Neflamapimod

Identification

Name
Neflamapimod
Accession Number
DB07138  (DB12790)
Type
Small Molecule
Groups
Investigational
Description

Neflamapimod has been used in trials studying the treatment of Alzheimer's Disease and Mild Cognitive Impairment.

Structure
Thumb
Synonyms
Not Available
External IDs
VD-31,745 / VD-31745 / VRT-031745 / VX 745 / VX-745 / VX745
Categories
Not Available
UNII
TYL52QM320
CAS number
209410-46-8
Weight
Average: 436.262
Monoisotopic: 434.981144439
Chemical Formula
C19H9Cl2F2N3OS
InChI Key
VEPKQEUBKLEPRA-UHFFFAOYSA-N
InChI
InChI=1S/C19H9Cl2F2N3OS/c20-11-2-1-3-12(21)17(11)18-14-5-7-16(25-26(14)9-24-19(18)27)28-15-6-4-10(22)8-13(15)23/h1-9H
IUPAC Name
5-(2,6-dichlorophenyl)-2-[(2,4-difluorophenyl)sulfanyl]-6H-pyrimido[1,6-b]pyridazin-6-one
SMILES
FC1=CC(F)=C(SC2=NN3C=NC(=O)C(=C3C=C2)C2=C(Cl)C=CC=C2Cl)C=C1

Pharmacology

Indication
Not Available
Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UMitogen-activated protein kinase 14Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
3038525
PubChem Substance
99443609
ChemSpider
2302086
BindingDB
15244
ChEBI
90528
ChEMBL
CHEMBL119385
HET
52P
PDB Entries
3fc1 / 3hp5 / 3zsi

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2Active Not RecruitingTreatmentAlzheimer's Disease (AD)1
2Active Not RecruitingTreatmentAlzheimer's Disease (AD) / Mild Cognitive Impairment (MCI)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000559 mg/mLALOGPS
logP5.17ALOGPS
logP4.89ChemAxon
logS-5.9ALOGPS
pKa (Strongest Basic)-3.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area45.03 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity108.15 m3·mol-1ChemAxon
Polarizability38.75 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9954
Blood Brain Barrier+0.944
Caco-2 permeable+0.5479
P-glycoprotein substrateNon-substrate0.8052
P-glycoprotein inhibitor INon-inhibitor0.5821
P-glycoprotein inhibitor IINon-inhibitor0.9321
Renal organic cation transporterNon-inhibitor0.7817
CYP450 2C9 substrateNon-substrate0.7705
CYP450 2D6 substrateNon-substrate0.808
CYP450 3A4 substrateSubstrate0.5676
CYP450 1A2 substrateInhibitor0.8606
CYP450 2C9 inhibitorInhibitor0.6849
CYP450 2D6 inhibitorNon-inhibitor0.8903
CYP450 2C19 inhibitorInhibitor0.6231
CYP450 3A4 inhibitorNon-inhibitor0.846
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7229
Ames testNon AMES toxic0.7209
CarcinogenicityNon-carcinogens0.8646
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.2006 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9919
hERG inhibition (predictor II)Non-inhibitor0.8667
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as diarylthioethers. These are organosulfur compounds containing a thioether group that is substituted by two aryl groups.
Kingdom
Organic compounds
Super Class
Organosulfur compounds
Class
Thioethers
Sub Class
Aryl thioethers
Direct Parent
Diarylthioethers
Alternative Parents
Dichlorobenzenes / Thiophenol ethers / Fluorobenzenes / Pyrimidones / Aryl chlorides / Aryl fluorides / Pyridazines and derivatives / Heteroaromatic compounds / Vinylogous amides / Sulfenyl compounds
show 8 more
Substituents
Diarylthioether / 1,3-dichlorobenzene / Thiophenol ether / Chlorobenzene / Fluorobenzene / Halobenzene / Pyrimidone / Aryl chloride / Aryl fluoride / Aryl halide
show 20 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellu...
Gene Name
MAPK14
Uniprot ID
Q16539
Uniprot Name
Mitogen-activated protein kinase 14
Molecular Weight
41292.885 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
  2. Duffy JP, Harrington EM, Salituro FG, Cochran JE, Green J, Gao H, Bemis GW, Evindar G, Galullo VP, Ford PJ, Germann UA, Wilson KP, Bellon SF, Chen G, Taslimi P, Jones P, Huang C, Pazhanisamy S, Wang YM, Murcko MA, Su MS: The Discovery of VX-745: A Novel and Selective p38alpha Kinase Inhibitor. ACS Med Chem Lett. 2011 Jul 28;2(10):758-63. doi: 10.1021/ml2001455. eCollection 2011 Oct 13. [PubMed:24900264]

Drug created on September 15, 2010 15:19 / Updated on December 01, 2017 15:46