- Synthesis of some novel pendant-armed cyclen derivatives
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A new easy-to-run route to some novel pendant-armed benzene-containing cyclen derivatives is proposed. In this route, the use of potassium carbonate instead of (N,N)-diisopropylethylamine as proton trapper caused a remarkable increase of yields.
- Wang, Aijian,Zhao, Wei,Sun, Xiaoqiang
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- Application of stimuli-responsive FRET behavior toward cyanide detection in a photo-switchable [2]pseudorotaxane polymer containing the BODIPY donor and the merocyanine acceptor
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We have developed a supramolecular (close form) [2]pseudorotaxane polymer containing the green-emissive (λem= 523 nm) BODIPY-based pillar[5]arene host and the non-emissive spiropyran (SP)-based cyano guest (close form), which can be converted t
- Gouda, Chinmayananda,Barik, Debashis,Maitra, Chandrima,Liang, Kai-Chieh,Ho, Feng-Cheng,Srinivasadesikan, Venkatesan,Chandran, Sarala,Wu, Shu-Pao,Lin, Ming-Chang,Lin, Hong-Cheu
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supporting information
p. 2321 - 2333
(2021/03/06)
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- Synthesis of Novel Aryloxyethylamine Derivatives and Evaluation of Their in Vitro and in Vivo Neuroprotective Activities
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A series of aryloxyethylamine derivatives were designed, synthesized and evaluated for their biological activity. Their structures were confirmed by 1H-NMR, 13C-NMR, FT-IR and HR-ESI-MS. The preliminary screening of neuroprotection of compounds in vitro was detected by MTT, and the anti-ischemic activity in vivo was tested using bilateral common carotid artery occlusion in mice. Most of these compounds showed potential neuroprotective effects against the glutamate-induced cell death in differentiated rat pheochromocytoma cells (PC12 cells), especially for (4-fluorophenyl){1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}methanone, {1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}(4-methoxyphenyl)methanone, (4-bromophenyl){1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}methanone, {1-[2-(4-chlorophenoxy)ethyl]piperidin-4-yl}(4-chlorophenyl)methanone, (4-chlorophenyl)(1-{2-[(naphthalen-2-yl)oxy]ethyl}piperidin-4-yl)methanone, (4-chlorophenyl){1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}methanone and {1-[2-(4-bromophenoxy)ethyl]piperidin-4-yl}(4-chlorophenyl)methanone, which exhibited potent protection of PC12 cells at three doses (0.1, 1.0, 10 μM). Compounds (4-fluorophenyl){1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}methanone, (4-fluorophenyl){1-[2-(naphthalen-2-yloxy)ethyl]piperidin-4-yl}methanone, {1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}(4-methoxyphenyl)methanone and {1-[2-(4-chlorophenoxy)ethyl]piperidin-4-yl}(4-chlorophenyl)methanone possessed the significant prolongation of the survival time of mice subjected to acute cerebral ischemia and decreased the mortality rate at all five doses tested (200, 100, 50, 25, 12.5 mg/kg) and had significant neuroprotective activity. In addition, (4-fluorophenyl){1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}methanone, {1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}(4-methoxyphenyl)methanone and {1-[2-(4-chlorophenoxy)ethyl]piperidin-4-yl}(4-chlorophenyl)methanone possessed outstanding neuroprotection in vitro and in vivo. These compounds can be used as a promising neuroprotective agents for future development of new anti-ischemic stroke agents. Basic structure–activity relationships are also presented.
- Gao, Yarong,Qi, Changyong,Wu, Bin,Xu, Yi,Zhong, Yan
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- 1-aryloxy ethyl piperidine-4-yl benzophenone derivative as well as preparation method and application thereof
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The invention discloses a 1-aryloxy ethyl piperidine-4-yl benzophenone derivative as well as a preparation method and application thereof. The compound is a free alkali or salt with a compound of a formula (I) shown in the specification; the salt is one of hydrochloride, hydrobromide, sulfate, trifluoroacetate, tartrate, lactate or mesylate; in the formula, R1 independently represents H, halogen,alkyl, halogen-substituted alkyl, nitryl, amino, nitrile, hydroxyl, alkoxy, aryl alkoxy, heterocyclic alkoxy, aryl, substituted heterocyclic ring or substituted aryl; and R2 is independently selectedfrom H, halogen, alkyl, halogen substituted alkyl, nitryl, amino, nitrile, hydroxyl, alkoxy, aryl alkoxy, heterocyclic alkoxy, aryl, substituted heterocyclic ring or substituted aryl. The 1-aryloxy ethyl piperidine-4-yl benzophenone derivative is applied to preparation of medicines for treating cerebral arterial thrombosis.
