GW-406381

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H19N3O3S
Molecular Weight	393.459
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOC1=CC=C(C=C1)C2=NN3N=CC=CC3=C2C4=CC=C(C=C4)S(C)(=O)=O

InChI

InChIKey=NXMZBNYLCVTRGB-UHFFFAOYSA-N

InChI=1S/C21H19N3O3S/c1-3-27-17-10-6-16(7-11-17)21-20(19-5-4-14-22-24(19)23-21)15-8-12-18(13-9-15)28(2,25)26/h4-14H,3H2,1-2H3

HIDE SMILES / InChI

Molecular Formula	C21H19N3O3S
Molecular Weight	393.459
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=19099009
Curator's Comment: https://clinicaltrials.gov/ct2/show/NCT00279032?term=GW-406381&rank=1; https://clinicaltrials.gov/ct2/show/NCT00120900?term=GW-406381&rank=3; https://clinicaltrials.gov/ct2/show/NCT00113308?term=GW-406381&rank=4

GW406381 is an investigational, highly selective cyclooxygenase-2 (COX-2) inhibitor for inflammatory pain treatment. It showed effectiveness in animal models of central sensitization such as chronic constriction injury and capsaicin-induced hyperalgesia. It's effect was also evaluated in several clinical trials in patients with peripheral nerve injury (Phase I ), rheumatoid arthritis (Phase III), the signs and symptoms of osteoarthritis of the knee to control of pain and improvement in function (Phase III), and in treating the signs and symptoms of dental pain following third molar tooth extraction (Phase III). Possessing favourable pharmacokinetic profiles and analgesic activity in vivo, GW406381 have also demonstrated relatively high brain penetration in the rat compared with the clinically available compounds, which may ultimately prove beneficial in the treatment of pain.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cyclooxygenase-2 196 Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=27547824	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Rheumatoid arthritis 316 Sources: https://clinicaltrials.gov/ct2/show/NCT00113308	Palliative		Phase III 656	Unknown Approved Use Unknown
Osteoarthritis of knee 23 Sources: https://clinicaltrials.gov/ct2/show/NCT00120900	Palliative		Phase III 656	Unknown Approved Use Unknown

AUC

Value	Dose	Co-administered	Analyte	Population
700 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26331692	35 mg 1 times / day multiple, oral dose: 35 mg route of administration: Oral experiment type: MULTIPLE co-administered:		GW-406381 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
70 mg single, oral Highest studied dose Dose: 70 mg Route: oral Route: single Dose: 70 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19692798 Page: p.581	unhealthy, 22.2 n = 50 Health Status: unhealthy Condition: Pain Age Group: 22.2 Sex: M+F Population Size: 50 Sources: https://pubmed.ncbi.nlm.nih.gov/19692798 Page: p.581	Sources: https://pubmed.ncbi.nlm.nih.gov/19692798 Page: p.581
50 mg 1 times / day multiple, oral Highest studied dose Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19099009	unhealthy, 61.7 n = 109 Health Status: unhealthy Condition: Osteoarthritis of the Knee Age Group: 61.7 Sex: M+F Population Size: 109 Sources: https://pubmed.ncbi.nlm.nih.gov/19099009	Disc. AE: Hypertension... AEs leading to discontinuation/dose reduction: Hypertension Sources: https://pubmed.ncbi.nlm.nih.gov/19099009

AEs

AE	Significance	Dose	Population
Hypertension	Disc. AE	50 mg 1 times / day multiple, oral Highest studied dose Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19099009	unhealthy, 61.7 n = 109 Health Status: unhealthy Condition: Osteoarthritis of the Knee Age Group: 61.7 Sex: M+F Population Size: 109 Sources: https://pubmed.ncbi.nlm.nih.gov/19099009

Sourcing

Vendor/Aggregator	ID	URL
Axon MedChem	1974	https://www.axonmedchem.com/product/1974
Chem Scene	CS-0066982	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0066982
MedChem Express	HY-119304	https://www.medchemexpress.com/search.html?q=HY-119304&ft=&fa=&fp=
MolPort	MolPort-042-665-791	https://www.molport.com/shop/molecule-link/MolPort-042-665-791
MuseChem	I007146	https://www.musechem.com/product/I007146.html
Norris Pharm	NSZB-A077912
eMolecules	44818050	https://orderbb.emolecules.com/search/#?query=44818050

PubMed

Title	Date	PubMed
Identification of 2,3-diaryl-pyrazolo[1,5-b]pyridazines as potent and selective cyclooxygenase-2 inhibitors.	2004 Nov 1	15454242
The cyclooxygenase-2 inhibitor GW406381X [2-(4-ethoxyphenyl)-3-[4-(methylsulfonyl)phenyl]-pyrazolo[1,5-b]pyridazine] is effective in animal models of neuropathic pain and central sensitization.	2005 Mar	15572651
A randomized, double-blind, placebo-controlled trial of a selective COX-2 inhibitor, GW406381, in patients with postherpetic neuralgia.	2009 Jun	19409858
Biomarker exposure-response relationships as the basis for rational dose selection: Lessons from a simulation exercise using a selective COX-2 inhibitor.	2016 May	26331692

Patents

Sample Use Guides

In Vivo Use Guide

5mg, 10mg, 25mg, and 50mg administered once daily for 12 weeks in adults with rheumatoid arthritis

Route of Administration: Oral

In Vitro Use Guide

Human whole blood stimulated with 100 ug/ml LPS was treated with GW406381. At 10 uM GW406381 profoundly reduced PGE2 and PGF2α (both by more than 90%, P < 0.0001), TxB2 (by more than 80%, P < 0.0001), and total 15-HETE (by more than 70%, P < 0.001)

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:41:24 GMT 2023` Edited by `admin` on `Fri Dec 15 15:41:24 GMT 2023`
Record UNII	5Y869C2THE
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

GW-406381

Common Name

English

GW 406381

Common Name

English

GW406381

Common Name

English

PYRAZOLO(1,5-B)PYRIDAZINE, 2-(4-ETHOXYPHENYL)-3-(4-(METHYLSULFONYL)PHENYL)-

Systematic Name

English

GW 406381 [WHO-DD]

Common Name

English

2-(4-ETHOXYPHENYL)-3-(4-(METHYLSULFONYL)PHENYL)PYRAZOLO(1,5-B)PYRIDAZINE

Systematic Name

English

Code System Code Type Description

EPA CompTox

DTXSID60202043