- N-(2,7-dimethyl-2-alkyl-2H-chromen-6-yl)sulfonamide derivatives as selective serotonin 5-HT6 receptor antagonists: Design, synthesis, and biological evaluation
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Serotonin 5-HT6 receptor, which is predominantly expressed in the central nervous system, is a valuable therapeutic target. Serotonin 5-HT6 receptor antagonists have potential for the treatment of various diseases that include psychotic disorders, dementia, depression, and obesity. In this study, we designed and synthesized the N-(2,7-dimethyl-2-alkyl-2H-chromen-6-yl)sulfonamide-based library as a potential serotonin 5-HT6 receptor antagonist. The library was subjected to a series of binding affinity tests to identify the lead compound, and check the selectivity of test compounds towards the 5-HT6 receptor. Accordingly, compound 6m was identified as the most active compound, with IC50 = 87 nM. The binding affinity of 95.3% of 6m (10 μM) with the 5-HT6 receptor among other serotonin 5-HT1a, 5-HT2a, 5-HT2c, and 5-HT7, and dopamine receptors D1, D2, D3, and D4, demonstrated the high selectivity of 6m towards the 5-HT6 receptor.
- Abdildinova, Aizhan,Kim, Young Chang,Lee, Gee-Hyung,Park, Woo-Kyu,Cho, Heeyeong,Gong, Young-Dae
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- A benzopyran with antiarrhythmic activity is an inhibitor of Kir3.1-containing potassium channels
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Atrial fibrillation (AF) is the most commonly diagnosed cardiac arrhythmia and is associated with increased morbidity and mortality. Currently approved AF antiarrhythmic drugs have limited efficacy and/or carry the risk of ventricular proarrhythmia. The c
- Cui, Meng,Alhamshari, Yaser,Cantwell, Lucas,EI-Haou, Said,Eptaminitaki, Giasemi C.,Chang, Mengmeng,Abou-Assali, Obada,Tan, Haozhou,Xu, Keman,Masotti, Meghan,Plant, Leigh D.,Thakur, Ganesh A.,Noujaim, Sami F.,Milnes, James,Logothetis, Diomedes E.
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- Enhanced enantioselectivity in heterogeneous manganese-catalyzed asymmetric epoxidation with nanosheets modified amino acid Schiff bases as ligands by modulating the orientation and the arrangement order
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Catalytic enantioselective epoxidation of olefins plays an important role in the production of optically-active epoxy. Transition-metal complexes prove efficient for the catalytic epoxidation of un-functionalized olefins by employing privileged chiral lig
- An, Zhe,Han, Hongbo,He, Jing,Jiang, Yitao,Ping, Qi,Shu, Xin,Song, Hongyan,Tang, Yuanzhong,Wang, Wenlong,Xiang, Xu,Zhu, Yanru
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- Identification of 3-hydroxy-4[3,4-dihydro-3-oxo-2H-1,4-benzoxazin-4-yl]-2,2-dimethyldihydro-2H-benzopyran derivatives as potassium channel activators and anti-inflammatory agents
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The present study described the design, synthesis and identification of 3-hydroxy-4[3,4-dihydro-3-oxo-2H-1,4-benzoxazin-4-yl]-2,2-dimethyldihydro-2H-benzopyran derivatives. Their biological activity was tested for KATP channel opener as antihypertensives, COX-1 and COX-2 activity. The results were compared with the activity of cromakalim, ibuprofen and celecoxib. The study aimed at exploring the influence of introduction of a benzoxazine substituent at position 6 of various derivatives of benzopyrans in order to improve biological activity. Several compounds were found to be equipotent or even more potent than cromakalim. Out of these nitro-substituted benzopyrans, nitro substitution at benzoxazino group possessed potent antihypertensive activity in the R/S isomers. With amino derivatives, activity remains constant when compared with standard cromakalim. Similarly, compounds 17b, 17c, 17e and 17h have exhibited around 40 % inhibition of COX-1 as compared to the inhibition of COX-2. Only two compounds 17g and 17i exhibited effective inhibition more than 50 % of COX-2 compared with the inhibition of COX-1 at a concentration of 0.3 mg/ml.