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Paragraph 0040-0042
(2019/11/20)
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- An integrative study to identify novel scaffolds for sphingosine kinase 1 inhibitors
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Sphingosine kinase 1 (SphK1), the enzyme that produces the bioactive sphingolipid metabolite, sphingosine-1-phosphate, is a promising new molecular target for therapeutic intervention in cancer and inflammatory diseases. In view of its importance, the main objective of this work was to find new and more potent inhibitors for this enzyme possessing different structural scaffolds than those of the known inhibitors. Our theoretical and experimental study has allowed us to identify two new structural scaffolds (three new compounds), which could be used as starting structures for the design and then the development of new inhibitors of SphK1. Our study was carried out in different steps: virtual screening, synthesis, bioassays and molecular modelling. From our results, we propose a new dihydrobenzo[b]pyrimido[5,4-f]azepine and two alkyl{3-/4-[1-hydroxy-2-(4-arylpiperazin-1-yl)ethyl]phenyl}carbamates as initial structures for the development of new inhibitors. In addition, our molecular modelling study using QTAIM calculations, allowed us to describe in detail the molecular interactions that stabilize the different Ligand-Receptor complexes. Such analyses indicate that the cationic head of the different compounds must be refined in order to obtain an increase in the binding affinity of these ligands.
- Vettorazzi, Marcela,Angelina, Emilio,Lima, Santiago,Gonec, Tomas,Otevrel, Jan,Marvanova, Pavlina,Padrtova, Tereza,Mokry, Petr,Bobal, Pavel,Acosta, Lina M.,Palma, Alirio,Cobo, Justo,Bobalova, Janette,Csollei, Jozef,Malik, Ivan,Alvarez, Sergio,Spiegel, Sarah,Jampilek, Josef,Enriz, Ricardo D.
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p. 461 - 481
(2017/08/21)
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- Pentavalent pillar[5]arene-based glycoclusters and their multivalent binding to pathogenic bacterial lectins
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Anti-adhesive glycoclusters offer potential as therapeutic alternatives to classical antibiotics in treating infections. Pillar[5]arenes functionalised with either five galactose or five fucose residues were readily prepared using CuAAC reactions and eval
- Galanos, Nicolas,Gillon, Emilie,Imberty, Anne,Matthews, Susan E.,Vidal, Sébastien
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supporting information
p. 3476 - 3481
(2016/04/09)
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- Discovery of 1-aryloxyethyl piperazine derivatives as Kv1.5 potassium channel inhibitors (part I)
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Kv1.5 potassium channel is an efficacious and safe therapeutic target for the treatment of atrial fibrillation (AF), the most common arrhythmia that threatens human. Herein, by modifying the hit compound 7k from an in-house database, 48 derivatives were synthesized for the assay of their Kv1.5 inhibitory effects by whole cell patch clamp technique. Six compounds which showed better potency than the positive compound dronedarone were selected for the next evaluation of their drug-like properties. Compound 8 exhibited balanced solubility and permeability. It also showed acceptable pharmacodynamics profile with very low acute toxicity. Taking all these data into account, compound 8 can serve as a promising lead for the development of novel therapeutic agent for the treatment of AF.
