ChemSpider 2D Image | AZD 7545 | C19H18ClF3N2O5S

AZD 7545

  • Molecular FormulaC19H18ClF3N2O5S
  • Average mass478.870 Da
  • Monoisotopic mass478.057709 Da
  • ChemSpider ID20572552

  • defined stereocentres - 1 of 1 defined stereocentres

More details:

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

252017-04-2 [RN]
4-[(3-Chlor-4-{[(2R)-3,3,3-trifluor-2-hydroxy-2-methylpropanoyl]amino}phenyl)sulfonyl]-N,N-dimethylbenzamid [German] [ACD/IUPAC Name]
4-[(3-Chloro-4-{[(2R)-3,3,3-trifluoro-2-hydroxy-2-methylpropanoyl]amino}phenyl)sulfonyl]-N,N-dimethylbenzamide [ACD/IUPAC Name]
4-[(3-Chloro-4-{[(2R)-3,3,3-trifluoro-2-hydroxy-2-méthylpropanoyl]amino}phényl)sulfonyl]-N,N-diméthylbenzamide [French] [ACD/IUPAC Name]
4-{3-chloro-4-[(2R)-3,3,3-trifluoro-2-hydroxy-2-methylpropanamido]benzenesulfonyl}-N,N-dimethylbenzamide
AZD 7545
Benzamide, 4-[[3-chloro-4-[[(2R)-3,3,3-trifluoro-2-hydroxy-2-methyl-1-oxopropyl]amino]phenyl]sulfonyl]-N,N-dimethyl- [ACD/Index Name]
(R)-4-((3-chloro-4-(3,3,3-trifluoro-2-hydroxy-2-methylpropanamido)phenyl)sulfonyl)-N,N-dimethylbenzamide
(R)-4-(3-chloro-4-(3,3,3-trifluoro-2-hydroxy-2-methylpropanamido)phenylsulfonyl)-N,N-dimethylbenzamide
(R)-N-{2-Chloro-4-[4-(N,N-dimethylcarbamoyl)phenylsulphonyl]phenyl}-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide
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  • Experimental Physico-chemical Properties
  • Miscellaneous

    • Chemical Class:

      A sulfone that is benzene substituted by [4-(dimethylcarbamoyl)phenyl]sulfonyl, chloro and [(2R)-3,3,3-trifluoro-2-hydroxy-2-methylpropanoyl]amino groups at positions 1, 3 and 4, respectively. It is a potent and non-ATP-competitive inhibitor of pyruvate dehydrogenase kinase 2 (PDHK2) with IC50 of 6.4 nM and exhibits glucose-lowering activity. Also inhibits PDHK1 at higher levels (IC50 = 36.8 nM). ChEBI CHEBI:49490

    • Bio Activity:

      AZD7545 is a novel, selective small-molecule inhibitor of PDHK2 (PDH kinase2) with an IC50 of 36.8 nM and 6.4 nM for PDHK1 and PDHK2 respectively. MedChem Express
      AZD7545 is a novel, selective small-molecule inhibitor of PDHK2 (PDH kinase2) with an IC50 of 36.8 nM and 6.4 nM for PDHK1 and PDHK2 respectively.; IC50 Value: 36.8 nM (PDHK1); 6.4 nM (PDHK2) [1]; Target: PDHK1/2; in vitro: The IC50 values for inhibition of PDHK2 and PDHK1 by AZD7545 were 6.4 ? 2.2 nM (n = 6) and 36.8 ? 18 nM (n = 3) respectively. MedChem Express HY-16082
      AZD7545 is a novel, selective small-molecule inhibitor of PDHK2 (PDH kinase2) with an IC50 of 36.8 nM and 6.4 nM for PDHK1 and PDHK2 respectively.;IC50 Value: 36.8 nM (PDHK1); 6.4 nM (PDHK2) [1];Target: PDHK1/2;In vitro: The IC50 values for inhibition of PDHK2 and PDHK1 by AZD7545 were 6.4 ? 2.2 nM (n = 6) and 36.8 ? 18 nM (n = 3) respectively. Other compounds in this series inhibited both PDHK1 and PDHK2 and a consistent trend of reduced potency (5-15-fold) towards PDHK1, as compared with PDHK2, was observed. In contrast, AZD7545 and related compounds failed to inhibit PDHK4 and paradoxically, at higher concentrations (>10 nM), AZD7545 stimulated PDHK4 activity [1]. In the presence of PDHK2, AZD7545 increased PDH activity with an EC(50) value of 5.2 nM. In rat hepatocytes, the rate of pyruvate oxidation was stimulated 2-fold (EC(50) 105 nM) [2].;In vivo: A single dose of AZD7545 to Wistar rats increased the proportion of liver PDH in its active, dephosphorylated form in a dose-r MedChem Express HY-16082
      Others MedChem Express HY-16082
      PDHK MedChem Express HY-16082

