2267-40-5Relevant articles and documents
Sulfamoylbenzamide-based Capsid Assembly Modulators for Selective Inhibition of Hepatitis B Viral Replication
Lee, Yeon Hee,Cha, Hyeon-Min,Hwang, Jun Yeon,Park, So Yeong,Vishakantegowda, Avinash G.,Imran, Ali,Lee, Joo-Youn,Yi, Yoon-Sun,Jun, Sangmi,Kim, Ga Hyeon,Kang, Hyo Jin,Chung, Sang J.,Kim, Meehyein,Kim, Hyejin,Han, Soo Bong
supporting information, p. 242 - 248 (2021/02/20)
As the spread of infections caused by hepatitis B virus (HBV) threatens public health worldwide, investigations from multiple perspectives and of various mechanisms of action are urgently required to increase the HBV cure rate. Targeting the encapsidation of the nuclear capsid protein (core protein, HBc) has emerged as an attractive strategy for inhibiting the viral assembly process; however, a drug targeting this mechanism has not yet been approved. We synthesized novel sulfamoylbenzamides (SBAs) as capsid assembly modulators of HBV and found that the effects and safety profiles of compounds 3 and 8 have potential therapeutic applicability against HBV. The formation of tubular particles was time-dependent in the presence of 3, indicating a new mode of protein assembly by SBA compounds. Our findings provide a new entity for developing safe and efficient treatments for HBV infection.
Synthesis of a new series of 3-functionalised-1-phenyl-1,2,3-triazole sulfamoylbenzamides as carbonic anhydrase I, II, IV and IX inhibitors
Swain, Baijayantimala,Angeli, Andrea,Angapelly, Srinivas,Thacker, Pavitra S.,Singh, Priti,Supuran, Claudiu T.,Arifuddin, Mohammed
, p. 1199 - 1209 (2019/07/02)
The synthesis of a novel series of 3-functionalised benzenesulfonamides incorporating phenyl-1,2,3-triazole with an amide linker was achieved by using the “click-tail” approach. The new compounds, including the intermediates, were assayed as inhibitors of human carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I and II (cytosolic isoforms) and also for hCA IV and IX (transmembrane isoforms) taking acetazolamide as standard drug. Most of these compounds exhibited excellent activity against all these isoforms. hCA I was inhibited with Kis in the range of 50.8–966.8 nM, while the glaucoma associated hCA II was inhibited with Kis in the range of 6.5–760.0 nM. Isoform hCA IV was inhibited with Kis in the range of 65.3–957.5 nM, whereas the tumor associated hypoxia induced hCA IX was inhibited with Kis in the range of 30.8–815.9 nM. The structure activity relationship study for the 3-functionalised-1-phenyl-1,2,3-triazole sulfamoylbenzamides against these isoforms was also inferred from the results.
Small Molecule Microarray Based Discovery of PARP14 Inhibitors
Peng, Bo,Thorsell, Ann-Gerd,Karlberg, Tobias,Schüler, Herwig,Yao, Shao Q.
supporting information, p. 248 - 253 (2016/12/30)
Poly(ADP-ribose) polymerases (PARPs) are key enzymes in a variety of cellular processes. Most small-molecule PARP inhibitors developed to date have been against PARP1, and suffer from poor selectivity. PARP14 has recently emerged as a potential therapeutic target, but its inhibitor development has trailed behind. Herein, we describe a small molecule microarray-based strategy for high-throughput synthesis, screening of >1000 potential bidentate inhibitors of PARPs, and the successful discovery of a potent PARP14 inhibitor H10 with >20-fold selectivity over PARP1. Co-crystallization of the PARP14/H10 complex indicated H10 bound to both the nicotinamide and the adenine subsites. Further structure–activity relationship studies identified important binding elements in the adenine subsite. In tumor cells, H10 was able to chemically knockdown endogenous PARP14 activities.