90869-71-9Relevant articles and documents
Design, synthesis and biological evaluation studies of novel small molecule ENPP1 inhibitors for cancer immunotherapy
Gangar, Mukesh,Goyal, Sandeep,Raykar, Digambar,Khurana, Princy,Martis, Ashwita M.,Goswami, Avijit,Ghoshal, Ishani,Patel, Ketul V.,Nagare, Yadav,Raikar, Santosh,Mukherjee, Apurba,Cyriac, Rajath,Paquin, Jean-Fran?ois,Kulkarni, Aditya
supporting information, (2021/12/20)
Ecto-nucleotide pyrophosphatase/phosphodiesterases 1 (ENPP1 or NPP1), is an attractive therapeutic target for various diseases, primarily cancer and mineralization disorders. The ecto-enzyme is located on the cell surface and has been implicated in the control of extracellular levels of nucleotide, nucleoside and (di) phosphate. Recently, it has emerged as a critical phosphodiesterase that hydrolyzes cyclic 2′3′- cGAMP, the endogenous ligand for STING (STimulator of INterferon Genes). STING plays an important role in innate immunity by activating type I interferon in response to cytosolic 2′3′-cGAMP. ENPP1 negatively regulates the STING pathway and hence its inhibition makes it an attractive therapeutic target for cancer immunotherapy. Herein, we describe the design, optimization and biological evaluation studies of a series of novel non-nucleotidic thioguanine based small molecule inhibitors of ENPP1. The lead compound 43 has shown good in vitro potency, stability in SGF/SIF/PBS, selectivity, ADME properties and pharmacokinetic profile and finally potent anti-tumor response in vivo. These compounds are a good starting point for the development of potentially effective cancer immunotherapy agents.
Design, Synthesis, and Bioactivity of α-Ketoamide Derivatives Bearing a Vanillin Skeleton for Crop Diseases
Chen, Shunhong,Dai, Ali,Guo, Shengxin,He, Feng,Luo, Dexia,Wu, Jian,Zhang, Renfeng
, p. 7226 - 7234 (2020/08/06)
A series of novel α-ketoamide derivatives bearing a vanillin skeleton were designed and synthesized. Bioactivity tests on virus and bacteria were performed. The results indicated that some compounds exhibited excellent antitobacco mosaic virus (TMV) activities, such as compound 34 exhibited an inactivation activity of 90.1percent and curative activity of 51.8percent and compound 28 exhibited a curative activity of 54.8percent at 500 μg mL-1, which is equivalent to that of the commercial ningnanmycin (inactivation of 91.9percent and curative of 51.9percent). Moreover, the in vitro antibacterial activity test illustrated that compounds 2, 22, and 33 showed much higher activities than commercial thiodiazole copper, which could be used as lead compounds or potential candidates. The findings of transmission electron microscopy and molecular docking indicated that the synthesized compounds exhibited strong and significant binding affinity to the TMV coat protein and could obstruct the self-assembly and increment of TMV particles. This study revealed that α-ketoamide derivatives bearing a vanillin skeleton could be used as a novel potential pesticide for controlling the plant diseases.
3-O-Substituted benzyl pyridazinone derivatives as COX inhibitors
Chintakunta, Vamsee Krishna,Akella, Venkateswarlu,Vedula, Manohar Sharma,Mamnoor, Prem Kumar,Mishra, Parimal,Casturi, Seshagiri Rao,Vangoori, Akhila,Rajagopalan, Ramanujam
, p. 339 - 347 (2007/10/03)
New 3-O-substituted benzyl pyridazinone compounds have been synthesised and evaluated for their cyclooxygenase inhibitory activity and COX-2 selectivity. Among the compounds synthesised, three compounds (11b-11d) have shown in vitro COX-2 selectivity. These compounds have been evaluated for their in vivo potential using carrageenan-induced rat paw edema assay. One compound (11b) showed 32% anti-inflammatory activity at 30 mg kg-1 dose.
