112378-38-8Relevant academic research and scientific papers
Ruthenium-catalyzed intramolecular cyclization of diazo-β-ketoanilides for the synthesis of 3-alkylideneoxindoles
Chan, Wai-Wing,Kwong, Tsz-Lung,Yu, Wing-Yiu
, p. 3749 - 3755 (2012)
With [Ru(p-cymene)Cl2]2 as catalyst, diazo-β-ketoanilides would undergo intramolecular carbenoid arene C-H bond functionalization to afford 3-alkylideneoxindoles in up to 92% yields. The reaction occurs under mild conditions and exhibits excellent chemoselectivity. The lack of primary KIE (kH/kD ～ 1) suggests that the reaction should not proceed by rate-limiting C-H bond cleavage; a mechanism involving cyclopropanation of the arene is proposed.
Discovery of 7-alkyloxy- [1,2,4] triazolo[1,5-a] pyrimidine derivatives as selective positive modulators of GABAA1 and GABAA4 receptors with potent antiepileptic activity
Wu, Jun,Hou, Zhipeng,Wang, Yan,Chen, Liping,Lian, Chengxi,Meng, Qingfei,Zhang, Chaoying,Li, Xiufen,Huang, Longjiang,Yu, Haibo
, (2021/12/20)
A series of 7-alkoxy - [1,2,4] triazolo [1, 5-a] pyrimidine derivatives were designed and synthesized. Maximal electroshock (MES) and pentylenetetrazole (PTZ) tests were utilized to access their anticonvulsant activity. Most of the series of compounds exhibited significant anti-seizure effects. Further studies demonstrated that the anticonvulsant activity of these compounds mainly depended on their allosteric potentiation of GABAA receptors. Among them, compound 10c was picked for the mechanism study due to its potent activity. The compound is more sensitive to subunit configurations of synaptic α1β2γ2 and extrasynaptic α4β3δ GABAA receptors, but there were no effects on NMDA receptors and Nav1.2 sodium channels. Meanwhile, 10c acted on the sites of GABAA receptors distinct from commonly used anticonvulsants benzodiazepines and barbiturates. Furthermore, studies from native neurons demonstrated that compound 10c also potentiated the activity of native GABAA receptors and reduced action potential firings in cultured cortical neurons. Such structural compounds may lay a foundation for further designing novel antiepileptic molecules.
Discovery of [1,2,4]-triazolo [1,5-a]pyrimidine-7(4H)-one derivatives as positive modulators of GABAA1 receptor with potent anticonvulsant activity and low toxicity
Huang, Longjiang,Ding, Jing,Li, Min,Hou, Zhipeng,Geng, Yanru,Li, Xiufen,Yu, Haibo
, (2019/11/26)
In searching for more effective and safer antiepileptic drugs, a series of 2,5-disubstituted [1,2,4]-triazolo[1,5-a]pyrimidine-7(4H)-one derivatives were designed and synthesized. Spontaneous Ca2+ oscillations (SCOs) of cortical neurons were used for in vitro phenotypic screening. Maximal electroshock test (MES) and pentylenetetrazole (PTZ) test were used to access their anticonvulsant activity, and rotarod test was used to estimate their neurotoxicity. The active compounds in in vitro model are specifically effective in pentylenetetrazole (PTZ)-induced epilepsy model but not maximal electroshock (MES) model, more importantly with lower neurotoxicity as compared to commonly used drugs. Among them, compound 5c and 5e showed significant anticonvulsant activities in PTZ-induced epilepsy model with ED50 values at 31.81 mg/kg and 40.95 mg/kg, respectively. These compounds have improved neurotoxicity with protective index (PI = TD50/ED50) values at 17.22 and 9.09, respectively. Finally we demonstrated that compound 5c and 5e mainly acted on GABAA receptor as positive modulators but not sodium channels. Thus the present study has provided potential candidates for further investigation in epilepsy.
Assembly of 3-acyloxindoles via Cul/L-proline-catalyzed intramolecular arylation of β-keto amides
Lu, Biao,Ma, Dawei
, p. 6115 - 6118 (2007/10/03)
(Chemical Equation Presented) Intramolecular coupling of β-keto 2-iodoanilides catalyzed by Cul/L-proline in DMSO occurs at room temperature, affording substituted 3-acyloxindoles in good yield. Electronic effects on the aromatic ring have little influenc
1,3-Oxazines and Related Compounds. XIII. Reaction of Acyl Meldrum's Acids with Schiff Bases Giving 2,3-Disubstituted 5-Acyl-3,4,5,6-tetrahydro-2H-1,3-oxazine-4,6-diones and 2,3,6-Trisubstituted 2,3-Dihydro-1,3-oxazin-4-ones
Yamamoto, Yutaka,Watanabe, Yukiyoshi,,Ohnishi, Shuhei
, p. 1860 - 1870 (2007/10/02)
The reaction of Schiff bases (2) with various acyl Meldrum's acids (1) were investigated.Refluxing of 1 and 2 in benzene caused an exchange reaction of the acetone moiety of 1 with the Schiff base moiety through the intermediate acylketenes 11 formed in s
