. Author manuscript; available in PMC: 2021 Mar 15.

Published in final edited form as: Bioorg Med Chem. 2020 Jan 31;28(6):115349. doi: 10.1016/j.bmc.2020.115349

Table 2.

Structural features of the CYP3A4-inhibitor complexes

compound	Fe-N bond		pyridine ring rotation (°)^b	I-helix displacement (Å)^c	H-bond with Ser119 (Å)^d	pyridine-R₂ ring angle and overlap	Phe304-R₁ ring angle and overlap	F-G disorder	Boc-group conformation/contacts
compound	distance (Å)	angle (°)^a	pyridine ring rotation (°)^b	I-helix displacement (Å)^c	H-bond with Ser119 (Å)^d	pyridine-R₂ ring angle and overlap	Phe304-R₁ ring angle and overlap	F-G disorder	Boc-group conformation/contacts
5a (S,R)^e	2.34	12	37	1.54–1.49	2.68	55°; half	parallel; half	210–212	disordered
5b (S,S)^e	2.20	2	30	1.89–1.85	2.85	56°; partial	20°; half	210–212	disordered
7a (S,R)	2.25	8	25	1.77–1.52	2.85	−38°; half	parallel; full	198–217	disordered
7b (R,S)	2.40	3	28	1.77–1.97	3.31	44°; half	42°; half	210–212	traceable; 105–108, 120
7c (S,R) molecule A	2.82	0	15	2.18–2.25	-	−85°; none^f	52°; partial^f	none	ordered; 213, 215, 371, 482
7d (R,S)	2.37	3	35	1.55–1.25	2.32	35°; partial	45°; partial	210–213	traceable; 106, 108, 215, 374
9a (S,R)^e	2.40	10	32	1.20–1.93	3.28	25°; half	20°; half	198–217	ordered; 108, 220
9b (S,S)^e molecule A	2.30	10	35	2.03–1.83	2.57	25°; full	25°; partial	204–217	traceable, 105–108, 374

^a–

Deviation from perpendicularity.

^b–

Angle between the planes passing through the pyridine ring and the NB-ND heme atoms

^c–

Distance between Cα-atoms of Phe304 and Ala305 in the inhibitor-bound and ligand-free CYP3A4 (PDB ID 5VCC).

^d–

Hydrogen bond length between inhibitor’s carbonyl oxygen atom and Ser119 hydroxyl group.

^e–

These setereoisomers selectively co-crystallized with CYP3A4.

^f–

In 7c, R₁ and R₂ side groups are in reverse orientation and placed near the heme-ligating pyridine and Phe304, respectively.