42252-34-6Relevant articles and documents
Dual inhibitors of Interleukin-6 and acetylcholinesterase for treatment of Alzheimer's disease: Design, docking, synthesis and biological evaluation
Bansal, Yogita,Kaur, Sukhvir
, (2021/11/13)
Multitarget compounds intercept two or more functionally complementary pathways simultaneously, and are therefore considered to have potential in effectively treating complex multifactorial diseases like Alzheimer's disease (AD). In the present study, novel molecules are designed by coupling a chromone and a N,N-disubstituted carbamoyl amine as pharmacophore for interleukin-6 (IL-6) and acetylcholinesterase (AChE) inhibition, respectively. Four series (Y1–Y4) of 40 compounds are designed by using alkyl linkers of different lengths (1–4 carbon atoms) for the coupling of the two selected pharmacophore. Docking of all designed compounds in AChE leads to the identification of twelve best fit compounds (Docking score >8.3). The data suggests that a 1- or 2-carbon atom linker is the most conducive to orient the pharmacophore for optimum binding with AChE active site. The predicted ADME properties of the 12 selected compounds suggest that these can cross the blood brain barrier (BBB) with good oral bioavailability. These compounds are synthesised and evaluated for anti-AChE activity. Five compounds, showing >45% inhibition of AChE, are further evaluated for IL-6 inhibitory activity. Compound Y1f is found to be the most potent inhibitor of both AChE and IL-6 (IC50 0.7 and 0.8 ?μM, respectively). It suggests that a chromone moiety connected to a piperidine ring through a 1-carbon atom linker may provide a useful template to medical chemists for the development of new chemical entities effective against AD.
Cannabidiol carbamate compound, pharmaceutical preparation, preparation method and application
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Paragraph 0038-0042, (2021/01/30)
The invention relates to a cannabidiol carbamate compound, a medicinal preparation, a preparation method and application, and belongs to the field of compounds for treating and preventing diseases related to aging, Alzheimer's disease and Parkinson's disease. The compound has a structure shown as a formula I or a pharmaceutically acceptable salt of the structure shown as the formula I. The compound has good butyrylcholine esterase resisting activity, shows good application prospect in treatment of Alzheimer's disease, and shows good application potential.
Synthesis and Biological Evaluation of Celastrol Derivatives with Improved Cytotoxic Selectivity and Antitumor Activities
Feng, Jia-Hao,He, Qi-Wei,Hou, Ji-Qin,Hu, Xiao-Long,Long, Huan,Wang, Bao-Lin,Wang, Hao,Wang, Quan,Wang, Rong,Ye, Wen-Cai,Zhang, Li-Xin,Zhang, Xiao-Qi
, p. 1954 - 1966 (2021/07/20)
Cdc37 associates kinase clients to Hsp90 and promotes the development of cancers. Celastrol, a natural friedelane triterpenoid, can disrupt the Hsp90-Cdc37 interaction to provide antitumor effects. In this study, 31 new celastrol derivatives, 2a - 2d , 3a - 3g , and 4a - 4t , were designed and synthesized, and their Hsp90-Cdc37 disruption activities and antiproliferative activities against cancer cells were evaluated. Among these compounds, 4f , with the highest tumor cell selectivity (15.4-fold), potent Hsp90-Cdc37 disruption activity (IC50= 1.9 μM), and antiproliferative activity against MDA-MB-231 cells (IC50= 0.2 μM), was selected as the lead compound. Further studies demonstrated 4f has strong antitumor activities both in vitro and in vivo through disrupting the Hsp90-Cdc37 interaction and inhibiting angiogenesis. In addition, 4f exhibited less toxicity than celastrol and showed a good pharmacokinetics profile in vivo. These findings suggest that 4f may be a promising candidate for development of new cancer therapies.
Novel cannabidiol?carbamate hybrids as selective BuChE inhibitors: Docking-based fragment reassembly for the development of potential therapeutic agents against Alzheimer's disease
Jiang, Xia,Liu, Xin-Hua,Shi, Jingbo,Tang, Wenjian,Wang, Sheng,Wu, Chengyao,Xu, Yingying,Zha, Liang,Zhang, Jing,Zhang, Ziwen,Zuo, Jiawei
, (2021/08/10)
Cannabidiol (CBD) and rivastigmine have been launched as drugs for treating dementia and cholinesterases (ChEs) are ideal drug targets. This study focused on developing novel ChE inhibitors as drug leads against dementia through molecular modeling and fragment reassembly approaches. A potent carbamate fragment binding to active site gorge of BuChE was found via a docking-based structural splicing approach, thus, 17 novel compounds were designed by structural reassembly. Compound C16 was identified as a highly selective potent BuChE inhibitor (IC50 = 5.3 nM, SI > 4000), superior to CBD (IC50 = 0.67 μM). C16 possessed BBB penetrating ability, benign safety, neuroprotection, antioxidant and pseudo-irreversible BuChE inhibition (Kd = 13 nM, k2 = 0.26 min?1), showing good drug-like properties. In vivo studies confirmed that C16 significantly ameliorated the scopolamine-induced cognition impairment, almost entirely recovered the Aβ1?42 (icv)-impaired cognitive function to the normal level, showed better behavioral performance than donepezil and good anti-amyloidogenic effect. Hence, the potential BuChE inhibitor C16 can be developed as a promising disease-modifying treatment of AD.
