68104-63-2Relevant articles and documents
Ligand-based rational design, synthesis and evaluation of novel potential chemical chaperones for opsin
Bassetto, Marcella,Brancale, Andrea,Pasqualetto, Gaia,Pileggi, Elisa,Rozanowska, Malgorzata,Schepelmann, Martin,Varricchio, Carmine
supporting information, (2021/09/24)
Inherited blinding diseases retinitis pigmentosa (RP) and a subset of Leber's congenital amaurosis (LCA) are caused by the misfolding and mistrafficking of rhodopsin molecules, which aggregate and accumulate in the endoplasmic reticulum (ER), leading to photoreceptor cell death. One potential therapeutic strategy to prevent the loss of photoreceptors in these conditions is to identify opsin-binding compounds that act as chemical chaperones for opsin, aiding its proper folding and trafficking to the outer cell membrane. Aiming to identify novel compounds with such effect, a rational ligand-based approach was applied to the structure of the visual pigment chromophore, 11-cis-retinal, and its locked analogue 11-cis-6mr-retinal. Following molecular docking studies on the main chromophore binding site of rhodopsin, 49 novel compounds were synthesized according to optimized one-to seven-step synthetic routes. These agents were evaluated for their ability to compete for the chromophore binding site of opsin, and their capacity to increase the trafficking of the P23H opsin mutant from the ER to the cell membrane. Different new molecules displayed an effect in at least one assay, acting either as chemical chaperones or as stabilizers of the 9-cis-retinal-rhodopsin complex. These compounds could provide the basis to develop novel therapeutics for RP and LCA.
Reductive cyanation of organic chlorides using CO2 and NH3 via Triphos–Ni(I) species
Dong, Yanan,Li, Yuehui,Yang, Peiju,Zhao, Shizhen
, (2020/08/19)
Cyano-containing compounds constitute important pharmaceuticals, agrochemicals and organic materials. Traditional cyanation methods often rely on the use of toxic metal cyanides which have serious disposal, storage and transportation issues. Therefore, there is an increasing need to develop general and efficient catalytic methods for cyanide-free production of nitriles. Here we report the reductive cyanation of organic chlorides using CO2/NH3 as the electrophilic CN source. The use of tridentate phosphine ligand Triphos allows for the nickel-catalyzed cyanation of a broad array of aryl and aliphatic chlorides to produce the desired nitrile products in good yields, and with excellent functional group tolerance. Cheap and bench-stable urea was also shown as suitable CN source, suggesting promising application potential. Mechanistic studies imply that Triphos-Ni(I) species are responsible for the reductive C-C coupling approach involving isocyanate intermediates. This method expands the application potential of reductive cyanation in the synthesis of functionalized nitrile compounds under cyanide-free conditions, which is valuable for safe synthesis of (isotope-labeled) drugs.
Synthesis and antitubercular evaluation of reduced lipophilic imidazo[1,2-a]pyridine-3-carboxamide derivatives
Wang, Hongjian,Wang, Apeng,Gu, Jian,Fu, Lei,Lv, Kai,Ma, Chao,Tao, Zeyu,Wang, Bin,Liu, Mingliang,Guo, Huiyuan,Lu, Yu
, p. 11 - 17 (2019/01/16)
A series of reduced lipophilic N-benzylic imidazo[1,2-a]pyridine carboxamides (IPAs) with various side chains were designed and synthesized as new anti-TB agents in this work. Five derivatives A2, A3, A4, B1 and B9 exhibit excellent in vitro activity (MIC: 0-∞ and Cmax than Q203 and PBTZ169, suggesting its promising potential to be a lead compound for future antitubercular drug discovery.
Biphenyl sulfonic acid ligands for catalytic C-N cross coupling of aryl halides with anilines and secondary amines
Wittel, B?rbel,Vogel, Till,Scharl, Heiko,Nerdinger, Sven,Lehnemann, Bernd,Meudt, Andreas,Snieckus, Victor
, p. 4583 - 4593 (2018/07/31)
The use of two biphenyl sulfonic acid ligands for the catalytic C-N cross coupling of aryl halides with anilines, 3-aminopyridine, and secondary amines is reported. Our results represent a significant improvement compared to state of the art methods especially with regards to the removal of palladium.
