191476-09-2Relevant articles and documents
Novel pyrrolo[2,1-c][1,4]benzodiazepine-3,11-dione (PBD) derivatives as selective HDAC6 inhibitors to suppress tumor metastasis and invasion in vitro and in vivo
Li, Dongzhu,Li, Yanchun,Ma, Chao,Ma, Enlong,Quan, Jishun,Song, Haoxuan,Wang, Yanjuan
, (2021/07/09)
Selective inhibition of histone deacetylase 6 (HDAC6) has been emerged as a promising approach to cancer treatment. As a pivotal strategy for drug discovery, molecular hybridization was introduced in this study and a series of pyrrolo[2,1-c][1,4] benzodia
Pyrrolo[2,1-c][1,4] benzodiazepine-3,11-diones protect SHSY-5Y cells from Cd-induced apoptosis involving suppression of endoplasmic reticulum stress
Ma, Chao,Du, Ke,Zhao, Ying,Zhang, Linkui,Hu, Baichun,Cheng, Maosheng
, p. 5151 - 5158 (2018/09/27)
Cadmium (Cd) is a potent toxic heavy metal, some studies showed that Cd-induced apoptosis is through ER stress pathway. Compounds of pyrrolo[2,1–c][1,4]benzodiazepine (PBD)-3,11-diones were discovered as potent neuroprotective agents against Cd-induced toxicity in SH-SY5Y cells for the first time. In this study, twenty-six PBD-3,11-dione derivatives were synthesized and evaluated for their neuroprotective activity against Cd-induced toxicity by CCK-8 assay. Their preliminary SARs studies indicated that various substituents were tolerated on the benzene ring, and alkyl heterocycles groups at the N10-position of the PBD-3,11-dione scaffold were important for the activities. Among them, compound 13c exhibited the best activity (cell viability = 68.6%, 25 μM). Furthermore, we found that the compound 13c could inhibit cadmium-induced cell apoptosis with the downregulation of the ER stress markers GRP78, CHOP, cleaved-caspase12 and cleaved-caspase3 through western blotting. The results of in silico evaluation of ADME/T properties showed that 13c exhibited medium BBB penetration level and promising toxicity profiles. These results proved the potential of 13c as a promising lead compound against Cd-induced neurotoxicity.
Design, synthesis and bioevaluation of 1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxylic acid derivatives as potent neuroprotective agents
Zhang, Linkui,Zhao, Ying,Wang, Jian,Yang, Donglin,Zhao, Chenwen,Wang, Changli,Ma, Chao,Cheng, Maosheng
, p. 27 - 38 (2018/04/02)
Diverse of 1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxylic acid derivatives were designed, synthesized and evaluated for their neuroprotective activity against NMDA-induced cytotoxicity in vitro, and 5q exhibited excellent neuroprotective activity. The compound 5q was selected for further investigation. We found that 5q could attenuate Ca2+ influx induced by NMDA, meanwhile, 5q could suppress the NR2B up-regulation and increase p-ERK1/2 expression. The molecular docking results showed that 5q might fit well in the binding pocket of 4 and interact with some key residues in the binding pocket of 1 simultaneously. Besides, 5q exhibited acceptable metabolic stability. These results suggested that 5q was a promising lead for further development of new potent and orally bioavailable NR2B-selective NMDAR antagonists.
Pyrrolo[2,1-b]quinazoline derivatives and preparation method and application thereof
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Paragraph 0072; 0073, (2018/07/30)
The invention relates to substituted pyrrolo[2,1-b]quinazoline derivatives as shown in the general formula I and pharmaceutically acceptable salts, optically active bodies or isomers of the pyrrolo[2,1-b]quinazoline derivatives, as well as a preparation method of the compounds, and application of the compounds as neuroprotective agents in the aspect of preparing anti-cerebral ischemic medicines. The invention further relates to the compounds and pharmaceutically acceptable salts of the compounds and pharmaceutical compositions taking the compounds as active components. The invention further relates to dosage forms of the compounds containing at least one compound with the structural formula or salt of the compound, the dosage forms of the compound comprise tablets, coated tablets, capsules, solutions for injection or ampoules, suppositories, patches, inhalable powder preparations, mixed preparations, emulsions and ointments. The definitions of R1, R2, R3, R4, R5, R6, R7, R8, X and Y inthe general formula I related in the invention are defined in the claims and the descriptions.
Synthesis and biological evaluation of (-)-Linarinic acid derivatives as neuroprotective agents against OGD-induced cell damage
Tian, Yu,Ma, Chao,Feng, Linyin,Zhang, Lei,Hao, Feiyue,Pan, Li,Cheng, Maosheng
experimental part, p. 423 - 430 (2012/08/29)
A series of novel (-)-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1- carboxylic acid derivatives were designed and synthesized. All of the prepared compounds were screened for their neuroprotective effects using an in vitro oxygen glucose deprivation (OGD
Assignment of the absolute configuration of (-)-linarinic acid by theoretical calculation and asymmetric total synthesis
Cheng, Maosheng,Li, Qiang,Lin, Bin,Sha, Yu,Ren, Jinhong,He, Yan,Wang, Qinghe,Hua, Huiming,Ruud, Kenneth
, p. 179 - 183 (2007/10/03)
The specific rotation of (-)-linarinic acid calculated using Hartree-Fock and density functional theory on 14 representative conformers of this molecule were all negative. The most stable conformer was found to be almost identical to the crystallographic
