Mozenavir is a non-peptidomimetic, water soluble, cyclic urea that is a selective inhibitor of HIV-1 protease. Mozenavir is active against the virus with the signature D30N nelfinavir resistance-associated mutation and the L90M mutants with decreased susceptibility to a number of other protease inhibitors. In a dose-ranging study assessing Mozenavir, in doses of 750 mg 3 times a day, 1250 mg twice daily, or 1250 mg 3 times a day, compared with standard doses of indinavir, both in combination with lamivudine and stavudine, plasma HIV-1 RNA levels were reduced to below 50 copies/mL in 75% to 80% of patients receiving Mozenavir-based treatment and in 70% of those receiving indinavir-based treatment. Mozenavir-based regimens were generally well tolerated. However, the virus was able to mount considerable resistance against this compound, which was not further developed, also because of poor oral bioavailability in humans and highly variable blood levels.

Colterol is a beta-2 adrenoreceptor agonist. Bitolterol, a diester prodrug of colterol, was marketed by Elan Pharmaceuticals for the treatment of reversible bronchospasm associated with asthma or chronic obstructive pulmonary diseases.

Lixazinone selectively inhibits the high-affinity form of cyclic AMP phosphodiesterase (type IV) isolated from human platelets with only weak effects on both the nonspecific and cyclic GMP-sensitive phosphodiesterases. The inhibitor reduces both maximum velocity and substrate affinity of the type IV enzyme. Lixazinone exhibits marked selectively for the platelet high-affinity enzyme. It also has significant inhibitory effects on cardiac membrane-bound phosphodiesterase. Lixazinone may be useful as an agent to increase cardiac output in the treatment of congestive heart failure. It is a potent PDE3 inhibitor. Lixazinone suppresses folic acid-induced proliferation of rat tubular epithelial cells in vivo.

Methoxyamine (TRC102) is an orally bioavailable small molecule with potential adjuvant activity, that may potentiate the antitumor activity of alkylating agents. Methoxyamine covalently binds to apurinic/apyrimidinic (AP) DNA damage sites and inhibits base excision repair (BER) that causes topoisomerase II-dependent irreversible strand breaks and apoptosis. Methoxyamine is currently being studied in multiple Phase 1 and Phase 2 clinical trials sponsored by the National Cancer Institute or Case Comprehensive Cancer Center.

Tiquinamide (Wy 24081) is a potent inhibitor of gastric secretion and gives good protection in animals against gastric and duodenal erosions induced by stress and chemical stimuli. It reduces basal as well as stimulated acid secretion but has no anticholinergic activity and is only a weak histamine H2 antagonist, since it is substantially more potent in inhibiting basal acid-secretion than the established H2-receptor antagonists, metiamide and burimamide. Since no other pharmacological effect of tiquinamide has been detected in isolated tissues, it seems unlikely that the gastric antisecretory effect of the compound results from a direct action on the peripheral autonomic nervous system. The report from Dr. Szabo on the protective effect of dopamine agonists against duodenal ulceration suggests a possible mechanism of action for tiquinamide.

Pirandamine is the potential antidepressant drug. It is a relatively selective inhibitor of the serotonin uptake mechanism and does not exhibit appreciable norepinephrine uptake blocking activity in contrast to the tricyclic antidepressant drugs imipramine and amitriptyline. Pirandamine is equivalent to amitriptyline and greater than imipramine in potency as a serotonin uptake blocker and a potentiator of central serotonin pharmacological actions, and in contrast, does not exhibit appreciable central anticholinergic effects. Pirandamine potentiated the behavioral effects of 5-hydroxytryptophan in mice. Pirandamine, in contrast to desimipramine and imipramine, did not prevent reserpine-induced hypothermia. The (-)-enantiomer of pirandamine retained the activity of the racemate; the (+I-enantiomer was much less effective.

Bisnafide (previously known as DMP 840), a bis-naphthalimide derivative that was developed by Bristol-Myers Squibb as a potential anticancer agent. Bisnafide acts as DNA intercalator and topo II inhibitor. This drug participated in phase I clinical trials in pediatric patients with refractory solid tumors. However, further, development has been discontinued.

Alvameline is a partial agonist of the M1 mAChR that also displays M2/M3 antagonist effects. It readily crosses the blood-brain barrier. It has an effect profile that makes it of interest to test its ability to counteract bladder overactivity in humans. Behaviorally, alvameline has been shown to significantly improve Morris water maze (MWM) performance in both young and ageimpaired rats. It failed to improve cognition in patients with mild to moderate Alzheimer's disease.

Early explorations of spider and scorpion venoms provided clues for the discovery of new classes of compounds, including delucemine, that act as neuroprotectants in animal models of stroke. This compound targets open NMDA receptor-operated calcium channels and blocks the channel. By blocking these channels, which open in response to the neurotransmitter glutamate, delucemine prevents excessive calcium influx during ischemia. This stabilizes cell chemistry and minimizes cell death. Delucemine attenuated short-term cognitive deficits and histopathological changes associated with traumatic brain injury. Delucemine improved measures of brain tissue edema and ion homeostasis.

Evatanepag (CP-533,536) is a prostaglandin E2 EP2 receptor agonist. It stimulates new bone formation on trabecular, endocortical, and periosteal surfaces and enhances fracture healing. Evatanepag was under development with Pfizer as a bone formation stimulant for therapeutic use in the healing of fractures.