3H-1,2-Benzoxaphosphepine 2-oxides as selective inhibitors of carbonic anhydrase IX and XII

Figures & data

Scheme 1. Reagents and conditions: (i) MePPh₃Br, t-BuOK, THF, rt, 18 h, 76–88%; (ii) NEt₃, DCM, 0 °C to rt, 18 h, 60–94%; (iii) 5, PhMe, 70 °C, 4 h, 63–86%; (iv) TMSBr, DCM, rt, 24 h, 71–90%.

Table 1. Inhibition data of compounds 6–7 and the standard inhibitor acetazolamide (AAZ) against human CA isoforms I, II, IX and XII.

Cmpd	R	R1	R2	KI (µM)^a,b
				hCA I	hCA II	hCA IX	hCA XII
6a	Et	H	H	>100	>100	0.82	0.82
7a	H	H	H	>100	>100	1.3	0.51
6b	Et	I	H	>100	>100	4.7	2.4
7b	H	I	H	>100	>100	0.88	0.68
6c	Et	Br	H	>100	>100	0.76	1.6
7c	H	Br	H	>100	>100	1.0	0.96
6d	Et	H	Br	>100	>100	11.3	3.3
7d	H	H	Br	>100	>100	2.5	1.8
6e	Et	H	OMe	>100	>100	9.0	7.4
7e	H	H	OMe	>100	>100	1.8	1.2
6f	Et	Cl	Cl	>100	>100	6.1	3.4
7f	H	Cl	Cl	>100	>100	0.80	1.7
6g	Et	NO2	H	>100	>100	3.9	0.95
7g	H	NO2	H	>100	>100	0.67	1.0
AAZ	–			0.25	0.012	0.025	0.006

^aValues are mean from three different assays using the stopped-flow technique (errors were in the range of ± 5–10% of the reported values).

^b6 h incubation.