Table 1.

Inhibition of Fluorescent Antagonist (2) Binding in hP2Y₁₄R-Expressing CHO Cells (X, Y, and Z = CH, Unless Noted)

Compound	Structurea =	IC50, hP2Y14R (nM, mean±SEM)	cLogPc
Archival compounds and close analogues
1ab		7.96±3.5	6.18
1bb		27.6±4.3	6.47
1c		36.6±10.9	5.99
1d		240±21	6.70
3ab		31.7±8.0	4.64
3b		60,500±6900	3.89
4b	R-CONH(CH2)3NH2	169±42	0.84
5b	R-CONH2	269±121	3.63
6b		233±26	3.95
Phenyl-CO or NH
7	R-NH2	1480±160	4.03
8	R-NH-Ac	811±95	4.07
9	R-NH-CO-phenyl	1860±540	5.19
10	R-NH-Boc	3160±310	4.98
11		197±29	3.85
12		22,500±3700	4.85
13	R-COOH	632±23	3.88
14	R-CONH(CH2)3NH2	588±43	0.92
Phenyl-halo or acyclic
15	R-Br	>10,000	4.71
16	R-CH2CONH2	1290±320	3.65
17	R-(CH2)2-CN	17,800±2900	4.74
18	R-(CH2)3-NH2	292±67	1.60
19	R-C≡CCH2-NH2	308±63	1.47
20	R-(CH2)3-NH-Boc	42,500±27,000	5.37
21	R-(CH2)4-OH	9220±1220	4.84
Phenyl-cyclic
22		14,100±900	1.36
23		8910±750	1.57
24		18,800±2000	5.41
25		2000±180	1.70
26		>10,000	5.41
27		2860±440	4.73
28		2230±380	4.98
29		296±13	4.44
30		389±42	4.59
31		895±122	3.65
Alternative scaffolds
32		15.0±144	5.77
33		7400±1050	4.36
Aza-scan of 3a
34		1690±280	4.16
35		4900±540	4.10
36		2920±310	4.01

^ap-Phenyl substituted, unless noted. The structure of 3b is shown in Chart 1. IC₅₀ values are mean ± SEM for three to four separate determinations, unless noted.

^bReported by Yu et al.,¹ Jung et al.,² and Mufti et al.⁷

^ccLogP calculated using the ALOGPS 2.1 program (www.vcclab.org/lab/alogps/).⁵⁷