Tubulozole is a stereospecific microtubule inhibitor. Structurally it is related to the benzimidazole carbamates by its carbamate moiety, which is essential for the activity of both types of compounds. The compound exists as a cis-isomer called tubulozole-C (R 46 846) and as a trans-isomer called tubulozole-T. The cis-isomer appears to be a potent and specific microtubule inhibitor, the trans-isomer being inactive at 100 times higher concentrations. At low concentrations, both isomers of tubulozole (C, T) inhibit Plasmodium falciparum but only tubulozole C inhibits mammalian cells. Since tubulozole C prevents polymerization of mammalian tubulin whereas tubulozole T does not, the antimalarial action of tubulozoles may not involve microtubules. Tubulozole-C, a new synthetic anticancer drug, interfered with the structure and function of microtubules in both interphase and mitotic cells. The activity of Tubulozole-C in experimental tumor systems can be explained partly by a direct antimitotic effect and partly by the disintegration of the normal subcellular organization of the nondividing cells. At concentrations which affect the microtubule system, tubulozole-C arrested directional migration of transformed cells and malignant invasion in a three-dimensional organ culture system. Investigations in vivo show that malignant L1210 leukemia cells are more susceptible to the antimicrotubular effect of tubulozole-C than are the normal leukocytes of the host. The trans-isomer of tubulozole (tubulozole-T, R 48 265), which has no antitumor activity in vivo, did not affect the microtubule system of cells in vitro or their capacity for directional migration or for malignant invasion.

Tropanserin (MDL 72422) is a potent and selective 5-HT3 receptor antagonist. It was investigated as a drug for the treatment of migraine. MDL 72222 was shown to be an effective antimigraine agent in a double-blind placebo-controlled study.

Semapimod (CNI-1493) is a cytokine inhibitor and synthetic guanylhydrazone mitogen-activated protein kinase blocker, is being developed by Cytokine PharmaSciences as a potential treatment for Crohn's disease and other inflammatory conditions. As of December 2001, a phase I study demonstrating the safety of the compound had been completed and phase II trials for psoriasis and Crohn's disease were ongoing. In April 2003, preclinical and early clinical studies were underway for a variety of indications, including congestive heart failure and pancreatitis. Semapimod inhibits activation of p38 MAPK and NF-κB and induction of cyclooxygenase-2 by TLR ligands, but not by IL-1β or stresses. Semapimod inhibits TLR4 signaling (IC50 ≈0.3 umol) and acts by desensitizing cells to LPS; it fails to block responses to LPS concentrations of ≥5 ug/ml. Semapimod had been in phase II clinical trials by Ferring Pharmaceuticals for the treatment of Crohn's disease. However, this research has been discontinued. Semapimod is in phase I clinical trials for the treatment of autoimmune disorders and inflammation.

Isoquercetin is a flavonoid, derivative of quercetin. It was isolated from various plant species including Ammothamnus Lehmanii, Caragana alaica, Cicer baldshuanicum, C. macroconthum, C. pungens, Euphorbia cyparissias, E. helioscapia, E. lathyris, E. lucida, E. purporata and others. It demonstrated radical scavenging activity, inhibitory effects on Na+/K+-ATPase and positive inotropic activity. It is protein disulfide isomerase (PDI) inhibitor. As a PDI inhibitor, this agent blocks PDI-mediated platelet activation, and fibrin generation, which prevents thrombus formation after vascular injury. Isoquercetin inhibited the replication of both influenza A and B viruses at the lowest effective concentration. Isoquercetin activates the ERK1/2-Nrf2 pathway and protects against cerebral ischemia-reperfusion injury in vivo and in vitro. It is being investigated for prevention of thromboembolism in selected cancer patients and as an anti-fatigue agent in kidney cancer patients treated with sunitinib.

Pfizer was developing UK-396,082, an imidazole-propionic acid, as an oral treatment for thrombosis and pulmonary fibrosis. UK-396,082 is a potent and selective inhibitor of activated thrombin-activatable fibrinolysis inhibitor (activated TAFI; TAFIa) with Ki of 10 nM. UK-396,082 displays excellent selectivity over plasma carboxypeptidase N (>1,000-fold); exhibits antithrombotic efficacy in a rabbit model of venous thrombosis, yet has no effect on surgical bleeding in the rabbit; possesses excellent preclinical and clinical pharmacokinetic profile. UK-396,082 showed potential for the treatment of thrombosis and other fibrin-dependent diseases in humans, however its development was discontinued.

Streptoniazid is a streptomycin derivative patented by Societe des usines chimiques de Rhone-Poulenc as antibiotic effective against tuberculosis.

Zonampanel (also known as YM872) was developed as selective, potent and highly water-soluble competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist. Zonampanel possesses the neuroprotective effect against focal cerebral ischemia and participated in phase II clinical trials in acute stroke patients. However, because of the severe effects, including hallucinations, agitation, and catatonia the further studied were terminated.

Giripladib (PLA 695) is a Cytosolic phospholipase A2 (cPLA2) inhibitor. cPLA2 is associated with tumor progression and radioresistance in mouse tumor models. In these models, treatment with giripladib attenuates radiation induced increases of phospho-ERK and phospho-Akt in endothelial cells. Combined with irradiation, giripladib reduces migration and proliferation in endothelial cells (HUVEC & bEND3) and induces cell death and attenuated invasion by tumor cells (LLC &A549). The combination treatment of giripladib and irradiation also delayes growth in both LLC and A549 tumors and results in reduced tumor vasculature. Phase I studies have been conducted to test the gastrointestinal safety of giripladib, and potential pharmacokinetic interaction with other compounds. A phase II study was terminated.

Mexrenoate potassium is an aldosterone antagonist, which was developed as an antihypertensive agent. However, this drug has never been marketed.