The new chemical entity KC12615 is a potent f neutral endopeptidase inhibitor with additional endothelin-converting enzyme (ECE)–inhibitory activity.2 KC12615 is the hydrolyzed form of the oral prodrug SLV306 (daglutril). In plasma, the compound increases natriuretic peptide levels and prevents the formation of endothelin-1 by inhibiting the degradation of its precursor, big endothelin. It is investigated for use/treatment in congestive heart failure and hypertension.

Proxicromil is substituted chromone patented in the late 1970s by Fisons Ltd. for the treatment of allergic asthma. Proxicromil acts on to FcεRIreceptor in mast cells, thereby inhibiting the production of histamines. Proxicromil is tested through a variety of independent studies for its beneficial effect as an anti-allergen, its efficacy against migraine, asthma and tumor enhancement. It shows no effect as a prophylactic against migraine. The reported side effects during this study related mainly to transient gastrointestinal troubles and were generally of a mild nature. For asthma and exercise-induced bronchospasm, Proxicromil was found to be mildly effective. But the investigation was discontinued when malignancies occurred in long-term animal studies.

Dexetozoline is a safe and effective diuretic agent in the treatment of acute cardiac failure. In isolated rings of guinea-pig aorta not responding to acetylcholine, the diuretic dexetozoline did not influence basal vascular tone but inhibited noradrenaline- and histamine-induced contractions. Dexetozoline has a very high bioavailability after oral administration and is fairly lipohilic. The half-life of etozolin is 2.5 h. Dexetozoline accumulates in cirrhosis.

Danegaptide (GAP-134) is a small dipeptide gap junction modifier, developed by Wyeth and Zealand Pharma. Danegaptide works by re-establishing of gap junction intercellular communications in adjacent cardiomyocytes, thus reversing cardiac conduction slowing and electrical heterogeneity thought to be responsible for arrhythmias. In a canine model of acute sterile pericarditis, Danegaptide significantly reduced AF duration and overall AF burden. Danegaptide was investigated in phase 2 clinical trial in patients with ST-segment elevation myocardial infarction (STEMI). It was found that administrations danegaptide to patients with STEMI did not improve myocardial salvage, and development of the drug was discontinued.

Terutroban (S18886), a specific thromboxane A2 receptor antagonist, which improves endothelial function and has an antiatherosclerotic effect. The compound is under development by Servier for the potential treatment of cardiovascular diseases and coronary artery disease. In addition, it participated in phase III clinical trials PERFORM (Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic attack), but this study was stopped, and the result was not achieved.

Deboxamet is a synthetic drug with anti-ulcer and anti-secretory activity, discovered by the Italian Istituto Biologico Chemioterapico ABC, S.p.A. The compound is claimed to have high anti-inflammatory action, as evidenced by the results of the tests of acute and chronic experimental phlogosis. Deboxamet demonstrated cytoprotective activity in a model of rat gastric mucosa necrosis. The cytoprotective effect of deboxamet is mediated by the rise of the availability of prostacyclins in the rat gastric mucosa.

Imitrodast is thianaphthene derivative and thromboxane A2 inhibitor patented by Japanese pharmaceutical company Sankyo Co as antithrombotic agent.

Romazarit, (Ro 31-3948, 7), 2-[[2-(4-chlorophenyl)-4-methyl-5-oxazolyl]methoxy]-2-methylpropionic acid is a substituted heterocyclic alkoxypropionic acid. Romazarit was considered to be a potential disease-modifying antirheumatic drug. Romazarit was withdrawn due to its toxicity profile.

Aceburic acid is the acetyl ester of gamma-hydroxybutyrate (GHB), it has analgesic effects as a prodrug to GHB. GHB is used medically as an anesthetic as well as a treatment for several neurologically affecting diseases.

Cicaprost is a prostacyclin receptor (IP) agonist and orally active prostacyclin analog with potent systemic and pulmonary vasodilatation and anti-inflammatory activity. In preclinical models, Cicaprost treatment largely prevented the hypercholesterolemia-related impairment of coronary vasodilation and nitric oxide release in Isolated Langendorff-hearts. Cicaprost inhibits proinflammatory chemokines production not only from lipopolysaccharides (LPS) or (tumor necrosis factor-alpha) induced primary human monocyte-derived macrophages but also from LPS-stimulated monocyte-derived dendritic cells. Besides that Cicapost strongly inhibits lymph node and organ metastases of spontaneously metastasizing mammary tumors with a mode of action different from cytostatic or antihormonal drugs. In animal models, Cicaprost prevents metastasis if given continuously from the day of tumor implantation, and is effective in reducing metastasis if treatment is begun following surgical removal of the primary tumor when micrometastases are already present. Clinical trials of Cicaprost in healthy male volunteers demonstrate significant anti-platelet and vasodilatory effects.