4442-53-9Relevant articles and documents
Synthesis of 2,3-dihydrobenzo[b][1,4]dioxine-5-carboxamide and 3-oxo-3,4-dihydrobenzo[b][1,4]oxazine-8-carboxamide derivatives as PARP1 inhibitors
Shao, Xuwei,Pak, Steven,Velagapudi, Uday Kiran,Gobbooru, Shruthi,Kommaraju, Sai Shilpa,Low, Woon-Kai,Subramaniam, Gopal,Pathak, Sanjai Kumar,Talele, Tanaji T.
, (2020/08/10)
Poly(ADP-ribose) polymerase 1 (PARP1), a widely explored anticancer drug target, plays an important role in single-strand DNA break repair processes. High-throughput virtual screening (HTVS) of a Maybridge small molecule library using the PARP1-benzimidazole-4-carboxamide co-crystal structure and pharmacophore model led to the identification of eleven compounds. These compounds were evaluated using recombinant PARP1 enzyme assay that resulted in the acquisition of three PARP1 inhibitors: 3 (IC50 = 12 μM), 4 (IC50 = 5.8 μM), and 10 (IC50 = 0.88 μM). Compound 4 (2,3-dihydro-1,4-benzodioxine-5-carboxamide) was selected as a lead and was subjected to further chemical modifications, involving analogue synthesis and scaffold hopping. These efforts led to the identification of (Z)-2-(4-hydroxybenzylidene)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-8-carboxamide (49, IC50 = 0.082 μM) as the most potent inhibitor of PARP1 from the series.
Discovery of 2-((2-chloro-6-fluorophenyl)amino)-N-(3-fluoro-5-(trifluoromethyl)phenyl)-1-methyl-7,8-dihydro-1H-[1,4]dioxino[2′,3′:3,4]benzo[1,2-d]imidazole-5-carboxamide as potent, selective and efficacious microsomal prostaglandin E2synthase-1
Muthukaman, Nagarajan,Deshmukh, Sanjay,Sarode, Neelam,Tondlekar, Shital,Tambe, Macchindra,Pisal, Dnyandeo,Shaikh, Mahamadhanif,Kattige, Vidya G.,Honnegowda, Srinivasa,Karande, Vikas,Kulkarni, Abhay,Jadhav, Satyawan B.,Mahat, Mahamad Yunnus A.,Gudi, Girish S.,Khairatkar-Joshi, Neelima,Gharat, Laxmikant A.
supporting information, p. 5977 - 5984 (2016/12/06)
The discovery and SAR of potent, selective dioxane-fused tricyclic benz[d]imidazole derivatives as mPGES-1 inhibitor are herein described. Various amide modifications in this series afforded many potent mPGES-1 inhibitors, of which 17d proved to be suitab
Synthesis, biological evaluation, and molecular docking studies of novel 2-styryl-5-nitroimidazole derivatives containing 1,4-benzodioxan moiety as FAK inhibitors with anticancer activity
Duan, Yong-Tao,Yao, Yong-Fang,Huang, Wei,Makawana, Jigar A.,Teraiya, Shashikant B.,Thumar, Nilesh J.,Tang, Dan-Jie,Tao, Xiang-Xiang,Wang, Zhong-Chang,Jiang, Ai-Qin,Zhu, Hai-Liang
, p. 2947 - 2954 (2014/05/20)
A series of 2-styryl-5-nitroimidazole derivatives containing 1,4-benzodioxan moiety (3a-3r) has been designed, synthesized and their biological activities were also evaluated as potential antiproliferation and focal adhesion kinase (FAK) inhibitors. Among all the compounds, 3p showed the most potent activity in vitro which inhibited the growth of A549 with IC 50 value of 3.11 μM and Hela with IC50 value of 2.54 μM respectively. Compound 3p also exhibited significant FAK inhibitory activity (IC50 = 0.45 μM). Docking simulation was performed for compound 3p into the FAK structure active site to determine the probable binding model.