THE SULPHON AMIDE SERIES 157 



sulphonamide half of the molecule was active both in the test-tube and the infected 

 mouse (see also Goisseidet et at. 1936, Buttle, Gray and Stephenson 1936). That 

 sulphonamido-crysoidin was broken down to yield the active sulphonamide in 

 the body was demonstrated by Fuller (1937), and ^oro-aminobenzene sulphonamide 

 was thereby established as the active principle of prontosil. 



The Sulphonamide Series. 



Since the establishment of j9-aminobenzene sulphonamide as the active portion 

 of the prontosil molecule, a large number of active sulphonamide compounds 

 have been synthesized in the search for compounds with increased antibacterial 

 power or range, or for compounds improved in respect of the animal under treat- 

 ment, such as increased solubility, decreased toxicity, or altered rates of absorption 

 and excretion. They may be conveniently divided into two classes, according 

 to their relation to jo-aminobenzene sulphonamide, which we may take as the 

 starting substance of the series. In one class, substitution has taken place in 

 the amino group ; in the other class, in the amide group. Examples of these 

 classes are depicted in Fig. 27. In each example both the formal chemical name, 

 and the convenient chemical abbreviation of the formal name, are given ; the 

 names in brackets are proprietary names, and are inserted either for historical 

 reasons, or because there is no convenient chemical abbreviation (see Ardley 1941). 

 Para-aminobenzene sulphonamide, being the amide of sulphanilic acid, is universally 

 referred to as sulphanilamide. 



Nearly all compounds of the first class are inactive per se and must be broken 

 down in the body to yield an active joara-amino compound. Sulphonamido- 

 crysoidin is the only example given, though there are many others whose structure 

 is therapeutically justified. The compounds of the second class are more interesting 

 from the bacteriological point of view, because great improvements in the anti- 

 bacterial action of sulphanilamide have been achieved by substitution in the 

 amide group, the most successful substituents being heterocyclic ring compounds. 



Sulphanilamide was chiefly successful against streptococci and pneumococci, 

 and some of the more complex compounds are selective in that they are particu- 

 larly effective against a certain species. In general, however, the more powerfully 

 antibacterial the sulphonamide the wider its range of action, and it is now clear 

 that most species of medically important bacteria are in some degree susceptible 

 to one or other of the sulphonamide drugs. 



The bacterial species include the coli-typhoid-dysentery group (Buttle et al. 1937 ; 

 Helmholz 1937, Kenny et al, 1937, Cokkinis 1938, Libby and Joyner 1940, Rammelkamp 

 and Jewell 1940, Cooper and KeUer 1943) ; the Brucella group (Nitti, Bovet and Depierre 

 1937, Francis 1938, Wise 1942) ; the Corynebacterium group (Murray 1940, Ouyang 1941) ; 

 CI. welchii (Long and BUss 1937a) ; the Hoemophilus group (Long and Bhss 19376, Pittman 

 1942) ; meningococci (Long and BUss 19376, Neter 1938a, b) and gonococci (Buttle 1937, 

 Wengatz et al. 1938, Levaditi and Vaisman 1938, Feike 1938) ; the Mycobacterium group 

 (Rist 1939, Rist et al. 1939, Fitzgerald and Feinstone 1943) ; Proteus vulgaris and Ps. 

 pyocyanea (Helmholz 1937) ; Staph, aureus (Pomagk 1937, Colebrook and Purdie 1937) ; 

 shigellae and V. choleroe (Marshall et. al. 1940) and B. anthracis (Cruickshank 1937). 



The substituted sulphonamides exempUfied in Fig. 27 are sulphapyridine 

 (Whitby 1938), sulphathiazole (Fosbinder 1939, McKee et al 1939), sulphadiazine 

 (RobUn et al. 1940, Feinstone et al. 1940), and sulphaguanidine (Marshall et al. 

 1940, 1941). Sulphapyridine was the first of the substituted heterocylic compounds 



