Delving into the Latest Updates on Setoperone with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

司托哌隆, R 52245

Target

5-HT2A receptor

Action

modulators

Mechanism

5-HT2A receptor modulators(Serotonin 2a (5-HT2a) receptor modulators)

Therapeutic Areas

Nervous System Diseases

Active Indication

Nervous System Diseases

Inactive Indication-

Originator Organization-

Active Organization-

Inactive Organization-

License Organization-

Drug Highest PhaseDiscovery

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC21H24FN3O2S

InChIKeyRBGAHDDQSRBDOG-UHFFFAOYSA-N

CAS Registry86487-64-1

Systems containing fused thiazole and pyrimidine rings play a significant role in organisms due to their biol. activity.Lipophilicity, as important parameter to expect biol. activity of the compounds, was evaluated for 27 potentially active thiazolo[3,2-a]pyrimidine derivatives using chromatog. methods: reversed phase thin layer chromatog. (RP-TLC) and reversed phase high performance liquid chromatog. (RP-HPLC) methods.Methanol was used as the organic modifier of the mobile phases.The corresponding relationship between compounds structure and lipophilicity parameters (RM0 and log kw) values were observed and featured.RM0 and log kw parameters were compared with computed log P values.For all of analyzed compounds, determined lipophilicitys parameters values are > 0 which means that there are hydrophobic substances, soluble in the lipid phase.Simultaneously, these values are < 5, i.e., are in accordance with Lipinskis rule in the range of lipophilicity.In the case of the possibility of their use as drugs, they will be active after oral application.

13 Jun 2013·JOURNAL OF MEDICINAL CHEMISTRY

Design and Selection Parameters to Accelerate the Discovery of Novel Central Nervous System Positron Emission Tomography (PET) Ligands and Their Application in the Development of a Novel Phosphodiesterase 2A PET Ligand

Article

Author: Humphrey, John M. ; Beck, Elizabeth M. ; Zasadny, Kenneth ; Lu, Jiemin ; Villalobos, Anabella ; Zhang, Lei ; Chen, Laigao ; Hou, Xinjun ; Chappie, Thomas A. ; Helal, Christopher J. ; Verhoest, Patrick R. ; Wager, Travis T. ; Grimwood, Sarah ; Bocan, Thomas ; McCarthy, Timothy J. ; Heck, Steven D. ; Skaddan, Marc B.

To accelerate the discovery of novel small molecule central nervous system (CNS) positron emission tomography (PET) ligands, we aimed to define a property space that would facilitate ligand design and prioritization, thereby providing a higher probability of success for novel PET ligand development. Toward this end, we built a database consisting of 62 PET ligands that have successfully reached the clinic and 15 radioligands that failed in late-stage development as negative controls. A systematic analysis of these ligands identified a set of preferred parameters for physicochemical properties, brain permeability, and nonspecific binding (NSB). These preferred parameters have subsequently been applied to several programs and have led to the successful development of novel PET ligands with reduced resources and timelines. This strategy is illustrated here by the discovery of the novel phosphodiesterase 2A (PDE2A) PET ligand 4-(3-[(18)F]fluoroazetidin-1-yl)-7-methyl-5-{1-methyl-5-[4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}imidazo[5,1-f][1,2,4]triazine, [(18)F]PF-05270430 (5).

01 Jun 2012·Archives of general psychiatry

Positron Emission Tomography Study of the Effects of Tryptophan Depletion on Brain Serotonin₂Receptors in Subjects Recently Remitted From Major Depression

Article

Author: Vafai, Nasim ; Sossi, Vesna ; Liddle, Peter F. ; Lam, Raymond W. ; Erez, Jonathan ; Blinder, Stephan ; Yatham, Lakshmi N.

CONTEXT:

Decreased brain serotonin (5-hydroxytryptamine) levels are considered to mediate depressive relapse induced by the tryptophan depletion paradigm. However, in patients who recently achieved remission from a major depressive episode with antidepressant treatment, only about half become depressed following tryptophan depletion. We hypothesized that downregulation of brain serotonin(2) receptors might be a compensatory mechanism that prevents some patients from becoming depressed with tryptophan depletion.

OBJECTIVE:

To assess, with use of positron emission tomography, whether brain serotonin(2) receptor downregulation occurs in patients with recently remitted depression who do not have depressive relapse, but not in those who become depressed, following tryptophan depletion.

DESIGN:

Each patient underwent 2 fluorine 18-labeled- setoperone positron emission tomography scans, one following a tryptophan depletion session and another following a control session. The order of scanning was counterbalanced.

SETTING:

Academic university hospital with imaging facilities.

PARTICIPANTS:

Seventeen patients in recent remission from a DSM-IV major depressive episode following treatment with selective serotonin reuptake inhibitors.

MAIN OUTCOME MEASURES:

Changes in brain serotonin(2) receptor binding.

RESULTS:

Of the 17 patients, 8 (47%) became depressed during the tryptophan depletion session, and none developed depression during the control session. The depletion session was associated with a significant reduction in brain serotonin(2) receptor binding compared with the control session for all participants. A subgroup analysis revealed that the reduction in serotonin(2) receptor binding was significant only for the nondepressed group.

CONCLUSION:

Reduction in brain serotonin(2) receptors might be a potential compensatory mechanism to prevent tryptophan depletion-induced depressive relapse.

100 Deals associated with Setoperone

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