| Structural highlights
2yoj is a 2 chain structure with sequence from 9hepc. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | ,
| | Activity: | RNA-directed RNA polymerase, with EC number 2.7.7.48 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Publication Abstract from PubMed
Starting from indole-based hepatitis C virus (HCV) NS5B polymerase inhibitor lead compound 1, structure modifications were performed at multiple indole substituents to improve potency and pharmacokinetic (PK) properties. Bicyclic quinazolinone was found to be the best substituent at indole nitrogen, while 4,5-furanylindole was identified as the best core. Compound 11 demonstrated excellent potency. Its C2 N,N-dimethylaminoethyl ester prodrug 12 (SCH 900188) demonstrated significant improvement in PK and was selected as the development candidate.
Discovery of SCH 900188: A Potent Hepatitis C Virus NS5B Polymerase Inhibitor Prodrug As a Development Candidate.,Chen KX, Venkatraman S, Anilkumar GN, Zeng Q, Lesburg CA, Vibulbhan B, Velazquez F, Chan TY, Bennet F, Jiang Y, Pinto P, Huang Y, Selyutin O, Agrawal S, Huang HC, Li C, Cheng KC, Shih NY, Kozlowski JA, Rosenblum SB, Njoroge FG ACS Med Chem Lett. 2013 Aug 12;5(3):244-8. doi: 10.1021/ml400192w. eCollection, 2014 Mar 13. PMID:24900812[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chen KX, Venkatraman S, Anilkumar GN, Zeng Q, Lesburg CA, Vibulbhan B, Velazquez F, Chan TY, Bennet F, Jiang Y, Pinto P, Huang Y, Selyutin O, Agrawal S, Huang HC, Li C, Cheng KC, Shih NY, Kozlowski JA, Rosenblum SB, Njoroge FG. Discovery of SCH 900188: A Potent Hepatitis C Virus NS5B Polymerase Inhibitor Prodrug As a Development Candidate. ACS Med Chem Lett. 2013 Aug 12;5(3):244-8. doi: 10.1021/ml400192w. eCollection, 2014 Mar 13. PMID:24900812 doi:http://dx.doi.org/10.1021/ml400192w
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