- Bano, Mohsina,Barot, Kuldipsinh P.,Jain, Shailesh V.,Ghate, Manjunath D.
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p. 3008 - 3020
(2015/03/18)
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- Asymmetric epoxidation of alkenes catalyzed by a porphyrin-inspired manganese complex
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A novel strategy for catalytic asymmetric epoxidation of a wide variety of olefins by a porphyrin-inspired chiral manganese complex using H 2O2 as a terminal oxidant in excellent yield with up to greater than 99% ee has been successfully developed.
- Dai, Wen,Li, Jun,Li, Guosong,Yang, Hua,Wang, Lianyue,Gao, Shuang
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supporting information
p. 4138 - 4141
(2013/09/12)
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- Asymmetric counteranion-directed transition-metal catalysis: Enantioselective epoxidation of alkenes with Manganese(III) salen phosphate complexes
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(Figure Presented) Figure Presentation Paired up: A highly active and enantioselective ion-pair epoxidation catalyst, consisting of an achiral Mn |||-salen complex and a chiral phosphate counteranion, mediates the epoxidization of a wide range of alkenes with high yields and enantioselectivities (see scheme). The unique role of the counteranion is to stabilize an enantiomorphic conformation of the cationic Mn catalyst.
- Liao, Saihu,List, Benjamin
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supporting information; experimental part
p. 628 - 631
(2010/04/06)
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- A simple two steps ytterbium triflate-catalysed preparation of 2,2-dimethyl-2H-chromenes from salicylaldehydes and 2-methylpropene
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The preparation of various 2,2-dimethyl-2H-chromenes was achieved in two steps via an ytterbium triflate-catalysed reaction between salicylaldehydes, trimethylorthoformate and 2-methylpropene. From salicylaldehyde, two reaction products were characterised
- Prado, Soizic,Janin, Yves L.,Bost, Pierre-Etienne
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p. 1605 - 1608
(2007/10/03)
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- PROCESS FOR PRODUCTION OF AN ACETYLENIC COMPOUND
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There is provided a process for producing an acetylene compound useful as an intermediate of pharmaceuticals, from 4-nitrofluorobenzene, in industrially and economically advantageous manner. Concretely, it is a method for producing an acetylene compound o
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Page/Page column 5
(2008/06/13)
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- Continuous processing to control a potentially hazardous process: Conversion of aryl 1,1-dimethylpropargyl ethers to 2,2-dimethylchromenes (2,2-dimethyl-2H-1-benzopyrans)
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The thermal Claisen rearrangement of 4-cyanophenyl 1,1-dimethylpropargyl ether (4) to 6-cyano-2,2-dimethylchromene (5), (6-cyano-2,2-dimethyl-2H-1-benzopyran), which is used in the synthesis of a potassium channel activator drug candidate, BMS-180448, created a significant process development issue. The resulting large heat release in this conversion posed not only a safety risk but could also cause product degradation if done in a batch-wise manner. The solution was to exploit the high surface-to-volume ratio of a plug-flow reactor that would maximize the heat transfer, thereby permitting tight and responsive temperature with better reaction control. In the course of successfully testing the plug-flow concept on "micro"-flow scale (gram quantity) and "kilo"-flow scale (~10 kg), a generalized mathematical model capable of predicting the reaction performance based on the physical properties of any given plug-flow reactor was generated. The model provides requisite information to design and operate a plug-flow reactor of any size for this reaction. This model would optimize reaction conditions for an acquired reactor system capable of producing ~7 kg/h of the dimethylchromene. Application of plug-flow reactor technology enabled production of high quality 2,2-dimethylchromenes in good yield (>98 mol %) without the use of solvents and with virtually no waste streams.
- Bogaert-Alvarez, Ricardo J.,Demena, Paul,Kodersha, Gus,Polomski, Robert E.,Soundararajan,Wang, Steve S. Y.
