Table 2.

Structural features of CYP3A4–inhibitor complexes.

Compound	Fe–N Bond		Pyridine ring	I-helix	H-Bond	Pyridine–R2 Ring		F304–R1 Ring		Boc-Group
	Distance (Å) Angle (°) a		Rotation (°) b	Shift (Å) c	with S119 (Å) d	Angle and Overlap		Angle and Overlap		Contacts
3a (R, S) mol A	2.11	3	30	2.04–2.18	2.82	42°	full	50°	partial	108, 211, 213
3b (S, R)	2.20	15	17	1.09–1.76	3.25	46°	half e	65°	partial e	disordered
3c (S, S)	2.18	7	12	1.23–1.76	3.08	35°	partial	36°	half	105, 106, 108, 374
3d (R, R) mol A	2.18	0	37	2.11–2.18	2.48	5°	full	50°	half	57, 108, 211, 213, 482
8 (R, S)	2.11	3	32	1.77–1.97	3.15 f	25°	half	20°	full	disordered
3e (R, S) mol A	2.08	2	37	0.81–1.34	2.30	33°	full	50°	half	108, 211, 213
3f (R, S) mol A	2.07	0	33	1.90–2.11	2.41	45°	half	40°	half	105–108
3g (S, R)	2.23	6	10	0.47–0.42	-	30°	half	85°	none	disordered
3h (S, S) mol A	2.07	3	35	1.98–2.21	2.35	45°	full	40°	half	105–108
3i (R, R) mol A	2.09	4	30	1.96–2.14	2.30	20°	full	30°	half	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 the Cα-atoms of F304 and A305 in the inhibitor- and water-bound CYP3A4 (5VCC structure). ^d Hydrogen bond length between the inhibitor’s carbonyl oxygen and S119 hydroxyl group. ^e In 3b, the R₁ and R₂ side groups are in reverse orientation and placed near the heme-ligating pyridine and F304, respectively. ^f H-bonding via the amide nitrogen atom.