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. Author manuscript; available in PMC: 2024 Jan 26.
Published in final edited form as: J Med Chem. 2023 Jan 11;66(2):1484–1508. doi: 10.1021/acs.jmedchem.2c01651

Table 2.

Optimization of P5

graphic file with name nihms-1891577-t0025.jpg EC50
(μM)		 β5 IC50 (μM) Permeability Metabolic stability m/hLM Clint Kinet. Solu. Cyto- tox. cLogP
ID P1 P2 3D7 Pf20S c-20S i-20S PAMPA Ratio /MDR1
9 A graphic file with name nihms-1891577-t0026.jpg 0.010 0.095 1.5 9.6 30 26/1 73.9/15.5 >140 97 4.0
12 A graphic file with name nihms-1891577-t0027.jpg 0.013 0.034 23.0 >100 10 >8/<1 112/16 65 4.1
13 B graphic file with name nihms-1891577-t0028.jpg 0.073 0.21 33.5 88.0 <1 >1/<1 203/54 >150 3.2
14 B graphic file with name nihms-1891577-t0029.jpg >2.8 2.0 >100 >100 <1 N.D. /<1 19/6 >140 2.7
15 B graphic file with name nihms-1891577-t0030.jpg 0.085 0.46 >100 59.8 <2 >0.5/<2 8/34 >140 3.1

PAMPA unit: nm/sec at pH7.4; MDR unit: ratio (B→A/A→B); A→B, nm/sec; Metabolic stability m/hLM Clint: mouse / human liver microsomes and unit- μL/min/mg; Kinet. Solu.: Kinetic solubility at pH6.8 (μg/mL); Cytotox.: cytotoxicity, % viability of HepG2 cells at 30 μM. “-”: not tested.