689303-75-1Relevant academic research and scientific papers
Discovery of a Potent and Selective CCR4 Antagonist That Inhibits Treg Trafficking into the Tumor Microenvironment
Jackson, Jeffrey J.,Ketcham, John M.,Younai, Ashkaan,Abraham, Betty,Biannic, Berenger,Beck, Hilary P.,Bui, Minna H. T.,Chian, David,Cutler, Gene,Diokno, Raymond,Hu, Dennis X.,Jacobson, Scott,Karbarz, Emily,Kassner, Paul D.,Marshall, Lisa,McKinnell, Jenny,Meleza, Cesar,Okal, Abood,Pookot, Deepa,Reilly, Maureen K.,Robles, Omar,Shunatona, Hunter P.,Talay, Oezcan,Walker, James R.,Wadsworth, Angela,Wustrow, David J.,Zibinsky, Mikhail
, p. 6190 - 6213 (2019/08/02)
Recruitment of suppressive CD4+ FOXP3+ regulatory T cells (Treg) to the tumor microenvironment (TME) has the potential to weaken the antitumor response in patients receiving treatment with immuno-oncology (IO) agents. Human Treg express CCR4 and can be recruited to the TME through the CC chemokine ligands CCL17 and CCL22. In some cancers, Treg accumulation correlates with poor patient prognosis. Preclinical data suggests that preventing the recruitment of Treg and increasing the population of activated effector T cells (Teff) in the TME can potentiate antitumor immune responses. We developed a novel series of potent, orally bioavailable small molecule antagonists of CCR4. From this series, several compounds exhibited high potency in distinct functional assays in addition to good in vitro and in vivo ADME properties. The design, synthesis, and SAR of this series and confirmation of its in vivo activity are reported.
New highly potent GABA uptake inhibitors selective for GAT-1 and GAT-3 derived from (R)- and (S)-proline and homologous pyrrolidine-2-alkanoic acids
Fuelep, Guenther H.,Hoesl, Cornelia E.,Hoefner, Georg,Wanner, Klaus T.
, p. 809 - 824 (2007/10/03)
We synthesized proline and pyrrolidine-2-alkanoic acid derivatives in their enantiomerically pure form and evaluated them for their affinity to the GABA transport proteins GAT-1 and GAT-3. Among the compounds presented herein, (R)-pyrrolidine-2-acetic aci
Asymmetric Baylis-Hillman reactions: Catalysis using a chiral pyrrolizidine base
Barrett, Anthony G. M.,Cook, Andrew S.,Kamimura, Akio
, p. 2533 - 2534 (2007/10/03)
A novel chiral pyrrolizidine base 5 derived from L-proline promotes the Baylis-Hillman reaction of ethyl and methyl vinyl ketones with electron deficient aromatic aldehydes with moderate levels of enantiomeric excess.
