AZD-1981

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H17ClN2O3S
Molecular Weight	388.868
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(=O)NC1=CC=CC2=C1C(SC3=CC=C(Cl)C=C3)=C(C)N2CC(O)=O

InChI

InChIKey=JWYIGNODXSRKGP-UHFFFAOYSA-N

InChI=1S/C19H17ClN2O3S/c1-11-19(26-14-8-6-13(20)7-9-14)18-15(21-12(2)23)4-3-5-16(18)22(11)10-17(24)25/h3-9H,10H2,1-2H3,(H,21,23)(H,24,25)

HIDE SMILES / InChI

Molecular Formula	C19H17ClN2O3S
Molecular Weight	388.868
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://openinnovation.astrazeneca.com/azd1981.html
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23827726

AZD-1981, developed by AstraZeneca, is a potent (binding IC50 of 4nM), fully reversible, functionally non-competitive antagonist of human CRTh2. It blocks agonist-induced human eosinophil CD11b expression, shape change (including in whole blood), and chemotaxis as well as an basophil shape change and Th2-cell chemotaxis at IC50's of 8.5-50nM. Potency is similar across species as is plasma protein binding (~97%). AZD-1981 is a weak (10s of μM) inhibitor in vitro of CYP2C9, OATP1B1 and UGT1A1 as well as an inducer of CYP3A4. AZD-1981 was well tolerated and no safety concerns were identified.There was no beneficial clinical effect of AZD-1981, at a dose of 1000 mg twice daily for 4 weeks, in patients with moderate to severe COPD. AZD-1981 has being discontinued for asthma and chronic obstructive pulmonary disease. AstraZeneca is collaborating with Johns Hopkins University for the development of AZD-1981 in the treatment of chronic idiopathic urticaria. It is in phase II clinicals studies for the treatment of Urticaria.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
G protein-coupled receptor 44 7 Target ID: CHEMBL5071 Sources: https://ncats.nih.gov/files/AZD1981.pdf	Antagonist 2778		4.3 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Urticaria 39 Sources: https://clinicaltrials.gov/ct2/show/NCT02031679	Primary	Phase II 1132	Unknown Approved Use Unknown
Chronic obstructive pulmonary disease 174 Sources: https://clinicaltrials.gov/ct2/show/NCT00690482	Primary	Phase II 1132	Unknown Approved Use Unknown
Asthma 241 Sources: https://clinicaltrials.gov/ct2/show/NCT01197794	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
9030 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27558866	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		AZD-1981 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
18900 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27558866	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		AZD-1981 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00G47G	https://www.1pchem.com/search?query=1P00G47G
AK Scientific	Z6201	https://aksci.com/item_detail.php?cat=Z6201
Angene	AGN-PC-0WHAMD	http://www.angenechemical.com/productshow/AGN-PC-0WHAMD.html
ApexBio Technology	B1534	https://www.apexbt.com/catalogsearch/result/?q=B1534
AstaTech	40631	http://astatechinc.com/CPSResult.php?CRNO=40631
Axon MedChem	2145	https://www.axonmedchem.com/product/2145
BLD Pharm	BD351238	http://www.bldpharm.com/search/Search.html?keyword=BD351238
Cayman Chemical	20763	http://www.caymanchem.com/app/template/Product.vm/catalog/20763
Chem Scene	CS-4189	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-4189
Excenen	EX-A662	http://www.excenen.com/searchresultlist.php?id=EX-A662
KeyOrganics	AS-75220	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-75220
Lab Network	LN01341701	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01341701
Lab Seeker	SC-94603	http://www.labseeker.com/search.php?keywords=SC-94603&category=0
LabSeeker	SC-94603	http://www.labseeker.com/search.php?keywords=SC-94603&category=0
MedChem Express	HY-15950	https://www.medchemexpress.com/search.html?q=HY-15950&ft=&fa=&fp=
MolPort	MolPort-035-395-811	https://www.molport.com/shop/molecule-link/MolPort-035-395-811
Molnova	M17599	https://www.molnova.com/en/serch-list.html?keywords=M17599
MuseChem	I004923	https://www.musechem.com/product/I004923.html
Ryan Scientific	101-94115	https://ryansci.com/products?q=101-94115&list_q=&search_type=exact
Selleck Chemicals	S7263	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7263
ShangHai Biochempartner	BCP20957	http://www.biochempartner.com/search_BCP20957
TargetMol	T6399	https://www.targetmol.com/search?keyword=T6399
Toronto Research Chemicals	A795140	https://www.trc-canada.com/product-detail/?CatNum=A795140
eMolecules	49383452	https://orderbb.emolecules.com/search/#?query=49383452
mcule	MCULE-5775856349	https://mcule.com/MCULE-5775856349/

PubMed

Title	Date	PubMed
		252160766
Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981.	2011 Nov 1	21944852
Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework.	2014 Jun	24833294

Patents

Sample Use Guides

In Vivo Use Guide

AZD-1981 has been administered orally in healthy volunteers (single oral dose up to 4,000 mg; multiple doses up to 2,000 mg twice daily [BID] for 2 wks), asthma or COPD patients (up to 100 mg, BID for 4 wks), and asthmatics (up to 400 mg BID for 12 wks).

Route of Administration: Oral

In Vitro Use Guide

AZD-1981 inhibits DK-PGD2-induced CD11b expression in human eosinophils with IC50 of 10 nM.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 19:47:55 GMT 2023` Edited by `admin` on `Fri Dec 15 19:47:55 GMT 2023`
Record UNII	2AD53WQ2CX
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

AZD-1981

Common Name

English

1H-INDOLE-1-ACETIC ACID, 4-(ACETYLAMINO)-3-((4-CHLOROPHENYL)THIO)-2-METHYL-

Common Name

English

AZD1981

Common Name

English

AZD 1981 [WHO-DD]

Common Name

English

Code System Code Type Description

PUBCHEM

11292191