Delving into the Latest Updates on Adoprazine Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

1-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-4- [5-(4-fluoro-phenyl)-pyridin-3-ylmethyl]-piperazine monohydrochloride, adoprazine, 阿哆嗪

+ [2]

Target

5-HT1A receptor x D2 receptor x D3 receptor

Mechanism

5-HT1A receptor agonists(Serotonin 1a (5-HT1a) receptor agonists), D2 receptor antagonists(Dopamine D2 receptor antagonists), D3 receptor antagonists(Dopamine D3 receptor antagonists)

Therapeutic Areas

Other Diseases

Active Indication-

Inactive Indication

Bipolar DisorderSchizoaffective disorderSchizophrenia

Originator Organization

Abbott Laboratories

Active Organization-

Inactive Organization

Abbott Laboratories

Solvay SA

Solvay Pharmaceuticals, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC24H25ClFN3O2

InChIKeyPAPGPUNOWOEIPA-UHFFFAOYSA-N

CAS Registry222551-05-5

On the basis of the structures of serotonin modulators or drugs (NAN-190, buspirone, aripiprazole) and phosphodiesterase 4 (PDE4) inhibitors (rolipram, RO-20-1724), a series of novel multitarget 5-arylidenehydantoin derivatives with arylpiperazine fragment was synthesized. Among these compounds, 5-(3,4-dimethoxybenzylidene-3-(4-(4-(2,3-dichlorophenyl)piperazine-1-yl)butyl)-imidazolidine-2,4-dione (13) and 5-(3-cyclopentyloxy-4-methoxybenzylidene-3-(4-(4-(2-methoxyphenyl)piperazine-1-yl)butyl)-imidazolidine-2,4-dione (18) were found to be the most promising showing very high affinity toward 5-HT_1A and 5-HT₇ receptors (K_i = 0.2-1.0 nM) but a negligible inhibitory effect on PDE4. The high affinity of the compounds for 5-HT_1A and 5-HT₇ receptors was further investigated by computer-aided studies. Moreover, compounds 13 and 18 showed no significant cytotoxicity in the MTT assay, but high clearance in the in vitro assay. In addition, these compounds behaved like 5-HT_1A and 5-HT₇ receptor antagonists and exhibited antidepressant-like activity, similar to the reference drug citalopram, in an animal model of depression.

31 May 2014·Medicinal ChemistryQ4 · MEDICINE

Synthesis and Dual D2 and 5-HT1A Receptor Binding Affinities of 7-piperazinyl and 7-piperidinyl-3,4-dihydroquinazolin-2(1H)-ones

Q4 · MEDICINE

Article

Author: Ullah, Nisar

A series of new 7-piperazinyl and 7-piperidinyl-3,4-dihydroquinazolin-2(1H)-ones has been synthesized. The described compounds are structurally related to adoprazine, a potential atypical antipsychotic bearing potent D2 receptor antagonist and 5-HT1A receptor agonist properties. Suitably modified aryl bromides were prepared and condensed with tert-butyl piperazine-1-carboxylate to afford the advanced intermediate piperazinyl-3,4-dihydroquinazolin-2(1H)-one. Likewise Suzuki-Miyaura cross-coupling reaction of cyclic vinyl boronate with appropriate aryl bromides rendered piperidinyl-3,4-dihydroquinazolin-2(1H)-one. The reductive amination of the piperazinyl and piperidinyl-3,4- dihydroquinazolin-2(1H)-ones with suitably designed biarylaldehydes accomplished the synthesis of these title compounds. The described compounds were screened for D2 and 5-HT1A receptors binding affinities. The structure-activity relationship studies revealed that cyclopentenylpyridine and cyclopentenylbenzyl groups contribute significantly to the dual D2 and 5-HT1A receptor binding affinities of these compounds.

31 Dec 2013·Current Medicinal Chemistry

Dual Ligands Targeting Dopamine D2 and Serotonin 5-HT1A Receptors as New Antipsychotical or Anti-Parkinsonian Agents

Review

Author: Na Ye ; Ao Zhang ; Zilan Song

Psychiatric disorders like schizophrenia and neurodegenerative diseases like Parkinson's disease are associated with poly-factorial pathogenic mechanisms, with several neurotransmitter systems closely involved. In addition to the cerebral dopaminergic (DA) system, the serotoninergic (5-HT) system also plays a crucial role in regulating psychoemotional, cognitive and motor functions in the central nervous system (CNS). Among the large 5-HT receptor family, accumulating data have revealed new insights into the therapeutic benefit of the 5-HT1A receptor in treating various CNS disorders, especially schizophrenia and Parkinson's disease. The present review discusses the advance of dual agents with mixed actions at the dopamine D2 and serotonin 5-HT1A receptors in the treatment of these diseases. Aripiprazole was the only marketed drug with dual D2 and 5-HT1A profile. It is a partial D2 and 5-HT1A receptor agonist and has been prescribed as an atypical antipsychotical drug. Two other drugs Cariprazine and Pardoprunox are being investigated in clinic. Most of the other candidate compounds, including Bifeprunox, Sarizotan, Mazapertine succinate, PF-217830, and Adoprazine were discontinued due to either non-optimal pharmacokinetic properties or insufficient therapeutical efficacy. Although much effort has been done to highlight the advantages of the 5-HT1A and D2 dual approach, it has to be pointed out that many of these drugs showed poly-pharmacological profile by targeting many other receptors and/or transporters besides the D2 and 5-HT1A receptors. In this regard, 'pure' compounds exclusively acting on the D2 and 5-HT1A receptors are highly needed to further validate this approach. Meanwhile, safety concerns and in vivo pharmacokinetic alerts should also be implanted to the drug design art early.

100 Deals associated with Adoprazine Hydrochloride

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Schizoaffective disorder	Phase 2	-	Solvay Pharmaceuticals, Inc.	01 Jan 2008
Bipolar Disorder	Phase 2	US	Solvay SA	-
Schizophrenia	Phase 2	-	Abbott Laboratories	-
Schizophrenia	Phase 2	EU	Solvay SA	-