498577-19-8Relevant academic research and scientific papers
Discovery of a new class of multi-target heterocycle piperidine derivatives as potential antipsychotics with pro-cognitive effect
Gao, Lanchang,Hao, Chao,Chen, Jiali,Ma, Ru,Zheng, Lu,Wu, Qingkun,Liu, Xin,Liu, Bi-Feng,Zhang, Guisen,Chen, Yin,Jin, Jian
supporting information, (2021/03/19)
A series of benzoisoxazoleylpiperidine derivatives were synthesized by using the multi-target strategies and their potent affinities for dopamine (DA), serotonin (5-HT) and human histamine H3 receptors have been evaluated. Of these compounds, t
Synthesis and biological evaluation of a new class of multi-target heterocycle piperazine derivatives as potential antipsychotics
Gao, Lanchang,Hao, Chao,Ma, Ru,Chen, Jiali,Zhang, Guisen,Chen, Yin
, p. 16931 - 16941 (2021/05/25)
In this study, we designed and synthesized a novel series of multi-receptor ligands as polypharmacological antipsychotic agents by using a multi-receptor affinity strategy. Among them,3wcombines a multi-receptor mechanism with high mixed affinities for D
Demonstration of in Vitro Resurrection of Aged Acetylcholinesterase after Exposure to Organophosphorus Chemical Nerve Agents
Zhuang, Qinggeng,Franjesevic, Andrew J.,Corrigan, Thomas S.,Coldren, William H.,Dicken, Rachel,Sillart, Sydney,Deyong, Ashley,Yoshino, Nathan,Smith, Justin,Fabry, Stephanie,Fitzpatrick, Keegan,Blanton, Travis G.,Joseph, Jojo,Yoder, Ryan J.,McElroy, Craig A.,Ekici, ?zlem Dogan,Callam, Christopher S.,Hadad, Christopher M.
supporting information, p. 7034 - 7042 (2018/06/13)
After the inhibition of acetylcholinesterase (AChE) by organophosphorus (OP) nerve agents, a dealkylation reaction of the phosphylated serine, referred to as aging, can occur. When aged, known reactivators of OP-inhibited AChE are no longer effective. Realkylation of aged AChE may provide a route to reversing aging. We designed and synthesized a library of quinone methide precursors (QMPs) as proposed realkylators of aged AChE. Our lead compound (C8) from an in vitro screen successfully resurrected 32.7 and 20.4% of the activity of methylphosphonate-aged and isopropyl phosphate-aged electric-eel AChE, respectively, after 4 days. C8 displays properties of both resurrection (recovery from the aged to the native state) and reactivation (recovery from the inhibited to the native state). Resurrection of methylphosphonate-aged AChE by C8 was significantly pH-dependent, recovering 21% of activity at 4 mM and pH 9 after only 1 day. C8 is also effective against isopropyl phosphate-aged human AChE.
Study of para-Quinone Methide Precursors toward the Realkylation of Aged Acetylcholinesterase
Yoder, Ryan J.,Zhuang, Qinggeng,Beck, Jeremy M.,Franjesevic, Andrew,Blanton, Travis G.,Sillart, Sydney,Secor, Tyler,Guerra, Leah,Brown, Jason D.,Reid, Carolyn,McElroy, Craig A.,Do?an Ekici, ?zlem,Callam, Christopher S.,Hadad, Christopher M.
supporting information, p. 622 - 627 (2017/06/13)
Acetylcholinesterase (AChE) is an essential enzyme that can be targeted by organophosphorus (OP) compounds, including nerve agents. Following exposure to OPs, AChE becomes phosphylated (inhibited) and undergoes a subsequent aging process where the OP-AChE adduct is dealkylated. The aged AChE is unable to hydrolyze acetylcholine, resulting in accumulation of the neurotransmitter in the central nervous system (CNS) and elsewhere. Current therapeutics are only capable of reactivating inhibited AChE. There are no known therapeutic agents to reverse the aging process or treat aged AChE. Quinone methides (QMs) have been shown to alkylate phosphates under physiological conditions. In this study, a small library of novel quinone methide precursors (QMPs) has been synthesized and examined as potential alkylating agents against model nucleophiles, including a model phosphonate. Computational studies have been performed to evaluate the affinity of QMPs for the aged AChE active site, and preliminary testing with electric eel AChE has been performed.
HISTAMINE-3 RECEPTOR ANTAGONISTS
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Page/Page column 160-161, (2008/06/13)
This invention is directed to a compound of the formula Ia or Ib. as defined herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical composition containing a compound of formula I, a method of treatment of a disorder or condition that may be treated by antagonizing histamine H3 receptors, the method comprising administering to a mammal in need of such treatment a compound of formula I as described above, and a method of treatment of a disorder or condition selected from the group consisting of depression, mood disorders, schizophrenia, anxiety disorders, Alzheimer's disease, attention-deficit disorder (ADD), attention-deficit hyperactivity disorder (ADHD), psychotic disorders, sleep disorders, obesity, dizziness, epilepsy, motion sickness, respiratory diseases, allergy, allergy- induced airway responses, allergic rhinitis, nasal congestion, allergic congestion, congestion, hypotension, cardiovascular disease, diseases of the Gl tract, hyper and hypo motility and acidic secretion of the gastro- intestinal tract, the method comprising administering to a mammal in need of such treatment a compound of formula I as described above.