Predicted data is generated using the ACD/Labs Percepta Platform - PhysChem Module, version: 14.00

Density: 1.5±0.1 g/cm3
Boiling Point: 683.1±55.0 °C at 760 mmHg
Vapour Pressure: 0.0±2.2 mmHg at 25°C
Enthalpy of Vaporization: 105.3±3.0 kJ/mol
Flash Point: 366.9±31.5 °C
Index of Refraction: 1.573
Molar Refractivity: 107.2±0.4 cm3
#H bond acceptors: 7
#H bond donors: 2
#Freely Rotating Bonds: 6
#Rule of 5 Violations: 0
ACD/LogP: 2.66
ACD/LogD (pH 5.5): 2.44
ACD/BCF (pH 5.5): 42.13
ACD/KOC (pH 5.5): 506.36
ACD/LogD (pH 7.4): 2.44
ACD/BCF (pH 7.4): 42.06
ACD/KOC (pH 7.4): 505.55
Polar Surface Area: 112 Å2
Polarizability: 42.5±0.5 10-24cm3
Surface Tension: 52.0±3.0 dyne/cm
Molar Volume: 325.1±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) =  1.15

 Boiling Pt, Melting Pt, Vapor Pressure Estimations (MPBPWIN v1.42):
    Boiling Pt (deg C):  619.23  (Adapted Stein & Brown method)
    Melting Pt (deg C):  268.29  (Mean or Weighted MP)
    VP(mm Hg,25 deg C):  7.71E-017  (Modified Grain method)
    Subcooled liquid VP: 3.63E-014 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):  101.4
       log Kow used: 1.15 (estimated)
       no-melting pt equation used

 Water Sol Estimate from Fragments:
    Wat Sol (v1.01 est) =  21.523 mg/L

 ECOSAR Class Program (ECOSAR v0.99h):
    Class(es) found:
       Neutral Organics

 Henrys Law Constant (25 deg C) [HENRYWIN v3.10]:
   Bond Method :   1.44E-015  atm-m3/mole
   Group Method:   Incomplete
 Henrys LC [VP/WSol estimate using EPI values]:  4.791E-019 atm-m3/mole

 Log Octanol-Air Partition Coefficient (25 deg C) [KOAWIN v1.10]:
  Log Kow used:  1.15  (KowWin est)
  Log Kaw used:  -13.230  (HenryWin est)
      Log Koa (KOAWIN v1.10 estimate):  14.380
      Log Koa (experimental database):  None

 Probability of Rapid Biodegradation (BIOWIN v4.10):
   Biowin1 (Linear Model)         :   0.0531
   Biowin2 (Non-Linear Model)     :   0.0004
 Expert Survey Biodegradation Results:
   Biowin3 (Ultimate Survey Model):   1.1008  (recalcitrant)
   Biowin4 (Primary Survey Model) :   2.9745  (weeks       )
 MITI Biodegradation Probability:
   Biowin5 (MITI Linear Model)    :  -0.2746
   Biowin6 (MITI Non-Linear Model):   0.0000
 Anaerobic Biodegradation Probability:
   Biowin7 (Anaerobic Linear Model): -1.9429
 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):  4.84E-012 Pa (3.63E-014 mm Hg)
  Log Koa (Koawin est  ): 14.380
   Kp (particle/gas partition coef. (m3/ug)):
       Mackay model           :  6.2E+005 
       Octanol/air (Koa) model:  58.9 
   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 =   2.9407 E-12 cm3/molecule-sec
      Half-Life =     3.637 Days (12-hr day; 1.5E6 OH/cm3)
      Half-Life =    43.647 Hrs
   Ozone Reaction:
      No Ozone Reaction Estimation
   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    :  365
      Log Koc:  2.562 

 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 = 0.187 (BCF = 1.539)
       log Kow used: 1.15 (estimated)

 Volatilization from Water:
    Henry LC:  1.44E-015 atm-m3/mole  (estimated by Bond SAR Method)
    Half-Life from Model River: 8.897E+011  hours   (3.707E+010 days)
    Half-Life from Model Lake : 9.706E+012  hours   (4.044E+011 days)

 Removal In Wastewater Treatment:
    Total removal:               1.90  percent
    Total biodegradation:        0.09  percent
    Total sludge adsorption:     1.81  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       0.242           87.3         1000       
   Water     45.6            4.32e+003    1000       
   Soil      54              8.64e+003    1000       
   Sediment  0.103           3.89e+004    0          
     Persistence Time: 1.62e+003 hr

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