- Guo, Xiaoke,Ma, Xianglei,Yang, Qian,Xu, Jing,Huang, Lu,Jia, Jianmin,Shan, Jiaojiao,Liu, Li,Chen, Weilin,Chu, Hongxi,Wei, Jinlian,Zhang, Xiaojin,Sun, Haopeng,Tang, Yiqun,You, Qidong
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supporting information
p. 89 - 94
(2014/06/09)
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- Electroactive imidazolium salts based on 1,4-dimethoxybenzene redox groups: Synthesis and electrochemical characterisation
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Three new redox-active ionic salts have been synthesised based on 1,4-dimethoxybenzene (1) and 2,5-di-tert-butyl-1,4-dimethoxybenzene (2 and 3). These imidazolium salts are the first organic redox-active groups to be incorporated into an ionic liquid stru
- Forgie, John C.,Rochefort, Dominic
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p. 12035 - 12038
(2013/09/02)
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- Development of unsymmetrical dyads as potent noncarbohydrate-based inhibitors against human β-N-acetyl-D-hexosaminidase
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Human β-N-acetyl-D-hexosaminidase has gained much attention due to its roles in several pathological processes and been considered as potential targets for disease therapy. A novel and efficient skeleton, which was an unsymmetrical dyad containing naphthalimide and methoxyphenyl moieties with an alkylamine spacer linkage as a noncarbohydrate-based inhibitor, was synthesized, and the activities were valuated against human β-N-acetyl-D- hexosaminidase. The most potent inhibitor exhibits high inhibitory activity with Ki values of 0.63 μM. The straightforward synthetic manners of these unsymmetrical dyads and understanding of the binding model could be advantageous for further structure optimization and development of new therapeutic agents for Hex-related diseases.
- Guo, Peng,Chen, Qi,Liu, Tian,Xu, Lin,Yang, Qing,Qian, Xuhong
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supporting information
p. 527 - 531
(2013/07/26)
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- New serotonin 5-HT1A receptor agonists endowed with antinociceptive activity in vivo
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We report the synthesis of new compounds 4-35 based on two different openings (A and B) of the chromane ring present in the previously identified 5-HT1A receptor (5-HT1AR) ligand 3. The synthesized compounds were assessed for binding affinity, selectivity, and functional activity at the 5-HT1AR. Selected candidates resulting from B opening were also evaluated for their potential antinociceptive effect in vivo and pharmacokinetic properties in vitro. Analogue 19 [2-(4-{[2-(2-ethoxyphenoxy) ethyl]amino}butyl)tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione] has been characterized as a high-affinity and potent 5-HT1AR agonist (K i = 2.3 nM; EC50 = 19 nM). Pharmacokinetic studies indicated that compound 19 displays a good metabolic stability in human liver microsomes (t1/2 ~ 3 h and CLint = 3.5 mL/min/kg, at 5 μM), and a low level of protein binding (25%, at 5 μM). Interestingly, 19 (3 mg/kg, ip, and 30 mg/kg, po) caused significant attenuation of formalin-induced behavior in early and late phases of the mouse intradermal formalin test of pain, and this in vivo effect was reversed by the selective 5-HT1AR antagonist WAY-100635. Thus, the new 5-HT1AR agonist identified in this work, 19, exhibits oral analgesic activity, and the results herein represent a step toward identifying new therapeutics for the control of pain.
- Valhondo, Margarita,Marco, Isabel,Martín-Fontecha, Mar,Vázquez-Villa, Henar,Ramos, José A.,Berkels, Reinhard,Lauterbach, Thomas,Benhamú, Bellinda,López-Rodríguez, María L.
