ChemSpider 2D Image | Afatinib | C24H25ClFN5O3

Afatinib

  • Molecular FormulaC24H25ClFN5O3
  • Average mass485.938 Da
  • Monoisotopic mass485.162994 Da
  • ChemSpider ID8360155
  • Double-bond stereo - Double-bond stereo

    defined stereocentres - 1 of 1 defined stereocentres


More details:



Featured data source



Validated by Experts, Validated by Users, Non-Validated, Removed by Users

(2E)-N-(4-[(3-chloro-4-fluorophenyl)amino]-7-{[(3S)-tetrahydrofuran-3-yl]oxy}quinazolin-6-yl)-4-(dimethylamino)but-2-enamide
(2E)-N-[4-(3-chloro-4-fluoroanilino]-7-{[(3S)-oxolan- 3-yl]oxy}quinazolin-6-y]-4-(diméthylamino)but-2-énamide [French]
(2E)-N-[4-(3-cloro-4-fluoroanilino)-7-{[(3S)-oxolan- 3-il]oxi}quinazolin-6-il]-4-(dimetilamino)but-2-enamida [Spanish]
(2E)-N-{4-[(3-Chlor-4-fluorphenyl)amino]-7-[(3S)-tetrahydro-3-furanyloxy]-6-chinazolinyl}-4-(dimethylamino)-2-butenamid [German] [ACD/IUPAC Name]
(2E)-N-{4-[(3-Chloro-4-fluorophenyl)amino]-7-[(3S)-tetrahydro-3-furanyloxy]-6-quinazolinyl}-4-(dimethylamino)-2-butenamide [ACD/IUPAC Name]
(2E)-N-{4-[(3-Chloro-4-fluorophényl)amino]-7-[(3S)-tétrahydro-3-furanyloxy]-6-quinazolinyl}-4-(diméthylamino)-2-buténamide [French] [ACD/IUPAC Name]
2-Butenamide, N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[[(3S)-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4-(dimethylamino)-, (2E)- [ACD/Index Name]
439081-18-2 [RN]
850140-72-6 [RN]
More...

Validated by Experts, Validated by Users, Non-Validated, Removed by Users

BIBW-2992 [DBID]
BIBW 2992 [DBID]
BIBW2992 [DBID]
S1011 [DBID]
  • Experimental Physico-chemical Properties
  • Miscellaneous
    • Safety:

      5 Axon Medchem 1544
      H303;H313;H317;H333;H334;H335;H373 Axon Medchem 1544
      IRRITANT Matrix Scientific 097289, 097732
      no pictogram Axon Medchem 1544
      P101;P102;P103;P260;P262;P263;P264;P270;P280;P304;P312;P340 Axon Medchem 1544
      Warning Axon Medchem 1544
    • Bio Activity:

      Afatinib (BIBW2992) irreversibly inhibits EGFR/HER2 including EGFR(wt), EGFR(L858R), EGFR(L858R/T790M) and HER2 with IC50 of 0.5 nM, 0.4 nM, 10 nM and 14 nM, respectively; 100-fold more active against Gefitinib-resistant L858R-T790M EGFR mutant.; IC50 value: 0.5 nM/0.4 nM/10 nM/14 nM (EGFR(wt)/EGFR(L858R)/EGFR(L858R/T790M) /HER2) [1]; Target: EGFR;EGFR mutant forms; HER2; in vitro: BIBW2992 shows potent activity against both wild-type and mutant forms of EGFR and HER2. MedChem Express HY-10261
      Afatinib (BIBW2992) irreversibly inhibits EGFR/HER2 including EGFR(wt), EGFR(L858R), EGFR(L858R/T790M) and HER2 with IC50 of 0.5 nM, 0.4 nM, 10 nM and 14 nM, respectively; 100-fold more active against Gefitinib-resistant L858R-T790M EGFR mutant.;IC50 value: 0.5 nM/0.4 nM/10 nM/14 nM (EGFR(wt)/EGFR(L858R)/EGFR(L858R/T790M) /HER2) [1];Target: EGFR;EGFR mutant forms; HER2;In vitro: BIBW2992 shows potent activity against both wild-type and mutant forms of EGFR and HER2. It is similar to Gefitinib in potency against L858R EGFR, but about 100-fold more active against the Gefitinib resistant L858R-T790M EGFR double mutant. BIBW2992 exhibits potent effects on both EGFR and HER2 phosphorylation in vivo. It compares favorably to reference compounds (such as Lapatinib et al.) in all cell types tested, such as human epidermoid carcinoma cell line A431 expressing wt EGFR, murine NIH-3T3 cells transfected with wt HER2, as well as breast cancer cell line BT-474 and gastric cancer cell line NCI-N8 MedChem Express HY-10261
      Afatinib (BIBW2992) irreversibly inhibits EGFR/HER2 including EGFR(wt), EGFR(L858R), EGFR(L858R/T790M) and HER2 with IC50 of 0.5 nM, 0.4 nM, 10 nM and 14 nM, respectively; 100-fold more active against Gefitinib-resistant L858R-T790M EGFR mutant. MedChem Express
      EGFR MedChem Express HY-10261
      JAK/STAT Signaling MedChem Express HY-10261
      JAK/STAT Signaling; Protein Tyrosine Kinase/RTK; MedChem Express HY-10261

