Novel Benzothiazolin-2-one and Benzoxazin-3-one Arylpiperazine Derivatives with Mixed 5HT<sub>1A</sub>/D<sub>2</sub>Affinity as Potential Atypical Antipsychotics

Taverne, Thierry; Diouf, Ousmane; Depreux, Patrick; Poupaert, Jacques H.; Lesieur, D.; Guardiola‐Lemaître, B.; Renard, Pierre; Rettori, Marie-Claire; Caignard, Daniel‐Henri; Pfeiffer, Bruno

doi:10.1021/jm970298c

Cited by 42 publications

(20 citation statements)

References 27 publications

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“…In view of the potential therapeutic interest for this class of compounds, compounds of general structure 30 were synthesized [69][70][71][72][73][74][75] (Fig. 7).…”

Section: Design Of Pharmacological Probesmentioning

confidence: 99%

2(3H)-Benzoxazolone and Bioisosters as “Privileged Scaffold” in the Design of Pharmacological Probes

Poupaert

Carato²,

Colacino³

et al. 2005

CMC

185

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The 2(3H)-benzoxazolone heterocycle and its bioisosteric surrogates (such as 2(3H)-benzothiazolinone, benzoxazinone, etc.) have received considerable attention from the medicinal chemists owing to their capacity to mimic a phenol or a catechol moiety in a metabolically stable template. These heterocycles and pyrocatechol have indeed similar pKa's, electronic charge distribution, and chemical reactivity. Therapeutic applications of this template are very broad, and range from analgesic anti-inflammatory compounds (including PPAR-gamma antagonists) to antipsychotic and neuroprotective anticonvulsant compounds. High affinity ligands have been obtained also for dopaminergic (D2 and D4), serotoninergic (5-HT1A and 5-HT-2A), sigma-1 and sigma-2 receptors. Owing to the high number of positive hits encountered with this heterocycle and its congeners, 2(3H)-benzoxazolone template certainly deserves the title of "privileged scaffold" in medicinal chemistry.

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“…In view of the potential therapeutic interest for this class of compounds, compounds of general structure 30 were synthesized [69][70][71][72][73][74][75] (Fig. 7).…”

Section: Design Of Pharmacological Probesmentioning

confidence: 99%

2(3H)-Benzoxazolone and Bioisosters as “Privileged Scaffold” in the Design of Pharmacological Probes

Poupaert

Carato²,

Colacino³

et al. 2005

CMC

185

View full text Add to dashboard Cite

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“…The drugs that contain imidazopyridine moiety such as zolimidine, saripidem, alpidem, necopidem, GSK812397 and zolpidem (Figure ) were clinically used, while piperazine moieties are significant pharmacophores in chemotherapy among various heterocycles for their various biological activities . Therefore, in the preset work we designed a novel series of imidazopyridine derivatives to investigate their anticancer activity against various cancer cell lines.…”

Section: Introductionmentioning

confidence: 99%

Design and Synthesis of Piperazine‐Linked Imidazo[1,2‐a]pyridine Derivatives as Potent Anticancer Agents

et al. 2019

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Designed, synthesized a series of novel imidazo[1,2-a]pyridine derivatives and evaluated for their in vitro cytotoxicity. Fluorine containing compounds, (2-fluorophenyl)(4-(2-(pyridin-2-yl)imidazo[1,2-a]pyridin-6-yl)piperazin-1-yl)methanone (7 e),(4-(2-(pyridin-2-yl)imidazo[1,2-a]pyridin-6-yl)piperazin-1-yl)(2-(trifluoromethyl)phenyl)methanone (7 h) and (3-fluorophenyl) (4-(2-(pyridin-2-yl)imidazo[1,2-a]pyridin-6-yl)piperazin-1-yl)methanone (7 i) were found to have an effective cytotoxic profile against HepG2, HeLa and MDA-MB-231. Compounds 7 h (IC 50 = 5.8 μM) and 7 i (IC 50 = 3.5 μM) were found potent when compared with control Paclitaxel (IC 50 = 2.8 μM), against HeLa. Compound 7 h also found to be potent against HepG2 (IC 50 = 2.0 μM) and MDAMB-231(IC 50 = 6.9 μM) respectively, when compared with Paclitaxel (HepG2, IC 50 = 0.56 μM; MDAMB-231, IC 50 = 1.9 μM). Compound 7 e also found to be potent against HepG2 (IC 50 = 9.8 μM) cell lines. Synthesized piperazine linked imidazo[1,2-a]pyridine derivatives (7 i, IC 50 = 3.5 μM) and (7 h, IC 50 = 5.8 μM) showed 1.74 fold, 1.12 fold increase in antiproliferative activity than reported homopiperazine linked imidazo [1,2-a]pyrimidine derivatives (4-Fluorophenyl)(4-(2-(4fluorophenyl)imidazo[1,2-a]pyrimidin-7-yl)-1,4-diazepan-1-yl)methanone(10 f, IC 50 = 6.12 μM) and (4-(2-(4-Fluorophenyl)imidazo[1,2-a]pyrimidin-7-yl)-1,4-diazepan-1-yl)(3methoxyphenyl)methanone (12, IC 50 = 6.54 μM) against Hela cell lines. Molecular docking studies showed that designed compounds occupy at the active site of both colchicine and human estrogen receptor which demonstrated that the designed compounds were able to bind with multiple targets, the biological activity of these compounds hold promise to find application in considering for treatment protocol.[a] M.

