2,4-dihydro-4-[4-[4-(4-methoxyphenyl)piperazin-1-yl]phenyl]-3H-1,2,4-triazol-3-one

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07 September 2016 - 22 December 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.7570 (Partition Coefficient, n-octanol / H2O, Estimation by Liquid Chromatography)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

HPLC method

Test material

Test material information

Constituent 1

Reference substance name:

2,4-dihydro-4-[4-[4-(4-methoxyphenyl)piperazin-1-yl]phenyl]-3H-1,2,4-triazol-3-one

EC Number:

278-009-6

EC Name:

2,4-dihydro-4-[4-[4-(4-methoxyphenyl)piperazin-1-yl]phenyl]-3H-1,2,4-triazol-3-one

Cas Number:

74853-07-9

Molecular formula:

C19H21N5O2

IUPAC Name:

4-{4-[4-(4-METHOXYPHENYL)PIPERAZIN-1-YL]PHENYL}-2,4-DIHYDRO-3H-1,2,4-TRIAZOL-3-ONE

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study reports): JNJ-1802905-AAA (T001328)
- Physical state: solid
- Appearance: Purple powder

Specific details on test material used for the study:

- Batch n°: I16AB0441
- Expiration date: 30 January 2018
- Analytical purity: 98% and 100% (based on acid and base titration assay respectively)
- Storage condition of test material: At room temperature

Study design

Analytical method:

high-performance liquid chromatography

mass spectrometry

Results and discussion

Partition coefficient

Key result

Type:

log Pow

Partition coefficient:

2.3

pH:

7

Remarks on result:

other: Column temperature was 35+-1°C.

Details on results:

Calculation method
- The Pow of the test item was calculated to be 2.0E+2 (log Pow 2.3) using the Rekker calculation method.
- The calculated pKa values are listed in the table in the next field "any other information on results incl. tables".

Main study
In the chromatogram of the test solution, one test-item related peak was observed. Other, earlier-eluting peaks were considered derived from DMF. These peak were sufficiently separated from the test item peak. The equation of the regression line was: log k’ = 0.464 x log Pow – 0.673 (r = 0.997, n = 12). The results of HPLC method are given in the table "any other information on results incl. tables".

Any other information on results incl. tables

- Calculated pKa values of the test item:

Acidic	Basic
None	RARN(R1R2)	pKa 5.5
	RARN(R1R2)	pKa 4.8

- Pow of the test and reference items:

Substance	tr,1 (min)	tr, 2 (min)	mean tr (n=2)	log Pow	Pow
Formamide (t0)	0.602	0.603	0.603
Benzylalcohol	1.004	1.005		1.1
Nitrobenzene	1.493	1.495		1.9
Toluene	3.338	3.342		2.7
1,4-Dichlorobenzene	5.604	5.608		3.4
Biphenyl	9.823	9.821		4.0
1,2,4-Trichlorobenzene	10.923	10.925		4.2
Test item	2.080	2.080	2.080	2.3	2.0 x 10^2

Applicant's summary and conclusion

Conclusions:

The HPLC method was applied for the determination of the partition coefficient (Pow) of JNJ-1802905-AAA (T001328).
The Pow of the test item at 20°C was 2.0E+2. This corresponds to a log Pow value of 2.3.