2. Academic Validation
  3. Discovery of SHR5133, a Highly Potent and Novel HBV Capsid Assembly Modulator

Discovery of SHR5133, a Highly Potent and Novel HBV Capsid Assembly Modulator

  • ACS Med Chem Lett. 2022 Feb 17;13(3):507-512. doi: 10.1021/acsmedchemlett.2c00002.
Xin Li 1,  Zhigao Zhang 1,  Yang Chen 1,  Bin Wang 1,  Guimei Yang 1,  Xiangbin Xu 1,  Baihui Yechao 1,  Dongdong Bai 1,  Binqiang Feng 1,  Yuchang Mao 1,  Jun Feng 1,  Chang Bai 1,  Feng He 1,  Weikang Tao 1
Affiliations

Affiliation

  • 1 Shanghai Hengrui Pharmaceutical Co., Ltd., R&D Center, 279 Wenjing Road, Shanghai 200245, China.
PMID: 35300087 DOI: 10.1021/acsmedchemlett.2c00002
Abstract

Capsid assembly modulators (CpAMs) represent a new class of antivirals targeting hepatitis B virus (HBV) core protein to disrupt the assembly process. In this work, a novel chemotype featuring a fused heterocycle amide was discovered through pharmacophore exploration. Lead optimization resulted in compound 8 with an EC50 value of 511 nM, and then methyl substitution on the piperazine was found to improve the in vitro potency remarkably. Further SAR studies established the key compound SHR5133, which showed high in vitro Antiviral potency, favorable pharmacokinetic profiles across species, and robust in vivo efficacy.

Figures
Products