115012-26-5Relevant academic research and scientific papers
Structure-Activity Relationship Studies of Pyrimido[5,4-b]indoles as Selective Toll-Like Receptor 4 Ligands
Chan, Michael,Kakitsubata, Yuhei,Hayashi, Tomoko,Ahmadi, Alast,Yao, Shiyin,Shukla, Nikunj M.,Oyama, Shin-Ya,Baba, Akihito,Nguyen, Brandon,Corr, Maripat,Suda, Yasuo,Carson, Dennis A.,Cottam, Howard B.,Wakao, Masahiro
, p. 9142 - 9161 (2017)
Previous high throughput screening studies led to the discovery of two novel, nonlipid-like chemotypes as Toll-like receptor 4 (TLR4) agonists. One of these chemotypes, the pyrimido[5,4-b]indoles, was explored for structure-activity relationship trends relative to production of TLR4 dependent cytokines/chemokines, resulting in a semioptimized lead (compound 1) that provided a starting point for further optimization studies. In this report, compounds belonging to three areas of structural modification were evaluated for biological activity using murine and human TLR4 reporter cells, primary murine bone marrow derived dendritic cells, and human peripheral blood mononuclear cells. The compounds bearing certain aryl groups at the C8 position, such as phenyl (36) and β-naphthyl (39), had potencies significantly greater than compound 1. Compound 36 displayed human TLR4 agonist activity at submicromolar concentrations. The computational analysis suggests that the improved potency of these C8-aryl derivatives may be the result of additional binding interactions at the interface of the TLR4/myeloid differentiation protein-2 (MD-2) complex.
Palladium-catalyzed β-C-H arylation of aliphatic aldehydes and ketones using amino amide as a transient directing group
Dong, Cong,Wu, Liangfei,Yao, Jianwei,Wei, Kun
supporting information, p. 2085 - 2089 (2019/03/26)
This paper describes a new amino-amide-based transient directing group (TDG). The TDG can exhibit better performance in the Pd-catalyzed arylation of aliphatic aldehydes and ketones. This reaction showed good substrate compatibility and regioselectivity. The results indicated that 3-amino-N-isopropylpropionamide was more beneficial to the β-arylation of aliphatic aldehydes than other TDGs under relatively mild conditions.
