PHA-543613 was discovered by Pfizer and has been under development primarily as a potential treatment of schizophrenia. PHA-543613 acts as an agonist to the Neuronal acetylcholine receptor protein alpha-7 subunit. A single human trial was conducted in healthy human volunteers, but the compound has been studied extensively in rat models for schizophrenia as well as Parkinson's disease and Alzheimer's disease.

AZ-1080 (AZD-1080) is an inhibitor of GSK-beta which was developed by AstraZeneca and initially tested in patients with Alzheimer’s disease (phase I). The drug was discontinued for the aforementioned condition, but now it is being investigated as a potential therapy for ovarina cancer and emdometrial carcinoma (basic research).

DOV-102,677 is a “Triple” Monoamine Neurotransmitter Uptake Inhibitor being developed by Merck for treating the major depressive disorder. In preclinical studies, DOV 102,677 increased extracellular levels of DA and 5-HT in the prefrontal cortex at 100 min after administration. DA levels were stably increased for the duration (240 min) of the study, but serotonin levels declined to baseline by 200 min after administration. NE levels increased linearly to a maximum of 240 min post-dosing. Consistent with these increases in NE levels, the density of β-adrenoceptors was selectively decreased in the cortex of rats treated with DOV 102,677. DOV 102,677 dose-dependently reduced the amount of time spent immobile by rats in the forced swim test, a model predictive of antidepressant activity, with a minimum effective dose (MED) of 20 mg/kg and a maximal efficacy comparable to imipramine. However, phase I clinical trials for treatment Depression in the USA was discontinued. Instead of being developed for depression, DOV-102,677 is being developed for the treatment of alcoholism.

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.

WAY-181187 is a high affinity and selective 5-HT6 agonist. It displays 60-fold selectivity over other 5-HT and monoamine receptors. WAY-181187 stimulates cAMP, ERK1/2 and Fyn kinase signaling pathway through serotonin receptor activation. WAY-181187 produced both antidepressant-like and anxiolytic-like effects in the animal model. It had been in phase I clinical trial for the treatment of anxiety disorders but this research has been discontinued.

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.

CI-966 is a GABA reuptake inhibitor, acting as an indirect and nonselective GABA agonist by blocking GABA transporter protein GAT-1. CI-966 was investigated in phase I clinical study for treatment of epilepsy, but its development was discontinued due to physical and mental disturbances at high doses.

PHA-543613 was discovered by Pfizer and has been under development primarily as a potential treatment of schizophrenia. PHA-543613 acts as an agonist to the Neuronal acetylcholine receptor protein alpha-7 subunit. A single human trial was conducted in healthy human volunteers, but the compound has been studied extensively in rat models for schizophrenia as well as Parkinson's disease and Alzheimer's disease.