Research Topics
| Kevin X ChenSummaryAffiliation: Schering-Plough Research Institute Country: USA Publications
|
Detail Information
Publications
Syntheses of novel 4-tert-alkyl ether proline-based 16- and 17-membered macrocyclic compoundsKevin X Chen
Schering Plough Research Institute, 2015 Galloping Hill Road, K 15 3 3545, Kenilworth, NJ 07033, USA
J Org Chem 67:2730-3. 2002..The macrocyclization of 2 was accomplished through a Mitsunobu reaction using triphenylphosphine and 1,1'-(azodicarbonyl)dipiperidine (ADDP), to afford novel 16- and 17-membered proline-based macrocyclic compounds of type 3...- A review of HCV protease inhibitorsKevin X Chen
Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
Curr Opin Investig Drugs 10:821-37. 2009..This review focuses on the recent advances in the development of HCV protease inhibitors... 
Second-generation highly potent and selective inhibitors of the hepatitis C virus NS3 serine proteaseKevin X Chen
Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
J Med Chem 52:1370-9. 2009..X-ray structure of inhibitor 46 bound to the enzyme revealed that there was an additional hydrogen bonding interaction between one of the imide carbonyls and Cys159...- Novel potent inhibitors of hepatitis C virus (HCV) NS3 protease with cyclic sulfonyl P3 cappingsKevin X Chen
Infectious Disease Tumor Biology, Schering Plough Research Institute, 2015 Galloping Hill Road, K 15 A 3545, Kenilworth, NJ 07033, USA
Bioorg Med Chem Lett 19:1105-9. 2009..This compound had the best overall profile in potency and PK profile: excellent K(i)(*) of 5.3 nM and activity in replicon (EC(90)) of 80 nM, extremely high selectivity of 6100, and a good rat PO AUC of 1.43 microMh... - Potent and selective small molecule NS3 serine protease inhibitors of Hepatitis C virus with dichlorocyclopropylproline as P2 residueKevin X Chen
Schering Plough Research Institute, 2015 Galloping Hill Road, K 15 3 3545, Kenilworth, NJ 07033, USA
Bioorg Med Chem 16:1874-83. 2008..Its bioavailabilities were above 10% in all three animal species (rats, monkeys, and dogs). It has provided a lead for future investigations... - Novel potent hepatitis C virus NS3 serine protease inhibitors derived from proline-based macrocyclesKevin X Chen
Schering Plough Research Institute, 2015 Galloping Hill Road, K 15 3 3545, Kenilworth, NJ 07033, USA
J Med Chem 49:995-1005. 2006..The strategy of macrocyclization has been proved to be successful in improving potency (>20-fold greater than that of 1) and in structural depeptization... - Potent 7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid-based macrocyclic inhibitors of hepatitis C virus NS3 proteaseKevin X Chen
Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
J Med Chem 49:567-74. 2006..The ketone carbonyl formed a reversible covalent bond with Ser139. The n-propyl of P1 novaline and the aromatic ring of P2' phenylglycine formed a C-shaped clamp around the Lys136 side chain... - Proline-based macrocyclic inhibitors of the hepatitis C virus: stereoselective synthesis and biological activityKevin X Chen
Schering-Plough Research Institute, 2015 Galloping Hill Road, K-15-3/3545, Kenilworth, NJ 07033, USA
Angew Chem Int Ed Engl 44:7024-8. 2005 - Synthesis and biological activity of macrocyclic inhibitors of hepatitis C virus (HCV) NS3 proteaseKevin X Chen
Schering Plough Research Institute, 2015 Galloping Hill Road, K 15 3 3545, Kenilworth, NJ 07033, USA
Bioorg Med Chem Lett 15:4475-8. 2005..The macrocyclic alpha-ketoamides were active inhibitors of the HCV NS3 protease, with the C-terminal acids and amides being more potent than tert-butyl esters... - Design, synthesis, and biological activity of m-tyrosine-based 16- and 17-membered macrocyclic inhibitors of hepatitis C virus NS3 serine proteaseKevin X Chen
Schering Plough Research Institute, 2015 Galloping Hill Road, K 15 3 3545, Kenilworth, New Jersey 07033, USA
J Med Chem 48:6229-35. 2005..P2' phenyl and P1 propyl groups wrapped around the Lys136 side chain, forming a "C"-shaped clamp. The 17-membered macrocyclic inhibitors 17-19 were significantly more potent than the acyclic pentapeptide 1... - A novel class of highly potent irreversible hepatitis C virus NS5B polymerase inhibitorsKevin X Chen
Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
J Med Chem 55:2089-101. 2012..The overall excellent profile of 47 made it an interesting candidate for further investigation... - Toward the back-up of boceprevir (SCH 503034): discovery of new extended P4-capped ketoamide inhibitors of hepatitis C virus NS3 serine protease with improved potency and pharmacokinetic profilesStephane L Bogen
Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
