248953-91-5Relevant articles and documents
Discovery of Hydroxyamidine Derivatives as Highly Potent, Selective Indoleamine-2,3-dioxygenase 1 Inhibitors
Jin, Fangfang,Hu, Qiyue,Fei, Hongbo,Lv, Hejun,Wang, Shenglan,Gui, Bin,Zhang, Junzhen,Tu, Wangyang,Zhang, Yun,Zhang, Lei,Wan, Hong,Zhang, Limin,Hu, Bin,Yang, Fanglong,Bai, Chang,He, Feng,Zhang, Lianshan,Tao, Weikang
supporting information, p. 195 - 201 (2021/02/06)
In this study, a series of novel hydroxyamidine derivatives were identified as potent and selective IDO1 inhibitors by structure-based drug design. Among them, compounds 13-15 and 18 exhibited favorable enzymatic and cellular activities. Compound 18 showed improved bioavailability in mouse, rat, and dog (F% = 44%, 58.8%, 102.1%, respectively). With reasonable in vivo pharmacokinetic properties, compound 18 was further evaluated in a transgenic MC38 xenograft mouse model. The combination of compound 18 with PD-1 monoclonal antibody showed a synergistic antitumor effect. These data indicated that compound 18 as a potential cancer immunotherapy agent should warrant further investigation.
Design and synthesis of 1,5- and 2,5-substituted tetrahydrobenzazepinones as novel potent and selective integrin αVβ3 antagonists
Kling, Andreas,Backfisch, Gisela,Delzer, Juergen,Geneste, Herve,Graef, Claudia,Hornberger, Wilfried,Lange, Udo E. W.,Lauterbach, Arnulf,Seitz, Werner,Subkowski, Thomas
, p. 1319 - 1341 (2007/10/03)
The design and synthesis of novel integrin αVβ3 antagonists based on a 1,5- or 2,5-substituted tetrahydrobenzaezpinone core is described. In vitro activity of respective compounds was determined via αVβ3 binding assay, and selected derivatives were submitted to further characterization in functional cellular assays. SAR was obtained by modification of the benzazepinone core, variation of the spacer linking guanidine moiety and core, and modification of the guanidine mimetic. These efforts led to the identification of novel αVβ3 inhibitors displaying potency in the subnanomolar range, selectivity versus αIIbβ3 and functional efficacy in relevant cellular assays. A method for the preparation of enantiomerically pure derivatives was developed, and respective enantiomers evaluated in vitro. Compounds 31 and 37 were assessed for metabolic stability, resorption in the Caco-2 assay and pharmacokinetics.
