1-amino-N-[6-cyano-5-(trifluoromethyl)-3-pyridyl]cyclobutanecarboxamide

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 SEP 2022 To 12 OCT 2022

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2022

Report date:

2022

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient - Shake Flask Method)

Version / remarks:

November 2019

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)

Version / remarks:

July 1995

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.7550 (Partition Coefficient, n-octanol / H2O, Shake Flask Method)

Version / remarks:

August 1996

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Test material

Test material information

Constituent 1

Reference substance name:

1-amino-N-[6-cyano-5-(trifluoromethyl)-3- pyridyl]cyclobutanecarboxamide

Cas Number:

1950587-17-3

Molecular formula:

C12H11F3N4O

IUPAC Name:

1-amino-N-[6-cyano-5-(trifluoromethyl)-3- pyridyl]cyclobutanecarboxamide

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material: JNJ-63632283-AAA (T003665)
- Physical state: solid (powder)
- Appearance: white powder

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- lot/batch number of test material: 22BN0551
- Expiry date: 28 April 2023 (retest date)
- Purity test date: 13 May 2022 (certificate of analysis release date)
- Physical Description: Off-white powder
- Purity: 98.3%
- Purity correction factor: no correction factor required
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature

Study design

Analytical method:

high-performance liquid chromatography

Results and discussion

Partition coefficient

Partition coefficient 1

Key result

Type:

log Pow

Partition coefficient:

0.8

Temp.:

20 °C

pH:

5

Partition coefficient 2

Key result

Type:

log Pow

Partition coefficient:

2.2

Temp.:

20 °C

pH:

9

Details on results:

Calculation method
Pow Calculation
The Pow of the test material was calculated to be 3.3 x 10E0.0 (log Pow 0.5) using the Rekker calculation method.
pKa Values
No pKa values for acidic group in the molecular structure of the test material in the logarithm range of 1 - 14 were calculated.
The pKa values in the logarithm range of 1 - 14 for basic groups in the molecular structure of the test material were calculated using the Perrin calculation method. A basic group with an estimated pKa value of 7.8 was identified (RNH3+).

Preliminary test
pH 5
The analyzed concentration of the stock solution was 1.04 g/L. Based on this the nominal quantity of the test material in the test samples was 2.07 mg. The recoveries were determined according to this value.
The log Pow values were within the criterion range of ± 0.3 log units. The Pow and log Pow of the test material is given as the mean value of all measurements.
No test material was detected in the pre-treated samples from the blank mixture. The pH of the blank samples was pH 5.3 and 5.4.

pH 9
The analyzed concentration of the stock solution was 1.03 g/L. Based on this the nominal quantity of the test material in the test samples was 2.06 mg. The recoveries were determined according to this value.
The log Pow values were within the criterion range of ± 0.3 log units. The Pow and log Pow of the test material is given as the mean value of all measurements.
No test material was detected in the pre-treated samples from the blank mixture. The pH of the blank samples was both pH 9.1.

Any other information on results incl. tables

Pow of the test material

pH5

pH 5: P_ow of the Test Material

Ratio n-octanol : Buffer pH5 [v:v]	Analyzed concentration		Pow		log Pow	pH
	n-octanol [g/L]	Buffer pH5 [g/L]	individual	mean
1:1	0.284	0.0452	6.3	6.4	0.8	5.4
	0.282	0.0439	6.4		0.8	5.4
1:2	0.376	0.0560	6.7	6.7	0.8	5.4
	0.383	0.0565	6.8		0.8	5.4
2:1	0.225	0.0354	6.3	6.3	0.8	5.4
	0.224	0.0360	6.2		0.8	5.4
Mean			6.5		0.8
Standard deviation			2.3 x 10^-1

pH 5: Recoveries

Ratio n-octanol : Buffer pH5 [v:v]	Analyzed quantity			Recovery [%]
	n-octanol [mg]	Buffer pH5 [mg]	total [mg]
1:1	1.71	0.271	1.98	95
	1.69	0.263	1.96	94
1:2	1.50	0.448	1.95	94
	1.53	0.452	1.99	96
2:1	1.80	0.142	1.94	94
	1.79	0.144	1.94	93

 

pH 9

pH 9: P_ow of the Test Material

Ratio n-octanol : Buffer pH9 [v:v]	Analyzed concentration		Pow		log Pow	pH
	n-octanol [g/L]	Buffer pH9 [g/L]	individual	mean
1:1	0.336	0.00215	1.6 x 10^2	1.5 x 10^2	2.2	9.1
	0.323	0.00216	1.5 x 10^2		2.2	9.1
1:2	0.501	0.00323	1.6 x 10^2	1.6 x 10^2	2.2	9.1
	0.495	0.00316	1.6 x 10^2		2.2	9.1
2:1	0.250	0.00161	1.6 x 10^2	1.6 x 10^2	2.2	9.1
	0.252	0.00161	1.6 x 10^2		2.2	9.1
Mean			1.5 x 10^2		2.2
Standard deviation			2.8 x 10^0

pH 9: Recoveries

Ratio n-octanol : Buffer pH9 [v:v]	Analyzed quantity			Recovery [%]
	n-octanol [mg]	Buffer pH9 [mg]	total [mg]
1:1	2.02	0.0129	2.03	99
	1.94	0.0130	1.95	95
1:2	2.00	0.0258	2.03	99
	1.98	0.0253	2.01	97
2:1	2.00	0.00643	2.00	97
	2.02	0.00645	2.02	98

Applicant's summary and conclusion

Conclusions:

The shake flask method at pH 5 and pH 9 was applied for the determination of the partition coefficient (Pow) of JNJ-63632283-AAA (T003665).
pH 5: The Pow value of the test material was 6.5. It corresponds with a log Pow value of 0.8.
pH 9: The Pow value of the test material was 1.5E2. It corresponds with a log Pow value of 2.2.