Synthesis and evaluation of amide, sulfonamide and urea – benzisoxazole derivatives as potential atypical antipsychotics

MedChemComm ◽  
2015 ◽  
Vol 6 (5) ◽  
pp. 831-838 ◽  
Author(s):  
Yin Chen ◽  
Yu Lan ◽  
Xudong Cao ◽  
Xiangqing Xu ◽  
Juecheng Zhang ◽  
...  
Keyword(s):  
Atypical Antipsychotic ◽  
Atypical Antipsychotics ◽  
Antipsychotic Activity ◽  
Amide Derivatives ◽  
Derivatives Of

A series of amide derivatives of benzisoxazole has been synthesized and the target compounds evaluated for atypical antipsychotic activity in vitro and vivo.

One Pot Synthesis and Pharmacological Evaluation of Aryl Substituted Imidazoles as Potential Atypical Antip

2020 ◽  
Vol 17 ◽  
Author(s):  
Arshjyoti Singh ◽  
Alka Bali ◽  
Pooja Kumari
Keyword(s):  
Atypical Antipsychotic ◽  
In Silico ◽  
Negative Symptoms ◽  
Atypical Antipsychotics ◽  
Docking Studies ◽  
D2 Receptors ◽  
One Pot ◽  
In Silico Docking ◽  
One Pot Synthesis ◽  
Antipsychotic Activity

Background: Second generation or ‘‘atypical’’ antipsychotics demonstrate an improved therapeutic profile over conventional neuroleptics. These are effective in both positive and negative symptoms of the disease and have a lower propensity to induce adverse symptoms. Objective: Main objective of the research was in silico design and synthesis of potential atypical antipsychotics with combined antiserotonergic / antidopaminergic effect. Method: A one pot synthesis of aryl substituted imidazole derivatives was carried out in green solvent PEG-400 and the prepared compounds were evaluated for atypical antipsychotic activity in animal models for dopaminergic and serotonergic antagonism. The compounds were designed based on their 3D similarity studies to standard drugs and in silico (docking studies) with respect to 5-HT2A and D2 receptors. Results and Discussion: Results from the docking studies with respect to 5-HT2A and D2 receptors suggested a potential atypical antipsychotic profile for the test compounds. Theoretical ADME profiling of the compounds based on selected physicochemical parameters suggested an excellent compliance with Lipinski’s rules. The potential of these compounds to penetrate the blood brain barrier (log BB) was computed through an online software program and the values obtained for the compounds suggested a good potential for brain permeation. Reversal of apomorphine induced mesh climbing behaviour coupled with inactivity in the stereotypy assay indicates antidopaminergic effect and a potential atypical profile for the test compounds 1-5. Further, activity of compounds in DOI assay indicated a 5-HT2 antagonistic profile (5-HT2 antagonism). Conclusion: Compound 5 emerged as important lead compound showing combined antidopaminergic and antiserotonergic (5-HT2A) activity with potential atypical antipsychotic profile.

Synthesis and Evaluation of Aryl Substituted Propyl Piperazines for Potential Atypical Antipsychotic activity

2019 ◽  
Vol 15 ◽  
Author(s):  
Shalu Singh ◽  
Alka Bali ◽  
Tania Peshin
Keyword(s):  
Atypical Antipsychotic ◽  
Physicochemical Parameters ◽  
Negative Symptoms ◽  
Atypical Antipsychotics ◽  
Lead Compounds ◽  
Antipsychotic Activity ◽  
Barrier Penetration ◽  
Good Potential ◽  
Log Bb ◽  
Online Software

Background: Schizophrenia is a disorder with complex etiology with hyperdopaminergia as the main underlying cause. Atypical antipsychotics are the agents which do not give rise to significant extrapyramidal side effects and are more effective against negative symptoms of schizophrenia. Introduction: A new series of chloro-substituted substituted aryloxypiperazine derivatives and their indole based derivatives was designed and evaluated for atypical antipsychotic activity based on established models for combined dopaminergic and serotonergic antagonism. Method: The present series of compounds were designed based on 3D similarity studies, synthesized and evaluated for atypical antipsychotic activity in animal models for combined dopaminergic and serotonergic antagonism. The blood brain barrier penetration potential was assessed from theoretical log BB values computed through an online software program. Results: Theoretical ADME profiling of the designed compounds based on selected physicochemical parameters suggested an excellent compliance with Lipinski’s rules. The log BB values obtained for the compounds suggested a good potential for brain permeation. Indole substitution contributed towards an improved efficacy over aryloxy analogs. Lead compounds showed a potential for combined dopaminergic and serotonergic antagonism. Conclusion: The 5-methoxy indole based compounds 16 and 17 were identified as the lead compounds displaying a potential atypical antipsychotic profile.

Synthesis and Biological Activity of 28-Amide Derivatives of 23-Hydroxy Betulinic Acid as Antitumor Agent Candidates

2013 ◽  
Vol 9 (7) ◽  
pp. 920-925 ◽  
Author(s):  
Yi Bi ◽  
Jinyi Xu ◽  
Fei Sun ◽  
Xiaoming Wu ◽  
Wencai Ye ◽  
...  
Keyword(s):  
Biological Activity ◽  
Betulinic Acid ◽  
Antitumor Agent ◽  
Amide Derivatives ◽  
Derivatives Of

Theoretical Study of the Process of Passage of Glycoside Amides through the Cell Membrane of Cancer Cell

2020 ◽  
Vol 20 ◽  
Author(s):  
Vasil Tsanov ◽  
Hristo Tsanov
Keyword(s):  
Cell Membrane ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Quantum Chemical ◽  
Density Functional ◽  
Enzyme Regulation ◽  
Amide Derivatives ◽  
Pass Through ◽  
Hydrolysis Of ◽  
Derivatives Of