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“…Effect of aryl piperazine substitution on bezothiazolin-2-one has been evaluated for D 2 and 5HT 2 antagonist activities (Taverne et al, 1998). We have selected these substituents in the amine series.…”

Section: Resultsmentioning

confidence: 99%

“…The discovery of new effective drugs for the treatment of the psychiatric disorders such as schizophrenia still remains a top priority as it affects approximately 1% of the world population (Taverne et al, 1998). Schizophrenia is a chronic and severe disabling mental illness independent of sex, location, social class, or color of the skin (Evans et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Benzo[d][1,3] oxathiols: synthesis and biological evaluation as potential atypical antipsychotic agents

et al. 2009

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The present research paper reports the synthesis and biological evaluation of 6-(3-substitutedpropoxyl)benzo[d] [1,3]oxathiol-2-ones as potential atypical antipsychotic agents. Accordingly, 10 derivatives with either amino or aryloxy substituents were synthesized. Potential antipsychotic activity of these compounds in terms of D 2 antagonism was evaluated by their ability to inhibit apomorphine-induced climbing behavior in mice and 5-HT 2 antagonistic activity of synthesized compounds was assessed by studying inhibition of 5-HTP-induced head twitches. Non-specific D 2 blockade was evaluated by studying propensity of these compounds to produce catalepsy in mice. All the synthesized compounds were found to exhibit D 2 and 5-HT 2 antagonist activity in behavioral models. However, they also induced mild to severe catalepsy. Among the 10 compounds tested, 5b and 5e exhibited maximum 'atypical antipsychotic activity like' profile.

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Novel Benzothiazolin-2-one and Benzoxazin-3-one Arylpiperazine Derivatives with Mixed 5HT_1A/D₂Affinity as Potential Atypical Antipsychotics

Cited by 42 publications

References 27 publications

2(3H)-Benzoxazolone and Bioisosters as “Privileged Scaffold” in the Design of Pharmacological Probes

2(3H)-Benzoxazolone and Bioisosters as “Privileged Scaffold” in the Design of Pharmacological Probes

Design and Synthesis of Piperazine‐Linked Imidazo[1,2‐a]pyridine Derivatives as Potent Anticancer Agents

Benzo[d][1,3] oxathiols: synthesis and biological evaluation as potential atypical antipsychotic agents

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Novel Benzothiazolin-2-one and Benzoxazin-3-one Arylpiperazine Derivatives with Mixed 5HT1A/D2Affinity as Potential Atypical Antipsychotics

Cited by 42 publications

References 27 publications

2(3H)-Benzoxazolone and Bioisosters as &#x201C;Privileged Scaffold&#x201D; in the Design of Pharmacological Probes

2(3H)-Benzoxazolone and Bioisosters as &#x201C;Privileged Scaffold&#x201D; in the Design of Pharmacological Probes

Design and Synthesis of Piperazine‐Linked Imidazo[1,2‐a]pyridine Derivatives as Potent Anticancer Agents

Benzo[d][1,3] oxathiols: synthesis and biological evaluation as potential atypical antipsychotic agents

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Novel Benzothiazolin-2-one and Benzoxazin-3-one Arylpiperazine Derivatives with Mixed 5HT_1A/D₂Affinity as Potential Atypical Antipsychotics

2(3H)-Benzoxazolone and Bioisosters as “Privileged Scaffold” in the Design of Pharmacological Probes

2(3H)-Benzoxazolone and Bioisosters as “Privileged Scaffold” in the Design of Pharmacological Probes