ROBALZOTAN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H23FN2O2
Molecular Weight	318.3858
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC(=O)C1=CC=C(F)C2=C1C[C@H](CO2)N(C3CCC3)C4CCC4

InChI

InChIKey=MQTUXRKNJYPMCG-CYBMUJFWSA-N

InChI=1S/C18H23FN2O2/c19-16-8-7-14(18(20)22)15-9-13(10-23-17(15)16)21(11-3-1-4-11)12-5-2-6-12/h7-8,11-13H,1-6,9-10H2,(H2,20,22)/t13-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C18H23FN2O2
Molecular Weight	318.3858
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/11249580
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18775020| https://www.ncbi.nlm.nih.gov/pubmed/9851589

AstraZeneca (formerly Astra) is developing robalzotan (NAD-299, AZD-7371), a 5-HT1A antagonist, for the potential treatment of depression and anxiety. The compound has entered phase II trials but was discontinued. Then it investigated for the treatment of irritable bowel syndrome, but the study was prematurely terminated. The same final has expected the development of robalzotan in phase II to treat overactive bladder, this investigation was terminated in July 2005.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serotonin 1a (5-HT1a) receptor 172 Target ID: CHEMBL214 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9851589	Antagonist 2778		0.6 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Depression 235 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11249580	Primary	Phase II 1132	Unknown Approved Use Unknown
Anxiety 267 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11249580	Primary	Phase II 1132	Unknown Approved Use Unknown
Irritable bowel syndrome 60 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18775020	Primary	Phase II 1132	Unknown Approved Use Unknown
Overactive bladder 38 Sources: https://business.highbeam.com/436989/article-1G1-143617696/azd-7371-astrazeneca-discontinued-europe	Primary	Phase II 1132	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1537

Drug as perpetrator

Target	Modality	Activity
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363677891	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363677891	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363677891	yes [IC50 10.684 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363677891	no

Sourcing

Vendor/Aggregator	ID	URL
BOC Sciences	169758-66-1	http://www.bocsci.com/description.asp?cas=169758-66-1
MolPort	MolPort-023-276-731	https://www.molport.com/shop/molecule-link/MolPort-023-276-731
MuseChem	I010732	https://www.musechem.com/product/I010732.html
MuseChem	M039709	https://www.musechem.com/product/M039709.html
Tocris	3282	https://www.tocris.com/search.php?Type=QuickSearch&Value=3282
Vesino Industrial Co Ltd	VC30713	http://www.vsnchem.com/search.do?a=s&psize=20&q=VC30713
eMolecules	110060629	https://orderbb.emolecules.com/search/#?query=110060629
eMolecules	31507411	https://orderbb.emolecules.com/search/#?query=31507411
eMolecules	49260570	https://orderbb.emolecules.com/search/#?query=49260570

PubMed

Title	Date	PubMed
The pharmacological characterization of a novel selective 5-hydroxytryptamine1A receptor antagonist, NAD-299.	1997 Oct	9336327
Effects of NAD-299, a new, highly selective 5-HT1A receptor antagonist, on bladder function in rats.	2002 Dec	12444493
Nad-299 antagonises 5-HT-stimulated and spiperone-inhibited [35S]GTPgammaS binding in cloned 5-HT1A receptors.	2002 Feb-Nov	12503636
Effect of different 5-HT1A receptor antagonists in combination with paroxetine on expression of the immediate-early gene Arc in rat brain.	2003 Jun	12726821
Studies of drug binding to plasma proteins using a variant of equilibrium dialysis.	2005 Jul 1	15925237
Randomized, double-blind, placebo-controlled trial of the 5-HT1A receptor antagonist AZD7371 tartrate monohydrate (robalzotan tartrate monohydrate) in patients with irritable bowel syndrome.	2008 Oct	18775020
The selective 5-hydroxytryptamine 1A antagonist, AZD7371 [3(R)-(N,N-dicyclobutylamino)-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxamide (R,R)-tartrate monohydrate] (robalzotan tartrate monohydrate), inhibits visceral pain-related visceromotor, but not autonomic cardiovascular, responses to colorectal distension in rats.	2009 Jun	19325032
Bidirectional modulation of classical fear conditioning in mice by 5-HT(1A) receptor ligands with contrasting intrinsic activities.	2009 Oct-Nov	19607850
Selective serotonin reuptake inhibitors potentiate the rapid antidepressant-like effects of serotonin4 receptor agonists in the rat.	2010 Feb 16	20169084
The selective 5-HT(1A) receptor antagonist NAD-299 increases acetylcholine release but not extracellular glutamate levels in the frontal cortex and hippocampus of awake rat.	2010 Jul	20413275

Patents

Sample Use Guides

In Vivo Use Guide

20 mg or 5 mg or matching placebo tablets twice daily for 12 wk

Route of Administration: Oral

In Vitro Use Guide

[3H]NAD-299 (Robalzotan) binding displayed a Kd value of 0.17 nM and a Bmax value of 26.7 pmol/g wet weight of rat hippocampus. Same binding affinity (Kd = 0.16 nM) was found to cloned human 5-HT1A receptors. Addition of the nonhydrolyzable GTP analog guanylylimidodiphosphate had no effect on the binding characteristics of [3H]NAD-299, while it significantly decreased both the affinity and density of receptors labeled with [3H]8-OH-DPAT. The rank order of potency of various compounds to inhibit [3H]NAD-299 binding is consistent with the labeling of 5-HT1A receptors.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 17:38:28 GMT 2023` Edited by `admin` on `Sat Dec 16 17:38:28 GMT 2023`
Record UNII	I18M56OGME
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ROBALZOTAN

Official Name

English

robalzotan [INN]

Common Name

English

AZD7371

Common Name

English

AZD-7371

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1509