Design, synthesis, and biological evaluation of novel piperidine-4-carboxamide derivatives as potent CCR5 inhibitors. 2014

Suwen Hu, and Quan Gu, and Zhilong Wang, and Zhiyong Weng, and Yunrui Cai, and Xiaowu Dong, and Yongzhou Hu, and Tao Liu, and Xin Xie
ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

Based on a putative 'Y shape' pharmacophore model of CCR5 inhibitors, a series of novel piperidine-4-carboxamide derivatives were designed and synthesized using a group-reverse strategy. Among synthesized target compounds, 16g (IC₅₀ = 25.73 nM) and 16i (IC₅₀ = 25.53 nM) showed equivalent inhibitory activity against CCR5 to that of the positive control maraviroc (IC₅₀ = 25.43 nM) in calcium mobilization assay. Selected compounds were further tested for their antiviral activity in HIV-1 single cycle assay. Two compounds, 16g and 16i, displayed antiviral activity with IC₅₀ values of 73.01 nM and 94.10 nM, respectively. Additionally, the pharmacokinetic properties and inhibitory potency against hERG of 16g were evaluated, providing a foundation for ongoing optimization.

UI MeSH Term Description Entries
D010880 Piperidines A family of hexahydropyridines.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015195 Drug Design The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis. Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D015658 HIV Infections Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS). HTLV-III Infections,HTLV-III-LAV Infections,T-Lymphotropic Virus Type III Infections, Human,HIV Coinfection,Coinfection, HIV,Coinfections, HIV,HIV Coinfections,HIV Infection,HTLV III Infections,HTLV III LAV Infections,HTLV-III Infection,HTLV-III-LAV Infection,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,T Lymphotropic Virus Type III Infections, Human
D019380 Anti-HIV Agents Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS. AIDS Drug,AIDS Drugs,Anti-AIDS Agents,Anti-AIDS Drug,Anti-HIV Agent,Anti-HIV Drug,Anti-AIDS Drugs,Anti-HIV Drugs,Agent, Anti-HIV,Agents, Anti-AIDS,Agents, Anti-HIV,Anti AIDS Agents,Anti AIDS Drug,Anti AIDS Drugs,Anti HIV Agent,Anti HIV Agents,Anti HIV Drug,Anti HIV Drugs,Drug, AIDS,Drug, Anti-AIDS,Drug, Anti-HIV,Drugs, AIDS,Drugs, Anti-AIDS,Drugs, Anti-HIV
D019713 Receptors, CCR5 CCR receptors with specificity for CHEMOKINE CCL3; CHEMOKINE CCL4; and CHEMOKINE CCL5. They are expressed at high levels in T-LYMPHOCYTES; B-LYMPHOCYTES; MACROPHAGES; MAST CELLS; and NK CELLS. The CCR5 receptor is used by the HUMAN IMMUNODEFICIENCY VIRUS to infect cells. Antigens, CD195,CC Chemokine Receptor 5,CCR5 Receptors,CD195 Antigens,CC-CKR5,CCR5 Receptor,CKR5 Receptors,Receptors, CKR5,Receptor, CCR5
D065100 CCR5 Receptor Antagonists Compounds and drugs that inhibit or block the activity of CCR5 RECEPTORS. CC Chemokine Receptor 5 Antagonists,CC Chemokine Receptor 5 Blockers,CCR5 Receptor Blockers,Chemokine Co-receptor 5 Antagonists,HIV-1 Fusion Coreceptor Antagonists,Antagonists, CCR5 Receptor,Blockers, CCR5 Receptor,Chemokine Co receptor 5 Antagonists,HIV 1 Fusion Coreceptor Antagonists,Receptor Antagonists, CCR5,Receptor Blockers, CCR5

Related Publications

Suwen Hu, and Quan Gu, and Zhilong Wang, and Zhiyong Weng, and Yunrui Cai, and Xiaowu Dong, and Yongzhou Hu, and Tao Liu, and Xin Xie
September 2021, Bioorganic chemistry,
Suwen Hu, and Quan Gu, and Zhilong Wang, and Zhiyong Weng, and Yunrui Cai, and Xiaowu Dong, and Yongzhou Hu, and Tao Liu, and Xin Xie
August 2016, Bioorganic & medicinal chemistry letters,
Suwen Hu, and Quan Gu, and Zhilong Wang, and Zhiyong Weng, and Yunrui Cai, and Xiaowu Dong, and Yongzhou Hu, and Tao Liu, and Xin Xie
January 2021, European journal of medicinal chemistry,
Suwen Hu, and Quan Gu, and Zhilong Wang, and Zhiyong Weng, and Yunrui Cai, and Xiaowu Dong, and Yongzhou Hu, and Tao Liu, and Xin Xie
April 2021, European journal of medicinal chemistry,
Suwen Hu, and Quan Gu, and Zhilong Wang, and Zhiyong Weng, and Yunrui Cai, and Xiaowu Dong, and Yongzhou Hu, and Tao Liu, and Xin Xie
January 2005, Bioorganic & medicinal chemistry,
Suwen Hu, and Quan Gu, and Zhilong Wang, and Zhiyong Weng, and Yunrui Cai, and Xiaowu Dong, and Yongzhou Hu, and Tao Liu, and Xin Xie
March 2015, Bioorganic & medicinal chemistry,
Suwen Hu, and Quan Gu, and Zhilong Wang, and Zhiyong Weng, and Yunrui Cai, and Xiaowu Dong, and Yongzhou Hu, and Tao Liu, and Xin Xie
March 2022, Bioorganic chemistry,
Suwen Hu, and Quan Gu, and Zhilong Wang, and Zhiyong Weng, and Yunrui Cai, and Xiaowu Dong, and Yongzhou Hu, and Tao Liu, and Xin Xie
June 2016, Bioorganic & medicinal chemistry,
Suwen Hu, and Quan Gu, and Zhilong Wang, and Zhiyong Weng, and Yunrui Cai, and Xiaowu Dong, and Yongzhou Hu, and Tao Liu, and Xin Xie
October 2000, Bioorganic & medicinal chemistry letters,
Suwen Hu, and Quan Gu, and Zhilong Wang, and Zhiyong Weng, and Yunrui Cai, and Xiaowu Dong, and Yongzhou Hu, and Tao Liu, and Xin Xie
February 2023, Bioorganic & medicinal chemistry,
Copied contents to your clipboard!