Details of the Drug

General Information of Drug (ID: DM7WPI0)

Drug Name
R-1487
Synonyms
449811-92-1; 6-(2,4-difluorophenoxy)-8-methyl-2-((tetrahydro-2H-pyran-4-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one; UNII-IO0DCY55NQ; R-1487; IO0DCY55NQ; CHEMBL1230122; 6-(2,4-difluorophenoxy)-8-methyl-2-[(tetrahydro-2H-pyran-4-yl)amino]-Pyrido[2,3-d]pyrimidin-7(8H)-one; 6-(2,4-difluorophenoxy)-8-methyl-2-(tetrahydro-2h-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8h)-one; Kinome_3762; SCHEMBL5120612; KKKRKRMVJRHDMG-UHFFFAOYSA-N; HMS3401C13; BDBM50341342; ZINC58633224; AKOS027420928; NCGC00262195-02; KB-80224; ACM449811921
Indication
Disease Entry ICD 11 Status REF
Rheumatoid arthritis FA20 Discontinued in Phase 1 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 388.4
Topological Polar Surface Area (xlogp) 2.8
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 8
Chemical Identifiers
Formula
C19H18F2N4O3
IUPAC Name
6-(2,4-difluorophenoxy)-8-methyl-2-(oxan-4-ylamino)pyrido[2,3-d]pyrimidin-7-one
Canonical SMILES
CN1C2=NC(=NC=C2C=C(C1=O)OC3=C(C=C(C=C3)F)F)NC4CCOCC4
InChI
InChI=1S/C19H18F2N4O3/c1-25-17-11(10-22-19(24-17)23-13-4-6-27-7-5-13)8-16(18(25)26)28-15-3-2-12(20)9-14(15)21/h2-3,8-10,13H,4-7H2,1H3,(H,22,23,24)
InChIKey
KKKRKRMVJRHDMG-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
11406590
CAS Number
449811-92-1
DrugBank ID
DB06518
TTD ID
D04YHW

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Stress-activated protein kinase 2a (p38 alpha) TTQBR95 MK14_HUMAN Inhibitor [2]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

ICD Disease Classification 15 Disease of the musculoskeletal system/connective tissue
Disease Class ICD-11: FA20 Rheumatoid arthritis
The Studied Tissue Synovial tissue
The Studied Disease Rheumatoid arthritis [ICD-11:FA20]
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Stress-activated protein kinase 2a (p38 alpha) DTT MAPK14 7.98E-04 1.33 2.48
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017105)
2 Discovery of 6-(2,4-difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl)propylamino]-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (pamapimod) and 6-(2,4-difluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (R1487) as orally bioavailable and highly selective inhibitors of p38alpha mitogen-activated protein kinase. J Med Chem. 2011 Apr 14;54(7):2255-65.
3 Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
4 Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled clinical studies. Arthritis Rheum. 2009 May;60(5):1232-41.
5 Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.
6 c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.