Edonentan (BMS 207940) is a highly selective biphenylsulfonamide endothelin A receptor antagonist. (11)C- and (18)F-labeled analogs of edonentan were evaluated of novel PET radioligands for imaging the endothelin-A receptor. Edonentan was in clinical trials for the treatment of heart failure however its development has been discontinued.

AstraZeneca developed disufenton (NXY-059), a free radical trapping agent, for the treatment of ischaemic stroke and other brain injuries. Nevertheless, large clinical trial (3306 versus 1722 patients) was neutral, providing no evidence for the efficacy of disufenton sodium in patients with stroke. One study using rat cortical brain slices concluded that NXY-059 improved neuronal survival. However, another study in mouse neuroblastoma cells reported no effect. Another study reported that NXY-059 restored endothelial blood-brain. Histological analyses revealed several therapeutic advantages associated with disufenton sodium treatment following acute acoustic trauma, including reductions in inner and outer hair cell loss; reductions in acute acoustic trauma-induced loss of calretinin-positive afferent nerve fibers in the spiral lamina; and reductions in fibrocyte loss within the spiral ligament. However, AstraZeneca terminated the development program.

Pelanserin is an antagonist of the serotonin 5-HT2 receptor and blocks alpha 1-adrenoceptor. Experiments on dogs have revealed that pelanserin showed adequate pharmacokinetic and pharmacodynamics profiles as an antihypertensive agent that is why the drug possessed potential therapeutic usefulness in the treatment of hypertension. Pelanserin was undergoing phase II clinical trials by Cinvestav in Mexico; however, these studied were discontinued.

Nifenalol is the beta-receptor antagonist. It has optical isomers. The racemic mixture and the levo-isomer are active in antagonizing beta-receptors, but the dextro-isomer is inactive. The levo-isomer seems to be about twice as active in blocking beta-receptors as the racemate. Nifenalol is virtually devoid of local anesthetic properties in contrast to procaine, propranolol, and butidrine. Nifenalol exacerbated the fighting behavior in male mice by foot-shock. Nifenalol has been studied in patients with coronary artery disease. It afforded the coronary patient good protection against angina and ischemic changes in the EKG. It was further noted that nifenalol had no antiarrhythmic action and that it was devoid of evident side effects. Nifenalol possessed weak action against tremorine and oxotremorine induced tremor.

Nicoxamat (nicotinohydroxamic acid) is a uricosuric drug that increased urinary excretion of urea and depressed urease activity in the stomach and the colon. Patients receiving nicoxamat showed significant improvement in blood ammonia levels as compared to patients receiving neomycin. In a double-blind clinical trial, 24 patients with the advanced chronic liver disease received 1.2 g of the drug daily. Nicoxamat induced some side effects, such as mild diarrhea, constipation, and anorexia.

Seganserin was developed as a specific serotonin 5HT2 receptor antagonist. It was tested neuropharmacologically in thioacetamide-induced acute liver failure in rats. Obtained results have shown that seganserin had no effect in encephalopathic rats.

Nicogrelate is an antithrombotic agent.

Nicopholine is an antitrypanosomal agent.

Elesclomol (also known as STA-4783), originally identified in a cell-based phenotypic screen for pro-apoptotic activity, is a novel small-molecule that potently induces apoptosis of cancer cells through the rapid generation of reactive oxygen species (ROS) and the induction of unmanageable levels of oxidative stress. Elesclomol exhibits antitumor activity against a broad spectrum of types of cancer cell in human tumour xenograft models due to its excessive ROS production and elevated levels of oxidative stress leading to the death of cancer cells. Elesclomol is currently being studied as novel cancer therapeutic, in which it has demonstrated the ability to prolong progression-free survival in study subjects. Elesclomol induces oxidative stress by provoking a buildup of reactive oxygen species within cancer cells. Elesclomol requires a redox-active metal ion to function; the Cu(II) complex is 34 times more potent than the Ni(II) complex and 1040-fold more potent than the Pt(II) complex. Elesclomol is an HSP-90 Inhibitor with pro-apoptotic and potential antineoplastic activities. Elesclomol induces oxidative stress and triggers mitochondrial-induced apoptosis in cancer cells. Elesclomol is being developed by Synta Pharmaceuticals and GlaxoSmithKline as a chemotherapy adjuvant and has received both fast track and orphan drug status from the U.S. Food and Drug Administration for the treatment of metastatic melanoma. Synta Pharmaceuticals announced on February 26, 2009, the suspension of all clinical trials involving Elesclomol due to safety concerns. In March 2010, Synta announced that the FDA had approved resuming clinical development of elesclomol, and that they expected to initiate one or more clinical trials for elesclomol in the second half of the year. In a small, randomized phase II study, elesclomol was shown to significantly increase progression-free survival in people with metastatic melanoma when given in addition to paclitaxel (Taxol).

Tumor hypoxia remains one of the greatest challenges in the treatment of solid tumors, as cancer cells in these regions are resistant to killing by radiation therapy and most anticancer drugs. Tirapazamine (3-Amino-1,2,4-benzotriazine-1,4-dioxide or SR 4233) is a cytotoxic drug with selective toxicity towards hypoxic mammalian cells. Under both aerobic and hypoxic conditions, tirapazamine is reduced by an intracellular reductase to form a highly reactive radical, which can cause DNA single- and double-strand breaks. In addition, tirapazamine under hypoxic conditions reduces the activity of topoisomerase II and stabilizes DNA topoisomerase II cleavable complexes, and these complexes remain bound to DNA. Despite the very promising results obtained in various preclinical studies and early-Phase clinical trials, several Phase III trials have failed to demonstrate any survival benefit of adding tirapazamine to chemotherapy or radiation therapy of cancers.