Succinobucol (also known as AGI-1067) is a probucol derivative patented by American pharmaceutical company Atherogenics, Inc as vascular protectant with antioxidant, anti-inflammatory and antiplatelet activities. In vitro, succinobucol inhibits the TNF-α induced expression of VCAM-1 and MCP-1 with little effect on intercellular adhesion molecule (ICAM)-1. In addition, succinobucol inhibits lipopolysaccharide (LPS)-induced expression of tissue factor in human monocytic cells and endothelial cells, an effect thought to be mediated independently from the nuclear factor κB pathway. Preclinical studies have shown reduced total cholesterol and low-density lipoprotein cholesterol concentrations, increased high-density lipoprotein cholesterol concentrations, decreased levels of inflammatory mediators, and reduced atheroma area with Succinobucol treatment in animal models. Unfortunately, in clinical trials, Succinobucol failed to demonstrate a strong cardioprotective effect. Undesired metabolic effects including high-density lipoprotein cholesterol-lowering have been consistently reported, and diarrhea appears to be an expected adverse effect.

Mitoflaxone, also known as flavone acetic acid is a synthetic flavonoid that has been studied as an antitumor agent. Mitoflaxone was involved in phase II clinical trials in Europe for patients with advanced colorectal carcinoma and for patients with advanced malignant melanoma. Despite the promising preclinical activity, this drug didn’t demonstrate any clinical activity. Further studies of the drug were suspended.

Azimexon, a synthetic derivative of the 2-cyanaziridines, possesses the immunorestorative properties that were shown for patients with acquired immunodeficiency syndrome. Besides, azimexon had a role in managing cancer-associated dysregulation of the immune response. It was studied in clinical trials phase I to determine the drug's tolerable dose, toxicity, and effects on immune and nonimmune host defense parameters.

ZK 200775, also known as fanapanel, an antagonist at the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor, possesses neuroprotective efficacy in patients with acute ischemic stroke. However, the phase II of clinical trials had revealed, that this compound had led to the neuronal dysfunction and the glial cell toxicity had occurred. In addition, was shown, that the antagonization of AMPA receptors by ZK200775 lead to alterations of color and dark vision, visual acuity, cone electroretinogram (ERG) modalities and the pattern-reversal visual evoked potentials and to a lesser extent on the scotopic ERG. At the same time, ZK 200775 did not alter eye morphology, the functioning of the extraocular muscles, binocular vision, visual fields or the pupil.

Ebselen is a small molecule mimic and inducer of glutathione peroxidase activity and possesses antioxidant and anti-inflammatory properties. This drug has been investigated in phase II clinical trials for the treatment of Meniere's disease, bipolar disorder and in the prevention of hearing loss. Besides, experiments on mice have shown that ZIKV infection could be on the list for potential use of ebselen. It alleviates testicular pathology in mice with Zika virus infection and prevents its sexual transmission. Ebselen has various mechanisms of action. It binds to the N-terminal domain of soluble epoxide hydrolase and chemically reacts with the enzyme to quickly and irreversibly inhibit one of the enzymes' activity: phosphatase (Nterm-phos). Besides, ebselen inhibits inositol monophosphatase and thus exhibits lithium-like on human central nervous system (CNS) function. In addition, ebselen inhibits the G4 isoform of acetylcholinesterase. It is a well-known relationship between the cholinergic system and learning, memory and other common cognitive processes, thus ebselen can be studied for the treatment of memory impairment diseases.

Selisistat (EX 527) was discovered by Elixir scientists as a selective human SIRT1 inhibitor and exhibits >200-fold selectivity against SIRT2 and SIRT3. Human SIRT1 is an enzyme that deacetylates the p53 tumor suppressor protein and has been suggested to modulate p53-dependent functions including DNA damage-induced cell death. It was shown that drug was highly safe in toxicology studies. Selisistat passed Phase II clinical trials to treat Huntington’s disease, but that study was discontinued.

Lanicemine is a low-trapping NMDA channel blocker, which was developed by Fisons Pharmaceuticals and later by AstraZeneca for the treatment of the major depressive disorder. The development was terminated in phase II as the drug did not meet the primary endpoint.

Imuracetam is a drug of the racetam family patented by Belgian pharmaceutical company UCB S. A. for enhancement of memory and prevention of damage due to hypoxia.

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.

Silicristin is a flavonolignan isolated from Silybum marianum and has been shown to exhibit inhibitory activities against lipoxygenase and prostaglandin synthetase. It has a role as a radical scavenger, a lipoxygenase inhibitor, a prostaglandin antagonist and a metabolite. It is a flavonolignan, a member of 1-benzofurans, a polyphenol, an aromatic ether and a secondary alpha-hydroxy ketone. Silicristin is a potent inhibitor of the thyroid hormone transporter MCT8. Silicristin is a sodium pump inhibitor, it inhibited Na(+)/K(+)-ATPase (NKA) with IC50 of 110 uM. Silicristin exhibits relatively good antioxidant effectiveness against phenylglyoxylic ketyl radicals and DPPH. Silicristin protects cardiomyocytes against doxorubicin-induced oxidative stress is due mainly to their cell membrane stabilization effect, radical scavenging and iron chelating potency.