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Administrative data

Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15 March - 25 April 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method A.8 (Partition Coefficient)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 830.7570 (Partition Coefficient, n-octanol / H2O, Estimation by Liquid Chromatography)
Deviations:
no
GLP compliance:
yes
Type of method:
HPLC method

Test material

Constituent 1
Chemical structure
Reference substance name:
METHYL (1R,2R,4S)-2-[HEX-5-EN-1-YL(METHYL)CARBAMOYL]-4-({7-METHOXY-8-METHYL-2-[4-(PROPAN-2-YL)-1,3-THIAZOL-2-YL]QUINOLIN-4-YL}OXY)CYCLOPENTANECARBOXYLATE
EC Number:
922-147-8
Cas Number:
1042695-87-3
Molecular formula:
C32H41N3O5S
IUPAC Name:
METHYL (1R,2R,4S)-2-[HEX-5-EN-1-YL(METHYL)CARBAMOYL]-4-({7-METHOXY-8-METHYL-2-[4-(PROPAN-2-YL)-1,3-THIAZOL-2-YL]QUINOLIN-4-YL}OXY)CYCLOPENTANECARBOXYLATE
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material (as cited in study reports): JNJ-39125593-AAA (T003019)
- Physical state: solid
- Appearance: white powder
Specific details on test material used for the study:
- Batch n°: M15FB2925
- Analytical purity: 99.5%
- Expiration date: 31 May 2017
- Storage condition: at room temperature protected from light

Study design

Analytical method:
high-performance liquid chromatography
photometric method

Results and discussion

Partition coefficientopen allclose all
Key result
Type:
log Pow
Partition coefficient:
> 7.2
pH:
4
Remarks on result:
other: the log Pow at pH 4 is unexpectedly high. Possibly there was increased retention due to interaction between the acetate buffer and the test item and the temperature was not specified
Key result
Type:
log Pow
Partition coefficient:
> 7.2
pH:
9
Remarks on result:
other: The temperature was not specified
Details on results:
Calculation method
The Pow of the test item was calculated to be 5.1E+6 (log Pow 6.7) using the Rekker calculation method.

Calculation of pKa values
pKa values between -1.6 and 6.4 were calculated for 3 basic groups in the molecule.
Based on these pKa values, it was decided to perform the test both at pH 4.0 (ionised form) and pH 9.0 (unionised form).

Main study at pH 4
The equation of the regression line was log k' = 0.306 log Pow - 0.748 (r=0.994, n=14). The retention time of the test item was outside the range of the references and therefore the log Pow is reported as > 7.2 (log Pow of the highest standard, benzo[ghi]perylene.

Main study at pH 9
The equation of the regression line was: log k’ = 0.311 log Pow – 0.922 (r=0.989, n=14). The retention time of the test item was outside the range of the references and therefore the log Pow is reported as > 7.2 (log Pow of the highest standard, benzo[ghi]perylene.

Considering the two calculated log Pow results for pH 4 and pH 9, which are 8.1 and 7.4 respectively, the result obtained for the log Pow of the ionised form at pH 4 is unexpectedly high. Though not observed frequently, a possible explanation is that there was increased retention due to interaction between the acetate buffer and the test item.

Any other information on results incl. tables

Results - pH 4:

 Substance  tr,1 (min)  tr,2 (min) Mean tr (min)  logPow
 Formamide (t0 )  0.470 0.469  0.470  
 Benzylalcohol  0.619  0.602  0.611  1.1
 Toluene  1.171  1.137  1.154  2.7
1,4 -Dichlorobenzene  1.492  1.450  1.471  3.4
1,2,4 -Trichlorobenzene  2.268  2.204  2.236  4.2
 Dibenzyl  3.178  3.091  3.135  4.8
 4,4’-DDT  8.033  7.840  7.937  6.5
 Benzo[ghi]perylene  12.804  12.683  12.744  7.2
 Test item  24.927  24.988  24.958  >7.2

Results - pH 9:

 Substance  tr,1 (min)  tr,2 (min) Mean tr (min)  logPow
 Formamide (t0 )  0.493 0.493  0.493  
 Benzylalcohol  0.584  0.582  0.583  1.1
 Toluene  1.032  1.027  1.030  2.7
1,4 -Dichlorobenzene  1.280  1.273  1.277  3.4
1,2,4 -Trichlorobenzene  1.897  1.884  1.891  4.2
 Dibenzyl  2.405  2.385  2.395  4.8
 4,4’-DDT  5.572  5.516  5.544  6.5
 Benzo[ghi]perylene  10.311  10.172  10.242  7.2
 Test item  12.175  12.180  12.178  >7.2

Applicant's summary and conclusion

Conclusions:
The HPLC method was applied for the determination of the partition coefficient (Pow) of JNJ-39125593-AAA (T003019).
The Pow value of the test item was 1.1E+8 at pH 4 (ionised form) and 2.4E+7 at pH 9 (unionised form).
The log Pow value of the test item was > 7.2 at pH 4 and at pH 9.