USE OF DISUBSTITUTED BENZENES TO CONTROL INSECTICIDE-RESISTANT PESTS
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Page/Page column 44, (2018/11/26)
The invention is in the technical field of insect control and relates to the use of a disubstituted benzenes for controlling insecticide-resistant pests such as mosquitoes and cockroaches.
Development of an SNAr Reaction: A Practical and Scalable Strategy to Sequester and Remove HF
Blacker, A. John,Moran-Malagon, Gabriel,Powell, Lyn,Reynolds, William,Stones, Rebecca,Chapman, Michael R.
, (2018/09/27)
A simple and operationally practical method to sequester and remove fluoride generated through the SNAr reaction between amines and aryl fluorides is reported. Calcium propionate acts as an inexpensive and environmentally benign in situ scrubbe
Development of an SNAr Reaction: A Practical and Scalable Strategy to Sequester and Remove HF
Blacker, A. John,Moran-Malagon, Gabriel,Powell, Lyn,Reynolds, William,Stones, Rebecca,Chapman, Michael R.
, p. 1086 - 1091 (2018/09/29)
A simple and operationally practical method to sequester and remove fluoride generated through the SNAr reaction between amines and aryl fluorides is reported. Calcium propionate acts as an inexpensive and environmentally benign in situ scrubbe
FATTY ACID SYNTHASE INHIBITORS
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Page/Page column 53; 54; 57, (2014/01/07)
Disclosed are compounds having Formula (I), wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, Y, m, and n are defined herein and methods of using the same.
Novel benzo[ b ]thiophene derivatives as new potential antidepressants with rapid onset of action
Berrade, Luis,Aisa, Bárbara,Ramirez, María J.,Galiano, Silvia,Guccione, Salvatore,Moltzau, Lise Román,Levy, Finn Olav,Nicoletti, Ferdinando,Battaglia, Giuseppe,Molinaro, Gemma,Aldana, Ignacio,Monge, Antonio,Perez-Silanes, Silvia
supporting information; experimental part, p. 3086 - 3090 (2011/07/07)
We report benzo[b]thiophene derivatives synthesized according to a dual strategy. 8j, 9c, and 9e with affinity values toward 5-HT7R and 5-HTT were selected to probe their antidepressant activity in vivo using the forced swimming text (FST). The results showed significant antidepressant activity after chronic treatment. 9c was effective in reducing the immobility time in FST even after acute treatment. These findings identify these compounds as a new class of antidepressants with a rapid onset of action.
Synthesis and antileishmanial activity of novel 5-(5-nitrofuran-2-y1)-1,3, 4-thiadiazoles with piperazinyl-linked benzamidine substituents
Tahghighi, Azar,Marznaki, Farzane Rezazade,Kobarfard, Farzad,Dastmalchi, Siavoush,Mojarrad, Javid Shahbazi,Razmi, Sepideh,Ardestani, Sussan Kabudanian,Emami, Saeed,Shafiee, Abbas,Foroumadi, Alireza
experimental part, p. 2602 - 2608 (2011/06/21)
In order to optimize the antileishmanial activity of piperazinyl-linked 5-(5-nitrofuran-2-yl)-1,3,4-thiadiazoles, we synthesized a series of 5-(5-nitrofuran-2-y1)-1,3,4-thiadiazoles with piperazinyl-linked benzamidine substituent as scaffold found in pentamidine related antiprotozoals. The structure of target compounds was confirmed by IR, 1H NMR, 13C NMR and Mass spectral data. All compounds were tested for in vitro activity against the promastigote and amastigote forms of Leishmania major. From the results, we found that the substitution on amidine nitrogen has profound role in the biological activity of these compounds. The 5-nitrofuran-2-yl-1,3,4-thiadiazoles having n-propyl, n-butyl and benzyl side chain on benzamidine (as in compounds 2d, 2e and 2g, respectively) showed very good activity in both forms of promastigote and amastigote. The most active compound was N-propyl-4-(4-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-yl) piperazin-1-yl) benzamidine hydrochloride (2d) with IC50 value of 0.08 μM in promastigote model. This compound showed a very low level of toxicity against macrophages (CC50 = 785 μM), with the highest selectivity index (SI = 78.5) among the tested compounds.