Predicted data is generated using the ACD/Labs Percepta Platform - PhysChem Module

Density: 1.4±0.1 g/cm3
Boiling Point: 676.9±55.0 °C at 760 mmHg
Vapour Pressure: 0.0±2.1 mmHg at 25°C
Enthalpy of Vaporization: 99.4±3.0 kJ/mol
Flash Point: 363.2±31.5 °C
Index of Refraction: 1.668
Molar Refractivity: 131.2±0.3 cm3
#H bond acceptors: 8
#H bond donors: 2
#Freely Rotating Bonds: 8
#Rule of 5 Violations: 0
ACD/LogP: 3.59
ACD/LogD (pH 5.5): 1.00
ACD/BCF (pH 5.5): 1.00
ACD/KOC (pH 5.5): 6.44
ACD/LogD (pH 7.4): 2.87
ACD/BCF (pH 7.4): 65.93
ACD/KOC (pH 7.4): 483.19
Polar Surface Area: 89 Å2
Polarizability: 52.0±0.5 10-24cm3
Surface Tension: 60.1±3.0 dyne/cm
Molar Volume: 352.0±3.0 cm3

Predicted data is generated using the US Environmental Protection Agency’s EPISuite™

                        
 Log Octanol-Water Partition Coef (SRC):
    Log Kow (KOWWIN v1.67 estimate) =  2.90

 Boiling Pt, Melting Pt, Vapor Pressure Estimations (MPBPWIN v1.42):
    Boiling Pt (deg C):  648.15  (Adapted Stein & Brown method)
    Melting Pt (deg C):  281.80  (Mean or Weighted MP)
    VP(mm Hg,25 deg C):  5.79E-015  (Modified Grain method)
    Subcooled liquid VP: 4.01E-012 mm Hg (25 deg C, Mod-Grain method)

 Water Solubility Estimate from Log Kow (WSKOW v1.41):
    Water Solubility at 25 deg C (mg/L):  2.957
       log Kow used: 2.90 (estimated)
       no-melting pt equation used

 Water Sol Estimate from Fragments:
    Wat Sol (v1.01 est) =  831.31 mg/L

 ECOSAR Class Program (ECOSAR v0.99h):
    Class(es) found:
       Aliphatic Amines
       Acrylamides

 Henrys Law Constant (25 deg C) [HENRYWIN v3.10]:
   Bond Method :   1.53E-024  atm-m3/mole
   Group Method:   Incomplete
 Henrys LC [VP/WSol estimate using EPI values]:  1.252E-015 atm-m3/mole

 Log Octanol-Air Partition Coefficient (25 deg C) [KOAWIN v1.10]:
  Log Kow used:  2.90  (KowWin est)
  Log Kaw used:  -22.204  (HenryWin est)
      Log Koa (KOAWIN v1.10 estimate):  25.104
      Log Koa (experimental database):  None

