TCS-OX2-29

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H31N3O3
Molecular Weight	397.5105
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=C(OC)C=C2CN(CCC2=C1)C(=O)[C@@H](NCC3=CC=NC=C3)C(C)(C)C

InChI

InChIKey=COFVZFLCAOUMJT-OAQYLSRUSA-N

InChI=1S/C23H31N3O3/c1-23(2,3)21(25-14-16-6-9-24-10-7-16)22(27)26-11-8-17-12-19(28-4)20(29-5)13-18(17)15-26/h6-7,9-10,12-13,21,25H,8,11,14-15H2,1-5H3/t21-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C23H31N3O3
Molecular Weight	397.5105
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/14643355 | https://www.ncbi.nlm.nih.gov/pubmed/23692283

TCS-OX2-29 is a potent and selective orexin-2 (OX2) receptor antagonist, displaying selectivity for OX2 over OX1. Also was shown, that TCS-OX2-29 inhibited orexin A induced inositol phosphate accumulation and ERK-1/2 phosphorylation in CHO cells stably expressing the OX2 receptor.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Orexin receptor 2 8 Target ID: CHEMBL4792 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14643355	Antagonist 2778		40.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Unknown 2578

PubMed

Title	Date	PubMed
N-acyl 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline: the first orexin-2 receptor selective non-peptidic antagonist.	2003 Dec 15	14643355
Orexins depolarize rostral ventrolateral medulla neurons and increase arterial pressure and heart rate in rats mainly via orexin 2 receptors.	2010 Aug	20494957
Binding kinetics differentiates functional antagonism of orexin-2 receptor ligands.	2014 Jan	23692283

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Unknown

In Vitro Use Guide

In order to determine whether the kinetics of ligand binding had meaningful effects in commonly used cell-based functional assays, the antagonist profile TCS-OX2-29 versus orexin-A activation was determined in inositol phosphate accumulation and ERK1/2 phosphorylation assays. Orexin-A potently stimulated inositol phosphate accumulation in CHO-OX2 cells, with a pEC50 = 8.4 ± 0.1 TCS-OX2-29 caused a concentration-dependent, parallel, rightward shift in the concentration response curve to orexin-A, with minimal effect on the maximum asymptote of the curve. Schild analysis estimated pA2 values of 7.4 ± 0.1 for TCS-OX2-29

Substance Class	Chemical Created by `admin` on `Sat Dec 16 17:00:34 UTC 2023` Edited by `admin` on `Sat Dec 16 17:00:34 UTC 2023`
Record UNII	KH2US47J8R
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TCS-OX2-29

Common Name

English

1-BUTANONE, 1-(3,4-DIHYDRO-6,7-DIMETHOXY-2(1H)-ISOQUINOLINYL)-3,3-DIMETHYL-2-((4-PYRIDINYLMETHYL)AMINO)-, (2S)-

Systematic Name

English

(2S)-1-(3,4-DIHYDRO-6,7-DIMETHOXY-2(1H)-ISOQUINOLINYL)-3,3-DIMETHYL-2-((4-PYRIDINYLMETHYL)AMINO)-1-BUTANONE

Systematic Name

English

OREXIN ANTAGONIST TCS-OX2-29

Common Name

English

(2S)-2-(4-PYRIDYLMETHYLAMINO)-1-(6,7-DIMETHOXY-1,2,3,4-TETRAHYDROISOQUINOLIN-2-YL)-3,3-DIMETHYLBUTAN-1-ONE

Systematic Name

English

ISOQUINOLINE, 2-((2S)-3,3-DIMETHYL-1-OXO-2-((4-PYRIDINYLMETHYL)AMINO)BUTYL)-1,2,3,4-TETRAHYDRO-6,7-DIMETHOXY-

Systematic Name

English

TCS-OX 2-29

Common Name

English

Code System Code Type Description

FDA UNII

KH2US47J8R