Table 1. CGRP Receptor Antagonist Data.

compd	R1	R2	X	Y	*	CGRP Kia,b (pM)	cAMP IC50a,c (nM)	cAMP + HS IC50a,d (nM)
3						770 ± 70 (13)	2.2 ± 0.3 (8)	11 ± 2 (10)
5	Me	Me	CH2	F	S	39 ± 12 (13)	0.16 ± 0.06 (5)	0.35 ± 0.10 (5)
6	Me	Me	CH2	H	S	120 (2)	0.59 (2)	1.4 (2)
7	Me	Me	O	H	R	82 ± 30 (5)	0.22 (2)	0.27 (2)
8	Et	Et	O	H	R	67 ± 18 (6)	0.23 ± 0.04 (3)	0.37 ± 0.05 (3)
9	Et	Et	O	F	R	18 ± 6 (3)	0.32 ± 0.08 (3)	0.44 ± 0.12 (3)
10	Me	Me	NH	F	R	34 ± 11 (27)	0.17 ± 0.03 (7)	0.25 ± 0.07 (7)
11	Et	Et	NH	F	R	20 ± 4 (4)	0.14 (2)	0.18 (2)
4	−CH2CH2CH2CH2−		NH	F	R	21 ± 6 (15)	0.12 ± 0.05 (6)	0.17 ± 0.07 (6)
12	−CH2CH2CH2CH2CH2−		NH	F	R	17 ± 5 (7)	0.22 ± 0.05 (3)	0.33 ± 0.12 (3)
13	−CH2CH2CH2CH2CH2−		NH	F	S	570 ± 110 (5)	10 (2)	11 (2)

^aMean value ± standard deviation, where appropriate; the number of replicates is in parentheses.

^bThe K_i value for inhibition of ¹²⁵I-hCGRP binding was determined using membranes from HEK293 cells stably expressing human CLR/RAMP1.¹⁷

^cInhibition of CGRP-induced cAMP production in HEK293 cells stably expressing human CLR/RAMP1.¹⁷

^dAssay conditions are as for footnote ^c but were determined in the presence of 50% human serum.¹⁷