3-[[(Aryloxy)alkyl]piperidinyl]-1,2-Benzisoxazoles as D2/5-HT2 Antagonists with Potential Atypical Antipsychotic Activity: Antipsychotic Profile of Iloperidone (HP 873)

1995 ◽  
Vol 38 (7) ◽  
pp. 1119-1131 ◽  
Author(s):  
Joseph T. Strupczewski ◽  
Kenneth J. Bordeau ◽  
Yulin Chiang ◽  
Edward J. Glamkowski ◽  
Paul G. Conway ◽  
...  
Keyword(s):  
Atypical Antipsychotic ◽  
Antipsychotic Activity

scholarly journals Synthesis, Computational Studies and Preliminary Pharmacological Evaluation of New Arylpiperazines

2011 ◽  
Vol 8 (3) ◽  
pp. 1044-1051
Author(s):  
Sushil Kumar ◽  
A. K. Wahi ◽  
Ranjit Singh
Keyword(s):  
Atypical Antipsychotic ◽  
Computational Studies ◽  
Lead Compound ◽  
Physiochemical Properties ◽  
Pharmacological Evaluation ◽  
Climbing Behavior ◽  
Head Twitches ◽  
Antipsychotic Activity ◽  
Albino Mice ◽  
Software Programs

A series of novel arylpiperazines were synthesized and the target compounds evaluated for atypical antipsychotic activity in apomorphine induced climbing behavior (D2antagonism), 5-HTP induced head twitches (5-HT2Aantagonism) and catalepsy studies in albino mice. The physicochemical similarity of the target compounds with respect to standard drugs clozapine, ketanserine and risperidone was assessed by calculating from a set of physiochemical properties using software programs. The test compounds(3a-j)demonstrated good similarity values with respect to the standard drugs. Among them, compound3dhas emerged as an important lead compound showing potential atypical antipsychotic like profile.

ChemInform Abstract: Enhanced D1 Affinity in a Series of Piperazine Ring Substituted 1- Piperazino-3-arylindans with Potential Atypical Antipsychotic Activity.

ChemInform ◽  
2010 ◽  
Vol 27 (10) ◽  
pp. no-no
Author(s):  
K. P. BOEGESOE ◽  
J. ARNT ◽  
K. FREDERIKSEN ◽  
H. O. HANSEN ◽  
J. HYTTEL ◽  
...  
Keyword(s):  
Atypical Antipsychotic ◽  
Piperazine Ring ◽  
Antipsychotic Activity ◽  
Substituted 1

BTS 73 947, a novel D1/D5 antagonist with predicted atypical antipsychotic activity

1996 ◽  
Vol 6 ◽  
pp. 105 ◽  
Author(s):  
P.L. Needham ◽  
D.J. Heal ◽  
B.J. Sargent ◽  
W.R. Buckett
Keyword(s):  
Atypical Antipsychotic ◽  
Antipsychotic Activity

scholarly journals NEW 7-(2-(BENZOL[d]THIAZOL-2-YLAMINO)ETHOXY)-4-METHYL-2HCHROMEN-2-0NE DERIVATIES WITH ATYPICAL ANTIPSYCHOTIC ACTIVITY

2013 ◽  
Vol 21 (21) ◽  
pp. 97-108
Author(s):  
Gawai ASHISH ◽  
Das SANJIB ◽  
Yasbwant PATHAK
Keyword(s):  
Atypical Antipsychotic ◽  
Dopamine D2 Receptor ◽  
Analytical Data ◽  
D2 Receptor ◽  
Antipsychotic Agents ◽  
Antagonistic Activity ◽  
High Potency ◽  
Climbing Behavior ◽  
Head Twitches ◽  
Antipsychotic Activity

A new series of 7-(2-(benzo[d]thiazol-2-ylamino)ethoxy)-4-methyl-2H-chromen-2-one derivatives(4a4k) was synthesized and evaluated for their D2 and 51HT2 antagonistic activity as a measure of atypical antipsychotic properly. Compounds 7-(2-(benzo[d]thiazo/-2-ylamino)ethoxy)-4-methyl-2H-chromen-2- one derivatives (4a-4k) was synthesized by refluxing 2-amino benzothiazoles substituted derivatives (3a3k) and 7-(2-Chloroethoxy)-4-melhyl-2H-chromen-2-one (2) in dry pyridine. The synthesized compounds were characterized with the help of spectral and analytical data. Most of these compounds showed dopamine D2 receptor antagonistic activity from moderate to high potency along with serotonin 5-HT2 receptor blockage activity: a property that has been suggested to be necessary for the atypical nature of antipsychotic agents. The D2 and 5-HT2 receptor blockage activity was evaluated by inhibition of apomorphine-induced climbing behavior and 5HTP induced head twitches in mice respectively.

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.

8-Substituted 3,4-dihydroquinolinones as a novel scaffold for atypical antipsychotic activity

2005 ◽  
Vol 15 (20) ◽  
pp. 4560-4563 ◽  
Author(s):  
Jamie M. Singer ◽  
Bridget M. Barr ◽  
Linda L. Coughenour ◽  
Tracy F. Gregory ◽  
Michael A. Walters
Keyword(s):  
Atypical Antipsychotic ◽  
Antipsychotic Activity ◽  
Novel Scaffold

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.

Aminimides as Potential CNS Acting Agents. II Design, Synthesis, and Receptor Binding of 4′-Arylalkyl Aminimide Analogues of Clozapine as Prospective Novel Antipsychotics

2008 ◽  
Vol 61 (1) ◽  
pp. 5 ◽  
Author(s):  
Ben Capuano ◽  
Ian T. Crosby ◽  
Edward J. Lloyd ◽  
Juliette E. Neve ◽  
David A. Taylor
Keyword(s):  
Atypical Antipsychotic ◽  
Receptor Binding ◽  
Structural Characterization ◽  
Marked Reduction ◽  
Second Generation ◽  
Functional Group ◽  
Design Synthesis ◽  
Biochemical Effects ◽  
Antipsychotic Activity

We report the synthesis of a series of second generation aminimide-based analogues of clozapine, investigating the length of the linker between the aminimide functional group and the introduced aryl moiety. The chemistry and structural characterization of this series of 4′-arylalkyl aminimide analogues of clozapine are described. Preliminary findings on the biochemical effects of linker length and type of aryl moiety on affinity for dopamine D4 and serotonin 5-HT2A receptors are discussed. All of the compounds showed a marked reduction in binding at the two receptors when compared with clozapine, thus showing a reduced potential for atypical antipsychotic activity.

Sign in / Sign up

Export Citation Format

Share Document