- Sustainable Synthesis of a Potent and Selective 5-HT7Receptor Antagonist Using a Mechanochemical Approach
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A mechanochemical procedure was developed to obtain PZ-1361, a potent and selective 5-HT7 receptor antagonist, with antidepressant properties in rodents. The elaborated protocol offered several advantages over classical batch synthesis, including improvement of the overall yield (from 34% to 64%), reduction of reaction time (from 60 to 5.5 h), limitation of the use of toxic solvents, and the formation of byproducts. This approach represents a rare example of the synthesis of biologically active compounds exclusively performed using mechanochemical reactions.
- Canale, Vittorio,Frisi, Valeria,Bantreil, Xavier,Lamaty, Frédéric,Zajdel, Pawe?
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supporting information
p. 10958 - 10965
(2020/09/18)
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- HIGH REFRACTIVE MONOMER, RESIN COMPOSITION FOR PRISM SHEET CONTAINING THE SAME AND PRISM SHEET USING THE SAME
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Disclosed are a high refractive monomer having at least one acryl functional group in a terminal and designed to meet a refractive index more than 1.57, a resin composition for forming the prism sheet capable of controlling refraction, viscosity, hardness, and yellowness by containing the high refractive monomer only or a mixture comprising the same, a prism sheet embodying high refraction and low viscosity of a liquid before curing and having excellent clarity and yellowing resistance by using the resin composition for forming the prism sheet which is made of the optimum mix. According to the present invention, the high luminance prism sheet is provided, thereby reducing the number of the sheet applied to embody the same luminance so as to contribute to slimming down the sheet, enhancing the performance, and saving costs. Therefore, the number of LED lamps used for a backlight unit can be reduced, thereby saving energy.
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Paragraph 0101; 0102; 0103; 0104
(2017/07/31)
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- Novel 5-HT7R antagonists, arylsulfonamide derivatives of (aryloxy)propyl piperidines: Add-on effect to the antidepressant activity of SSRI and DRI, and pro-cognitive profile
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A novel series of arylsulfonamide derivatives of (aryloxy)propyl piperidines was designed to obtain potent 5-HT7R antagonists. Among the compounds evaluated herein, 3-chloro-N-{1-[3-(1,1-biphenyl-2-yloxy)2-hydroxypropyl]piperidin-4-yl}benzenesulfonamide (25) exhibited antagonistic properties at 5-HT7R and showed selectivity over selected serotoninergic and dopaminergic receptors, as well as over serotonin, noradrenaline and dopamine transporters. Compound 25 demonstrated significant antidepressant-like activity in the forced swim test (0.625–2.5?mg/kg, i.p.) and in the tail suspension test (1.25?mg/kg, i.p.), augmented the antidepressant effect of inactive doses of escitalopram (selective serotonin reuptake inhibitor) and bupropion (dopamine reuptake inhibitor) in the FST in mice, and similarly to SB-269970, exerted pro-cognitive properties in the novel object recognition task in cognitively unimpaired conditions in rats (0.3?mg/kg, i.p.). Such an extended pharmacological profile, especially the augmentation effect of the identified 5-HT7R antagonist on SSRI activity, seems promising regarding the complexity of affective disorders and potentially improved outcomes, including mnemonic performance.
- Canale, Vittorio,Partyka, Anna,Kurczab, Rafa?,Krawczyk, Martyna,Kos, Tomasz,Sata?a, Grzegorz,Kubica, Bart?omiej,Jastrz?bska-Wi?sek, Magdalena,Weso?owska, Anna,Bojarski, Andrzej J.,Popik, Piotr,Zajdel, Pawe?
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p. 2789 - 2799
(2017/04/18)
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- Nonpeptidic propargylamines as inhibitors of lysine specific demethylase 1 (LSD1) with cellular activity
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Lysine demethylases play an important role in epigenetic regulation and thus in the development of diseases like cancer or neurodegenerative disorders. As the lysine specific demethylase 1 (LSD1/KDM1) has been strongly connected to androgen and estrogen dependent gene expression, it serves as a promising target for the therapy of hormone dependent cancer. Here, we report on the discovery of new small molecule inhibitors of LSD1 containing a propargylamine warhead, starting out from lysine containing substrate analogues. On the basis of these substrate mimicking inhibitors, we were able to increase potency by a combination of similarity-based virtual screening and subsequent synthetic optimization resulting in more druglike LSD1 inhibitors that led to histone hypermethylation in breast cancer cells.
- Schmitt, Martin L.,Hauser, Alexander-Thomas,Carlino, Luca,Pippel, Martin,Schulz-Fincke, Johannes,Metzger, Eric,Willmann, Dominica,Yiu, Teresa,Barton, Michelle,Schüle, Roland,Sippl, Wolfgang,Jung, Manfred
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supporting information
p. 7334 - 7342
(2013/10/21)
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- Analysis of β-amino alcohols as inhibitors of the potential anti-tubercular target N-acetyltransferase
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The synthesis and inhibitory potencies of a novel series of β-amino alcohols, based on the hit-compound 3-[3′-(4″-cyclopent-2?- en-1?-ylphenoxy)-2′-hydroxypropyl]-5,5 dimethylimidazolidine-2,4- dione as specific inhibitors of mycobacterial N-acetyltransferase (NAT) enzymes are reported. Effects of synthesised compounds on growth of Mycobacterium tuberculosis have been determined.
- Fullam, Elizabeth,Abuhammad, Areej,Wilson, David L.,Anderton, Matthew C.,Davies, Steve G.,Russell, Angela J.,Sim, Edith
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supporting information; experimental part
p. 1185 - 1190
(2011/04/16)
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- Antihypertensive indole derivatives of phenoxypropanolamines with β-adrenergic receptor antagonist and vasodilating activity
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A series of 25 aryloxypropanolamines containing the 3-indolyl-tert-butyl[i.e., 1,1-dimethyl-2-(1H-indol-3-yl)ethyl] or substituted 3-indolyl-tert-butyl moiety as the N substituent is reported. These compounds have been tested for antihypertensive activity in spontaneously hypertensive rats (SHR), β-adrenergic receptor antagonist action in conscious normotensive rats, vasodilating activity in ganglion-blocked rats with blood pressure maintained by angiotensin II infusion, and for intrinsic sympathomimetic action (ISA) in reserpinized rats. Some of the compounds exhibit antihypertensive activity in combination with β-adrenergic receptor antagonist and vasodilating action. The structure-activity relationships in these tests are discussed.
- Kreighbaum,Matier,Dennis,Minielli,Deitchman,Perhach Jr.,Comer
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p. 285 - 289
(2007/10/02)
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- 1-(TRIALKYLAMINO)-3-(PHENYLPHENOXY)-2-PROPANOL QUARTERNARY SALTS
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The above captioned compounds exhibit potent and long acting anti-arrhythmic activity while lacking the undesirable side effects, e.g. . beta.-adrenergic receptor blocking activity and local anesthetic activity, characteristic of related prior art compounds.
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