. Author manuscript; available in PMC: 2021 Jul 23.

Published in final edited form as: J Med Chem. 2020 Jul 6;63(14):7569–7600. doi: 10.1021/acs.jmedchem.9b01733

Table 4.

Optimization of A- and C-Ring Functionality for Thiophene Core^c


#	R₁	C-ring	R₂	pEC₅₀ [95% CI] (max) (%)^a		p(doubling conc.) (GluN2C/2D)^b	sol. (μM)	cLogP	LLE (GluN2C/2D)
#	R₁	C-ring	R₂	GluN2C	GluN2D	p(doubling conc.) (GluN2C/2D)^b	sol. (μM)	cLogP	LLE (GluN2C/2D)
CIQ^c (TIQ core)				5.3 (230)	5.3 (220)	4.9/4.5	8	5.6	−0.7/−1.1
25a	H			5.4 [5.3–5.5] (280)	5.4 [5.3–5.5] (350)	5.3/S.6	46	5.6	−0.3/0.0
25h	H			5.4 [5.3–5.4] (330)	5.3 [5.2–5.3] (340)	5.5/5.4	-	5.6	−0.1/−0.2
25b	H			5.3 [5.3–5.3] (290)	5.3 [5.2–5.4] (400)	5.3/5.6	-	5.4	−0.1/0.2
25c	H			4.9 [4.8–5.0] (290)	4.8 [4.6–4.9] (330)	4.8/4.9	-	3.6	1.2/1.3
25d	OMe			5.3 [5.2–5.4] (220)	5.2 [5.1–5.2] (220)	4.6/4.5	-	5.7	−1.1/−1.2

Fitted pEC₅₀ values are shown to have two significant figures when potentiation at 30 μM exceeded 130% of control; values in brackets are the 95% confidence interval for the corresponding log-fitted pEC₅₀ value; and values in parentheses are the fitted maximum response as a percentage of the initial glutamate (100 μM) and glycine (30 μM) current. Data are between 10 and 12 oocytes from 2 frogs for each compound and receptor.

p(doubling conc.) is the negative log of the doubling concentration.

Previously published data for CIQ were included for comparison.