Synthesis and Biological Evaluation of 2-Hydroxy-3-[(2-aryloxyethyl)amino]propyl 4-[(Alkoxycarbonyl)amino]benzoates

Table 1

Structure of the target compounds 19a–23d and comparison of calculated lipophilicities (log 𝑃) with determined log 𝑘 values; calculated values of solubility (log 𝑆), molar volume (MV [cm³]), surface tension (ST [dyne/cm]), and determined p𝐾_a values, and in vitro antimycobacterial activity (MIC [𝜇mol/L]) of compounds compared to ciprofloxacin (CPX), isoniazid (INH), pyrazinamide (PZA), and rifampicin (RIF) standards.

Compound	R^1	R^2	Log 𝑘	Log 𝑃^a	Log 𝑆^a	p𝐾a	MV^a [cm^3]	ST^a [dyne/cm]	MIC [𝜇mol/L]
									MAP	MI
19a	CH3	2-OCH3	0.3870	2.52	−3.07	8.82	331.92	50.65	275	550
19b	C2H5	2-OCH3	0.3976	2.71	−3.39	8.90	348.43	49.73	128	533
19c	C3H7	2-OCH3	0.4089	3.15	−3.70	8.67	364.93	48.91	64	259
19d	C4H9	2-OCH3	0.4228	3.44	−4.00	8.73	381.44	48.16	62	201
20a	CH3	4-OCH3	0.3881	2.95	−3.12	8.25	331.92	50.65	550	550
20b	C2H5	4-OCH3	0.3999	3.40	−3.44	8.23	348.43	49.73	533	533
20c	C3H7	4-OCH3	0.4108	3.70	−3.75	7.99	364.93	48.91	259	259
20d	C4H9	4-OCH3	0.4241	4.09	−4.05	8.18	381.44	48.16	62	121
21a	CH3	2,6-OCH3	0.3865	2.33	−3.03	9.14	355.92	49.10	516	516
21b	C2H5	2,6-OCH3	0.3956	2.54	−3.34	8.88	372.43	48.32	501	501
21c	C3H7	2,6-OCH3	0.4052	2.84	−3.65	8.90	388.94	47.62	117	487
21d	C4H9	2,6-OCH3	0.4177	3.13	−3.94	8.58	405.44	46.99	59	114
22a	CH3	2-F	0.3904	3.00	−3.51	7.98	316.28	51.45	564	564
22b	C2H5	2-F	0.4011	3.13	−3.84	7.99	341.42	50.42	547	547
22c	C3H7	2-F	0.4206	3.54	−4.15	7.97	348.54	49.51	265	265
22d	C4H9	2-F	0.4341	3.88	−4.46	7.96	364.66	48.69	124	124
23a	CH3	4-F	0.3915	2.63	−3.52	8.04	316.28	51.45	564	564
23b	C2H5	4-F	0.4032	3.21	−3.82	8.09	341.42	50.42	547	547
23c	C3H7	4-F	0.4228	3.66	−4.11	8.16	348.54	49.51	66	265
23d	C4H9	4-F	0.4365	4.16	−4.39	8.08	364.66	48.69	64	258
CPX	—	—	—	—	—	—	—	—	181	181
INH	—	—	—	—	—	—	—	—	>1823	>729
PZA	—	—	—	—	—	—	—	—	>2031	>812
RIF	—	—	—	—	—	—	—	—	>109	—

aCalculated for the uncharged molecule; MAP: Mycobacterium avium subsp. paratuberculosis CIT03; MI: Mycobacterium intracellulare.