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Diuretic Activity of Chlorothiazide Derivatives

 

作者:

 

期刊: Nature  (Nature Available online 1958)
卷期: Volume 182, issue 4648  

页码: 1510-1511

 

ISSN:0028-0836

 

年代: 1958

 

DOI:10.1038/1821510a0

 

出版商: Nature Publishing Group

 

数据来源: Nature

 

摘要:

1,2,4.benzothiadiazine-1,1.dioxide (Table 1, a) has no diuretic activity. The introduction of a sulphamyl-group (Table 1, b) gives barely active compound. Therefore, the activity is not mainly due to the sulphamyl-group. Further, ring-closure to thiadiazin-dioxide is not necessary for diuretic activity, since it is known3 that 4.amino-6.chlorobenzene-l,3.disul-phonamide and its N-acyl-compounds have a high activity. We found that chlorine cannot be omitted in these compounds (Table 1, c), and that it cannot be replaced by an amino-group (Table 1, d). Substitution of the sulphamyl-group by alkylation should result in an inactive compound, since this group is responsible for the anti-enzymic effect. It is known4 that N-alkyl-chlorothiazides have no diuretic activity, but to our great surprise we found a highly active and considerably less toxic compound in 4-amino-6.chloro -benzene -1,3. disulphonmethylamide (Table 1, e). Therefore, a free sulphonamide group is definitely not necessary for diuretic activity.Table 1 Compound Melting point (deg. C.) Activitya l,2,4.benzothiadiazine-l,l-di- I oxide 219.220 1.46b 7.sulphamyl-l,2,4.benzothia- diazine-., 1 -di oxide 319.320 1.34c 4.amino-benzene-.,3.di- sulphonamide 232 1.24d 4,6.diamino-benzene-l,3. disulphonamide 253 0.62e 4.amino-6.chloro-benzene-l,3. disulphonmethylamide 182 2.48f 4.amino-6.chloro-benzene-.,3. disulphonallylamide 132 1.64g 4.amino-6.chloro-benzene-.,3. disulphonbutylamide 97 1.79h 4.amino-6.chloro-benzene-.,3. i Disulphondimethylamide- 4-amino-6.chloro-benzene-.,3. 184 1.99disulphonmorpholinamide 158 0.82 j 4.amino-6.chloro-benzene-1 .3.disulphoncs/cZohexylamide 189 1.19Activity : urinary excretion of treated animals (ref 5) Urinary excretion of untreated animals Activity decreases rapidly with increasing molecular weight of the alkyl-group (Table 1, f and g). The dimethyl compound (Table 1, k) still has activity and, the morpholine compound slight activity, but the cyclohexyl-compound (Table 1, i and j) is inactive.Further particulars, especially the pharmacological properties of the compound of Table 1, e will be described elsewhere.

 

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