58950-89-3Relevant academic research and scientific papers
Iminophosphorane-Mediated Synthesis of the Fascaplysin Alkaloid of Marine Origin and Nitramarine
Molina, Pedro,Fresneda, Pilar M.,Garcia-Zafra, Sagrario,Almendros, Pedro
, p. 8851 - 8854 (1994)
New and efficient syntheses of the fascaplysin alkaloid of marine origin and nitramarine are described.In both syntheses the key step, formation of the β-carboline ring, involve a tandem aza-Wittig/electrocyclic ring closure process.
Bioinspired Synthesis of the Furopyrazine Alkaloid Hyrtioseragamine A
Kim, Shi-Wei,Hume, Paul A.,Sperry, Jonathan
, p. 4779 - 4785 (2021)
A biosynthetic hypothesis proposed herein was used to guide the total synthesis of the marine-derived alkaloid hyrtioseragamine A. In the key biomimetic step, an enedione underwent acid-mediated isomerization-cyclodehydration to form the rare furopyrazine
Mono- or di-substituted imidazole derivatives for inhibition of acetylcholine and butyrylcholine esterases
Kuzu, Burak,Tan, Meltem,Taslimi, Parham,Gül?in, ?lhami,Ta?p?nar, Mehmet,Menges, Nurettin
, p. 187 - 196 (2019/02/06)
Mono- or di-substituted imidazole derivatives were synthesized using a one-pot, two-step strategy. All imidazole derivatives were tested for AChE and BChE inhibition and showed nanomolar activity similar to that of the test compound donepezil and higher than that of tacrine. Structure activity relationship studies, docking studies to on X-ray crystal structure of AChE with PDB code 1B41, and adsorption, distribution, metabolism, and excretion (ADME) predictions were performed. The synthesized core skeleton was bound to important regions of the active site of AChE such as the peripheral anionic site (PAS), oxyanion hole (OH), and anionic subsite (AS). Selectivity of the reported test compounds was calculated and enzyme kinetic studies revealed that they behave as competitive inhibitors, while two of the test compounds showed noncompetitive inhibitory behavior. ADME predictions revealed that the synthesized molecules might pass through the blood brain barrier and intestinal epithelial barrier and circulate freely in the blood stream without binding to human serum albumin. While the toxicity of one compound on the WS1 (skin fibroblast) cell line was 1790 μM, its toxicity on the SH-SY5Y (neuroblastoma) cell line was 950 μM.
Syntheses, Cholinesterases Inhibition, and Molecular Docking Studies of Pyrido[2,3-b]pyrazine Derivatives
Hameed, Abdul,Zehra, Syeda T.,Shah, Syed J. A.,Khan, Khalid M.,Alharthy, Rima D.,Furtmann, Norbert,Bajorath, Jürgen,Tahir, Muhammad N.,Iqbal, Jamshed
, p. 1115 - 1120 (2015/10/28)
Cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), have a role in cholinergic deficit which evidently leads to Alzheimer's disease (AD). Inhibition of cholinesterases with small molecules is an attractive strategy in AD therapy. This study demonstrates synthesis of pyrido[2,3-b]pyrazines (6a-6q) series, their inhibitory activities against both cholinesterases, AChE and BChE, and molecular docking studies. The bioactivities data of pyrido[2,3-b]pyrazines showed 3-(3′-nitrophenyl)pyrido[2,3-b]pyrazine 6n a potent dual inhibitor among the series against both AChE and BChE with IC50 values of 0.466 ± 0.121 and 1.89 ± 0.05 μm, respectively. The analogues 3-(3′-methylphenyl)pyrido[2,3-b]pyrazine 6c and 3-(3′-fluorophenyl)pyrido[2,3-b]pyrazine 6f were found to be selective inhibition for BChE with IC50 values of 0.583 ± 0.052 μm and AChE with IC50 value of 0.899 ± 0.10 μm, respectively. Molecular docking studies of the active compounds suggested the putative binding modes with cholinesterases. The potent compounds among the series could potentially serves as good leads for the development of new cholinesterase inhibitors. A series of pyrido[2,3-b]pyrazine (6a-6q) derivatives has been synthesized and evaluated for inhibitory activities against cholinesterases; acetylcholinesterase, and butyrylcholinesterase. Molecular docking of active compounds was also performed to suggest the putative binding modes with cholinesterases.
Quinoxaline derivatives: Novel and selective butyrylcholinesterase inhibitors
Zeb, Aurang,Hameed, Abdul,Khan, Latifullah,Khan, Imran,Dalvandi, Kourosh,Choudhary, M. Iqbal,Basha, Fatima Z.
, p. 724 - 729 (2015/04/14)
Alzheimer's disease (AD) is a progressive brain disorder which occurs due to lower levels of acetylcholine (ACh) neurotransmitters, and results in a gradual decline in memory and other cognitive processes. Acetycholinesterase (AChE) and butyrylcholinesterase (BChE) are considered to be primary regulators of the ACh levels in the brain. Evidence shows that AChE activity decreases in AD, while activity of BChE does not change or even elevate in advanced AD, which suggests a key involvement of BChE in ACh hydrolysis during AD symptoms. Therefore, inhibiting the activity of BChE may be an effective way to control AD associated disorders. In this regard, a series of quinoxaline derivatives 1-17 was synthesized and biologically evaluated against cholinesterases (AChE and BChE) and as well as against achymotrypsin and urease. The compounds 1-17 were found to be selective inhibitors for BChE, as no activity was found against other enzymes. Among the series, compounds 6 (IC50 = 7.7 ± 1.0μM) and 7 (IC50 = 9.7 ± 0.9 μM) were found to be the most active inhibitors against BChE. Their IC50 values are comparable to the standard, galantamine (IC50 = 6.6 ± 0.38 μM). Their considerable BChE inhibitory activity makes them selective candidates for the development of BChE inhibitors. Structure-activity relationship (SAR) of this new class of selective BChE inhibitors has been discussed.
New 1,2,4-triazine derivatives and biological applications thereof
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Page/Page column 13, (2010/01/29)
The invention relates to new 1,2,4-triazine derivatives of formula (I): wherein A, B, R2 and Y are defined in the application, their preparation and intermediates, their use as drugs and pharmaceutical compositions and associations containing them. The compounds of formula (I) are capable of inhibiting bacterial heptose synthesis.
Studies directed toward the synthesis of cryptoheptine
Zhang, Pingsheng,Bierer, Donald E.
, p. 643 - 645 (2007/10/03)
Synthesis of 5,10-dihydro-10-methylindolo[3,2-b][1]benzazepin-12(11H)- one (2), an isomer of the reported structure for cryptoheptine (1), is presented. Attempts to convert 2 to 1 led to 10-methylindolo[3,2-b][1]- benzazepin-12-one (10), an oxidation prod
