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209410-46-8,MFCD09834070
Catalog No.:AA002K56

209410-46-8 | 5-(2,6-Dichlorophenyl)-2-((2,4-difluorophenyl)thio)-6h-pyrimido[1,6-b]pyridazin-6-one

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1mg
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5mg
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$199.00   $139.00
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10mg
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100mg
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  • Technical Information
  • Properties
  • Downstream Synthesis Route
  • Literature
  • Request for Quotation
  • Download SDS
  • Technical Information
  • Properties
  • Downstream Synthesis Route
  • Literature
Technical Information
Catalog Number:
AA002K56
Chemical Name:
5-(2,6-Dichlorophenyl)-2-((2,4-difluorophenyl)thio)-6h-pyrimido[1,6-b]pyridazin-6-one
CAS Number:
209410-46-8
Molecular Formula:
C19H9Cl2F2N3OS
Molecular Weight:
436.2621
MDL Number:
MFCD09834070
SMILES:
Fc1ccc(c(c1)F)Sc1ccc2n(n1)cnc(=O)c2c1c(Cl)cccc1Cl
Properties
Computed Properties
 
Complexity:
762  
Covalently-Bonded Unit Count:
1  
Heavy Atom Count:
28  
Hydrogen Bond Acceptor Count:
5  
Rotatable Bond Count:
3  
XLogP3:
5.1  

Downstream Synthesis Route

[1]Bagley,MarkC.;Davis,Terence;Dix,MatthewC.;Rokicki,MichalJ.;Kipling,David[BioorganicandMedicinalChemistryLetters,2007,vol.17,#18,p.5107-5110]

[2]Locationinpatent:experimentalpartBagley,MarkC.;Davis,Terence;Dix,MatthewC.;Fusillo,Vincenzo;Pigeaux,Morgane;Rokicki,MichalJ.;Kipling,David[JournalofOrganicChemistry,2009,vol.74,#21,p.8336-8342]

[3]Duffy,JohnP.;Harrington,EdmundM.;Salituro,FrancescoG.;Cochran,JohnE.;Green,Jeremy;Gao,Huai;Bemis,GuyW.;Evindar,Ghotas;Galullo,VincentP.;Ford,PamellaJ.;Germann,UrsulaA.;Wilson,KeithP.;Bellon,StevenF.;Chen,Guanging;Taslimi,Paul;Jones,Peter;Huang,Cassey;Pazhanisamy;Wang,Yow-Ming;Murcko,MarkA.;Su,MichaelS.S.[ACSMedicinalChemistryLetters,2011,vol.2,#10,p.758-763]

3215-64-3   
VX-745 

[1]BioorganicandMedicinalChemistryLetters,2007,vol.17,p.5107-5110

Literature

Title: Neflamapimod: Clinical Phase 2b-Ready Oral Small Molecule Inhibitor of p38α to Reverse Synaptic Dysfunction in Early Alzheimer's Disease.

Journal: The journal of prevention of Alzheimer's disease 20170101

Title: Selective Brain-Targeted Antagonism of p38 MAPKα Reduces Hippocampal IL-1β Levels and Improves Morris Water Maze Performance in Aged Rats.

Journal: Journal of Alzheimer's disease : JAD 20150101

Title: Identification of potent Yes1 kinase inhibitors using a library screening approach.

Journal: Bioorganic & medicinal chemistry letters 20130801

Title: Identification, synthesis, and biological evaluation of 6-[(6R)-2-(4-fluorophenyl)-6-(hydroxymethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl]-2-(2-methylphenyl)pyridazin-3(2H)-one (AS1940477), a potent p38 MAP kinase inhibitor.

Journal: Journal of medicinal chemistry 20120913

Title: 1,7-Naphthyridine 1-oxides as novel potent and selective inhibitors of p38 mitogen activated protein kinase.

Journal: Journal of medicinal chemistry 20111124

Title: Comprehensive analysis of kinase inhibitor selectivity.

Journal: Nature biotechnology 20111030

Title: The Discovery of VX-745: A Novel and Selective p38α Kinase Inhibitor.

Journal: ACS medicinal chemistry letters 20111013

Title: Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.

Journal: Journal of medicinal chemistry 20110714

Title: Design, synthesis and activity of a potent, selective series of N-aryl pyridinone inhibitors of p38 kinase.

Journal: Bioorganic & medicinal chemistry letters 20110701

Title: Discovery, synthesis, and investigation of the antitumor activity of novel piperazinylpyrimidine derivatives.