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p. 636 - 645
(2013/09/07)
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- Natural product-like combinatorial libraries based on privileged structures. 1. General principles and solid-phase synthesis of benzopyrans
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Herein we report a novel strategy for the design and construction of natural and natural product-like libraries based on the principle of privileged structures, a term originally introduced to describe structural motifs capable of interacting with a variety of unrelated molecular targets. The identification of such privileged structures in natural products is discussed, and subsequently the 2,2-dimethylbenzopyran moiety is selected as an inaugural template for the construction of natural product-like libraries via this strategy. Initially, a novel solid-phase synthesis of the benzopyran motif is developed employing a unique cycloloading strategy that relies on the use of a new, polystyrene-based selenenyl bromide resin. Once the loading, elaboration, and cleavage of these benzopyrans was established, this new solid-phase method was then thoroughly validated through the construction of six focused combinatorial libraries designed around natural and designed molecules of recent biological interest.
- Nicolaou,Pfefferkorn,Roecker,Cao,Barluenga,Mitchell
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p. 9939 - 9953
(2007/10/03)
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- Synthesis of 6-Cyano-2,2-dimethyl-2H-1-benzopyran and Other Substituted 2,2-dimethyl-2H-1-benzopyrans
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A practical synthesis of 6-cyano-2,2-dimethyl-2H-1-benzopyran (1) has been developed.This process involves the pyridine-catalyzed condensation of 1,1-diethoxy-3-methyl-2-butene (6) with 4-cyanophenol (3) in toluene or xylene at elevated temperatures.The development of this process, including an evaluation of solvents, bases, acid catalysts, and alterantive acetals, along with an improved synthesis of 1,1-diethoxy-3-methyl-2-butene, is discussed.Using this method, a variety of other substituted 2,2-dimethyl-2H-1-benzopyrans were synthesized.
- North, Jeffrey T.,Kronenthal, David R.,Pullockaran, Annie J.,Real, Sharon D.,Chen, Helen Y.
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p. 3397 - 3400
(2007/10/02)
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- Copper(I) iodide: A catalyst for the improved synthesis of aryl propargyl ethers
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Copper(I) iodide catalyses the reaction between phenols and dialkylpropargyl chlorides to give aryl 1,1-dialkylpropargyl ethers 5 a-k and 7a-e in good yields and purity. These ethers are important as precursors to the 2H-1-benzopyrans 8a-l and 9a-e.
- Bell,Davies,Geen,Mann
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p. 707 - 712
(2007/10/02)
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- The Synthesis and Potassium Channel Blocking Activity of Some (4-Methanesulfonamidophenoxy)propanolamines as Potential Class III Antiarrhythmic Agents
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The synthesis of 22 (4-methanesulfonamidophenoxy)propanolamines and their testing on isolated guinea pig cardiac myocytes, on isolated preparations from guinea pig atria, and on rat blood pressure are described.Secondary amines in the series (11a-f) showe
- Connors, Sean P.,Dennis, Paul D.,Gill, Edward W.,Terrar, Derek A.
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p. 1570 - 1577
(2007/10/02)
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- Synthesis and antihypertensive activity of substituted trans-4-amino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-3-ols
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A series of novel substituted trans-4-amino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-3-ols was prepared and tested for antihypertensive activity in the conscious deoxycorticosterone acetate (DOCA)/saline treated hypertensive rat. Optimum blood pressure lowering activity requires 6-substitution by a strong electron-withdrawing group, together with a pyrrolidino or piperidino group at the 4 position. Exceptions to this were the 7-nitro-4-pyrrolidine analogue and the 6-nitro-3-chloropropylamine, which retained marked antihypertensive activity. All of these compounds were direct vasodilators and had comparable antihypertensive activity to hydralazine and to the calcium antagonist, nifedipine. The synthetic route to these compounds involves cyclization of propargyl ethers to 2H-1-benzopyrans, followed by conversion via bromohydrins to 3,4-epoxides, which were ring opened with the appropriate amines. Meta-substituted propargyl ethers gave both 5- and 7-substituted benzopyrans on thermal cyclization, the former predominating. A new route to 2,2-dimethyl-7-nitrobenzopyran is described.
- Evans, John M.,Fake, Charles S.,Hamilton, Thomas C.,Poyser, Robert H.,Watts, Eric A.
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p. 1582 - 1589
(2007/10/02)
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