54739-26-3Relevant articles and documents
Design, synthesis and biological evaluation of 1-Aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as novel microtubule destabilizers
Wang, Chao,Li, Yuelin,Liu, Zi,Wang, Zeyu,Liu, Zihan,Man, Shuai,Zhang, Yujing,Bao, Kai,Wu, Yingliang,Guan, Qi,Zuo, Daiying,Zhang, Weige
, p. 549 - 560 (2021/02/05)
A series of 1-aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as microtubule destabilizers were designed, synthesised and evaluated for anticancer activity. Based on bioisosterism, we introduced the tetrazole moiety containing the hydrogen-bond acceptors as B-ring of XRP44X analogues. The key intermediates ethyl 1-aryl-1H-tetrazole-5-carboxylates 10 can be simply and efficiently prepared via a microwave-assisted continuous operation process. Among the compounds synthesised, compound 6–31 showed noteworthy potency against SGC-7901, A549 and HeLa cell lines. In mechanism studies, compound 6–31 inhibited tubulin polymerisation and disorganised microtubule in SGC-7901 cells by binding to tubulin. Moreover, compound 6–31 arrested SGC-7901cells in G2/M phase. This study provided a new perspective for development of antitumor agents that target tubulin.
Chemical hybridizing agents for chickpea (Cicer arietinum L.): Leads from QSAR analysis of ethyl oxanilates and pyridones
Chakraborty, Kajal,Devakumar
, p. 1868 - 1873 (2007/10/03)
In the self-pollinated crops such as chickpea, induction of male sterility by deployment of chemical hybridizing agents (CHAs) facilitating "two-line" approach holds immense potential in heterosis breeding. A total of 40 test CHAs comprising 20 ethyl oxanilates and 20 pyridones were screened as potential CHAs on chickpea (variety BG 1088) at 500, 800, and 1000 ppm. Three test compounds mostly having either F (4)/Br (5)/CF3 (19) at the para position of the aryl ring from a pool of 20 ethyl oxanilates were identified as the most potent CHAs causing >99% induction of pollen sterility and >90% total flower sterility at 1000-ppm test concentration. Among pyridone derivatives, N-(4-chlorophenyl)-5-carbethoxy-4,6-dimethyl, 1,2-dihydropyrid-2-one (26) was found to be the most active. Quantitative structure activity relationship (QSAR) analysis has revealed a direct involvement of Swain-Lupton field constant, Fp, with the target bioactivity which implied that field rather than resonance effect (R) had a positive effect on the activity. The real guiding principle for selectivity was found out to be the hydrophobic parameter π value. The QSAR models indicated that increased steric bulk at the 4-position on the phenyl ring is associated with enhanced activity. The CHAs appeared to act by mimicking UDP-glucose, the key substrate in the synthesis of callose, or lead to an imbalance in acid-base equilibrium in pollen mother cells resulting in dissolution of callose wall by premature callase secretion.
Novel AMPA receptor antagonists: Synthesis and structure-activity relationships of 1-hydroxy-7-(1H-imidazol-1-yl)-6-nitro-2,3(1H,4H)- quinoxalinedione and related compounds
Ohmori,Shimizu-Sasamata,Okada,Sakamoto
, p. 3971 - 3979 (2007/10/03)
As part of our study of novel antagonists at the α-amino-3-hydroxy-5- methylisoxazole-4-propionate (AMPA) subtype of excitatory amino acid (EAA) receptors and the pharmacophoric requirements of the receptor, we designed and synthesized a series of 1-substituted 6-imidazolyl-7-nitro-, and 7- imidazolyl-6-nitroquinoxalinediones, as well as related compounds, 6a-j, 7, 11a-e, 15, and 17, which are 1- and 4-substituted analogues of 1 (YM90K), and evaluated their activity to inhibit [3H]AMPA binding from rat whole brain. On the basis of their structure-activity relationships (SAR), we deduced that the amide proton of the imidazolyl-near side of the quinoxalinedione nucleus is not essential for AMPA receptor binding, whereas that of the imidazolyl- far amide is. Further, the receptors possess size-limited bulk tolerance for their N-substituents on the imidazolyl-near amide portion. Moreover, we found that introduction of a hydroxyl group at the imidazolyl-near amide portion causes a severalfold improvement in AMPA receptor affinity over unsubstituted derivatives. Among the compounds, 1-hydroxy-7-(1H-imidazol-1-yl)-6-nitro- 2,3(1H,4H)-quinoxalinedione (11a) showed high affinity for AMPA receptor with a K(i) value of 0.021 μM, which is severalfold greater than that of 1 and NBQX (2) (1, K(i) = 0.084 μM; 2, K(i) = 0.060 μM). Compound 11a also showed over 100-fold selectivity for the AMPA receptor than for the N-methy]-D- aspartate (NMDA) receptor and the glycine site on NMDA receptor.
