... Sopkova-de Oliveira Santos, Christophe Rochais, Vincent Lisowski, Jean-Charles Lancelot, and ... more ... Sopkova-de Oliveira Santos, Christophe Rochais, Vincent Lisowski, Jean-Charles Lancelot, and Sylvain Rault. Centre d'Etudes et de Recherche sur le Médicament de Normandie, Université de Basse-Normandie, 5, rue Vaubénard, 14032 Caen, France. J. Chem. Inf. Model. ...
The synthesis of a series of benzo(iso)quinoline and phenanthroline derivatives has been achieved... more The synthesis of a series of benzo(iso)quinoline and phenanthroline derivatives has been achieved using an efficient one-pot procedure. It proceeds through a Suzuki–Miyaura cross-coupling followed by a Dieckmann–Thorpe ring closure under microwave irradiation and provides easy access to building blocks not readily available through other methods.
We herein describe the synthesis of novel 3-(het)aryl-pyrrolo[2,3-b]pyrrolizin-8(1H)-ones startin... more We herein describe the synthesis of novel 3-(het)aryl-pyrrolo[2,3-b]pyrrolizin-8(1H)-ones starting from commercial (het)aryl-acetonitriles. A more convergent route was also described through the first synthesis of ethyl 3-amino-4-bromo-1H-pyrrole-2-carboxylate 17. The antiproliferative activities of these compounds were tested toward various cell lines and one of them 10k shows interesting cytotoxic properties, although it was less potent than our lead compound in thiophene series
5-HT4 and 5-HT6 serotonergic receptors are located in brain structures involved in memory process... more 5-HT4 and 5-HT6 serotonergic receptors are located in brain structures involved in memory processes. Neurochemical and behavioural studies have demonstrated that acute activation of 5-HT4 receptors (5-HT4R) or blockade of 5-HT6 receptors (5-HT6R) improves memory. To evaluate the potential of these two receptors as targets in the treatment of memory disorders encountered in several situations (ageing, Alzheimer's disease, schizophrenia, etc.), it is necessary to assess whether their beneficial effects occur after chronic administration, and if such treatment induces adverse effects. The goal of this study was to assess the effects of chronic 5-HT4R or 5-HT6R modulation on recognition memory, and to observe the possible manifestation of side effects (modification of weight gain, locomotor activity or exploratory behaviour, etc.). Mice were treated for 14 days with a 5-HT4R partial agonist (RS-67333) or a 5-HT6R antagonist (SB-271046) at increasing doses. Memory performances, locomotor activity, and exploration were assessed. Both chronic 5-HT4R activation and 5-HT6R blockade extended memory traces in an object recognition test, and were not associated with any adverse effects in the parameters assessed. Chronic modulation of one or both of these receptors thus seems promising as a potential strategy for the treatment memory deficits.
A one-pot Suzuki—Miyaura cross-coupling/Dieckmann—Thorpe ring closure protocol under microwave ir... more A one-pot Suzuki—Miyaura cross-coupling/Dieckmann—Thorpe ring closure protocol under microwave irradiation allows the introduction of diversity on various positions of the phenanthrene ring system.
Given its predominant expression in the central nervous system (CNS), 5-hydroxytryptamine (5-HT: ... more Given its predominant expression in the central nervous system (CNS), 5-hydroxytryptamine (5-HT: serotonin) subtype 6 receptor (5-HT6R) has been considered as a valuable target for the development of CNS drugs with limited side effects. After two decades of intense research, numerous selective ligands have been developed to target this receptor; this holds potential interest for the treatment of neuropathological disorders. In fact, some agents - mainly antagonists - are currently undergoing clinical trial. More recently a series of potent and selective agonists have been developed, and preclinical studies have been conducted that suggest the therapeutic interest of 5-HT6R agonists. This Perspective details the medicinal chemistry of these agonists, highlights their activities, and discusses their potential for treating cognitive issues associated with Alzheimer's disease (AD), depression or obesity. Surprisingly some studies have shown that both 5-HT6R agonists and antagonists exert similar procognitive activities. This article summarizes the hypotheses that could explain this paradox.
