Carbonic anhydrase inhibitory properties of novel sulfonamide derivatives of aminoindanes and aminotetralins

Figures & data

Figure 1. Some sulfonamide drugs.

Scheme 1. Putative CA inhibition mechanism by sulfonamide inhibitors.

Scheme 2. Synthesis of benzylamine hydrochloride salts: (i) NaBH₄, MeOH, 0–25 °C, 3 h; (ii) DPPA/DBU, THF, 0 °C, 2 h, then 25 °C, 12 h, Ar(g); and (iii) H₂/Pd-C, CHCl₃–MeOH, 25 °C, 20 h.

Scheme 3. Synthesis of 2-aminoindane hydrochloride 20: (i) (MeO)₂CO/NaH, THF, 66 °C, 12 h; (ii) Et₃SiH, TFA, 72 °C, 2.5 h; (iii) a) 4 M NaOH solution, MeOH, 25 °C, 20 h; (b) 37% HCl; (iv) (PhO)₂PON₃, Et₃N, C₆H₆, reflux, 4 h then PhCH₂OH, reflux, 30 h; and (v) H₂/Pd-C, CHCl₃–MeOH, 25 °C, 20 h.

Scheme 4. Synthesis of sulfonamides: (i) 10% NaOH solution, MeOH, 0–25 °C, 3 h and (ii) MeSO₂Cl/NEt₃, CH₂Cl₂, 15 h.

Table 1. Human CA isoenzymes (hCA I and hCA II) inhibition data with some novel sulfonamides 28-33 by an esterase assay with 4-nitrophenylacetate as substrate.

	KI (µM)
Compounds	hCA-I	r^2	hCA-II	r^2
28	52 ± 9.2	0.982	215 ± 81.9	0.998
29	173 ± 47.7	0.972	211 ± 12.6	0.985
30	185 ± 15.4	0.968	112 ± 28.0	0.968
31	228 ± 64.3	0.954	94 ± 7.6	0.982
32	46 ± 5.4	0.978	372 ± 12.3	0.971
33	104 ± 32.1	0.952	170 ± 42.4	0.890