GW406381 | CAS#221148-46-5 | COX-2 inhibitor

MedKoo Cat#: 526879 | Name: GW406381 free base

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

GW406381 is a novel COX-2 inhibitor as a potential treatment for acute migraine. GW406381 is highly selective cyclooxygenase-2 (COX-2) inhibitor that is effective in animal models of central sensitization and of inflammatory pain. GW406381 attenuates spontaneous ectopic discharge in sural nerves of rats following chronic constriction injury. GW406381 is effective in animal models of neuropathic pain and central sensitization.

Chemical Structure

GW406381 free base

CAS#221148-46-5 (free base)

Theoretical Analysis

MedKoo Cat#: 526879

Name: GW406381 free base

CAS#: 221148-46-5 (free base)

Chemical Formula: C21H19N3O3S

Exact Mass: 393.1147

Molecular Weight: 393.46

Elemental Analysis: C, 64.11; H, 4.87; N, 10.68; O, 12.20; S, 8.15

Price and Availability

Size	Price	Availability
5mg	USD 350.00	2 Weeks
10mg	USD 650.00	2 Weeks
25mg	USD 1,070.00	2 Weeks

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Related CAS #

221148-46-5 (free base) 537697-89-5 (HCl)

Synonym

GW-406381; GW 406381; GW406381; GW 406381X; GW406381X; GW-406381X

IUPAC/Chemical Name

2-(4-ethoxyphenyl)-3-(4-(methylsulfonyl)phenyl)pyrazolo[1,5-b]pyridazine

InChi Key

NXMZBNYLCVTRGB-UHFFFAOYSA-N

InChi Code

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

SMILES Code

O=S(C1=CC=C(C2=C3C=CC=NN3N=C2C4=CC=C(OCC)C=C4)C=C1)(C)=O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

GW406381, a highly selective cyclooxygenase-2 (COX-2) inhibitor, attenuates spontaneous ectopic discharge in sural nerves of rats following chronic constriction injury.

In vitro activity:

TBD

In vivo activity:

GW406381 (5mg/kg, 5 days of treatment) significantly reversed the CCI-induced decrease in paw withdrawal thresholds (PWTs), assessed using both von Frey hair and paw pressure tests, whereas an equi-effective dose of rofecoxib (5mg/kg, 5 days of treatment) in inflammatory pain models was ineffective. In rats treated with GW406381, the proportion of fibres showing spontaneous activity was significantly lower (15.58%) than that in the vehicle (32.67%)- and rofecoxib (39.66%)-treated rats. Reference: Pain. 2007 Mar;128(1-2):78-87. https://pubmed.ncbi.nlm.nih.gov/17055166/

	Solvent	mg/mL	mM
Solubility
	DMSO, sonicated	25.0	63.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 393.46 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Zhao FY, Spanswick D, Martindale JC, Reeve AJ, Chessell IP. GW406381, a novel COX-2 inhibitor, attenuates spontaneous ectopic discharge in sural nerves of rats following chronic constriction injury. Pain. 2007 Mar;128(1-2):78-87. doi: 10.1016/j.pain.2006.08.032. Epub 2006 Oct 19. PMID: 17055166.

In vitro protocol:

TBD

In vivo protocol:

1: Moore RA, Chi CC, Wiffen PJ, Derry S, Rice AS. Oral nonsteroidal anti-inflammatory drugs for neuropathic pain. Cochrane Database Syst Rev. 2015 Oct 5;(10):CD010902. doi: 10.1002/14651858.CD010902.pub2. Review. PubMed PMID: 26436601. 2: Taneja A, Oosterholt SP, Danhof M, Della Pasqua O. Biomarker exposure-response relationships as the basis for rational dose selection: Lessons from a simulation exercise using a selective COX-2 inhibitor. J Clin Pharmacol. 2016 May;56(5):609-21. doi: 10.1002/jcph.629. Epub 2015 Dec 27. PubMed PMID: 26331692. 3: Wilkinson MC. "Greener" Friedel-Crafts acylations: a metal- and halogen-free methodology. Org Lett. 2011 May 6;13(9):2232-5. doi: 10.1021/ol200482s. Epub 2011 Mar 25. PubMed PMID: 21438589. 4: Varner J, Lomax M, Blum D, Quessy S. A randomized, controlled, dose-ranging study investigating single doses of GW406381, naproxen sodium, or placebo in patients with acute pain after third molar tooth extraction. Clin J Pain. 2009 Sep;25(7):577-83. doi: 10.1097/AJP.0b013e3181a085fa. PubMed PMID: 19692798. 5: Shackelford S, Rauck R, Quessy S, Blum D, Hodge R, Philipson R. A randomized, double-blind, placebo-controlled trial of a selective COX-2 inhibitor, GW406381, in patients with postherpetic neuralgia. J Pain. 2009 Jun;10(6):654-60. doi: 10.1016/j.jpain.2009.01.328. Epub 2009 May 5. PubMed PMID: 19409858. 6: Boswell DJ, Ostergaard K, Philipson RS, Hodge RA, Blum D, Brown JC, Quessy SN. Evaluation of GW406381 for treatment of osteoarthritis of the knee: two randomized, controlled studies. Medscape J Med. 2008;10(11):259. Epub 2008 Nov 12. PubMed PMID: 19099009; PubMed Central PMCID: PMC2605121. 7: Wentz AL, Jimenez TB, Dixon RM, Aurora SK, Gold M; CXA20008 Study Investigators. A double-blind, randomized, placebo-controlled, single-dose study of the cyclooxygenase-2 inhibitor, GW406381, as a treatment for acute migraine. Eur J Neurol. 2008 Apr;15(4):420-7. doi: 10.1111/j.1468-1331.2008.02093.x. Epub 2008 Feb 26. PubMed PMID: 18312401. 8: Zhao FY, Spanswick D, Martindale JC, Reeve AJ, Chessell IP. GW406381, a novel COX-2 inhibitor, attenuates spontaneous ectopic discharge in sural nerves of rats following chronic constriction injury. Pain. 2007 Mar;128(1-2):78-87. Epub 2006 Oct 19. PubMed PMID: 17055166. 9: Bingham S, Beswick PJ, Bountra C, Brown T, Campbell IB, Chessell IP, Clayton N, Collins SD, Davey PT, Goodland H, Gray N, Haslam C, Hatcher JP, Hunter AJ, Lucas F, Murkitt G, Naylor A, Pickup E, Sargent B, Summerfield SG, Stevens A, Stratton SC, Wiseman J. 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. J Pharmacol Exp Ther. 2005 Mar;312(3):1161-9. Epub 2004 Nov 30. PubMed PMID: 15572651. 10: Beswick P, Bingham S, Bountra C, Brown T, Browning K, Campbell I, Chessell I, Clayton N, Collins S, Corfield J, Guntrip S, Haslam C, Lambeth P, Lucas F, Mathews N, Murkit G, Naylor A, Pegg N, Pickup E, Player H, Price H, Stevens A, Stratton S, Wiseman J. Identification of 2,3-diaryl-pyrazolo[1,5-b]pyridazines as potent and selective cyclooxygenase-2 inhibitors. Bioorg Med Chem Lett. 2004 Nov 1;14(21):5445-8. PubMed PMID: 15454242. 11: Sertsou G, Butler J, Scott A, Hempenstall J, Rades T. Factors affecting incorporation of drug into solid solution with HPMCP during solvent change co-precipitation. Int J Pharm. 2002 Oct 1;245(1-2):99-108. PubMed PMID: 12270247.