Preladenant (SCH-420814) is an adenosine A(2A) receptor antagonist with a high affinity and very high selectivity for adenosine A(2A) receptors, which is being developed by Merck & Co Inc (following its acquisition of Schering-Plough Corp) for the potential treatment of Parkinson's disease. Preladenant is a potent competitive antagonist of the human A2Areceptor (Ki = 1.1 nM) and has >1000-fold selectivity over all other adenosine receptors, making this compound the most selective A2A receptor antagonist reported to date. Preladenant was being researched as a potential treatment for Parkinson's disease. Positive results were reported in Phase II clinical trials in humans, but it did not prove itself to be more effective than a placebo during Phase III trials, and so was discontinued in May 2013.

The novel compounds clamikalant (HMR 1883) or its sodium salt HMR 1098) have been shown to block selectively Kir6.2/SUR1-composed K(ATP) channels. Clamikalant is under development by Aventis Pharma (formerly Hoechst Marion Roussel) for the potential treatment of heart arrest and ventricular arrhythmias. Nevertheless, clamikalant and its sodium salt did not pass the clinical trials

Darusentan is an orally active, propanoic acid-based endothelin receptor antagonist (ERA) that selectively blocks endothelin-1 (ET-1) binding to the endothelin type-A (ETA) receptor. Darusentan exhibited subnanomolar binding affinity and approximately 1000-fold selectivity for the ETA receptor in binding experiments conducted in vitro under steady-state conditions. Darusentan is orally bioavailable and, when administered to humans, maximum plasma concentrations are observed within 1–2 h post dosing. The mean elimination half-life is relatively long (>15 h), which is consistent with once-daily dosing. Darusentan is primarily glucuronidated by Phase II enzymes in the liver, and the major route of elimination of Darusentan and its metabolites is via the bile. Some glucuronidated metabolites of Darusentan are also excreted in the urine. Darusentan doses up to 300 mg/day were well tolerated and associated with a manageable safety profile in patients with resistant hypertension (RHTN). The most frequently reported adverse events in Ddarusentan-treated subjects were peripheral edema (17%) and headache (11%), which were mostly mild or moderate in severity. Other commonly reported adverse events in the Darusentan treatment group were sinusitis (8%), dizziness (7%), upper respiratory tract infection (5%) and gastroenteritis (5%). In phase III clinical trial the mean reductions in clinic systolic and diastolic blood pressures were 9/5 mm Hg with placebo, 17/10 mm Hg with Darusentan 50 mg, 18/10 mm Hg with Darusentan 100 mg, and 18/11 mm Hg with Darusentan 300 mg. Unfortunately, phase III clinical trial evaluating Darusentan did not achieve its co-primary efficacy endpoints of achieving a change in systolic and diastolic blood pressure after 14 weeks compared to a placebo. Perhaps for this reason, shortly after the top-line results of this study became known, the sponsor announced that Darusentan would not be developed further for resistant hypertension.

Glemanserin is a selective antagonist of the 5-HT2A receptor. It was tested in a clinical trial, in patients with generalized anxiety disorder, however, it did not demonstrate significant anxiolytic effects.

Spirilene is an antipsychotic agent. In rabbit caudate nucleus (CN) spirilene exhibited Ki value of 3.5 uM at the 5-HT1R site, but produced less than 50% inhibition of [3H]5-HT binding to the 5-HT1D site even at concentrations as high as 100 uM.

Vercirnon (GSK-1605786, CCX-282, nTraficet-EN) is a selective, and potent antagonist of human CCR9. Vercirnon binds to the intracellular side of the receptor, exerting allosteric antagonism and preventing G-protein coupling. CCR9 is a tissue-specific lymphocyte trafficking molecule that selectively attracts both B- and T-cells to the small gut. Inhibition of CCR9 by GSK-1605786 may inhibit B- and T-cell entry to the small gut and ameliorate inflammation while leaving immune function at other anatomical sites unaffected. Vercirnon is an orally bioavailable, anti-inflammatory agent that is being developed by ChemoCentryx for treatment of inflammatory bowel disease with an initial focus in Crohn's disease. A pivotal phase III programme of vercirnon was initiated in patients with moderate-to-severe Crohn's disease, however, the programme was suspended when the first pivotal trial failed to meet its primary endpoint. Phase II trials for ulcerative colitis and celiac disease were conducted, however investigations for ulcerative colitis were suspended while no further development has been reported for celiac disease.

Topilutamide is a non-steroidal anti-androgen. Topilutamide downregulated androgen receptor expression by 40% at 3 uM and up to 95% at 10 uM in LNCaP Cells After 48-h drug incubation. While highly hydrophobic and hydrolytically degradable, it is systemically nonresorbable. In animals, fluridil demonstrated high local and general tolerance. After 3 months of topical application of topilutamide, the average anagen percentage did not change in placebo subjects but increased in topilutamide subjects (male with androgenetic alopecia) from 76% to 85%, and at 9 months to 87%. In former placebo subjects, topilutamide increased the anagen percentage after 6 months from 76% to 85%. Sexual functions, libido, hematology, and blood chemistry values were normal.

FLOSATIDIL is an antihypertensive drug discontinued in Phase II for angina pectoris.