An efficient synthesis of 9,10-disubstituted phenanthrenes is described in this Letter. These nov... more An efficient synthesis of 9,10-disubstituted phenanthrenes is described in this Letter. These novel useful building blocks were obtained in a one-pot reaction including Suzuki–Miyaura cross-coupling followed by a Dieckmann–Thorpe ring closure under microwave irradiation. The selection of the appropriate reagents and the optimal reaction conditions to isolate the intermediate biphenyl compound or the final substituted phenanthrenes in high yields will
Proceedings of the National Academy of Sciences of the United States of America, Jan 9, 2014
RS67333 is a partial serotonin subtype 4 receptor (5-HT4R) agonist that has been widely studied f... more RS67333 is a partial serotonin subtype 4 receptor (5-HT4R) agonist that has been widely studied for its procognitive effect. More recently, it has been shown that its ability to promote the nonamyloidogenic cleavage of the precursor of the neurotoxic amyloid-β peptide leads to the secretion of the neurotrophic protein sAPPα. This effect has generated great interest in RS67333 as a potential treatment for Alzheimer's disease (AD). We show herein that RS67333 is also a submicromolar acetylcholinesterase (AChE) inhibitor and therefore, could contribute, through this effect, to the restoration of the cholinergic neurotransmission that becomes altered in AD. We planned to pharmacomodulate RS67333 to enhance its AChE inhibitory activity to take advantage of this pleiotropic pharmacological profile in the design of a novel multitarget-directed ligand that is able to exert not only a symptomatic but also, a disease-modifying effect against AD. These efforts allowed us to select donecopr...
ABSTRACT A one-pot synthesis of novel poly-substituted phenanthrenes is described in this article... more ABSTRACT A one-pot synthesis of novel poly-substituted phenanthrenes is described in this article through a Suzuki–Miyaura cross-coupling followed by a Dieckmann–Thorpe ring closure under microwave irradiation. The selection of the appropriate starting materials allowed us to introduce diversity on various positions of the phenanthrene ring system.
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
... Sopkova-de Oliveira Santos, Christophe Rochais, Vincent Lisowski, Jean-Charles Lancelot, and ... more ... Sopkova-de Oliveira Santos, Christophe Rochais, Vincent Lisowski, Jean-Charles Lancelot, and Sylvain Rault. Centre d'Etudes et de Recherche sur le Médicament de Normandie, Université de Basse-Normandie, 5, rue Vaubénard, 14032 Caen, France. J. Chem. Inf. Model. ...
The synthesis of a series of benzo(iso)quinoline and phenanthroline derivatives has been achieved... more The synthesis of a series of benzo(iso)quinoline and phenanthroline derivatives has been achieved using an efficient one-pot procedure. It proceeds through a Suzuki–Miyaura cross-coupling followed by a Dieckmann–Thorpe ring closure under microwave irradiation and provides easy access to building blocks not readily available through other methods.
We herein describe the synthesis of novel 3-(het)aryl-pyrrolo[2,3-b]pyrrolizin-8(1H)-ones startin... more We herein describe the synthesis of novel 3-(het)aryl-pyrrolo[2,3-b]pyrrolizin-8(1H)-ones starting from commercial (het)aryl-acetonitriles. A more convergent route was also described through the first synthesis of ethyl 3-amino-4-bromo-1H-pyrrole-2-carboxylate 17. The antiproliferative activities of these compounds were tested toward various cell lines and one of them 10k shows interesting cytotoxic properties, although it was less potent than our lead compound in thiophene series
5-HT4 and 5-HT6 serotonergic receptors are located in brain structures involved in memory process... more 5-HT4 and 5-HT6 serotonergic receptors are located in brain structures involved in memory processes. Neurochemical and behavioural studies have demonstrated that acute activation of 5-HT4 receptors (5-HT4R) or blockade of 5-HT6 receptors (5-HT6R) improves memory. To evaluate the potential of these two receptors as targets in the treatment of memory disorders encountered in several situations (ageing, Alzheimer's disease, schizophrenia, etc.), it is necessary to assess whether their beneficial effects occur after chronic administration, and if such treatment induces adverse effects. The goal of this study was to assess the effects of chronic 5-HT4R or 5-HT6R modulation on recognition memory, and to observe the possible manifestation of side effects (modification of weight gain, locomotor activity or exploratory behaviour, etc.). Mice were treated for 14 days with a 5-HT4R partial agonist (RS-67333) or a 5-HT6R antagonist (SB-271046) at increasing doses. Memory performances, locomotor activity, and exploration were assessed. Both chronic 5-HT4R activation and 5-HT6R blockade extended memory traces in an object recognition test, and were not associated with any adverse effects in the parameters assessed. Chronic modulation of one or both of these receptors thus seems promising as a potential strategy for the treatment memory deficits.
