. 2024 Jan 17;67(2):1225–1242. doi: 10.1021/acs.jmedchem.3c01714

Table 2. SAR: Introduction of R¹ Substituents Underneath the Nucleotide Binding Loop and Combination with a N-Methylpiperazine Moiety.

compd	IRAK4 IC₅₀ (nM)^a	A	R¹	R²
7	111	N	Me	benzoyl
8	83	N	F	benzoyl
9	51	N	Cl	benzoyl
10	6	N	OEt	benzoyl
11	13	N	OiPr	benzoyl
12	961	N	F	Me
13	126	N	Cyano	Me
14	57	N	OMe	Me
15	38	N	OCF₃	Me
16	5	N	OEt	Me
17	4	N	OiPr	Me
18	3	N	cyclopropylmethoxy	Me
19	12	O	OMe
20	12	O	OEt

Biochemical potency of IRAK4 inhibition (1 mM ATP).

Table 2. SAR: Introduction of R1 Substituents Underneath the Nucleotide Binding Loop and Combination with a N-Methylpiperazine Moiety.