. 2020 May 1;11(10):1799–1809. doi: 10.1021/acsmedchemlett.9b00599

Table 2. Compared to Erlotinib, a Fused Dioxane Ring Improves Brain Penetration, but Reduces Potency, while the Addition of an ortho-Fluorine on the Aniline Ring Improves Potency while Retaining BBB Penetration^a.

Compound	MW	clogP	HBA	TPSA (Å)	NRB	EGFR IC₅₀ (nM)	p-wtEGFR IC₅₀ (nM)	p-EGFRvIII IC₅₀ (nM)	HK301 GI₅₀ (nM)	GBM39 GI₅₀ (nM)
Erlotinib	393	2.39	7	75	10	2.17 ± 0.58	3.90 ± 0.24	12.5 ± 1.1	700.2 ± 76.8	2788 ± 179
1	303	2.98	5	56	2	48.7 ± 7.8	59.8 ± 1.6	188.4 ± 26.9	8824 ± 1109	20536 ± 1212
2	321	3.71	5	56	2	19.7 ± 3.7	20.5 ± 0.1	32.2 ± 1.2	791.1 ± 108.1	2946 ± 353

All EGFR inhibition data are represented as mean ± SEM from n = 2 or more independent replicates. All growth inhibition data are represented as mean ± SEM from n = 3 or more independent replicates.

Table 2. Compared to Erlotinib, a Fused Dioxane Ring Improves Brain Penetration, but Reduces Potency, while the Addition of an ortho-Fluorine on the Aniline Ring Improves Potency while Retaining BBB Penetrationa.

Table 2. Compared to Erlotinib, a Fused Dioxane Ring Improves Brain Penetration, but Reduces Potency, while the Addition of an ortho-Fluorine on the Aniline Ring Improves Potency while Retaining BBB Penetration^a.