Table 2.

Interactions of Carboxylic Acids 5–8 with Wild-type TTR and its V30M Variant

compound	Kd,2 (μM)	wild-type TTR		V30M TTR		binding modeb
		%FF 1:1a	%FF 2:1a	%FF 1:1a	%FF 2:1a
5	1.8 ± 0.1	75 ± 24	77 ± 14	112 ± 25	120 ± 32	forward
6	0.99 ± 0.02	21 ± 4	11 ± 2	48 ± 12	28 ± 8	reverse
7	0.47 ± 0.01	21 ± 4	3 ± 1	41 ± 10	9 ± 2	forward
8	0.45 ± 0.01	16 ± 4	4 ± 1	32 ± 9	10 ± 2	reverse

^a%FF, percent fibril formation.

^b”forward”: upper phenyl ring depicted in Chart 2 lies in the outer pocket of the T₄-binding site, according to X-ray diffraction analysis (Figures 2 and 3); “reverse”: upper ring lies in the inner pocket.¹⁸