Background:: This article concentrates on the processes occurring in the medium around the cancer cell and the transfer of glycoside amides through their cell membrane. They are obtained by modification of natural glycoside-nitriles (cyano-glycosides). Hydrolysis of starting materials in the blood medium and associated volume around physiologically active healthy and cancer cells, based on quantum-chemical semi-empirical methods, is considered. Objective:: Based on the fact that the cancer cell feeds primarily on carbohydrates, it is likely that organisms have adapted to take food containing nitrile glycosides and / or modified forms to counteract "external" bioactive activity. Cancers, for their part, have evolved to create conditions around their cells that eliminate their active apoptotic forms. This is far more appropriate for them than changing their entire enzyme regulation to counteract it. In this way, it protects itself and the gene sets and develops according to its instructions. Methods:: Derived pedestal that closely defines the processes of hydrolysis in the blood, the transfer of a specific molecular hydrolytic form to the cancer cell membrane and with the help of time-dependent density-functional quantum- chemical methods, its passage and the processes of re-hydrolysis within the cell itself, to forms causing chemical apoptosis of the cell - independent of its non-genetic set, which seeks to counteract the process. Results:: Used in oncology it could turn a cancer from a lethal to a chronic disease (such as diabetes). The causative agent and conditions for the development of the disease are not eliminated, but the amount of cancer cells could be kept low for a long time (even a lifetime). Conclusion:: The amide derivatives of nitrile glycosides exhibit anti-cancer activity, the cancer cell probably seeks to displace hydrolysis of these derivatives in a direction that would not pass through its cell membrane and the amide- carboxyl derivatives of nitrile glycosides could deliver extremely toxic compounds within the cancer cell itself and thus block and / or permanently damage its normal physiology.

scholarly journals Amide Derivatives of Ginkgolide B and Their Inhibitory Effects on PAF-Induced Platelet Aggregation

ACS Omega ◽  
2021 ◽  
Author(s):  
Qiang Shang ◽  
Xiaobo Zhou ◽  
Ming-Rong Yang ◽  
Jing-Guang Lu ◽  
Yu Pan ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Ginkgolide B ◽  
Inhibitory Effects ◽  
Amide Derivatives ◽  
Derivatives Of

ChemInform Abstract: SYNTHESES FROM DIMETHYLPYRAZOLES. VII. PYRAZOLE ANALOGS OF ANTHRANILIC ACID AND ITS AMIDE. DERIVATIVES OF N-PYRAZOLYLNAPHTHALIMIDES

1984 ◽  
Vol 15 (37) ◽  
Author(s):  
V. P. PEREVALOV ◽  
M. A. ANDREEVA ◽  
YU. A. MANAEV ◽  
SH. G. ISAEV ◽  
L. I. BARYSHNENKOVA ◽  
...  
Keyword(s):  
Anthranilic Acid ◽  
Amide Derivatives ◽  
Derivatives Of

Amide Derivatives of the Isomeric Dichlorobenzoic Acids.

1966 ◽  
Vol 11 (2) ◽  
pp. 250-250 ◽  
Author(s):  
Robert G. Splies ◽  
Robert E. Lenya
Keyword(s):  
Amide Derivatives ◽  
Derivatives Of

scholarly journals Review of the efficacy of placebo in comparative clinical trials between typical and atypical antipsychotics

2009 ◽  
Vol 31 (1) ◽  
pp. 52-56 ◽  
Author(s):  
Irismar Reis de Oliveira ◽  
Paulo Menezes Nunes ◽  
Domingos Macedo Coutinho ◽  
Eduardo Pondé de Sena
Keyword(s):  
Clinical Trials ◽  
Atypical Antipsychotic ◽  
Atypical Antipsychotics ◽  
Rating Scale ◽  
Study Drug ◽  
Typical Antipsychotic ◽  
The Difference ◽  
Psychiatric Rating Scale ◽  
Efficacy Parameters ◽  
Typical Antipsychotics

OBJECTIVE: To review the efficacy of placebo in comparison with atypical and typical antipsychotics for the treatment of schizophrenia and schizoaffective disorder and to evaluate the pertinence of using placebo in clinical trials with antipsychotics. METHOD: Trials in which the atypical antipsychotics were compared with typical antipsychotics and placebo were included. A search was conducted using the terms "amisulpride", "aripiprazole", "clozapine", "olanzapine", "quetiapine", "risperidone", "sertindole", "ziprasidone" and "zotepine". Main efficacy parameters were calculated using the proportion of "events" (defined as a deterioration or lack of improvement by at least 20% in Positive and Negative Syndrome Scale or Brief Psychiatric Rating Scale) and the pooled relative risk with random effects, with their respective 95% confidence intervals. We also calculated the necessary sample sizes in studies in which the study drug is compared to a typical antipsychotic or placebo. RESULTS: The pooled efficacy rates observed were 40.8%, 34.9% and 21.3% for the atypical antipsychotics, typical antipsychotics and placebo, respectively. One hundred and sixty six patients would have to be included when a new drug is compared with placebo if calculation is based on a difference of 20% found between the atypical antipsychotic and placebo and 2,054 if the difference sought were that found between the atypical antipsychotic and the typical antipsychotic, i.e. 6%. The estimated therapeutic failures would be 115 of the 166 patients when the study drug is compared with placebo, and 1,274 failures in the 2,054 patients when the study drug is compared to the typical antipsychotic. CONCLUSIONS: Placebo controlled studies may reduce the number of individuals exposed to the harmful effects of ineffective drugs.

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