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 177 Target ID: CHEMBL214 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9851589	Antagonist 2849		0.6 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Depression 240 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11249580	Primary	Phase II 1147	Unknown Approved Use Unknown
Anxiety 275 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11249580	Primary	Phase II 1147	Unknown Approved Use Unknown
Irritable bowel syndrome 61 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18775020	Primary	Phase II 1147	Unknown Approved Use Unknown
Overactive bladder 39 Sources: https://business.highbeam.com/436989/article-1G1-143617696/azd-7371-astrazeneca-discontinued-europe	Primary	Phase II 1147	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 2052

Drug as perpetrator

Target	Modality	Activity
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363677891	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363677891	no
CYP3A4 2633	inhibitor 4027 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 2052	substrate 4014 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
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
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

PubMed

Title	Date	PubMed
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.	2010-07	20413275
Selective serotonin reuptake inhibitors potentiate the rapid antidepressant-like effects of serotonin4 receptor agonists in the rat.	2010-02-16	20169084
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.	2009-06	19325032
Bidirectional modulation of classical fear conditioning in mice by 5-HT(1A) receptor ligands with contrasting intrinsic activities.	2008-12-19	19607850
Randomized, double-blind, placebo-controlled trial of the 5-HT1A receptor antagonist AZD7371 tartrate monohydrate (robalzotan tartrate monohydrate) in patients with irritable bowel syndrome.	2008-10	18775020
New agents in the treatment of premature ejaculation.	2006-12	19412497
Studies of drug binding to plasma proteins using a variant of equilibrium dialysis.	2005-07-01	15925237
Analysis of the role of 5-HT1A receptors in spatial and aversive learning in the rat.	2005-05	15829255
Effect of different 5-HT1A receptor antagonists in combination with paroxetine on expression of the immediate-early gene Arc in rat brain.	2003-06	12726821
Positron emission tomographic analysis of dose-dependent NAD-299 binding to 5-hydroxytryptamine-1A receptors in the human brain.	2003-04	12632244
Selective 5-HT1A antagonists WAY 100635 and NAD-299 attenuate the impairment of passive avoidance caused by scopolamine in the rat.	2003-02	12589378
Nad-299 antagonises 5-HT-stimulated and spiperone-inhibited [35S]GTPgammaS binding in cloned 5-HT1A receptors.	2002-12-31	12503636
Effects of NAD-299, a new, highly selective 5-HT1A receptor antagonist, on bladder function in rats.	2002-12	12444493
PET-examination and metabolite evaluation in monkey of [(11)C]NAD-299, a radioligand for visualisation of the 5-HT(1A) receptor.	2002-01	11786274
Hypothermia reduces the rate of dissociation of specific ligands from dopamine-D2 and 5-hydroxytryptamine1A receptors in the mouse brain in vivo.	2001-11	11692232
The pharmacological characterization of a novel selective 5-hydroxytryptamine1A receptor antagonist, NAD-299.	1997-10	9336327

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 `Wed Apr 02 09:24:08 GMT 2025` Edited by `admin` on `Wed Apr 02 09:24:08 GMT 2025`
Record UNII	I18M56OGME
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ROBALZOTAN

Official Name

English

AZD-7371

Preferred Name

English

robalzotan [INN]

Common Name

English

AZD7371

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1509