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supporting information
p. 7851 - 7861
(2013/11/06)
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- Synthesis, biological activity evaluation and molecular modeling study on the new isoconessimine derivatives as acetylcholinesterase inhibitors
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New isoconessimine derivatives were synthesized from conessine (1) and evaluated as acetylcholinesterase (AChE) inhibitors. The derivatives were prepared via two reaction steps, N-demethylation and nucleophilic substitution. All of the synthesized derivatives exhibited more potential anti- acetylcholinesterase activities than conessine (1) (IC50=16 μmol·L-1) and isoconessimine (2) (IC50>300 μmol·L-1). Compound 7b (3β-[methyl-[2-(4-nitrophenoxy) ethyl]amino]con-5-enine) showed the most potent inhibitory activity with an IC50 of 110 nmol/L which is close to that of reference compound huperzine A (IC50=70 nmol/L). The mode of AChE inhibition by 7b was reversible and non-competitive. In addition, molecular modeling was performed to explore the binding mode of inhibitor 7b at the active site of AChE and the results showed that 7b could be docked into the acetylcholinesterase active site and compound 7b had hydrophobic interactions with Trp279 and Leu282. A series of 3-N-aryloxyethyl substitutional isoconessimine derivatives were synthesized and evaluated as acetylcholinesterase (AChE) inhibitors. All of the synthesized derivatives exhibited potential anti-acetylcholinesterase activities with IC50 values at micromolar to sub-micromolar range. 7b showed the most potent inhibitory activity with an IC50of 110 nmol/L. The molecular docking results showed that 7b can be well docked into the active site of acetylcholinesterase. Copyright
- Jin, Guofei,Yang, Zhongduo,Xue, Weiwei,Sheng, Jie,Shi, Yin,Yao, Xiaojun
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p. 1228 - 1233
(2013/10/21)
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- 'Hybrid' benzofuran-benzopyran congeners as rigid analogs of hallucinogenic phenethylamines
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Phenylalkylamines that possess conformationally rigidified furanyl moieties in place of alkoxy arene ring substituents have been shown previously to possess the highest affinities and agonist functional potencies at the serotonin 5-HT2A recepto
- Schultz, Danielle M.,Prescher, Jennifer A.,Kidd, Stephanie,Marona-Lewicka, Danuta,Nichols, David E.,Monte, Aaron
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p. 6242 - 6251
(2008/12/21)
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- Novel cyclic amide derivatives
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Novel compounds represented by the following formula (I) that act as a ligand to sigma receptor/binding cite and a medicament comprising the same as an active ingredient: wherein X represents an alkyl group, an aryl group, a heterocyclic group or the like; Q represents a group represented by —CH2—, —CO—, —O—, —CH(OR7)— or the like wherein R7 represents a hydrogen atom, an alkyl group or the like; n represents an integer of from 0 to 5; R1 and R2 each represent a hydrogen atom, an alkyl group or the like; B represents either of the following groups: wherein R3, R4, R5, and R6 each represent a hydrogen atom, a halogen atom, an alkoxyl group or the like; m represents 1 or 2; and the ring of: represents an aromatic heterocyclic ring.
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- A simple modification of the known preparation procedure of 2-Phenoxyethyl bromides providing high yields
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A modification of preparation method was developed for synthesis of a number of 1-bromo-2-phenoxyethanes from 1,2-dibromoethanes and sodium phenolates in two-phase water-organic system with or without addition of triethylbenzylammonium chloride as phase-transfer catalyst. Addition of NaOH in two portions for transforming phenols into phenolates ensured high yields (60-80%) of phenoxylation products.
- Slyn'ko,Tormyshev
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p. 254 - 257
(2007/10/03)
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- 1-[(Aryloxy)alkyl]-1H-imidazoles as inhibitors of neuronal nitric oxide synthase
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A series of 1-[(aryloxy)alkyl]-1 H-imidazoles were synthesized from imidazole and various (aryloxy)alkyl bromides and tested for inhibitory activity against the three isoforms of nitric oxide synthase. 1-[2-(4-Bromophenoxy)ethyl]-1 H-imidazole and 1-[2-[4-(trifluoromethyl)phenoxy]ethyl]-1H-imidazole showed inhibitory activity against the neuronal isoform but were less potent against the endothelial isoform. Thus they could be considered interesting for their selectivity. The remaining compounds had only modest activity.
- Salerno,Sorrenti,Guerrera,Sarva,Siracusa,Di Giacomo,Vanella
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p. 491 - 494
(2007/10/03)
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- Squalene synthase inhibitors: Isosteric replacements of the farnesyl chain of benzyl farnesyl amine
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Squalene synthase catalyzes the committed step of cholesterol biosynthesis. We report here the synthesis and in vivo activity of a series of squalene synthase inhibitors that contain isosteric replacements for the farnesyl chain of the known inhibitor ben
- Brinkman, John A.,Damon, Robert E.,Fell, Jay B.,Perez, Lawerence B.,Scallen, Terence J.,Vedananda
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p. 2491 - 2494
(2007/10/03)
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