280772-00-1Relevant articles and documents
Optimization of Small Molecules That Sensitize HIV-1 Infected Cells to Antibody-Dependent Cellular Cytotoxicity
Abrams, Cameron F.,Chapleau, Jean-Philippe,Ding, Shilei,Grenier, Melissa C.,Pazgier, Marzena,Sherburn, Rebekah,Smith, Amos B.,Somisetti, Sambasivarao,Tolbert, William D.,Finzi, Andrés,Sch?n, Arne,Vézina, Dani
supporting information, p. 371 - 378 (2019/12/02)
With approximately 37 million people living with HIV worldwide and an estimated 2 million new infections reported each year, the need to derive novel strategies aimed at eradicating HIV-1 infection remains a critical worldwide challenge. One potential strategy would involve eliminating infected cells via antibody-dependent cellular cytotoxicity (ADCC). HIV-1 has evolved sophisticated mechanisms to conceal epitopes located in its envelope glycoprotein (Env) that are recognized by ADCC-mediating antibodies present in sera from HIV-1 infected individuals. Our aim is to circumvent this evasion via the development of small molecules that expose relevant anti-Env epitopes and sensitize HIV-1 infected cells to ADCC. Rapid elaboration of an initial screening hit using parallel synthesis and structure-based optimization has led to the development of potent small molecules that elicit this humoral response. Efforts to increase the ADCC activity of this class of small molecules with the aim of increasing their therapeutic potential was based on our recent cocrystal structures with gp120 core.
COMPOUNDS
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, (2018/12/13)
Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: (I) wherein R1, R2, R3, R4, R5, R6, R8, R9, X, X1, X2, X3, L1 and n are as defined herein. The compounds are inhibitors of adrenomedullin receptor subtype 2 (AM2). Also disclosed are the compounds for use in the treatment of diseases modulated AM2, including proliferative diseases such as cancer; pharmaceutical compositions comprising the compounds; methods for preparing the compounds;and intermediates useful in the preparation of the compounds.
CCR5 antagonists as anti-HIV-1 agents. Part 3: Synthesis and biological evaluation of piperidine-4-carboxamide derivatives
Imamura, Shinichi,Nishikawa, Youichi,Ichikawa, Takashi,Hattori, Taeko,Matsushita, Yoshihiro,Hashiguchi, Shohei,Kanzaki, Naoyuki,Iizawa, Yuji,Baba, Masanori,Sugihara, Yoshihiro
, p. 397 - 416 (2007/10/03)
Replacement of the 5-oxopyrrolidin-3-yl fragment in the previously reported lead structure with a 1-acetylpiperidin-4-yl group led to the discovery of a novel series of potent CCR5 antagonists. Introduction of small hydrophobic substituents on the central phenyl ring increased the binding affinity, providing low to sub-nanomolar CCR5 antagonists. The selected compound 11f showed excellent antiviral activity against CCR5-using HIV-1 replication in human peripheral blood mononuclear cells (EC50 = 0.59 nM) and an acceptable pharmacokinetic profile in dogs.
