
• 32159-21-0 Cbz-L-pGlu-OH 

Downstream Products

• 1033714-69-0 benzyl (2S,5R)-2-{[(3R)-3,4-dimethylpiperazin-1-yl]carbonyl}-5-ethylpyrrolidine-1-carboxylate 
• 1033709-65-7 (5R,6S)-5,6-bis(4-chlorophenyl)-2-[((2S,5R)-2-{[(3R)-3,4-dimethylpiperazin-1-yl]carbonyl}-5-ethylpyrrolidin-1-yl)carbonyl]-3-isopropyl-6-methyl-5,6-dihydroimidazo[2,1-b][1,3]thiazole 

Relevant academic research and scientific papers

Synthesis and evaluation of novel orally active p53-MDM2 interaction inhibitors

We have discovered and reported potent p53-MDM2 interaction inhibitors possessing dihydroimidazothiazole scaffold. Our lead showed strong activity in vitro, but did not exhibit antitumor efficacy in vivo for the low metabolic stability. In order to obtain orally active compounds, we executed further optimization of our lead by the improvement of physicochemical properties. Thus we furnished optimal compounds by introducing an alkyl group onto the pyrrolidine at the C-2 substituent to prevent the metabolism; and modifying the terminal substituent of the proline motif improved solubility. These optimal compounds exhibited good PK profiles and significant antitumor efficacy with oral administration on a xenograft model using MV4-11 cells having wild type p53.

IMIDAZOTHIAZOLE DERIVATIVE HAVING 4,7-DIAZASPIROY2.5¨OCTANE RING STRUCTURE

There is provided a novel compound that inhibits the interaction between murine double minute 2 (Mdm2) protein and p53 protein and exhibits anti-tumor activity. The present invention provides an imidazothiazole derivative represented by the following formula (1) having various substituents that inhibits the interaction between Mdm2 protein and p53 protein and exhibits anti-tumor activity: wherein R1 R2, R3, R4, R5, Ar1, and Ar2 in formula (1) each have the same meanings as defined in the specification.