Table 3.

Physicochemical properties and in vitro safety profile of macrocycles 6, 9, and 10

Macrocycle	PAMPA permeability (nm/s)	Solubility pH 6.8 (μg/mL)a	Stability in human plasmab	Viability of HepG2 at 30 μMc	Microsome stability CLint (μL/min/mg) h/me
6	227	1.4	94%	98%	>768/>768
9	260	–d	86%	91%	>768/>768
10	206	33	97%	102%	>768/>768

^aKinetic solubility.

^bPlasma stability was determined as the percentage remaining after incubation for 2 h with fresh human plasma.

^cHepG2 cells were treated with 30 μM test compounds for 72 h and viability was assessed.

^dBelow the level of detection.

^eStability of the macrocycles in human (h) and mouse (m) liver microsomes. Cl_int: intrinsic clearance.