1033713-89-1

Upstream product

• 35418-16-7 L-t-butyl pyroglutamate 
• 540-88-5 acetic acid tert-butyl ester 
• 67-56-1 methanol 
• 81470-51-1 tert-butyl N-benzyloxycarbonyl-L-pyroglutamate 
• 32159-21-0 Cbz-L-pGlu-OH 

Downstream Products

• 1033709-61-3 tert-butyl (5R)-1-{[(5R,6S)-5,6-bis(4-chlorophenyl)-3-isopropyl-6-methyl-5,6-dihydroimidazo[2,1-b][1,3]thiazol-2-yl]carbonyl}-5-methyl-L-prolinate 
• 1443977-81-8 tert-butyl (5R)-1-{[(5R,6S)-5,6-bis(4-chlorophenyl)-3-isopropyl-6-methyl-5,6-dihydroimidazo[2,1-b][1,3]thiazol-2-yl]carbonyl}-5-ethyl-L-prolinate 
• 1033709-62-4 (5R)-1-{[(5R,6S)-5,6-bis(4-chlorophenyl)-3-isopropyl-6-methyl-5,6-dihydroimidazo[2,1-b][1,3]thiazol-2-yl]carbonyl}-5-methyl-L-proline 
• 1033709-22-6 (5R)-1-{[(5R,6S)-5,6-bis(4-chlorophenyl)-3-isopropyl-6-methyl-5,6-dihydroimidazo[2,1-b][1,3]thiazol-2-yl]carbonyl}-5-ethyl-L-proline 
• 1033714-59-8 (5R)-1-[(benzyloxy)carbonyl]-5-methyl-L-proline 
• 1033713-91-5 (5R)-1-[(benzyloxy)carbonyl]-5-ethyl-L-proline 
• 1033714-79-2 benzyl (2S,5R)-2-{[(3S)-3,4-dimethylpiperazin-1-yl]carbonyl}-5-methylpyrrolidine-1-carboxylate 
• 1033714-69-0 benzyl (2S,5R)-2-{[(3R)-3,4-dimethylpiperazin-1-yl]carbonyl}-5-ethylpyrrolidine-1-carboxylate 
• 1443977-66-9 (5R)-1-{[(5R,6S)-5,6-bis(4-chlorophenyl)-3-isopropyl-6-methyl-5,6-dihydroimidazo[2,1-b][1,3]thiazol-2-yl]carbonyl}-N,N,5-trimethyl-L-prolinamide 
• 1033708-88-1 (5R)-1-{[(5R,6S)-5,6-bis(4-chlorophenyl)-3-isopropyl-6-methyl-5,6-dihydroimidazo[2,1-b][1,3]thiazol-2-yl]carbonyl}-5-ethyl-N,N-dimethyl-L-prolinamide 
• 1443977-67-0 (5R,6S)-5,6-bis(4-chlorophenyl)-2-({(2R,5S)-2-methyl-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-1-yl}carbonyl)-3-isopropyl-6-methyl-5,6-dihydroimidazo[2,1-b][1,3]thiazole 
• 1443977-68-1 (5R,6S)-2-({(2S,5R)-2-[(4-acetylpiperazin-1-yl)carbonyl]-5-methylpyrrolidin-1-yl}carbonyl)-5,6-bis(4-chlorophenyl)-3-isopropyl-6-methyl-5,6-dihydroimidazo[2,1-b][1,3]thiazole 
• 1033709-23-7 (5R,6S)-5,6-bis(4-chlorophenyl)-2-({(2R,5S)-2-ethyl-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-1-yl}carbonyl)-3-isopropyl-6-methyl-5,6-dihydroimidazo[2,1-b][1,3]thiazole 
• 1033709-30-6 (5R,6S)-2-({(2S,5R)-2-[(4-acetylpiperazin-1-yl)carbonyl]-5-ethylpyrrolidin-1-yl}carbonyl)-5,6-bis(4-chlorophenyl)-3-isopropyl-6-methyl-5,6-dihydroimidazo[2,1-b][1,3]thiazole 

Relevant academic research and scientific papers

The Discovery of Conformationally Constrained Bicyclic Peptidomimetics as Potent Hepatitis C NS5A Inhibitors

HCV NS5A inhibitors are the backbone of directly acting antiviral treatments against the hepatitis C virus (HCV). While these therapies are generally highly curative, they are less effective in some specific HCV patient populations. In the search for broader-acting HCV NS5A inhibitors that address these needs, we explored conformational restrictions imposed by the [7,5]-azabicyclic lactam moiety incorporated into daclatasvir (1) and related HCV NS5A inhibitors. Unexpectedly, compound 5 was identified as a potent HCV genotype 1a and 1b inhibitor. Molecular modeling of 5 bound to HCV genotype 1a suggested that the use of the conformationally restricted lactam moiety might have resulted in reorientation of its N-terminal carbamate to expose a new interaction with the NS5A pocket located between amino acids P97 and Y93, which was not easily accessible to 1. The results also suggest new chemistry directions that exploit the interactions with the P97-Y93 site toward new and potentially improved HCV NS5A inhibitors.

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.