Sunepitron (CP-93,393) is an anxiolytic drug with highly selective serotonin 5-hydroxytryptamine 1A autoreceptor agonist, alpha2-adrenergic antagonist, and dopamine D2 agonist properties. Sunepitron hydrochloride had been in Phase III clinical trials by Pfizer for the treatment of anxiety disorder and depression. However, this research has been discontinued.

Sparfosate (PALA) is a stable transition state analogue for an aspartate transcarbamylase- cartalyzed reaction with antineoplastic activity. PALA is a potent inhibitor of aspartate transcarbamylase (Ki about 10(-8) M for ACTases of various origins), which in whole cells blocks the de novo synthesis of pyrimidines. Thus PALA inhibits de novo pyrimidine biosynthesis and increases the extent to which fluorouracil metabolites are incorporated into RNA. In vivo, low doses of PALA inhibit whole body pyrimidine synthesis. While this action is cytotoxic in vitro, extensive human testing demonstrates that PALA alone is devoid of selective antitumor activity. Interest in the therapeutic action of PALA derives from the demonstration that its action potentiates the cytotoxicity of several cytotoxic drugs, notably 5-fluorouracil (5-FU). Development of Sparfosate for cancer and Hepatitis B treatment is assumed to have been discontinued.

Lersivirine (UK-453,061) is a novel second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI). It binds reverse transcriptase in a distinct way leading to a unique resistance profile. Lersivirine is a second-line NNRTI, which was investigated in a Phase IIb clinical trial. Lersivirine has shown encouraging virologic efficacy in a Phase IIa monotherapy study in NNRTI-naive patients. In a Phase IIb clinical trial in ART naive patients, clinical efficacy of lersivirine was compared with efavirenz, each administered together with tenofovir disoproxil fumarate/emtricitabine. After 48 weeks, lersivirine exhibited a slightly lower virologic response but similar immunologic efficacy. However, the trial was not powered for formal hypothesis testing of noninferiority of lersivirine. The development of lersivirine was recently stopped because the developing company determined that the compound would not provide an improvement over existing NNRTIs.

Imagabalin is a ligand to the α(2)δ subunit of voltage-sensitive calcium channel and was developed to treat generalized anxiety disorder. Imagabalin was involved in phase III clinical trials when was made a decision to terminate all studies. However, this decision was not based on any safety concerns.

Rolziracetam (CI-911) is a nootropic drug. In several animal species (monkey, dogs, and rats) it was found to be rapidly eliminated from the body with a half-life of less than 25 min. Rolziracetam improved performance on a delayed-response task in aged rhesus monkeys. The drug was ineffective in a scopolamine-induced amnesia mouse model, in contrast to other nootropic drugs. Development of this piracetam-type cognitive enhancer was terminated.

Revatropate is a muscarinic antagonist with selectivity for M1 and M3 receptor subtypes. Significant improvement in airway function was shown in horses with heaves after inhalation of revatropate, and it was found to be a safe and effective bronchodilator. Early clinical studies in chronic obstructive airway disease (COAD) patients also showed that inhaled revatropate was an effective bronchodilator, and well tolerated.

Losoxantrone is an anthrapyrazole that induces both single and double strand breaks in DNA and is a potent inhibitor of DNA synthesis. The drug is in clinical trials for the treatment of breast cancer and of prostate cancer that is refractory to androgen ablation. Acute toxicity is negligible. Losoxantrone may be less cardiotoxic than doxorubicin. Up to 40% of patients encounter alopecia. 3% of patients develop congestive heart failure. Losoxantrone had been in phase II clinical trial for the treatment of breast and prostate cancer. However, this development was discontinued.

Mazokalim is a potassium channel agonist. It was studied in the treatment of asthma and hypertension.

PH-797804 is a diarylpyridinone inhibitor of p38alpha mitogen-activated protein. The drug was developed by Pfizer for the treatment of inflammatory diseases. PH-797804 is being tested in phase II of clinical trials in patients with COPD, osteoarthritis, rheumatoid arthritis and post-herpetic neuralgia.

PF-03715455 is a potent p38 inhibitor, showing some selectivity for p38-alpha over p38-beta. PF-03715455 inhibited IL-6, MCP-1, MIP1β, CC16 and CRP levels in plasma of healthy subjects. PF-03715455 was optimized for delivery by inhalation. PF-03715455 substantially reduced tobacco-smoke--induced lung neutrophilia and inflammatory damage to the lungs. PF-03715455 had been in phase II clinical trial for the treatment of asthma and phase I clinical trial for the treatment of chronic obstructive pulmonary disease. However, these investigations were discontinued.