A one-pot Suzuki—Miyaura cross-coupling/Dieckmann—Thorpe ring closure protocol under microwave ir... more A one-pot Suzuki—Miyaura cross-coupling/Dieckmann—Thorpe ring closure protocol under microwave irradiation allows the introduction of diversity on various positions of the phenanthrene ring system.
Given its predominant expression in the central nervous system (CNS), 5-hydroxytryptamine (5-HT: ... more Given its predominant expression in the central nervous system (CNS), 5-hydroxytryptamine (5-HT: serotonin) subtype 6 receptor (5-HT6R) has been considered as a valuable target for the development of CNS drugs with limited side effects. After two decades of intense research, numerous selective ligands have been developed to target this receptor; this holds potential interest for the treatment of neuropathological disorders. In fact, some agents - mainly antagonists - are currently undergoing clinical trial. More recently a series of potent and selective agonists have been developed, and preclinical studies have been conducted that suggest the therapeutic interest of 5-HT6R agonists. This Perspective details the medicinal chemistry of these agonists, highlights their activities, and discusses their potential for treating cognitive issues associated with Alzheimer's disease (AD), depression or obesity. Surprisingly some studies have shown that both 5-HT6R agonists and antagonists exert similar procognitive activities. This article summarizes the hypotheses that could explain this paradox.
An efficient synthesis of 9,10-disubstituted phenanthrenes is described in this Letter. These nov... more An efficient synthesis of 9,10-disubstituted phenanthrenes is described in this Letter. These novel useful building blocks were obtained in a one-pot reaction including Suzuki–Miyaura cross-coupling followed by a Dieckmann–Thorpe ring closure under microwave irradiation. The selection of the appropriate reagents and the optimal reaction conditions to isolate the intermediate biphenyl compound or the final substituted phenanthrenes in high yields will
Proceedings of the National Academy of Sciences of the United States of America, Jan 9, 2014
RS67333 is a partial serotonin subtype 4 receptor (5-HT4R) agonist that has been widely studied f... more RS67333 is a partial serotonin subtype 4 receptor (5-HT4R) agonist that has been widely studied for its procognitive effect. More recently, it has been shown that its ability to promote the nonamyloidogenic cleavage of the precursor of the neurotoxic amyloid-β peptide leads to the secretion of the neurotrophic protein sAPPα. This effect has generated great interest in RS67333 as a potential treatment for Alzheimer's disease (AD). We show herein that RS67333 is also a submicromolar acetylcholinesterase (AChE) inhibitor and therefore, could contribute, through this effect, to the restoration of the cholinergic neurotransmission that becomes altered in AD. We planned to pharmacomodulate RS67333 to enhance its AChE inhibitory activity to take advantage of this pleiotropic pharmacological profile in the design of a novel multitarget-directed ligand that is able to exert not only a symptomatic but also, a disease-modifying effect against AD. These efforts allowed us to select donecopr...
ABSTRACT A one-pot synthesis of novel poly-substituted phenanthrenes is described in this article... more ABSTRACT A one-pot synthesis of novel poly-substituted phenanthrenes is described in this article through a Suzuki–Miyaura cross-coupling followed by a Dieckmann–Thorpe ring closure under microwave irradiation. The selection of the appropriate starting materials allowed us to introduce diversity on various positions of the phenanthrene ring system.
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
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Papers by Christophe Rochais