Table 3.

Description of physicochemical, medicinal, absorption, distribution, metabolism, excretion, and toxicological properties with their permissible range of rofecoxib, aspirin, AGP, and A1–A7 AGP analogs.

Category	Parameters	Permissible range	Rofecoxib	Aspirin	AGP	A1	A2	A3	A4	A5	A6	A7
Physicochemical property	MW	100 ~ 600	314.06	180.04	350.21	334.21	320.2	334.21	320.2	388.19	376.19	362.21
	HA	< 38	22	13	25	24	23	24	23	27	27	26
	nHA	0–12	4	4	5	4	4	4	4	4	6	5
	nHD	0–7	1	1	3	2	2	2	2	2	1	1
	TPSA	0–140	67.51	63.6	86.99	66.76	66.76	66.76	66.76	66.76	82.06	64.99
	logP (log mol/L)	0–3	3.014	1.237	1.58	2.763	2.435	2.763	2.435	3.229	2.458	2.556
Medicinal chemistry	NPscore	− 5 to 5	− 0.256	0.122	3.02	2.793	2.936	2.793	2.936	2.224	2.591	2.741
	Lipinski Rule	MW ≤ 500, logP ≤ 5, nHA ≤ 10, nHD ≤ 5, < 2 violations	Accepted	Accepted	Accepted	Accepted	Accepted	Accepted	Accepted	Accepted	Accepted	Accepted
	Pfizer Rule	logP > 3, TPSA < 75	Rejected	Accepted	Accepted	Accepted	Accepted	Accepted	Accepted	Rejected	Accepted	Accepted
Absorption	Caco-2 Permeability (log cm/s)	> − 5.15	− 5.598	− 5.062	− 4.793	− 4.604	− 4.647	− 4.604	− 4.647	− 4.665	− 4.732	− 4.822
	Pgp-inhibitor	0–0.3	0.01	0	0	0	0	0	0	0	0.001	0.002
	HIA	0–0.3	0.005	0.007	0.245	0.028	0.217	0.028	0.217	0.01	0.007	0.008
	F30%	0–0.3	0.003	0.003	0.036	0.006	0.049	0.006	0.049	0.007	0.501	0.02
Distribution	PPB	≤ 0.90	0.99	0.59	0.30	0.57	0.52	0.57	0.52	0.73	0.43	0.47
	VD (L/kg)	0.04–20	0.626	0.234	0.612	0.811	0.885	0.811	0.885	0.803	0.839	0.997
	BBB Penetration (cm/s)	0 to 1	0.037	0.661	0.955	0.996	0.987	0.996	0.987	0.987	0.995	0.983
	Fu	≥ 5%	0.02	0.61	0.67	0.52	0.54	0.52	0.54	0.31	0.63	0.55
Metabolism	CYP inhibitor	0–1	0.146	0.016	0.167	0.407	0.155	0.407	0.155	0.351	0.466	0.412
	CYP substrate	0–1	0.358	0.114	0.219	0.283	0.252	0.283	0.252	0.32	0.26	0.246
Excretion	CL (ml/min/kg)	> 15 high clearance; 5–15 moderate clearance; < 5 low clearance	0.535	2.736	8.907	14.47	14.712	14.47	14.712	9.945	13.704	13.431
	T 1/2	0–0.3 excellent 0.3–0.7 medium; 0.7–1.0 poor	0.116	0.91	0.249	0.119	0.134	0.119	0.134	0.04	0.121	0.087
Toxicology	hERG Blockers	0–0.3 excellent 0.3–0.7 medium; 0.7–1.0 poor	0.087	0.015	0.003	0.004	0.004	0.004	0.004	0.005	0.001	0.002
	H-HT	0–0.3 excellent 0.3–0.7 medium; 0.7–1.0 poor	0.592	0.258	0.012	0.017	0.017	0.017	0.017	0.029	0.012	0.015
	AMES Toxicity	0–0.3 excellent 0.3–0.7 medium; 0.7–1.0 poor	0.006	0.013	0.327	0.266	0.227	0.266	0.227	0.158	0.065	0.271
	Skin Sensitization	0–0.3 excellent 0.3–0.7 medium; 0.7–1.0 poor	0.048	0.511	0.026	0.018	0.022	0.018	0.022	0.018	0.032	0.023
	IGC50 {− log10[(mg/L)/(1000*MW)]}	–	3.199	2.661	4.909	4.825	4.967	4.825	4.967	5.002	5.28	5.257
	LC50 {− log10[(mg/L)/(1000*MW)]}	–	4.275	3.748	6.605	6.114	6.293	6.114	6.293	6.461	6.613	6.973

MW, Molecular Weight; nHA, Number of hydrogen bond acceptors; nHD, Number of hydrogen bond donors; TPSA, Topological polar surface area; logP, The logarithm of the n-octanol/water distribution coefficient; NPscore, Natural Product-likeness score; Caco-2 Permeability, The human colon adenocarcinoma cell lines; Pgp-inhibitor, Inhibitor of P-glycoprotein; HIA, Human intestinal absorption; F 30%, The human oral bioavailability 30%; PPB, Plasma protein binding; VD, Volume Distribution; BBB, blood–brain barrier; Fu, fraction unbound in plasma; CYP, cytochrome; CL, clearance; hERG, human ether–A-go-go related gene; H-HT, human hepatotoxicity; IGC₅₀, 50% inhibition growth concentration; LC₅₀, 50% lethal concentration.