2-Thiophenecarboxylic acid, 3-[[(2-methoxy-2-oxoethyl)amino]sulfonyl]-, methyl ester

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Materials and methods

Principles of method if other than guideline:

The octanol-water partition coefficient was estimated by using three different predictors, ACD/Percepta LogP Classic, ACD/Percepta LogP GALAS and KOWWIN predictors.

GLP compliance:

no

Type of method:

other: in silico prediction

Partition coefficient type:

octanol-water

Results and discussion

Partition coefficient

Type:

log Pow

Partition coefficient:

0.62

Any other information on results incl. tables

ACD/logPClassic	ACD/logP GALAS	KOWWINLogP	Consensus LogPprediction
0.65 (± 1.08)	0.87 (RI = 0.80)	0.03	0.62

ACD/Percepta LogP Classic (ACD/logP classic) estimates the reliability of the prediction based on the

confidence interval at 95% (logP  Err); since in silico predictions for octanol-water coefficient partition are

affected by an error which in the best case is not less than 0.3 logarithmic unit, predictions affected by an

error greater than 0.5 are considered not reliable. For the target 2-Thiophenecarboxylic acid, 3-[[(2-methoxy-

2-oxoethyl)amino]sulfonyl]-, methyl ester, ACD/Percepta LogP Classic predicted a LogKow value of 0.65

but the prediction is not reliable according to the error estimation. In fact a warning message was provided to

highlight that the logP value was calculated with a high degree of uncertainty since the target contains

aromatic interactions not known in the ACD/LogP classic algorithm.

ACD/Percepta LogP GALAS

ACD/Percepta LogP GALAS (ACD/logP GALAS) estimates the reliability in terms of reliability index which ranges from 0 to 1 and takes into account the similarity of the tested compound to the training set and the consistency of experimental values for similar compounds. Values greater than 0.75 indicate highly reliable predictions, values in the range 0.5-0.75 indicate moderately reliable predictions, values in the range 0.3-0.5 indicate borderline predictions, while for values lower than 0.3 predictions are considered as NOT reliable. For the target 2-Thiophenecarboxylic acid, 3-[[(2-methoxy-2-oxoethyl)amino]sulfonyl]-, methyl ester, ACD/Percepta LogP GALAS predicted a LogKow value of 0.87 and the prediction is highly reliable since the reliability index is equal to 0.80.

KOWWIN estimation methodology was developed at Syracuse Research Corporation and it is described in Meylan and Howard paper (Meylan, W.M. and P.H. Howard. 1995. Atom/fragment contribution method for estimating octanol-water partition coefficients. J. Pharm. Sci. 84, 83-92). The prediction is not supported by a specific reliability evaluation however it is generally assumed that logKow estimates for compounds outside the MW range of the training set compounds (minimum MW = 18.02; maximum MW = 719.92) are less accurate. For the target 2-Thiophenecarboxylic acid, 3-[[(2-methoxy-2-oxoethyl)amino]sulfonyl]-, methyl ester, KOWWIN predicted a LogKow value of 0.03 and the prediction is considered reliable, being the target in the MW range of the model training set (the MW value is equal to 293.31 for a training set of 18.02 to 719.92).

Applicant's summary and conclusion

Conclusions:

The octanol-water partition coefficient of the target 2-Thiophenecarboxylic acid, 3-[[(2-methoxy-2-oxoethyl)amino]sulfonyl]-, methyl ester was estimated by using three different predictors in order to apply a consensus approach to enhance the reliability of the prediction. The consensus assessment was computed as weighted mean among ACD/Percepta LogP GALAS and KOWWIN predictions. ACD/Percepta LogP GALAS prediction was weighted more (weight = 0.7) than KOWWIN (weight = 0.3), because its reliability is very well assessed and documented. For the target 2-Thiophenecarboxylic acid, 3-[[(2-methoxy-2-oxoethyl)amino]sulfonyl]-, methyl ester the consensus assessment led to an octanol-water partition coefficient of 0.62.