Binding of isotryptamines and indenes at h5-HT6 serotonin receptors

Kolanoś, Renata; Siripurapu, Uma; Pullagurla, Manik R.; Riaz, Muhammad Shahid; Setola, Vincent; Roth, Bryan L.; Dukat, Małgorzata; Glennon, Richard A.

doi:10.1016/j.bmcl.2005.02.070

Cited by 43 publications

(19 citation statements)

References 23 publications

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“…7,8 Subsequent pharmacophoric studies have revealed that the 5-methoxy group of 1a is not required for binding (i.e., 1b; K i = 4 nM), that the benzenesulfonyl moiety can be replaced by a benzyl group (2; K i = 6 nM) with retention of antagonist action, 5 and that the indole N 1 nitrogen atom is not required for binding, as evidenced by the high affinity of, for example, isotryptamine 3 (K i = 32 nM) and indene 4 (K i = 3 nM) for this receptor population. 9 Various tryptamines lacking an N 1 substituent generally bind with reduced affinity and, like 5-hydroxytryptamine (i.e., serotonin; K i ca. 100 nM), can display agonist character.…”

Section: -Htmentioning

confidence: 99%

Interaction of chiral MS-245 analogs at h5-HT6 receptors

Abate¹,

Kolanoś²,

Dukat³

et al. 2005

Bioorganic & Medicinal Chemistry Letters

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Section: -Htmentioning

confidence: 99%

Interaction of chiral MS-245 analogs at h5-HT6 receptors

Abate¹,

Kolanoś²,

Dukat³

et al. 2005

Bioorganic & Medicinal Chemistry Letters

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“…Kolanos et al .,[26] studied the binding affinity of indolic nitrogen for h5-HT 6 serotonin receptors. They concluded that indolic nitrogen atom is essential for the binding of N1-benzyltryptamines at h5-HT 6 serotonin receptors.…”

Section: Indolementioning

confidence: 99%

Antidepressant potential of nitrogen-containing heterocyclic moieties: An updated review

et al. 2011

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Depression is currently the fourth leading cause of disease or disability worldwide. Antidepressant is approved for the treatment of major depression (including paediatric depression), obsessive-compulsive disorder (in both adult and paediatric populations), bulimia nervosa, panic disorder and premenstrual dysphoric disorder. Antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. Many drugs produce an antidepressant effect, but restrictions on their use have caused controversy and off-label prescription a risk, despite claims of superior efficacy. Our current understanding of its pathogenesis is limited and existing treatments are inadequate, providing relief to only a subset of people suffering from depression. Reviews of literature suggest that heterocyclic moieties and their derivatives has proven success in treating depression.

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“…Indene 66 ( K i = 57 nM), lacking an indolic N 1 nitrogen atom, displayed 10-fold lower affinity than 17 ( K i = 6 nM); but, the reduced affinity of 66 might be explained by the conformational restraint imposed on the “benzyl” group by the benzylidene moiety [26]. The reduced analog of 66 (i.e., 67 , K i = 3 nM) displayed an affinity comparable to 17 indicating that the indole nitrogen atom was not required for binding [26].…”

Section: Indole Ringmentioning

confidence: 99%

The Medicinal Chemistry of 5-HT6 Receptor Ligands with a Focus on Arylsulfonyltryptamine Analogs

Glennon

Siripurapu

Roth³

et al. 2010

CTMC

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Arylsulfonyl analogs of aminopyrimidines (e.g. Ro 04-6790; 2), aminopyridines (e.g. Ro 63-0563; 3), 1-phenylpiperazines (e.g. SB-271046; 4), and tryptamines (e.g. MS-245; 5) were described as the first examples of selective 5-HT6 receptor antagonists only ten years ago. Today, hundreds of compounds of seemingly diverse structure have been reported. The early antagonists featured an arylsulfonyl group leading to the widespread assumption that an arylsulfonyl moiety might be critical for binding and antagonist action. With respect to the arylsulfonyltryptamines, it seems that neither the “arylsulfonyl” nor the “tryptamine” portion of these compounds is essential for binding or for antagonist action, and some such derivatives even display agonist action. The present review describes many of the currently available 5-HT6 receptor ligands and, unlike prior reviews, provides a narrative of the thinking (where possible) that led to their design, synthesis, and evaluation. The arylsulfonyltryptamines are also used as the structural basis of attempts to relate various structure-types to one another to afford a better understanding of the overall structural requirements for 5-HT6 receptor binding.

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Binding of isotryptamines and indenes at h5-HT6 serotonin receptors

Cited by 43 publications

References 23 publications

Interaction of chiral MS-245 analogs at h5-HT6 receptors

Interaction of chiral MS-245 analogs at h5-HT6 receptors

Antidepressant potential of nitrogen-containing heterocyclic moieties: An updated review

The Medicinal Chemistry of 5-HT6 Receptor Ligands with a Focus on Arylsulfonyltryptamine Analogs

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