. Author manuscript; available in PMC: 2020 Dec 15.

Published in final edited form as: J Med Chem. 2020 Nov 18;63(23):14989–15012. doi: 10.1021/acs.jmedchem.0c01581

Table 5.

Physicochemical, solubility and PK properties of compounds 1, 84, and 90.

Compound^a	cAMP EC₅₀ (nM)	clog P^b	TPSA^b	Kinetic solubility at pH 7.4 (μM)	rat PK (i.p., 10 mg/kg)
					Plasma		Brain		B/P
					C_max (ng/mL)	AUC_0-inf (ng/mL • h)	C_max (ng/mL)	AUC_0-inf (ng/mL • h)	B/P
1	414	4.53	64.3	<1
84	59	4.20	103.3	<1
90	71	3.76	103.3	2.9 ± 0.3	270	1001	39	95	0.1
RTI-13951-33^c	25	3.34	77.7		874	1510	287	825	0.5

All compounds were tested as the HCl salt.

clog P and TPSA were calculated using Instant JChem 5.4.0 (ChemAxon Ltd.).

Data were obtained from reference 29.