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. Author manuscript; available in PMC: 2019 Jul 12.

Published in final edited form as: J Med Chem. 2018 Jun 25;61(13):5679–5691. doi: 10.1021/acs.jmedchem.8b00641

Table 3.

Microsomal Stability: Half-Lives and Estimated Clearance of VNI and New Derivatives in Human, Rat, and Mouse Microsomes

	human			rat			mouse
cmpds	CL_INT^a	CL_HEP	t_1/2 (min)^b	CL_INT	CL_HEP	t_1/2 (min)	CL_INT	CL_HEP	t_1/2 (min)
VNI	8.31	5.95	150	26.4	19.2	106	87	44	62
1	7.53	5.54	166	31	21	91	55	34	98
2	6.06	4.07	206	36	24	77	60	36	92
3	16.5	9.24	76	64	34	44	88	44	62
4	11.3	7.33	111	50.4	29	56	84.7	43.6	65
5	11.4	7.39	110	70	35	40	107	49	51
6	9.47	6.53	132	27	19	106	126	55	43
9	13.1	8.06	95	68	35	41	152	56	36
10	10.8	7.15	115	94	40	30	95	46	57
11	96.6	17.3	13	36.0	24.0	78	55.0	34	99
12	15	8.75	83	51.6	29.7	54	36.5	26.0	149
13	10.2	6.85	123	49.4	29.0	57	238	65	23
14	9.31	6.45	134	104	42	27	56	34.5	97
15	14.9	8.37	84	27.0	19.5	104	104	48.3	52

^a

Intrinsic (CL_INT) and hepatic clearance (CL_HEP) expressed in mL/min/kg body weight.

^b

In vitro half-life values in minutes.