Identification of a new class of HBV capsid assembly modulator

Scott D Kuduk; Bart Stoops; Richard Alexander; Angela M Lam; Christine Espiritu; Robert Vogel; Vincent Lau; Klaus Klumpp; Osvaldo A Flores; George D Hartman

doi:10.1016/j.bmcl.2021.127848

Identification of a new class of HBV capsid assembly modulator

Bioorg Med Chem Lett. 2021 May 1:39:127848. doi: 10.1016/j.bmcl.2021.127848. Epub 2021 Feb 18.

Authors

Affiliations

¹ Novira Therapeutics, a Janssen Pharmaceuticals Company, 1400 McKean Road, Spring House, PA 19477, United States. Electronic address: skuduk@its.jnj.com.
² Janssen Pharmaceutica, N. V. Turnhoutseweg 30, 2340 Beerse, Belgium.
³ Janssen Research and Development, 1400 McKean Road, Spring House, PA 19477, United States.
⁴ Novira Therapeutics, a Janssen Pharmaceuticals Company, 1400 McKean Road, Spring House, PA 19477, United States.

PMID: 33610748
DOI: 10.1016/j.bmcl.2021.127848

Abstract

The HBV core protein is a druggable target of interest due to the multiple essential functions in the HBV life cycle to enable chronic HBV infection. The core protein oligomerizes to form the viral capsid, and modulation of the HBV capsid assembly has shown efficacy in clinical trials. Herein is described the identification and hit to lead SAR of a novel series of pyrazolo piperidine HBV capsid assembly modulators.

Keywords: Capsid; HBV; Modulator; Urea.

MeSH terms

Antiviral Agents / chemistry
Antiviral Agents / pharmacology*
Capsid Proteins / antagonists & inhibitors*
Capsid Proteins / metabolism
Dose-Response Relationship, Drug
Hepatitis B virus / drug effects*
Hepatitis B virus / metabolism
Microbial Sensitivity Tests
Molecular Structure
Piperidines / chemistry
Piperidines / pharmacology*
Pyrazoles / chemistry
Pyrazoles / pharmacology*
Structure-Activity Relationship

Substances

Antiviral Agents
Capsid Proteins
Piperidines
Pyrazoles
pyrazole
piperidine