Design, synthesis and biological evaluation of isoxazole-containing biphenyl derivatives as small-molecule inhibitors targeting the programmed cell death-1/ programmed cell death-ligand 1 immune checkpoint

Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases

“…sPD-L1 is an active entity that must be also considered in the design of therapeutic molecules targeting the immune checkpoint. The development of small molecules’ modulators of mPD-L1 is a very active field [ 193 ], notably with compounds capable of inducing dimerization or stabilizing PD-L1 dimers [ 194 , 195 , 196 , 197 ]. These drug design approaches should consider further the specific value of sPD-L1 as a potential co-target capable of influencing the efficacy of the designed ligands.…”

Progress in small-molecule inhibitors targeting PD-L1

“…Its prodrug, YPD-30 (IMMH-010), which is expected to be hydrolyzed efficiently to produce YPD-29B as the active metabolite in vivo, exhibits profound antitumor activity and is well tolerated in vivo. 46 Zhu et al 47 A lead compound (ZE132) was proved to be a potent inhibitor with robust antitumour efficacy and favourable drug-like properties in vitro and in vivo with the advantage of overcoming the barrier of the TIME (tumor immune microenvironment) compared to antibodies. The structure of ZE132 contains a taurine moiety, which significantly improved the potency of biphenyl compounds.…”

“…Zhu et al 47 designed and synthesized a novel series of isoxazole-containing biphenyl compounds based on BMS-3054 . Compound II- 12 was proved a promising anti-PD-1/PD-L1 inhibitor with the IC 50 value of 23.0 nM.…”

A fruitful century for the scalable synthesis and reactions of biphenyl derivatives: applications and biological aspects

“…Finally, compound 75 was reacted with (3-bromophenyl)isoxazole derivatives 76 via Suzuki coupling reaction yielded biphenyl oxazole derivatives 77 (Scheme 30). 90…”

“…4-Phenylbenzoyl-propionic acid (89) can be easily prepared via Friedel-Cras acylation of biphenyl (2) and succinic anhydride in the presence of AlCl 3 and dichloromethane (DCM). 111 While, treatment of biphenyl (2) with dihydro-2H-pyran-2,6(3H)-dione in the presence of AlCl 3 and nitrobenzene (C 6 H 5 NO 2 ) afforded biphenyl-4-yl-5-oxopentanoic acid (90). 112 Further, biphenyl-4carbonyl-benzoic acid (91) was synthesized through freesolvent mechanochemical ball milling method via reaction of biphenyl (2) with phthalic anhydride in the presence of AlCl 3 .…”