Coptisine (COP), a protoberberine alkaloid, is widely found in Chinese medicinal plants (family Berberidaceae, Ranunculaceae and Papaveraceae). It is reported that COP has a wide range of pharmacological and biological activities, including antibacterial, hypoglycemic, anti-tumorigenic, and gastric-mucous membrane protection. Considerable attention has been focused on its activity against central nervous system disorders, such as improving the symptoms of Alzheimer’s disease and even preventing its onset, by exerting antidepressant effects as a potent type A monoamine oxidase inhibitor. Coptisine was found to be an efficient uncompetitive Indoleamine 2,3-dioxygenase inhibitor. Coptisine is a potent inhibitor of human organic cation transporters.

Doxapram is racemic and exists as a racemate with positive ( ) and negative (−) enantiomers. The respiratory stimulant properties of doxapram would be stereoselective and could be evaluated by chirally separating doxapram into its ( ) enantiomer (GAL-054) and (−) enantiomer (GAL-053). Pre-clinically we demonstrated that the ( ) enantiomer, GAL-054, and not the (−) enantiomer, GAL-053, dose-dependently increased minute volume when administered intravenously to drug naïve and opioid challenged rats and cynomolgus monkeys. Moreover, the deleterious side-effects of agitation and seizures were restricted to GAL-053. There were minimal behavioral changes observed in rats and monkeys receiving GAL-054. Thus, GAL-054 is the eutomer and GAL-053 the distomer of doxapram. Unfortunately, in conscious rats GAL-054 increased blood pressure approximately 15–20% above baseline values at doses that were moderately respiratory stimulant. This effect was confirmed in a Phase 1 clinical trial evaluating the effects of GAL-054 in healthy volunteers (Galleon Pharmaceuticals, unpublished data). Thus, the ventilatory stimulant and pressor effects of doxapram cannot be separated by enantiomeric separation of the racemate.

Doxapram is racemic and exists as a racemate with positive ( ) and negative (−) enantiomers. The respiratory stimulant properties of doxapram would be stereoselective and could be evaluated by chirally separating doxapram into its ( ) enantiomer (GAL-054) and (−) enantiomer (GAL-053). Pre-clinically we demonstrated that the ( ) enantiomer, GAL-054, and not the (−) enantiomer, GAL-053, dose-dependently increased minute volume when administered intravenously to drug naïve and opioid challenged rats and cynomolgus monkeys. Moreover, the deleterious side-effects of agitation and seizures were restricted to GAL-053. There were minimal behavioral changes observed in rats and monkeys receiving GAL-054. Thus, GAL-054 is the eutomer and GAL-053 the distomer of doxapram. Unfortunately, in conscious rats GAL-054 increased blood pressure approximately 15–20% above baseline values at doses that were moderately respiratory stimulant. This effect was confirmed in a Phase 1 clinical trial evaluating the effects of GAL-054 in healthy volunteers (Galleon Pharmaceuticals, unpublished data). Thus, the ventilatory stimulant and pressor effects of doxapram cannot be separated by enantiomeric separation of the racemate.

5F-DF-203-L-LYSINAMIDE (Phortress) is an experimental antitumor agent with potent and selective activity against human-derived carcinomas of breast, ovarian and renal origin. The mechanism of action of Phortress is distinct from all classes of chemotherapeutic agents currently in the clinic, and involves metabolic activation by cytochrome P450 (CYP) 1A1 to electrophilic species, which generate DNA adducts in sensitive tumors only. Phortress is in phase I clinical trials for the treatment of solid tumours. The compound was co-developed by Pharminox, University of Nottingham and Cancer Research UK.