Indibulin is a novel synthetic compound that was identified in a cell-based screening assay to discover cytotoxic drugs. Indibulin destabilizes microtubules and blocks cell cycle transition specifically at the G2-M phase. Indibulin effectively induces apoptosis through Bcl-2 phosphorylation and Bax translocation in human malignant glioma cells in a p53-independent manner. This agent has been shown to be active against multidrug-resistant (MDR) and taxane-resistant tumour cell lines. Indibulin was used in phase I/II clinical trials of patients with advanced solid tumours (metastatic breast cancer). Pharmacokinetic analysis showed a better tolerability underfeeding condition. Dose-limiting toxicities were nausea and vomiting, which seemed to be related to solvent lactic acid.

Cilutazoline is phenoxymethyl-imidazoline derivative useful as cardiotonics and vasoconstrictors

Perzinfotel (EAA-090) is a novel squaric acid amide derivative that has been identified as a potential treatment for ischemic brain damage resulting from stroke. EAA-090 is a competitive inhibitor at the NMDA-selective subtype of the glutamate receptor. The compound demonstrates potent inhibitory activity in both in vitro and in vivo models of NMDA-induced excitotoxicity and provides neuroprotective efficacy in several animal models of stroke. EAA-090 is unique among competitive NMDA antagonists in displaying a clear separation between predicted efficacious dose and doses that induce PCP-like psychotomimetic side effects in both animals and humans. This unique profile makes EAA-090 an exciting candidate for assessing the neuroprotective potential of the competitive NMDA mechanism.

Roxibolone, an androstane derivative, possesses the anti-glucocorticoid activity and devoid of any affinity for the androgenic prostate and muscle receptors. This anabolic drug has never been marketed.

Crotoniazide is a derivative of isonicotinic hydrazide. Crotoniazide demonstrated antituberculous activity in vitro and in vivo.

Cortisuzol is a glucocorticoid corticosteroid, discovered by the French company Roussel Uclaf, and claimed to have anti-inflammatory activity in a number of clinical case reports.

LAUROGUADINE is a bactericide, topical antiseptic.

Zaprinast is (M&B 22,948; 2-o-propoxy-phenyl-8-azapurin-6-one) is a selective inhibitor of cyclic GMP (cGMP)-dependent phosphodiesterases, with vasodilation activity in a variety of species and tissues. The potency of zaprinast as a vasorelaxant varies with the species, the tissue, and the presence and absence of endothelium. Zaprinast apparently loses all or most of its vasorelaxant capacity when arteries have been denuded of the endothelial cell layer. Alternatively, the vasorelaxant effects of zaprinast can be attenuated using methylene blue, an inhibitor of soluble guanylate cyclase and hemoglobin inhibitor of nitric oxide synthesis. Therefore, zaprinast-induced relaxations appear to be endothelium-dependent. In human platelets zaprinast, at a dose of 10 mkM, caused a modest (20%) inhibition of aggregation as well as a small increase in cGMP content. In anesthetized rats, zaprinast dose-dependently lowered mean arterial blood pressure (MAP), an effect that correlated well with increased levels of plasma cGMP. Zaprinast decreased mean arterial pressure, the reduction being inversely related to zaprinast concentration. Zaprinast had no effect on heart rate, but increased cardiac output, urinary output, urinary sodium excretion, as well as renal blood flow. Oral administration of zaprinast to spontaneously hypertensive rats at a dose of 200 mg/kg/day normalized blood pressure. In normotensive rats, however, no changes in blood pressure were observed with the same treatment. In an initial placebo-controlled, double-blind crossover trial, 10 mg of zaprinast was effective in reducing exercise-, but not histamine-induced bronchoconstriction in adult asthmatics. However, in a similar study with asthmatic children, zaprinast was ineffective in preventing exercise-induced bronchoconstriction. Since then the clinical development of zaprinast has been discontinued.

Clinafloxacin is a broad-spectrum fluoroquinolone antibiotic that was originally developed and subsequently abandoned in the late 1990s as a human health antibiotic for respiratory diseases. Clinafloxacin displays broad-spectrum antibacterial activity against Gram-positive, Gram-negative, and anaerobic pathogens by inhibiting the bacterial regulatory enzyme DNA gyrase (IC50 = 0.92 ug/ml) as well as topoisomerase IV (IC50 = 1.62 ug/ml).

Glycovir (SC-49483) is an ester produg (a biologically inactive compound that can be metabolized in the body to produce a drug) of SC 48334, an α-glycosidase 1 inhibitor that has anti-HIV activity. Glycovir was thus studied for treatment in HIV. It is targeted against viral glycoprotein processing in host cell endoplasmic reticulum. Bioavailability of the pharmacologically active SC-48334 observed after glycovir administration was found to be very different between species, but monkeys are a good animal model for prediction of bioavailability of SC-48334 in humans. A phase II trial was conducted to determine the safety and anti-HIV activity of a combination treatment of glycovir with zidovudine (AZT).