2174940-65-7Relevant academic research and scientific papers
Novel Piperidinyl-Azetidines as Potent and Selective CCR4 Antagonists Elicit Antitumor Response as a Single Agent and in Combination with Checkpoint Inhibitors
Robles, Omar,Jackson, Jeffrey J.,Marshall, Lisa,Talay, Oezcan,Chian, David,Cutler, Gene,Diokno, Raymond,Hu, Dennis X.,Jacobson, Scott,Karbarz, Emily,Kassner, Paul D.,Ketcham, John M.,McKinnell, Jenny,Meleza, Cesar,Reilly, Maureen K.,Riegler, Erin,Shunatona, Hunter P.,Wadsworth, Angela,Younai, Ashkaan,Brockstedt, Dirk G.,Wustrow, David J.,Zibinsky, Mikhail
, p. 8584 - 8607 (2020)
The C-C chemokine receptor 4 (CCR4) is broadly expressed on regulatory T cells (Treg) as well as other circulating and tissue-resident T cells. Treg can be recruited to the tumor microenvironment (TME) through the C-C chemokines CCL17 and CCL22. Treg accumulation in the TME has been shown to dampen the antitumor immune response and is thought to be an important driver in tumor immune evasion. Preclinical and clinical data suggest that reducing the Treg population in the TME can potentiate the antitumor immune response of checkpoint inhibitors. We have developed small-molecule antagonists of CCR4, featuring a novel piperidinyl-Azetidine motif, that inhibit the recruitment of Treg into the TME and elicit antitumor responses as a single agent or in combination with an immune checkpoint blockade. The discovery of these potent, selective, and orally bioavailable CCR4 antagonists, and their activity in in vitro and in vivo models, is described herein.
UBIQUITIN-SPECIFIC-PROCESSING PROTEASE 7 (USP7) MODULATORS AND USES THEREOF
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, (2021/10/15)
Disclosed herein, inter alia, compounds and methods of use thereof for the modulation of USP7 activity.
Preparation method of chiral anti-tumor drug FLX475 and preparation method intermediate of chiral anti-tumor drug FLX475
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, (2020/10/14)
The invention relates to a preparation method of a chiral drug FLX475 and a preparation method of an intermediate of the chiral drug FLX475. The method for preparing the intermediate comprises the following step: performing catalytic hydrogenation on a compound 6 under the action of a hydrogenation catalyst to prepare the key intermediate (compound 7). The chiral preparation method of the antitumor drug FLX475 is completely different from the prior art, and has the remarkable characteristics of economy, mildness, simplicity, convenience and capability of realizing large-scale production; and in the preparation of the key chiral intermediate compound 7, PtO2 is used as a catalyst, and the target product with high chiral purity can be obtained through catalytic hydrogenation at normal temperature and normal pressure.
