151239-47-3Relevant articles and documents
Synthesis and biological evaluation of N-cyclopropylbenzamide-benzophenone hybrids as novel and selective p38 mitogen activated protein kinase (MAPK) inhibitors
Heo, Jinyuk,Shin, Hanbo,Lee, Jun,Kim, Taelim,Inn, Kyung-Soo,Kim, Nam-Jung
, p. 3694 - 3698 (2015)
A series of hybrid molecules consisting of benzophenones and N-cyclopropyl-3-methylbenzamides were synthesized and biologically evaluated as novel p38 mitogen activated protein kinase (MAPK) inhibitors. In particular, we found that compound 10g displayed
Identification and optimization of biphenyl derivatives as novel tubulin inhibitors targeting colchicine-binding site overcoming multidrug resistance
Cheng, Bao,Zhu, Guirong,Meng, Linghua,Wu, Guolin,Chen, Qin,Ma, Shengming
supporting information, (2021/11/22)
Microtubule targeting agents (MTAs) are among the most successful chemotherapeutic drugs, but their efficacy is often limited by the development of multidrug resistance (MDR). Therefore, the development of novel MTAs with the ability to overcome MDR is urgently needed. In this contribution, through modification of the unsymmetric biaryl compounds, we discovered a novel compound dxy-1-175 with potent anti-proliferative activity against cancer cells. Mechanistic study revealed that dxy-1-175 inhibited tubulin polymerization by interacting with the colchicine-binding site of tubulin, which caused cell cycle arrest at G2/M phase. Based on the predicted binding model of dxy-1-175 with tubulin, a series of new 4-benzoylbiphenyl analogues were designed and synthesized. Among them, the hydrochloride compound 12e with improved solubility and good stability in human liver microsome, exhibited the most potent anti-proliferative activity with IC50 value in the low nanomolar range, and markedly inhibited the growth of breast cancer 4T1 xenograft in vivo. Notably, 12e effectively overcame P-gp-mediated MDR and our preliminary data suggested that 12e may not be a substrate of P-glycoprotein (P-gp). Taken together, our study reveals a novel MTA 12e targeting the colchicine-binding site with potent anticancer activity and the ability to circumvent MDR.
AIBN initiated functionalization of the benzylic sp3 C[sbnd]H and C[sbnd]C bonds in the presence of dioxygen
Hu, Yingying,Shao, Yu,Zhang, Shuwei,Yuan, Yuan,Sun, Zheng,Yuan, Yu,Jia, Xiaodong
supporting information, (2021/02/01)
A sp3 C[sbnd]H bond functionalization and C[sbnd]C bond cleavage were realized by AIBN/O2 catalyst system, providing a series of benzophenones under mild reaction conditions. The mechanistic study shows that a peroxide intermediate is involved in this transformation, and in the case of diphenylmethanes, the sp3 C[sbnd]C bond is cleaved through the peroxide rearrangement, which might provides a new way to cleave relatively strong C[sbnd]C bond and be applied to more general C[sbnd]C bond activation.
Discovery of a new class of bicyclic substituted hydroxyphenylmethanones as 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2) inhibitors for the treatment of osteoporosis
Wetzel, Marie,Gargano, Emanuele M.,Hinsberger, Stefan,Marchais-Oberwinkler, Sandrine,Hartmann, Rolf W.
, p. 1 - 17 (2012/03/08)
E2 deficiency in elderly people has directly an effect on the skeleton and can lead to osteoporosis. As 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2) catalyses the conversion between active 17β-hydroxysteroid estradiol (E2) and testosterone (T) into their less active 17-ketosteroid and has been found in bones, 17β-HSD2 inhibitor may provide a new approach in the onset of osteoporosis. Bicyclic substituted hydroxyphenylmethanone derivatives were synthesised as steroidomimetics of the substrate E2 and were evaluated for their 17β-HSD2 inhibition and their selectivity toward 17β-HSD1, catalysing the reverse reaction the conversion of estrone (E1) into E2. Highly selective compounds (11, 12, 14, 21 and 22) have been identified, the most promising one (12) showing an IC50 value in the low nanomolar range (101 nM) and a selectivity factor of 13 toward 17β-HSD1. These results make compound 12 an interesting candidate for further biological evaluation.
Addition of Grignard reagents to aryl acid chlorides: An efficient synthesis of aryl ketones
Wang, Xiao-Jun,Zhang, Li,Sun, Xiufeng,Xu, Yibo,Krishnamurthy, Dhileepkumar,Senanayake, Chris H.
, p. 5593 - 5595 (2007/10/03)
(Chemical Equation Presented) Direct addition of Grignard reagents to acid chlorides in the presence of bis[2-(N,N-dimethylamino)ethyl] ether proceeds selectively to provide aryl ketones in high yields. A possible tridentate interaction between Grignard reagents and bis[2-(N,N-dimethylamino)ethyl] ether moderates the reactivity of Grignard reagents, preventing the newly formed ketones from nucleophilic addition by Grignard reagents.
3,3-biarylpiperidine and 2,2-biarylmorpholine derivatives
-
, (2008/06/13)
The present invention relates to compounds of the formula I, wherein Z1, Z2, X, Q, R1, R2and R3are defined as in the specification, pharmaceutical compositions containing such compounds the use of suc