SARIZOTAN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H21FN2O
Molecular Weight	348.4142
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

c1ccc2c(c1)CC[C@]([H])(CNCc3cc(cnc3)-c4ccc(cc4)F)O2

InChI

InChIKey=HKFMQJUJWSFOLY-OAQYLSRUSA-N

InChI=1S/C22H21FN2O/c23-20-8-5-17(6-9-20)19-11-16(12-24-14-19)13-25-15-21-10-7-18-3-1-2-4-22(18)26-21/h1-6,8-9,11-12,14,21,25H,7,10,13,15H2/t21-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C22H21FN2O
Molecular Weight	348.4142
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.businesswire.com/news/home/20150714005335/en/Newron-Receives-FDA-Orphan-Drug-Designation-Sarizotan | http://www.pharmatimes.com/news/merck_drops_late-stage_parkinsons_drug_996337 | https://clinicaltrials.gov/ct2/show/NCT02790034

Sarizotan (also known as EMD-128,130), a chromane derivative that was developed as a selective 5-HT1A receptor agonist and D2 receptor antagonist. Experiments on animal models have shown that the drug effectively suppressed levodopa-induced dyskinesia in primate and rodent models of Parkinson's disease, and tardive dyskinesia in a rodent model. Sarizotan participated in phase II/III clinical trials in the treatment of dyskinesia associated with the dopaminergic treatment of Parkinson's disease. However, further development for this disease was discontinued by Merk, because phase III did not confirm earlier Phase II findings. On July 14, 2015, Newron Pharmaceuticals, research, and development company focused on the novel central nervous system (CNS) and pain therapies, announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to sarizotan for treatment of Rett syndrome. Besides, the drug now is an ongoing clinical trial phase II/III to investigate its the tolerability and efficacy in reducing respiratory abnormalities in Rett Syndrome.

Originator

Approval Year

PubMed

Title	Date	PubMed
Contribution of the serotonin 5-HT1A receptor agonism of 8-OH-DPAT and EMD 128130 to the regulation of haloperidol-induced muscle rigidity in rats.	2003 Dec	14614949
Gateways to clinical trials.	2003 May	12808477
Sarizotan, a serotonin 5-HT1A receptor agonist and dopamine receptor ligand. 1. Neurochemical profile.	2004 Feb	14767715
Drugs in development for Parkinson's disease.	2004 Jul	15298067
Multicenter, open-label, trial of sarizotan in Parkinson disease patients with levodopa-induced dyskinesias (the SPLENDID Study).	2004 Mar-Apr	15252265
Novel antipsychotic agents with 5-HT(1A) agonist properties: role of 5-HT(1A) receptor activation in attenuation of catalepsy induction in rats.	2005 Aug	15996562
Changes in sleep electroencephalogram and nocturnal hormone secretion after administration of the antidyskinetic agent sarizotan in healthy young male volunteers.	2005 Jul	15717211
Translation of nondopaminergic treatments for levodopa-induced dyskinesia from MPTP-lesioned nonhuman primates to phase IIa clinical studies: keys to success and roads to failure.	2006 Oct	16874752
The novel antidyskinetic drug sarizotan elicits different functional responses at human D2-like dopamine receptors.	2006 Sep	16844149
[Dyskinesia in Parkinson's disease--major clinical features, aetiology, therapy].	2007 Jul	17443441
Differential agonist and inverse agonist profile of antipsychotics at D2L receptors coupled to GIRK potassium channels.	2007 Mar	17239906
Antipsychotics differ in their ability to internalise human dopamine D2S and human serotonin 5-HT1A receptors in HEK293 cells.	2008 Feb 26	18190908
Low doses of sarizotan reduce dyskinesias and maintain antiparkinsonian efficacy of L-Dopa in parkinsonian monkeys.	2009 Jul	19196540
In vitro characterization of sarizotan metabolism: hepatic clearance, identification and characterization of metabolites, drug-metabolizing enzyme identification, and evaluation of cytochrome p450 inhibition.	2010 Jun	20219851

Patents

Sample Use Guides

In Vivo Use Guide

Subjects will receive sarizotan 1 milligram orally twice daily for 24 weeks.

Route of Administration: Oral

Substance Class	Chemical Created by `admin` on `Sat Jun 26 11:53:54 UTC 2021` Edited by `admin` on `Sat Jun 26 11:53:54 UTC 2021`
Record UNII	467LU0UCUW
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SARIZOTAN

Official Name

English

3-PYRIDINEMETHANAMINE, 5-(4-FLUOROPHENYL)-N-(((2R)-3,4,4A,8A-TETRAHYDRO-2H-1-BENZOPYRAN-2-YL)METHYL)-

Common Name

English

SARIZOTAN [MI]

Common Name

English

EMD-77697

Code

English

3-PYRIDINEMETHANAMINE, N-(((2R)-3,4-DIHYDRO-2H-1-BENZOPYRAN-2-YL)METHYL)-5-(4-FLUOROPHENYL)-

Systematic Name

English

SARIZOTAN [INN]

Common Name

English

1-(5-(4-FLUOROPHENYL)PYRIDIN-3-YL)-N-((2R)-3,4,4A,8A-TETRAHYDRO-2H-CHROMEN-2-YLMETHYL)METHANAMINE

Common Name

English

SARIZOTAN [WHO-DD]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

484015