Anacetrapib is a CETP inhibitor being developed by Merck to treat hypercholesterolemia (elevated cholesterol levels) and prevent cardiovascular disease. Anacetrapib is a cholesterol ester transfer protein (CETP) inhibitor that blocks the transfer of cholesterol from highdensity lipoprotein to other lipoproteins. This results in an increase in high-density lipoprotein cholesterol (HDL-C) and a decrease in lowdensity lipoprotein cholesterol (LDL-C), which may reduce the development of atherosclerosis. Anacetrapib has not been approved for sale in Canada or the United States. Clinical evidence to support the use of anacetrapib for dyslipidemia has been reported in two clinical trials. REVEAL is an ongoing, large-scale phase 3 trial evaluating the effectiveness of anacetrapib with a statin for the secondary prevention of major coronary events in patients who have a history of cardiovascular disease. Results are anticipated in January 2017.

Eniporide belongs to the new class of drugs that specifically inhibit the Sodium/hydrogen exchanger 1 (NHE-1) isoform, which is the predominant isoform in the cardiac myocytes. Extensive preclinical studies, in vitro and in animals, have suggested that NHE inhibition with eniporide before the onset of ischemia is a very effective and reproducible means of limiting the extent of infarction and that this agent provides protective benefit even when given just before reperfusion. Eniporide had been in phase II clinical trial for the treatment of myocardial infarction. Administration of the eniporide, before reperfusion therapy in patients with acute ST-elevation myocardial infarction, did not limit infarct size or improve clinical outcome.

MK-0893, developed by Merck, is a reversible and competitive antagonist with high binding affinity (IC(50) of 6.6 nM) and functional cAMP activity (IC(50) of 15.7 nM). MK-0893 reached Phase 2; 12 weeks of once daily oral dosing led to significant and dose-dependent reductions in fasting and post-prandial plasma glucose and in HbA1c, with similar low incidences of hypoglycaemia as a metformin cohort. Combinations with metformin and sitagliptin were also trialled, and risk for hypoglycaemia was assessed in healthy males which showed the drug caused lengthening of recovery times. However, plasma levels of LDL cholesterol and liver transaminases were increased in some studies, as was body weight and blood pressure, all of which were not evident pre-clinically, and MK-0893 was discontinued.

Carmoxirole is a dopamine D2 receptor agonist with limited central activity that modulates sympathetic activation and subsequently reduces pre-load and afterload in animals. It was shown, that carmoxirole induced beneficial effects on hemodynamic and neurohumoral parameters in heart failure. In addition, experimental evidence showed that carmoxirole lowered blood pressure in various models of hypertension mainly or exclusively through inhibition of noradrenaline release from sympathetic nerve endings. That effect of carmoxirole was mediated by presynaptic dopamine receptors with the characteristic that release inhibition was restricted to low rates of sympathetic nerve discharge.

Normorphine is an opiate analog, specifically the N-demethylated derivative of morphine. It was first described in the 1953 as part of an effort to characterize N-substituted morphine analogs. Normorphine has relatively little opioid activity, but it is a useful intermediate for the production of more potent morphine analogs. It is also a major metabolite of morphine.

Carboxyamidotriazole (L651582) is a carboxyamide-amino-imidazole compound originally developed as a coccidiostat, an antiprotozoal agent that acts upon Coccidia parasites. Carboxyamidotriazole (L651582) is an orally-active agent with potential antineoplastic activity. Carboxyamidotriazole binds to and inhibits non-voltage-operated Ca2 channels, blocking both Ca2 influx into cells and Ca2 release from intracellular stores and resulting in the disruption of calcium channel-mediated signal transduction and inhibition of vascular endothelial growth factor (VEGF) signaling, endothelial proliferation, and angiogenesis. This agent may also inhibit tumor cell growth, invasion, and metastasis.

Asimadoline is an orally active, highly selective kappa-opioid receptor agonist with approximately 500-fold greater affinity for human kappa-, as compared with either delta- or mu-opioid receptors. Due to its high selectivity for the kappa-opioid receptor, asimadoline does not produce mu-opioid like side effects. It is investigated for use/treatment in irritable bowel syndrome, pruritus, postoperative ileus. A drug interaction study investigating the coadministration of asimadoline with ketoconazole was performed in healthy volunteers - a two to three-fold increase in AUC and Cmax of asimadoline was observed with concomitant administration of ketoconazole. The most common adverse events are diarrhea, nausea, sinusitis, headache and fatigue.

DMP-777 (also termed L-694458) a cell permeant b-lactam inhibitor of a human leukocyte elastase was developed for treatment cystic fibrosis, juvenile rheumatoid arthritis.

MK-3697 a drug, currently being developed by Merck, for the treatment Insomnia. MK-3697 is a potent and selective Orexin receptor type 2 antagonist.

MK-5046 is an orally active, potent, selective agonist of the orphan G protein-coupled receptor bombesin receptor subtype-3 (BRS-3). In pharmacological testing using diet-induced obese mice, MK-5046 caused mechanism-based, dose-dependent reductions in food intake and body weight.