J Med Chem 52:3679-88. 2009..In addition to being potent inhibitors of HCV subgenomic RNA replication, some of the new P(4)-capped inhibitors were also found to have improved PK profile... - Structure-activity relationship (SAR) development and discovery of potent indole-based inhibitors of the hepatitis C virus (HCV) NS5B polymeraseKevin X Chen
Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States
J Med Chem 55:754-65. 2012..02 μM) assays and a good oral PK profile with area-under-the curve (AUC) of 14 and 8 μM·h in rats and dogs, respectively. X-ray structure of inhibitor 56 bound to the enzyme was also reported... - II. Novel HCV NS5B polymerase inhibitors: discovery of indole C2 acyl sulfonamidesGopinadhan N Anilkumar
Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
Bioorg Med Chem Lett 22:713-7. 2012..Further SAR investigation resulted in identification of acyl sufonamide analog 7q (NS5B IC(50)=0.039μM, replicon EC(50)=0.011μM) with >100-fold improved replicon activity... - P4 capped amides and lactams as HCV NS3 protease inhibitors with improved potency and DMPK profileLatha G Nair
Chemical Research, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
Bioorg Med Chem Lett 20:567-70. 2010..Extensive SAR studies resulted in the identification of 36 bearing 4, 4-dimethyl lactam as the new P4 cap unit with improved potency (K(i)( *)=15nM, EC 90=70nM) and pharmacokinetic properties (Rat AUC (PO)=3.52microMh) compared to 1... - The introduction of P4 substituted 1-methylcyclohexyl groups into Boceprevir: a change in direction in the search for a second generation HCV NS3 protease inhibitorFrank Bennett
Schering Plough Research Institute, K 15 A 3545, Kenilworth, NJ 07033, USA
Bioorg Med Chem Lett 20:2617-21. 2010..Subsequent modeling and SAR studies led to the pyridine 38 and sulfone analogues 52 and 53 with vastly improved PK parameters in monkeys, forming a new foundation for further exploration... - P2-P4 macrocyclic inhibitors of hepatitis C virus NS3-4A serine proteaseAshok Arasappan
Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
Bioorg Med Chem Lett 16:3960-5. 2006..X-ray structure of inhibitor 38 bound to the protease is discussed... - Toward second generation hepatitis C virus NS3 serine protease inhibitors: discovery of novel P4 modified analogues with improved potency and pharmacokinetic profileAshok Arasappan
Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
J Med Chem 52:2806-17. 2009..Combining the preferred moieties, identified from comprehensive SAR studies, resulted in inhibitors that displayed superior potency and very good oral as well as target organ exposure in rats... - Discovery and structure-activity relationship of P1-P3 ketoamide derived macrocyclic inhibitors of hepatitis C virus NS3 proteaseSrikanth Venkatraman
Schering Plough Research Institute, K 15, MS 3545, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
J Med Chem 52:336-46. 2009..X-ray structure of 52 bound to NS3 protease and biological data are also discussed... - Challenges in modern drug discovery: a case study of boceprevir, an HCV protease inhibitor for the treatment of hepatitis C virus infectionF George Njoroge
Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
Acc Chem Res 41:50-9. 2008..Boceprevir is well tolerated in humans and demonstrated antiviral activity in phase I clinical trials. It is currently in phase II trials. This Account details the complexity and challenges encountered in the drug discovery process... - Novel dipeptide macrocycles from 4-oxo, -thio, and -amino-substituted proline derivativesAshok Arasappan
Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
J Org Chem 67:3923-6. 2002..Dipeptide macrocycles of type A have been constructed in a versatile manner from the corresponding 4-heteroatom-substituted proline derivatives using an intramolecular Mitsunobu strategy... - The role of P-glycoprotein in the pharmacokinetics and tissue distribution of a hepatitis C virus protease inhibitorKevin X Chen
Schering Plough Research Institute, Kenilworth, NJ 07033, USA
Drug Metab Lett 3:290-5. 2009..These results suggest that P-gp efflux limits exposure to S5 in the brain and liver, and that the effect is dependent on the route of administration... - I. Novel HCV NS5B polymerase inhibitors: discovery of indole 2-carboxylic acids with C3-heterocyclesGopinadhan N Anilkumar
Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
Bioorg Med Chem Lett 21:5336-41. 2011..SAR development resulted in leads 7q (NS5B IC(50)=0.032 μM, replicon EC(50)=1.4 μM) and 7r (NS5B IC(50)=0.017 μM, replicon EC(50)=0.3 μM) with improved enzyme and replicon activity...