Piroxantrone is one of a series of compounds commonly known as anthrapyrazoles developed in an effort to combine the broad antitumor activity of the anthracyclines with decreased myocardial toxicity. The mechanism of action of piroxantrone and other anthrapyrazoles is incompletely understood but likely involves DNA binding with induction of DNA strand breaks, DNA-protein cross-linking, and inhibition of DNA, RNA, and protein synthesis. Collectively, these findings suggested an interaction with topoisomerase II. Piroxantrone demonstrated antitumor activity in a wide spectrum of experimental systems against breast carcinoma, colon carcinoma, sarcoma, melanoma and leukemia. Piroxantrone is inactive in patients with persistent, progressive, or recurrent ovarian cancer who recently had received a platinum-based regimen. Piroxantrone has detectable but minimal activity against disseminated malignant melanoma. A phase II clinical trial of the piroxantrone administration for the treatment of advanced metastatic or recurrent endometrial cancer was prematurely terminated due to lack of patient accrual.

Fandosentan (CI 1034 or PD 180988) is an endothelin A receptor antagonist. It inhibits pulmonary vasoconstriction. Fandosentan was being developed for the treatment of chronic obstructive pulmonary disease and pulmonary hypertension.

Gisadenafil is a phosphodiesterase V inhibitor in clinical development at Pfizer. It had been in phase II clinical trials for the treatment of Benign prostatic hyperplasia; Chronic obstructive pulmonary disease; Erectile dysfunction; Overactive bladder. Treatment-emergent adverse events were: headache, myalgia, dyspepsia, back pain.

Imazodan, a phosphodiesterase III inhibitor was developed by Parke-Davis to treat heart failure and ischemic heart disorders. However, the study of this drug was discontinued.

Levonantradol is a synthetic cannabinoid analogue of delta (9)-tetrahydrocannabinol (delta(9)-THC) administered intramuscularly. It has antiemetic and anti-analgesic properties. Although its precise mechanism of action is unknown, levonantradol appears to bind and activate the cannabinoid receptors CB1 and/or CB2. Antiemetic effect of levonantradol significantly superior to chlorpromazine. However, its adverse central effects limit its utility. The main adverse events are drowsiness and dizziness. Levonantradol, administered intramuscularly to the patients suffering from postoperative pain, manifested significant analgesic efficacy. Analgesia persisted for more than 6 h with the 2.5 and 3 mg doses of levonantradol. Drowsiness was frequent but few other psychoactive effects were reported.

Enazadrem (CP-70490-09) is an antipsoriatic agent inhibiting arachidonate 5-lipoxygenase.

Pfizer developed AG-013958, also known as AG-13958 for treatment of age-related macular degeneration (AMD). As a VEGFR tyrosine kinase inhibitor, AG13958 was targeted to FLT/TYK receptor inhibition.

Zoniporide hydrochloride is a novel, potent and selective NHE-1 inhibitor (IC50 = 14 nM). Reduces infarct size in the isolated heart (EC50 = 0.25 nM). Attenuates post-ischemic cardiac contractile dysfunction and ischemia-reperfusion-induced ventricular fibrillation in vivo. Zoniporide hydrochloride represents a novel class of potent and selective human NHE-1 inhibitors with potential utility for providing cardioprotection in a clinical setting.

Ingliforib, aka CP-368296, is a glycogen phosphorylase inhibitor with antihyperglycemic and cardioprotective properties. It has been implicated for use in the treatment of diabetes and for myocardial ischemic protection. Ingliforib was in phase II clinical trials for diabetes, but these efforts have been discontinued.

PF-03463275 is the novel azabicyclic glycine transporter 1 (GlyT1) inhibitor. Ketamine induced hallucinatory-like behaviors that were not reversed by PF-3463275. In contrast, all doses of PF-3463275 alleviated the deficit in spatial working memory induced by ketamine. PF-03463275 causes changes in electroretinogram (ERG) responses in albino rats. There was dose-dependent reduction in the amplitude of the rat ERG oscillatory potentials (OPs) following single subcutaneous administrations of the PF-03463275. Furthermore, the amplitude of OPs was negatively correlated to the concentration of PF-03463275 in the vitreous humor collected from rats immediately following ERG recordings. A slight increase in the amplitude and latency of the a-wave component of the ERG with PF-03463275 treatment was observed. Since the ERG changes occur in our rodent model with PF-03463275 at exposures comparable with those associated with visual disturbance in the clinic, it was proposed that the visual adverse effects reported in healthy volunteers treated with selective GlyT1 inhibitors may represent a retinal class effect. The dose-related GlyT1 occupancy of PF-03463275 is linear. While PF-03463275 did not show evidence of facilitating N-methyl-D-aspartate receptor function in the ketamine assay, it enhanced neuroplasticity in schizophrenia patients. PF-03463275 had been in phase II clinical trial for the treatment of schizophrenia. However, this development was discontinued.