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. Author manuscript; available in PMC: 2021 Feb 13.
Published in final edited form as: J Med Chem. 2020 Jan 16;63(3):1032–1050. doi: 10.1021/acs.jmedchem.9b01218

Table 2.

Middle ring modified EP2 antagonists. Potency and aqueous solubilitya

Entry graphic file with name nihms-1607948-t0002.jpg EP2 KB (nM) Aqueous Solubilityb (μM) Solubility in SGF c (μM)
2a graphic file with name nihms-1607948-t0003.jpg 28.6 70 ND
2b graphic file with name nihms-1607948-t0004.jpg 118 206 ND
2c graphic file with name nihms-1607948-t0005.jpg 185 ND ND
8a graphic file with name nihms-1607948-t0006.jpg 23.2 25 >100
8b graphic file with name nihms-1607948-t0007.jpg 9.5 13 >100
8c graphic file with name nihms-1607948-t0008.jpg 10 28 >100
8d graphic file with name nihms-1607948-t0009.jpg 11.5 8 50c
8e graphic file with name nihms-1607948-t0010.jpg 48.4 22 >100
8f graphic file with name nihms-1607948-t0011.jpg 4.4 25 >100
8g graphic file with name nihms-1607948-t0012.jpg 2.9 12 >100
11a graphic file with name nihms-1607948-t0013.jpg 48.6 14 14
11b graphic file with name nihms-1607948-t0014.jpg 33.6 10 10
11c graphic file with name nihms-1607948-t0015.jpg 12.8 10 10
14a graphic file with name nihms-1607948-t0016.jpg 29.6 71 >100
14b graphic file with name nihms-1607948-t0017.jpg 250 10 10d
14c graphic file with name nihms-1607948-t0018.jpg 7.7 5 ND
a

The potency of the compounds is presented in the form of Schild KB values, which are calculated using the formula log (dr-1) = log XB −log KB, where dr (dose ratio) = fold shift in EC50 of PGE2 by the antagonist compound, XB is antagonist concentration 1 μM. KB value indicates a concentration required to produce a 2-fold rightward shift of PGE2 EC50. KB values are average of 2 measurements run in duplicate.

b

The solubility of the compounds is measured in PBS buffer (pH 7.4) with 1% DMSO by nephelometry.46

c

The numbers are derived by measuring solubility in simulated gastric fluid (SGF) at pH 2.0 with 1% DMSO by nephelometry.