Design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived SARS-CoV 3CLpro inhibitors

Arun K. Ghosh; Gangli Gong; Valerie Grum-Tokars; Debbie C. Mulhearn; Susan C. Baker; Melissa Coughlin; Bellur S. Prabhakar; Katrina Sleeman; Michael E. Johnson; Andrew D. Mesecar

doi:10.1016/j.bmcl.2008.08.082

Design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived SARS-CoV 3CLpro inhibitors

Arun K. Ghosh^*, Gangli Gong, Valerie Grum-Tokars, Debbie C. Mulhearn, Susan C. Baker, Melissa Coughlin, Bellur S. Prabhakar, Katrina Sleeman, Michael E. Johnson, Andrew D. Mesecar

^*Corresponding author for this work

Pharmacology

Research output: Contribution to journal › Article › peer-review

89 Scopus citations

Abstract

Design, synthesis and biological evaluation of a series of 5-chloropyridine ester-derived severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors is described. Position of the carboxylate functionality is critical to potency. Inhibitor 10 with a 5-chloropyridinyl ester at position 4 of the indole ring is the most potent inhibitor with a SARS-CoV 3CLpro IC₅₀ value of 30 nM and an antiviral EC₅₀ value of 6.9 μM. Molecular docking studies have provided possible binding modes of these inhibitors.

Original language	English (US)
Pages (from-to)	5684-5688
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	20
DOIs	https://doi.org/10.1016/j.bmcl.2008.08.082
State	Published - Oct 15 2008

Keywords

Antiviral
Ester
Inhibitor
SARS 3CLpro
Synthesis

ASJC Scopus subject areas

Drug Discovery
Molecular Medicine
Molecular Biology
Biochemistry
Clinical Biochemistry
Pharmaceutical Science
Organic Chemistry

Access to Document

10.1016/j.bmcl.2008.08.082

Cite this

Ghosh, A. K., Gong, G., Grum-Tokars, V., Mulhearn, D. C., Baker, S. C., Coughlin, M., Prabhakar, B. S., Sleeman, K., Johnson, M. E., & Mesecar, A. D. (2008). Design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived SARS-CoV 3CLpro inhibitors. Bioorganic and Medicinal Chemistry Letters, 18(20), 5684-5688. https://doi.org/10.1016/j.bmcl.2008.08.082

@article{98a33d2c44204552a2f176c70b2bff21,

title = "Design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived SARS-CoV 3CLpro inhibitors",

abstract = "Design, synthesis and biological evaluation of a series of 5-chloropyridine ester-derived severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors is described. Position of the carboxylate functionality is critical to potency. Inhibitor 10 with a 5-chloropyridinyl ester at position 4 of the indole ring is the most potent inhibitor with a SARS-CoV 3CLpro IC50 value of 30 nM and an antiviral EC50 value of 6.9 μM. Molecular docking studies have provided possible binding modes of these inhibitors.",

keywords = "Antiviral, Ester, Inhibitor, SARS 3CLpro, Synthesis",

author = "Ghosh, {Arun K.} and Gangli Gong and Valerie Grum-Tokars and Mulhearn, {Debbie C.} and Baker, {Susan C.} and Melissa Coughlin and Prabhakar, {Bellur S.} and Katrina Sleeman and Johnson, {Michael E.} and Mesecar, {Andrew D.}",

note = "Funding Information: The financial support of this work is provided by the National Institute of Health (NIAID, P01 A1060915).",

year = "2008",

month = oct,

day = "15",

doi = "10.1016/j.bmcl.2008.08.082",

language = "English (US)",

volume = "18",

pages = "5684--5688",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "20",

}

Ghosh, AK, Gong, G, Grum-Tokars, V, Mulhearn, DC, Baker, SC, Coughlin, M, Prabhakar, BS, Sleeman, K, Johnson, ME & Mesecar, AD 2008, 'Design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived SARS-CoV 3CLpro inhibitors', Bioorganic and Medicinal Chemistry Letters, vol. 18, no. 20, pp. 5684-5688. https://doi.org/10.1016/j.bmcl.2008.08.082

TY - JOUR

T1 - Design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived SARS-CoV 3CLpro inhibitors

AU - Ghosh, Arun K.

AU - Gong, Gangli

AU - Grum-Tokars, Valerie

AU - Mulhearn, Debbie C.

AU - Baker, Susan C.

AU - Coughlin, Melissa

AU - Prabhakar, Bellur S.

AU - Sleeman, Katrina

AU - Johnson, Michael E.

AU - Mesecar, Andrew D.

N1 - Funding Information: The financial support of this work is provided by the National Institute of Health (NIAID, P01 A1060915).

PY - 2008/10/15

Y1 - 2008/10/15

N2 - Design, synthesis and biological evaluation of a series of 5-chloropyridine ester-derived severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors is described. Position of the carboxylate functionality is critical to potency. Inhibitor 10 with a 5-chloropyridinyl ester at position 4 of the indole ring is the most potent inhibitor with a SARS-CoV 3CLpro IC50 value of 30 nM and an antiviral EC50 value of 6.9 μM. Molecular docking studies have provided possible binding modes of these inhibitors.

AB - Design, synthesis and biological evaluation of a series of 5-chloropyridine ester-derived severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors is described. Position of the carboxylate functionality is critical to potency. Inhibitor 10 with a 5-chloropyridinyl ester at position 4 of the indole ring is the most potent inhibitor with a SARS-CoV 3CLpro IC50 value of 30 nM and an antiviral EC50 value of 6.9 μM. Molecular docking studies have provided possible binding modes of these inhibitors.

KW - Antiviral

KW - Ester

KW - Inhibitor

KW - SARS 3CLpro

KW - Synthesis

UR - http://www.scopus.com/inward/record.url?scp=53349165585&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=53349165585&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2008.08.082

DO - 10.1016/j.bmcl.2008.08.082

M3 - Article

C2 - 18796354

AN - SCOPUS:53349165585

SN - 0960-894X

VL - 18

SP - 5684

EP - 5688

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 20

ER -

Design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived SARS-CoV 3CLpro inhibitors

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this