35577-92-5Relevant articles and documents
Inter- and intra-molecular C-H borylation for the formation of PAHs containing triarylborane and indole units
Escande,Crossley,Cid,Cade,Vitorica-Yrezabal,Ingleson
, p. 17160 - 17167 (2016)
Inter-/intra-molecular electrophilic C-H borylation of C4-substituted indoles enables the formation of fused polycyclic aromatic structures containing triarylborane and N-heterocyclic units. These compounds are B-(C)n-N isosteres of carbocyclic PAHs that do not contain B-N bonds and comparison of one pair of BN/CC isosteres reveals that different resonance structures dominate. These compounds are highly sensitive to protodeboronation, of both the chloroborane intermediates and the mesityl protected products, which results in low isolated yields of the latter. Protodeboronation can be utilised productively for a C-H directed, C-H electrophilic borylation to make a previously unknown pinacol boronate ester by selective protodeboronation of the chloroborane intermediate. Intermolecular and double intramolecular electrophilic C-H borylation of a C4-substituted indole leads to a more highly fused structure containing two boracycles which represents a B-(C)n-N analogue of the unknown carbon isostere indeno[1,7ab]perylene.
Discovery of the programmed cell death-1/programmed cell death-ligand 1 interaction inhibitors bearing an indoline scaffold
Qin, Mingze,Cao, Qi,Wu, Xia,Liu, Chunyang,Zheng, Shuaishuai,Xie, Hongbo,Tian, Ye,Xie, Jun,Zhao, Yanfang,Hou, Yunlei,Zhang, Xian,Xu, Boxuan,Zhang, Haotian,Wang, Xiaobo
, (2019/11/26)
Inhibiting the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway is an attractive strategy for tumor immunotherapy. Here, a novel series of indoline-containing compounds were developed, among which, A13 was identified as the most promising PD-1/PD-L1 pathway inhibitor. At the biochemical level, A13 demonstrated strong inhibition of the PD-1/PD-L1 interaction, with an IC50 of 132.8 nM. Notably, it exhibited outstanding immunoregulatory activity, and significantly elevated interferon-γ secretion in a Hep3B/OS-8/hPD-L1 and CD3 T cell co-culture model, without significant toxic effect. Therefore, A13 could be employed as a suitable lead compound for further design of non-peptide inhibitors targeting the PD-1/PD-L1 interaction. In addition, the preliminary structure-activity relationships of these new indoline compounds were investigated in this study, providing valuable information for future drug development.
New Generation of Selective Androgen Receptor Degraders: Our Initial Design, Synthesis, and Biological Evaluation of New Compounds with Enzalutamide-Resistant Prostate Cancer Activity
Hwang, Dong-Jin,He, Yali,Ponnusamy, Suriyan,Mohler, Michael L.,Thiyagarajan, Thirumagal,McEwan, Iain J.,Narayanan, Ramesh,Miller, Duane D.
, p. 491 - 511 (2019/01/11)
In our effort to find small-molecule treatments of advanced prostate cancers (PCs), a novel series of indolyl and indolinyl propanamides (series II and III) were discovered as selective androgen receptor degraders (SARDs). Initial studies of androgen receptor (AR) antagonist (1) and agonist (2) propanamides yielded a tertiary aniline (3) with novel SARD activity but poor metabolic stability. Cyclization to II and III produced submicromolar AR antagonism and protein degradation selective to AR and AR splice variant (AR SV). II and III maintained potency against enzalutamide-resistant (Enz-R) mutant ARs and PC cells and were efficacious in Enz-R xenografts, suggesting their potential to treat advanced PCs. Design, synthesis, and biological activity of novel SARDs that could potentially be used for the treatment of a wide spectrum of PCs including castration-resistant, Enz-R, and/or AR SV-dependent advanced PCs that are often untreatable with known hormone therapies are discussed.
