Rationale and design The drug was developed in the laboratory of
Harkishan Singh at
Panjab University as part of a research program seeking a non-depolarizing neuromuscular blocker to replace the widely used depolarizing agent
suxamethonium (
succinylcholine). The design of candocuronium places it in a series of
mono- and
bis-quaternary
azasteroid. The approach adopted in its development used the rigid steroid skeleton as a spacer to hold two quaternary
ammonium groups (inspired by the
alkaloid malouetine), which incorporate fragments resembling
choline or
acetylcholine, at a specific distance. Subsequent chemical modifications of HS-342 led to the synthesis of two related
derivatives: HS-310 (later named
candocuronium) and HS-347.
Further modifications and legacy H-310 did not achieve the desired clinical profile, which led to the continued modification of its structure, ultimately resulting in the creation of
dihydrochandonium (HS-626). The new variant was an analog, and was reported to be a slightly better neuromuscular blocking profile and had no vagolytic effects. However, this benefit was not considered significant enough to advance the compound to human trials. The discovery of candocuronium prompted further research into modifications of the
androstane nucleus, particularly at the 3- and 16-positions, leading to the development of other agents considered for clinical testing. ==References==