In middle of the 20th century, Dr Paul Janssen had begun synthesising products of the phenylpepiridines. Dextromoramide (the right handed sister of levomoramide, an opioid with no analgesic activity), was on the scene by 1956 and three times more potent that morphine but investigation was underway to identify new analgesics.
Pethidine (meperidine), a true phenylpepiridine, had been had been synthesised in Germany by Otto Eisleb some 20 years earlier and proved to be a very good starting point for drug discovery.
At some stage, he arrived at propiophenone which was extended to butyrophenone, the bases for various derivatives. R-1625 was synthesised at Janssen’s lab by Bert Hermans and went into testing in February of 1958. They devised experiments that differentiated anticholinergics, narcotics, and neuroleptics. This compound is now know as haloperidol.
Further reading:
- Granger B, Albu S. The Haloperidol Story. Annals of Clinical Psychiatry. 2005 Jul 1;17(3):137–40. doi:10.1080/10401230591002048