 Probability of Rapid Biodegradation (BIOWIN v4.10):
   Biowin1 (Linear Model)         :  -0.9205
   Biowin2 (Non-Linear Model)     :   0.0000
 Expert Survey Biodegradation Results:
   Biowin3 (Ultimate Survey Model):   1.0010  (recalcitrant)
   Biowin4 (Primary Survey Model) :   2.8712  (weeks       )
 MITI Biodegradation Probability:
   Biowin5 (MITI Linear Model)    :  -0.4457
   Biowin6 (MITI Non-Linear Model):   0.0000
 Anaerobic Biodegradation Probability:
   Biowin7 (Anaerobic Linear Model): -2.7393
 Ready Biodegradability Prediction:   NO

Hydrocarbon Biodegradation (BioHCwin v1.01):
    Structure incompatible with current estimation method!

 Sorption to aerosols (25 Dec C)[AEROWIN v1.00]:
  Vapor pressure (liquid/subcooled):  5.35E-010 Pa (4.01E-012 mm Hg)
  Log Koa (Koawin est  ): 25.104
   Kp (particle/gas partition coef. (m3/ug)):
       Mackay model           :  5.61E+003 
       Octanol/air (Koa) model:  3.12E+012 
   Fraction sorbed to airborne particulates (phi):
       Junge-Pankow model     :  1 
       Mackay model           :  1 
       Octanol/air (Koa) model:  1 

 Atmospheric Oxidation (25 deg C) [AopWin v1.92]:
   Hydroxyl Radicals Reaction:
      OVERALL OH Rate Constant = 354.7560 E-12 cm3/molecule-sec [Cis-isomer]
      OVERALL OH Rate Constant = 357.4160 E-12 cm3/molecule-sec [Trans-isomer]
      Half-Life =   21.708 Min (12-hr day; 1.5E6 OH/cm3) [Cis-isomer]
      Half-Life =   21.547 Min (12-hr day; 1.5E6 OH/cm3) [Trans-isomer]
   Ozone Reaction:
      OVERALL Ozone Rate Constant =     0.568750 E-17 cm3/molecule-sec [Cis-]
      OVERALL Ozone Rate Constant =     1.137500 E-17 cm3/molecule-sec [Trans-]
      Half-Life =     2.015 Days (at 7E11 mol/cm3) [Cis-isomer]
      Half-Life =     1.007 Days (at 7E11 mol/cm3) [Trans-isomer]
   Fraction sorbed to airborne particulates (phi): 1 (Junge,Mackay)
    Note: the sorbed fraction may be resistant to atmospheric oxidation

 Soil Adsorption Coefficient (PCKOCWIN v1.66):
      Koc    :  3.179E+004
      Log Koc:  4.502 

 Aqueous Base/Acid-Catalyzed Hydrolysis (25 deg C) [HYDROWIN v1.67]:
    Rate constants can NOT be estimated for this structure!

 Bioaccumulation Estimates from Log Kow (BCFWIN v2.17):
   Log BCF from regression-based method = 1.531 (BCF = 33.94)
       log Kow used: 2.90 (estimated)

 Volatilization from Water:
    Henry LC:  1.53E-024 atm-m3/mole  (estimated by Bond SAR Method)
    Half-Life from Model River: 8.436E+020  hours   (3.515E+019 days)
    Half-Life from Model Lake : 9.203E+021  hours   (3.834E+020 days)

 Removal In Wastewater Treatment:
    Total removal:               4.92  percent
    Total biodegradation:        0.12  percent
    Total sludge adsorption:     4.81  percent
    Total to Air:                0.00  percent
      (using 10000 hr Bio P,A,S)

 Level III Fugacity Model:
           Mass Amount    Half-Life    Emissions
            (percent)        (hr)       (kg/hr)
   Air       1.52e-012       0.713        1000       
   Water     7.57            4.32e+003    1000       
   Soil      92.3            8.64e+003    1000       
   Sediment  0.166           3.89e+004    0          
     Persistence Time: 6.18e+003 hr




                    

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