Direct and Indirect Drug Design Approaches for the Development of Novel Tricyclic Antipsychotics: Potential 5‐HT<sub>2A</sub> Antagonist

Jadhav, Mahantesh; Kokil, Ganesh R.; Harak, Shilpa Sudhakar; Wagh, Sanjay B

doi:10.1155/2013/930354

Cited by 3 publications

(1 citation statement)

References 18 publications

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“…Given literature reports citing the importance of both basic amino functionality and a hydrophobic substituent (e.g., chloroaryl group) for optimal receptor binding [15,16], a more elaborate substrate 5 was also prepared from hydrazide 4 (readily available from m-chloro-o-toluic acid), leading to the target compound in 87% yield (see Scheme 3). Given the impressive results with the MW Pellizzari reaction, a second family of analogues were prepared which contain the chloroaryl functionality on the parent tricyclic ring system.…”

Section: Resultsmentioning

confidence: 99%

Flow and Microwave Induced Pellizzari Reactions: Synthesis of Heterocyclic Analogues of the Benzoxazepine Antipsychotic Agents Loxapine and JL-13

Ranasinghe

Mongeau

Yuan

et al. 2017

Advances in Chemistry

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An expeditious route to fused triazolo-pyrido benzoxazepines has been developed using flow and microwave-mediated cyclization chemistry. A range of substituted aryl hydrazides are coupled with a core chloroimine in good to excellent yield via a Pellizzari type process, producing 1,2,4-triazolo-pyrido [2,3-b] [1,5] benzoxazepines with structural similarity to known antipsychotic agents. Modifications allow for strategically functionalized derivatives, and installation of a fluoro group for use in PET imaging is also demonstrated. Given the affinity of the tricyclic core for 5-HT and dopamine receptors, the derivatives are expected to find utility in CNS research.

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Section: Resultsmentioning

confidence: 99%

Flow and Microwave Induced Pellizzari Reactions: Synthesis of Heterocyclic Analogues of the Benzoxazepine Antipsychotic Agents Loxapine and JL-13

Ranasinghe

Mongeau

Yuan

et al. 2017

Advances in Chemistry

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Computational Approaches in Multitarget Drug Discovery

Scotti

Ishiki

Duarte

et al. 2018

Methods in Molecular Biology

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Current therapeutic strategies entail identifying and characterizing a single protein receptor whose inhibition is likely to result in the successful treatment of a disease of interest, and testing experimentally large libraries of small molecule compounds "in vitro" and "in vivo" to identify promising inhibitors in model systems and determine if the findings are extensible to humans. This highly complex process is largely based on tests, errors, risk, time, and intensive costs. The virtual computational study of compounds simulates situations predicting possible drug linkages with multiple protein target atomic structures, taking into account the dynamic protein inhibitor, and can help identify inhibitors efficiently, particularly for complex drug-resistant diseases. Some discussions will relate to the potential benefits of this approach, using HIV-1 and Plasmodium falciparum infections as examples. Some authors have proposed a virtual drug discovery that not only identifies efficient inhibitors but also helps to minimize side effects and toxicity, thus increasing the likelihood of successful therapies. This chapter discusses concepts and research of bioactive multitargets related to toxicology.

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Design, Synthesis, Molecular Docking, and Preliminary Pharmacological Screening of some New Benzo[d]thiazol-2-ylamino Containing Chromen-2- one Derivatives with Atypical Antipsychotic Profile

Dhawale¹,

Gawai²,

Biyani

et al. 2023

CAD

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Introduction: Mental disorders are very serious complicated disorders. Schizophrenia is one of the most baffling mental disorders. The new series 7-(2-(benzo[d]thiazol-2-ylamino)ethoxy)-4-methyl-2H-chromen-2- 1(4a-4k) was synthesized in search of newer compounds for Schizophrenia. Methods: Synthesis is done by refluxing in dry pyridine with various substituted 2-amino benzothiazoles derivatives (3a-3k) and 7-(2-Chloroethoxy)-4-methyl-2H-chromen-2-one(2). The molecular docking approach was used to screen these generated derivatives. Chem Bio Draw Ultra 12 was used to draw the compounds, which were then exposed to all potential conformations of compounds interacting with receptors. The Glide 7.6, Schrodinger 2017 Maestro 11.3 was used to achieve molecular docking. The Dopamine receptor 6CM4 serotonin 5TUD PDBs were acquired from the database of Brookhaven Protein. Using the OPLS 2005 force field, the ligand-protein hydrogen-bond network was acquired, along with the overall energy reduced. A glide score was used to rate the docking poses. Results: The produced compounds have been identified with the use of analytical and spectral data. All of the produced substances were tested and analyzed for serotonin 5HT2 antagonistic and dopamine D2 activity, which can be considered as a measure of typical antipsychotic properties. Conclusion: Compounds 4b, 4c, 4e, 4g & 4i have demonstrated promising pharmacological action in preliminary studies. According to the preceding findings, compounds with electron-withdrawing substitutions, such as 4e & 4b, have a good atypical profile of antipsychotics

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Direct and Indirect Drug Design Approaches for the Development of Novel Tricyclic Antipsychotics: Potential 5‐HT_2A Antagonist

Cited by 3 publications

References 18 publications

Flow and Microwave Induced Pellizzari Reactions: Synthesis of Heterocyclic Analogues of the Benzoxazepine Antipsychotic Agents Loxapine and JL-13

Flow and Microwave Induced Pellizzari Reactions: Synthesis of Heterocyclic Analogues of the Benzoxazepine Antipsychotic Agents Loxapine and JL-13

Computational Approaches in Multitarget Drug Discovery

Design, Synthesis, Molecular Docking, and Preliminary Pharmacological Screening of some New Benzo[d]thiazol-2-ylamino Containing Chromen-2- one Derivatives with Atypical Antipsychotic Profile

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Direct and Indirect Drug Design Approaches for the Development of Novel Tricyclic Antipsychotics: Potential 5‐HT2A Antagonist

Cited by 3 publications

References 18 publications

Flow and Microwave Induced Pellizzari Reactions: Synthesis of Heterocyclic Analogues of the Benzoxazepine Antipsychotic Agents Loxapine and JL-13

Flow and Microwave Induced Pellizzari Reactions: Synthesis of Heterocyclic Analogues of the Benzoxazepine Antipsychotic Agents Loxapine and JL-13

Computational Approaches in Multitarget Drug Discovery

Design, Synthesis, Molecular Docking, and Preliminary Pharmacological Screening of some New Benzo[d]thiazol-2-ylamino Containing Chromen-2- one Derivatives with Atypical Antipsychotic Profile

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Direct and Indirect Drug Design Approaches for the Development of Novel Tricyclic Antipsychotics: Potential 5‐HT_2A Antagonist