1241377-38-7Relevant academic research and scientific papers
Design and synthesis of potent inhibitor of apoptosis (IAP) proteins antagonists bearing an octahydropyrrolo[1,2-a]pyrazine scaffold as a novel proline mimetic
Hashimoto, Kentaro,Saito, Bunnai,Miyamoto, Naoki,Oguro, Yuya,Tomita, Daisuke,Shiokawa, Zenyu,Asano, Moriteru,Kakei, Hiroyuki,Taya, Naohiro,Kawasaki, Masanori,Sumi, Hiroyuki,Yabuki, Masato,Iwai, Kenichi,Yoshida, Sei,Yoshimatsu, Mie,Aoyama, Kazunobu,Kosugi, Yohei,Kojima, Takashi,Morishita, Nao,Dougan, Douglas R.,Snell, Gyorgy P.,Imamura, Shinichi,Ishikawa, Tomoyasu
supporting information, p. 1228 - 1246 (2013/03/28)
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).
HEPATITIS C VIRUS INHIBITORS
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, (2012/02/15)
The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.
HEPATITIS C VIRUS INHIBITORS
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Page/Page column 127-128, (2011/07/07)
The present disclosure relates to compounds, compositions and methods for the treatment of Hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.
HEPATITIS C VIRUS INHIBITORS
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, (2011/06/16)
The present disclosure relates to methods for making compounds useful in the treatment of Hepatitis C virus (HCV) infection.
Heterocyclic Compound
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Page/Page column 80, (2011/02/26)
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.
Hepatitis C Virus Inhibitors
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, (2010/10/19)
This disclosure concerns novel compounds of Formula (I) as defined in the specification and compositions comprising such novel compounds. These compounds are useful antiviral agents, especially in inhibiting the function of the NS5A protein encoded by Hepatitis C virus (HCV). Thus, the disclosure also concerns a method of treating HCV related diseases or conditions by use of these novel compounds or a composition comprising such novel compounds.
HEPATITIS C VIRUS INHIBITORS
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Page/Page column 199, (2010/11/04)
This disclosure concerns novel compounds of Formula (I) or Formula (II) as defined in the specification and compositions comprising such novel compounds. These compounds are useful antiviral agents, especially in inhibiting the function of the NS5A protein encoded by Hepatitis C virus (HCV). Thus, the disclosure also concerns a method of treating HCV related diseases or conditions by use of these novel compounds or a composition comprising such novel compounds.
HEPATITIS C VIRUS INHIBITORS
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Page/Page column 185-186, (2010/12/26)
This disclosure concerns novel compounds of Formula (I) as defined in the specification and compositions comprising such novel compounds. These compounds are useful antiviral agents, especially in inhibiting the function of the NS5A protein encoded by Hepatitis C virus (HCV). Thus, the disclosure also concerns a method of treating HCV related diseases or conditions by use of these novel compounds or a composition comprising such novel compounds.
HEPATITIS C VIRUS INHIBITORS
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Page/Page column 142, (2010/12/26)
The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.
