Diapamide is an effective diuretic and saluretic agent in rats, dogs, and monkeys. A pharmacologic animal study indicated that diapamide may be equal or superior to furosemide in experimentally induced congestive failure. Diapamide possessed the ability to induce water loss approximately equally from cells and extracellular fluid with or without the presence of excess water. The most frequently occurring ad- verse reaction was mild to moderate nausea, diarrhea and vomiting. In human, urine output with furosemide was significantly greater than with diapamide. Thus, diapamide would appear to serve a role between the milder thiazide diuretics and the more effective furosemide.

Omecamtiv mecarbil (CK-1827452) is a specific cardiac myosin activator and a clinical drug for left ventricular systolic heart failure (in Phase 2 of development). Omecamtiv mecarbil is an inotropic agent that prolongs systolic ejection time and increases ejection fraction through myosin ATPase activation.

Cericlamine (INN) is a potent and moderately selective serotonin reuptake inhibitor (SSRI) of the amphetamine family that was investigated as an antidepressant for the treatment of depression, anxiety disorders, and anorexia nervosa by Jouveinal

Cenicriviroc (also referred to as TBR-652 and TAK-652) is an orally active, potent inhibitor of ligand binding to C-C chemokine receptor type 2 (CCR2) and C-C chemokine receptor type 5 (CCR5). Cenicriviroc does not inhibit ligand binding to CCR1 (an alternative target of CCR5 ligands). The mean half-life in healthy volunteers is 35 to 40 hours, which allows daily dosing of the drug. Due to its CCR5 blocking activity, Cenicriviroc has initially been tested as a drug against CCR5-tropic HIV infection. In a double-blind placebo-controlled trial involving 54 HIV infected participants, Cenicriviroc monotherapy at different doses (25, 50, 75, 100, or 150 mg) led to a dose-dependent reduction in HIV-1 RNA levels and concomitant increases in circulating levels of the CCR2 ligand monocyte chemoattractant protein 1 (MCP-1, or CCL2), suggesting potent CCR2 and CCR5 inhibition in vivo. According to clinical trials, Cenicriviroc is a very safe drug with a wide therapeutic range and fairly low pharmacokinetic variability. In animal models of liver diseases, Cenicriviroc potently inhibits macrophage accumulation in the liver and ameliorates fibrosis. In a phase 2b clinical trial on 289 patients with NASH and fibrosis, Cenicriviroc consistently demonstrated liver fibrosis improvement after 1 year of therapy and had an excellent safety profile.

Edivoxetine (LY-2216684) is a highly selective norepinephrine reuptake inhibitor. It is under development as adjunctive or monotherapy of disorders believed to be associated with alterations in norepinephrine transmission within the central nervous system. Currently, edivoxetine is being studied in the treatment of attention-deficit hyperactivity disorder. Edivoxetine development in the treatment of major depressive disorder has been discontinued.

Temodox is an antibacterial agent that was studied as a veterinary growth stimulant. Information about the current use of this compound is not available.

Esmirtazapine (S-(+)mirtazapine or ORG-50081) is an enantiomer of mirtazapine (REMERON®), a high-affinity antagonist at 5-HT2/5-HT3 and H1 receptors, used in the treatment of depression. Esmirtazapine has a shorter plasma half-life than the R(−) enantiomer. Esmirtazapine is preferentially metabolized into an 8-hydroxy glucuronide. Organon was developing esmirtazapine for the treatment of hot flushes (vasomotor symptoms) associated with the menopause and insomnia.

Nafazatrom [BAY G 6575] is a leukotriene synthesis inhibitor that was being developed by Bayer in Germany. It is a pyrazolinone derivative with potential antimetastatic activities. Nafazatrom, originally developed as an antithrombotic agent, inhibits the key prostaglandin catabolic enzyme, 15-hydroxyprostaglandin dehydrogenase, which prolongs the biological half-life of prostacyclin (prostaglandin I2; PGI2) and prevents intravascular coagulation. Nafazatrom, in the micromolar range, inhibits the metabolism of PGs (prostaglandins) by 15-OH PGDH in a dose-dependent manner. The IC50 for inhibition of 15-OH PGDH was estimated to be 18.5 uM when [3H]PGF2 alpha was used as substrate. This agent also serves as a reducing cofactor with the hydroperoxidase moiety of cyclooxygenase and accelerates the conversion of arachidonic acid into precursors of PGI2. An elevated level of PGI2 prevents aggregation of platelets; subsequently it decreases the formation of tumor cell-platelet aggregates as well as their sequestration in blood vessels, which is an important initiating step in the development of metastasis. Nafazatrom may have had potential as an antithrombotic, anti-ischaemic and antiasthmatic agent. However, the development of nafazatrom was discontinued.

Beloranib (also known as ZGN-433 or CKD-732), a fumagillin anticancer drug that initially was developed by CKD Pharmaceuticals for the treatment of solid tumors. Beloranib is a potent inhibitor of methionine aminopeptidase 2 (MetAP2), an enzyme that modulates the activity of key cellular processes that control metabolism. This drug was studied for the treatment of Prader-Willi syndrome and obesity caused by hypothalamic injury, including craniopharyngioma-associated obesity and severe obesity in the general population. European Commission has granted orphan drug designation for beloranib for the treatment of craniopharyngioma, a rare form of benign brain tumor and for the treatment of Prader-Willi syndrome. Beloran participated in phase III clinical trials to evaluate efficacy and safety in obese adolescent and adult subjects with Prader-Willi Syndrome, but these studies were terminated. In 2016, Zafgen, the company developed the drug, based on discussions with the regulatory authority and review of obstacles, costs and development timelines to gain marketing approval for beloranib, has decided to discontinue further development of the drug.