Journal: European journal of medicinal chemistry 20110601

Title: Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.

Journal: Chemistry & biology 20101124

Title: Gram-scale synthesis of the p38α MAPK-inhibitor VX-745 for preclinical studies into Werner syndrome.

Journal: Future medicinal chemistry 20100901

Title: Selective p38alpha inhibitors clinically evaluated for the treatment of chronic inflammatory disorders.

Journal: Journal of medicinal chemistry 20100325

Title: Microwave-assisted Ullmann C-S bond formation: synthesis of the P38alpha MAPK clinical candidate VX-745.

Journal: The Journal of organic chemistry 20091106

Title: Inhibition of p38: has the fat lady sung?

Journal: Arthritis and rheumatism 20090201

Title: Synthesis and biological activity of quinolinone and dihydroquinolinone p38 MAP kinase inhibitors.

Journal: Bioorganic & medicinal chemistry letters 20080315

Title: The design and synthesis of novel alpha-ketoamide-based p38 MAP kinase inhibitors.

Journal: Bioorganic & medicinal chemistry letters 20080315

Title: A quantitative analysis of kinase inhibitor selectivity.

Journal: Nature biotechnology 20080101

Title: A novel p38 alpha MAPK inhibitor suppresses brain proinflammatory cytokine up-regulation and attenuates synaptic dysfunction and behavioral deficits in an Alzheimer's disease mouse model.

Journal: Journal of neuroinflammation 20070101

Title: p38 MAP kinase inhibitors. Part 6: 2-arylpyridazin-3-ones as templates for inhibitor design.

Journal: Bioorganic & medicinal chemistry letters 20061115

Title: The development of novel C-2, C-8, and N-9 trisubstituted purines as inhibitors of TNF-alpha production.

Journal: Bioorganic & medicinal chemistry letters 20060815

Title: p38 MAP kinase inhibitors. Part 3: SAR on 3,4-dihydropyrimido[4,5-d]pyrimidin-2-ones and 3,4-dihydropyrido[4,3-d]pyrimidin-2-ones.

Journal: Bioorganic & medicinal chemistry letters 20060815

Title: Small molecular anti-cytokine agents.

Journal: Medicinal research reviews 20060101

Title: A small molecule-kinase interaction map for clinical kinase inhibitors.

Journal: Nature biotechnology 20050301

Title: P38 MAP kinase inhibitors: evolution of imidazole-based and pyrido-pyrimidin-2-one lead classes.

Journal: Current topics in medicinal chemistry 20050101

Title: Synthesis and structure-activity relationship of aminobenzophenones. A novel class of p38 MAP kinase inhibitors with high antiinflammatory activity.

Journal: Journal of medicinal chemistry 20031218

Title: Structural basis for p38alpha MAP kinase quinazolinone and pyridol-pyrimidine inhibitor specificity.

Journal: Nature structural biology 20030901

Title: Targeting p38 MAPK inhibits multiple myeloma cell growth in the bone marrow milieu.

Journal: Blood 20030115

Title: Duffy JP, et al. The Discovery of VX-745: A Novel and Selective p38α Kinase Inhibitor. ACS Med Chem Lett. 2011 Jul 28;2(10):758-63.

Title: Cicenas J, et al. JNK, p38, ERK, and SGK1 Inhibitors in Cancer. Cancers (Basel). 2017 Dec 21;10(1).

Title: Pradal J, et al. Intra-articular bioactivity of a p38 MAPK inhibitor and development of an extended-release system. Eur J Pharm Biopharm. 2015 Jun;93:110-7.

Title: Alam JJ. Selective Brain-Targeted Antagonism of p38 MAPKα Reduces Hippocampal IL-1β Levels and Improves Morris Water Maze Performance in Aged Rats. J Alzheimers Dis. 2015;48(1):219-27.

Title: Bagley MC, et al. Rapid synthesis of VX-745: p38 MAP kinase inhibition in Werner syndrome cells. Bioorg Med Chem Lett. 2007 Sep 15;17(18):5107-10. Epub 2007 Jul 13.

Title: Hideshima T, et al. Targeting p38 MAPK inhibits multiple myeloma cell growth in the bone marrow milieu. Blood, 2003, 101(2), 703-705.

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Tags:209410-46-8 Molecular Formula|209410-46-8 MDL|209410-46-8 SMILES|209410-46-8 5-(2,6-Dichlorophenyl)-2-((2,4-difluorophenyl)thio)-6h-pyrimido[1,6-b]pyridazin-6-one