Table 2. Structure–Activity Investigations of the 2-Fluoro Alkyne Agonists.

			pEC50 (efficacy, %)
compd	R1	X	hFFA1, calciuma	hFFA4, BRETb	ClogPc	LEd	LLEe
9	2-Me	H	7.34 ± 0.07 (103)	5.84 ± 0.01 (103)	5.04	0.50	2.30
10	2-Me	F	7.48 ± 0.03 (107)	5.80 ± 0.03 (98)	5.18	0.49	2.30
11	3-Me	F	7.65 ± 0.03 (100)	5.41 ± 0.07 (124)	5.18	0.50	2.47
12	2-Me, 5-CN	F	7.77 ± 0.03 (104)	5.02 ± 0.04 (123)	4.62	0.46	3.15
13	2-CF2H, 5-F	F	7.74 ± 0.04 (97)	5.93 ± 0.04 (117)	5.02	0.44	2.72
14	3,5-Cl	F	7.42 ± 0.07 (99)	5.50 ± 0.25 (90)	6.11	0.46	1.31
15	2-CH2Ms	F	5.84 ± 0.02 (97)	n.a.	2.67	0.33	3.17
16	3-CH2Ms	F	5.71 ± 0.02 (104)	4.19 ± 0.06 (26)	2.67	0.33	3.04
17	2-CH2O(CH2)2Ms	F	6.21 ± 0.03 (94)	n.a.	3.33	0.31	2.88
18	3-CH2O(CH2)2Ms	F	6.44 ± 0.03 (93)	n.a.	3.33	0.33	3.11
19	2-CH2O(CH2)3Ms	F	6.14 ± 0.04 (92)	n.a.	3.59	0.30	2.55
20	3-CH2O(CH2)3Ms	F	6.43 ± 0.04 (83)	n.a.	3.59	0.31	2.84
21	2-CH2CN	H	7.70 ± 0.04 (103)	6.11 ± 0.06 (99)	3.96	0.48	3.76
22	2-CH2CN	F	8.21 ± 0.03 (102)	6.03 ± 0.06 (98)	4.11	0.49	4.10
23	3-CH2CN	F	7.13 ± 0.03 (104)	5.41 ± 0.07 (115)	4.11	0.42	3.02
24	2-CH2CH2CN	F	7.74 ± 0.04 (97)	5.86 ± 0.00 (114)	4.25	0.44	3.50

^aEfficacy is given as % response relative to 10 μM TUG-20.¹⁹

^bEfficacy is given as % response relative to 9; n.a. = no activity (pEC₅₀ < 4).¹⁴

^cCalculated by BioByte’s algorithm as implemented in ChemBioDraw Ultra 12.0 (ClogP option).

^dLE = RTln K_D, presuming that EC₅₀ ≈ K_D. Values are given in kcal mol^–1 per non-hydrogen atom.¹⁷

^eLLE = pEC₅₀ – ClogP.¹⁸