CARBOSIC ANHYDRASE INHIBITION
AIarch 1968
229
TABLE I 160
( X 10')
OF
-
SGLFONAMIDESAGAINST CRUDE DOGRBC CARBONIC ANHYDRASE AT 0.3'u
---SEI-
Class and coinpd
Carbonate
Barbital R R
A. Bcnzenesulfouamides: R . 0 5 0 / / It 2
Time, min
__-__
EI-
_ I -
Carbonate
Barbital
Time, min
...
4 2 2 2 Ne 2
hH-
R3
H H
19 5 113 34 40 28
H CHICONH CHI H H NHz
H KH2
H H
...
Se 2 2 Ne Ne Ne
13
... ... ... 57
2 0.2 2.0 2.7 1.3 6.0
0.2
... ... ...
4.0
B. Aliphatic Sulfouamides: RCI-IISO,XH~
...
3000 7200 600
C.
Benzothiazole Sulfonamides:
...
...
?I000 7200 300
15 10
...
...
*.. ... ...
2 2 2
Ra:,=/C-SO:h.Hr
...
0.04 0.04
OCzHb (ethoxzolamide)
Ne Ne Se
0.03
0.01
.
I
.
...
0.02
2
...
S-1
D. Thiadiazole Sulfonamides: R-$,
,{-SO,NH, S
R
NH2 CHICOXH (acetazolamide) CeHjSOzNH ( I ) p-NH&e,H$02NH o-ClCBH4 (11)
0.6 0.2 0.03 0.04 0.03
...
0.03
2 2 2 2 1
CH,N-S I ll CH,CON=C, ,C--SO?NH$
0.17
0.12
0.03
0.02
2 2 2 2 2
2
0.07
0.07
5
E. Disulfonamides (Saluretics) and Congeners lJ3-Disulfamylbenzene 21 ... Se 1,4-Disulfamylbenzene 14 ... Ne 1,3-Disulfamyl-4,5-dichlorobenzene(dichlorphenamide) 0.7 0.7 10 5-Chloro-2,4-disulfamylaniline (salamid) 22 ... 5
0.08 0.06 0.03
...
2 2 2
(methazolamide)
S
(chlorothiazide)
II 0
...
...
0.02 0.023
...
... 0.03
...
..
14
5
0.07
0.06
5
(hydrochlorothiazide)
225
240
10
1.8
1.2
3
(flumethiazide)
123
...
Se
4
...
2
350
...
2
0.2
...
2
2
0.03
0.03
20
Ke
0.1
...
...
9
...
2
c1 *C-cH.SCH H-XSO a y , Aso. H
a
(benzthiazide)
(chlorthalidone)
&Qc, C'NH
...
0.03 0.02
18
(trichlormethiazide)
'
0.2 0.03
14
2
16
...
SOJH,
F. Quaternary Ammonium Sulfonamide 300
...
2
Procedure is given in ref 2 and Methods section. The time given is the minimum needed for equilibration. The enzyme used was 0.25 ml of a 1: 100 suspension of whole dog blood in water. This is approximately 5 X to 2 enzyme units in the carbonate system and 5 in barbital.2' (L
S e means
