Zaurategrast (CDP323) is an ethyl ester prodrug of CT7758, a potent carboxylic acid antagonist of integrin alpha4-beta1 (α4β1) or very late antigen 4 (VLA4). CDP323 was under development with UCB and Biogen Idec for the treatment of multiple sclerosis. Its development was discontinued in 2009 based on inadequate interim efficacy data in a phase II clinical trial.

Pinadoline is a competitive PGE2 antagonist. It is an analgesic agent. Pinadoline demonstrated the antinociceptive activity in the rat using the writhing and the formalin tests. In the writhing test, pinadoline was significantly more potent than inhibitors of PG synthesis, but less potent than opiate analgesics. In the formalin test, pinadoline appeared less active than aspirin and ibuprofen and more active than acetaminophen. Pinadoline does not possess the antiinflammatory activity of aspirin and ibuprofen and may be more like acetaminophen, which had diminished antiinflammatory activity. At high concentrations, pinadoline is a non-competitive antagonist of serotonin in guinea-pig ileum.

Timefurone is a benzopyranone derivative patented by pharmaceutical company Upjohn Co. for the treatment of atherosclerosis. Timefurone mediates the hypolipidemic effect via the reduction of the intracellular synthesis of cholesterol. In preclinical studies, Timefurone significantly lowered low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and total cholesterol in cholesterol-fed male rats and monkeys. Timefurone caused small but significant changes in several clinical chemistry parameters including creatinine, total bilirubin, albumin, glucose, serum glutamic-oxalacetic transaminase, and serum glutamic-pyruvic transaminase in cynomolgus monkeys

Imiglitazar (also known as TAK-559) is a dual peroxisome proliferator-activated receptor (PPAR) alpha and gamma agonist patented by Japanese pharmaceutical company Takeda Chemical Industries for the prevention or treatment of diabetes mellitus, hyperlipemia, insulin insensitivity, insulin resistance, and impaired glucose tolerance. Imiglitazar shows potent hypoglycemic and hypolipidemic activity and has been studied in clinical trials in treating subjects receiving a stable dose of insulin to control type 2 diabetes mellitus. Unfortunately, Imiglitazar shows hepatotoxicity and has never been marketed.

Clazolimine is an imidazolidinone-based aldosterone antagonist with potassium-sparing diuretic activity. Clazolimine antagonizes aldosterone at the mineralocorticoid receptor in the kidneys, thereby increasing sodium excretion and inhibiting potassium excretion. Clazomiline was discovered by the American Cyanamid Company in the 1970s.

Quinotolast (also known as FK021) is an orally active mast cell stabilizer which has a cytoprotective effect on the gastric mucosa. Quinotolast was patented in 1985 by Japanese pharmaceutical company Fujisawa Pharmaceutical Co., Ltd. as an antiallergic and antiulcer agent. In preclinical models, Quinotolast potently inhibited such type I allergic reactions as passive cutaneous anaphylaxis (PCA) and anaphylactic bronchoconstriction in rats by both intravenous and oral dosing. Quinotolast inhibited histamine release from rat peritoneal cells, but it had no antagonistic effect on histamine-, serotonin-, platelet activating factor- or bradykinin-induced cutaneous reactions in rats. Moreover, it was clearly demonstrated that quinotolast and DSCG had a cross tachyphylaxis to inhibit PCA in rats, suggesting that these drugs, at least in part, share the same mechanism of action. Quinotolast caused a significant increase in the mucociliary transport rate in quails. Quinotolast significantly depressed the cough reflex induced by citric acid in normal and bronchitic guinea pigs.

Tolamolol is a phenoxypropranolamine derivative that preferentially inhibits myocardial beta adrenoreceptors, possesses beta blocking potency equivalent to propranolol, has little or no direct cell membrane effect and lacks beta adrenergic stimulating action. Cardioselective beta adrenergic blockade with tolamolol was highly effective in controlling ventricular rate in supraventricular arrhythmias and reduced the frequency of ventricular ectopic beats in half of the small group of patients with this arrhythmia. It is particularly applicable in patients with obstructive pulmonary disease in whom cardiac beta adrenergic blockade is indicated. Hypotension is an important potential side effect. Tolamolol and propranolol are equal in anti-anginal efficacy but tolamolol has the advantage of being cardioselective. It is superior to practolol. Tolamolol had no effect on sperm motility.

Traxoprodil (CP-101,606) is a potent, selective N-Methyl-D-aspartate (NMDA) receptor (NR2B subunit) antagonist under development by Pfizer for its potential as a neuroprotectant in head injury and neurodegenerative disease. It is in phase II trials in the US and in phase I in Japan for the potential treatment of head injury, such as, Depressive Disorder, Major and Parkinson's Disease. CP-101,606 does not protect against glutamate-induced neurotoxicity in cultured cerebellar neurons, up to a dose of 10 uM. These results are consistent with CP-101,606 being a potent NMDA antagonist, selective for the type of NMDA receptor associated with the hippocampus. Some further investigation revealed that CP-101,606 was associated with a dose-related dissociation and amnesia. These results support the hypothesis that glutamate antagonists may be useful antidyskinetic agents. However, future studies will have to determine if the benefits of dyskinesia suppression can be achieved without adverse cognitive effects.

Tozasertib, originally developed as VX-680 by Vertex (Cambridge, MA) and later renamed MK-0457 by Merck (Whitehouse Station, NY), was the first aurora kinase inhibitor to be tested in clinical trials. The drug, a pyrimidine derivative, has affinity for all aurora family members at nanomolar concentrations with inhibitory constant values (Ki(app)) of 0.6, 18, and 4.6 nM for aurora A, aurora B, and aurora C, respectively. Preclinical studies confirmed that tozasertib inhibited both aurora A and aurora B kinase activity, and activity has been reported against prostate, thyroid, ovarian, and oral squamous cancer cell lines. Upon treatment with tozasertib, cells accumulate with a 4N DNA content due to a failure of cytokinesis. This ultimately leads to apoptosis, preferentially in cells with a compromised p53 function. Tozasertib is an anticancer chemotherapeutic pan-aurora kinase (AurK) inhibitor that also inhibits FMS-like tyrosine kinase 3 (FLT3) and Abl. Tozasertib is currently in clinical trials as a potential treatment for acute lymphoblastic leukemia (ALL). In cellular models of cancer, tozasertib activates caspase-3 and PARP and decreases expression of HDAC, increasing apoptosis and inhibiting cell growth. In other cellular models, tozasertib inhibits cell proliferation and metastasis by blocking downstream ERK signaling and downregulating cdc25c and cyclin B. This compound also decreases tumor growth in an in vivo model of prostate cancer.