Design, synthesis and biological evaluation of 4'-aminochalcone-rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer's disease
Xiao, Ganyuan,Li, Yan,Qiang, Xiaoming,Xu, Rui,Zheng, Yunxiaozhu,Cao, Zhongcheng,Luo, Li,Yang, Xia,Sang, Zhipei,Su, Fu,Deng, Yong
, p. 1030 - 1041 (2017/02/05)
A series of 4'-aminochalcone-revastigmine hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. The results showed that most of these compounds exhibited good multifunctional activities. In particular, compound 6c displayed the best inhibitory potency on acetylcholinesterase (IC50= 4.91 μM), and significant antioxidative activity with a value 2.83-fold of Trolox. The kinetic analysis of AChE inhibition revealed that 6c showed mixed-type inhibition, binding simultaneously to the catalytic active site and peripheral anionic site of AChE. In addition, 6c inhibited self-induced Aβ1-42aggregation and Cu2+-induced Aβ1-42aggregation by 89.5% and 79.7% at 25 μM respectively, as well as acted as a selective monoamine oxidase B inhibitor (IC50= 0.29 μM) and a selective biometal chelator. Furthermore, 6c could cross the blood-brain barrier in vitro. Based on these results, Compound 6c could be considered as a very promising lead compound for Alzheimer's disease.
Synthesis of pterostilbene and resveratrol carbamate derivatives as potential dual cholinesterase inhibitors and neuroprotective agents
Yuan, Wen,Shang, Zhipei,Qiang, Xiaoming,Tan, Zhenghuai,Deng, Yong
, p. 787 - 800 (2014/02/14)
Pterostilbene and resveratrol carbamate derivatives were designed and synthesized by use of a multi-target directed drug-design strategy. Their acetylcholinesterase and butylcholinesterase inhibitory activity and neuroprotective effects against hydrogen peroxide-induced PC12 cell injury were evaluated in vitro. The results indicated that some of the compounds had dual inhibitory potency against acetylcholinesterase and butylcholinesterase, and potential neuroprotective effects, and could be considered as potential multi-target-directed agents.
INDOLE, INDOLINE DERIVATIVES, COMPOSITIONS COMPRISING THEM AND USES THEREOF
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Page/Page column 24; 25; 28; 29, (2013/10/22)
The invention provides indole and indoline derivatives and slats thereof, compositions comprising them and uses thereof for the treatment of diseases and disorders.
Development of an improved method for conversion of thiuram disulfides into N,N-dialkylcarbamoyl halides and derivatives
Adeppa,Rupainwar,Misra, Krishna
experimental part, p. 285 - 290 (2011/03/20)
A convenient procedure for preparing N,N-disubstituted carbamoyl halides is reported. It consists of two steps: (1) reaction of carbon disulfide and a secondary amine in the presence of a polar organic solvent and oxygen to produce the corresponding tetraalkyl thiuram disulfides and (2) reaction of tetraalkyl thiuram disulfide with a halide in the presence of an aprotic organic solvent to produce the corresponding N,N-disubstituted carbamoyl halide. Copyright Taylor & Francis Group, LLC.
An improved one-pot cost-effective synthesis of N,N-disubstituted carbamoyl halides and derivatives
Adeppa,Rupainwar,Misra, Krishna
experimental part, p. 1277 - 1280 (2011/02/23)
A convenient one-pot procedure is reported for preparing N,N-disubstituted carbamoyl chlorides by using chlorocarbonylsulfenyl chloride as a carbonylating agent. It comprises the reaction of secondary amines with chlorocarbonylsulfenyl chloride in the presence of an aprotic organic solvent to produce the corresponding N,N-disubstituted carbamoyl halides. Insertion of the carbonyl group without using phosgene is the novelty of this method.
Chemoenzymatic synthesis of rivastigmine via dynamic kinetic resolution as a key step
Han, Kiwon,Kim, Cheolwoo,Park, Jaiwook,Kim, Mahn-Joo
body text, p. 3105 - 3108 (2010/08/06)
A practical and efficient procedure for the synthesis of rivastigmine was developed. This procedure includes dynamic kinetic resolution using a polymer-bound ruthenium complex and a lipase in combination as a key step. Enantiopure (-)-rivastigmine was obtained from commercially available 3′-hydroxyacetophenone via five steps in overall 57% yield.
