They wanted new types of intermediate for direct azo dyes, a problem which Rose solved in 1932 with a method suitable for large scale manufacture.
“From that time until his death 52 years later Rose was entirely consumed by his love for the biological activity of chemicals.”[1] In the new Medical Chemicals Section of the ICI (later Pharmaceuticals Division, which ended up demerged into Zeneca) at Blackley he was joined by Frank Curd and other dyestuff chemists.
[4] When the Japanese attack on Pearl Harbor started World War II in the Pacific, the US became much more interested in antimalarials and funded a large joint US-UK program to find new non-toxic and easy to produce drugs of the type, which was joined by the ICI team including Rose, Curd and two newly recruited scientists Garnet Davey and Alfred Spinks.
[4] Rose and Curd decided to concentrate on pyrimidines as relatively simple to synthetise, even though the Advisory Panel recommended against that because most antimalarials by then were either quinolines or acridines.
Checking prospective 2,4-diaminopyridine derivatives with a basic side chain and a benzenoid moiety one after another, they noticed a geometric pattern in the effective analogs and wondered if they could reproduce their interesting biologic activity with molecules even simpler, without the pyrimidine ring, and tried biguanides (then called diguanides) with which Rose was familiar due to his earlier sulphonamide research to great effect.
[5] As a result, in 1945 ICI introduced paludrine, and only much later it was found that an oxidative cyclization of this prodrug led to the active dihydrotriazine derivative cycloguanil (the mechanism of its work is still debated).