170570-83-9Relevant academic research and scientific papers
Design, synthesis and evaluation of novel diaryl-1,5-diazoles derivatives bearing morpholine as potent dual COX-2/5-LOX inhibitors and antitumor agents
Li, Zhang,Wang, Zhong-Chang,Li, Xin,Abbas, Muhammad,Wu, Song-Yu,Ren, Shen-Zhen,Liu, Qi-Xing,Liu, Yi,Chen, Peng-Wen,Duan, Yong-Tao,Lv, Peng-Cheng,Zhu, Hai-Liang
, p. 168 - 184 (2019/03/17)
In this paper, 41 hybrid compounds containing diaryl-1,5-diazole and morpholine structures acting as dual COX-2/5-LOX inhibitors have been designed, synthesized and biologically evaluated. Most of them showed potent antiproliferative activities and COX-2/5-LOX inhibitory in vitro. Among them, compound A33 displayed the most potency against cancer cell lines (IC50 = 6.43–10.97 μM for F10, HeLa, A549 and MCF-7 cells), lower toxicity to non-cancer cells than celecoxib (A33: IC50 = 194.01 μM vs. celecoxib: IC50 = 97.87 μM for 293T cells), and excellent inhibitory activities on COX-2 (IC50 = 0.17 μM) and 5-LOX (IC50 = 0.68 μM). Meanwhile, the molecular modeling study was performed to position compound A33 into COX-2 and 5-LOX active sites to determine the probable binding models. Mechanistic studies demonstrated that compound A33 could block cell cycle in G2 phase and subsequently induced apoptosis of F10 cells. Furthermore, compound A33 could significantly inhibit tumor growth in F10-xenograft mouse model, and pharmacokinetic study of compound A33 indicated that it showed better stability in vivo. In general, compound A33 could be a promising candidate for cancer therapy.
Synthesis of novel hybrids of pyrazole and coumarin as dual inhibitors of COX-2 and 5-LOX
Shen, Fa-Qian,Wang, Zhong-Chang,Wu, Song-Yu,Ren, Shen-Zhen,Man, Ruo-Jun,Wang, Bao-Zhong,Zhu, Hai-Liang
supporting information, p. 3653 - 3660 (2017/07/27)
In our previous study, we designed a series of pyrazole derivatives as novel COX-2 inhibitors. In order to obtain novel dual inhibitors of COX-2 and 5-LOX, herein we designed and synthesized 20 compounds by hybridizing pyrazole with substituted coumarin w
Design, synthesis and evaluation of benzenesulfonamide-substituted 1,5-diarylpyrazoles containing phenylacetohydrazide derivatives as COX-1/COX-2 agents against solid tumors
Lu, Xiao-Yuan,Wang, Zhong-Chang,Wei, Ting,Yan, Xiao-Qiang,Wang, Peng-Fei,Zhu, Hai-Liang
, p. 22917 - 22935 (2016/03/15)
Novel benzenesulfonamide-substituted 1,5-diarylpyrazoles containing phenylacetohydrazide derivatives have been designed, synthesized and evaluated for their biological activities as selective COX-2 inhibitors with anticancer potential. In vitro the bioass
Coumarin sulfonamides derivatives as potent and selective COX-2 inhibitors with efficacy in suppressing cancer proliferation and metastasis
Lu, Xiao-Yuan,Wang, Zhong-Chang,Ren, Shen-Zhen,Shen, Fa-Qian,Man, Ruo-Jun,Zhu, Hai-Liang
supporting information, p. 3491 - 3498 (2016/07/21)
Cyclooxygenase-2 is frequently overexpression in malignant tumors and the product PGE2promotes cancer cell progression and metastasis. We designed novel series of coumarin sulfonamides derivatives to improve biological activities of COX-2 inhib
Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: Identification of 4-[5-(4-methylphenyl)- 3(trifluoromethyl)-1h-pyrazol-1-yl]benzenesulfonamide (sc-58635, celecoxib)
Penning, Thomas D.,Talley, John J.,Bertenshaw, Stephen R.,Carter, Jeffery S.,Collins, Paul W.,Docter, Stephen,Graneto, Matthew J.,Lee, Len F.,Malecha, James W.,Miyashiro, Julie M.,Rogers, Roland S.,Rogier,Yu, Stella S.,Anderson, Gary D.,Burton, Earl G.,Cogburn, J. Nita,Gregory, Susan A.,Koboldt, Carol M.,Perkins, William E.,Seibert, Karen,Veenhuizen, Amy W.,Zhang, Yan Y.,Isakson, Peter C.
, p. 1347 - 1365 (2007/10/03)
A series of sulfonamide-containing 1,5-diarylpyrazole derivatives were prepared and evaluated for their ability to block cyclooxygenase-2 (COX-2) in vitro and in vivo. Extensive structure-activity relationship (SAR) work was carried out within this series, and a number of potent and selective inhibitors of COX-2 were identified. Since an early structural lead (1f, SC- 236) exhibited an unacceptably long plasma half-life, a number of pyrazole analogs containing potential metabolic sites were evaluated further in vivo in an effort to identify compounds with acceptable pharmacokinetic profiles. This work led to the identification of 1i (4-[5-(4-methylphenyl)-3- (trifluoromethyl)-1H-pyrazol-1-y1]benzenesulfonamide, SC-58635, celecoxib), which is currently in phase III clinical trials for the treatment of rheumatoid arthritis and osteoarthritis.
