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.

Methfuroxam is a systemic fungicide active against Basidiomycetes pathogens. This compound is also used as a seed treatment against loose smut and against Rhizoctonia solani.

AR-67 is a third-generation camptothecin analogue that was being developed by Arno Therapeutics for the treatment of cancer, but has been discontinued. AR-67 had been in phase II clinical trials for the treatment of glioblastoma multiforme and myelodysplastic syndrome. AR-67is a synthetic, highly lipophilic derivative of camptothecin, with potential antineoplastic and radiosensitizing activities. AR-67 binds to and stabilizes the topoisomerase I-DNA covalent complex, inhibiting the religation of topoisomerase I-mediated single-stranded DNA breaks and producing lethal double-stranded DNA breaks when encountered by the DNA replication machinery; inhibition of DNA replication and apoptosis follow. Camptothecin readily undergoes hydrolysis at physiological pH, changing its conformation from the active lactone structure to an inactive carboxylate form. Modifications on the E ring of camptothecin prevent binding of human serum albumin, which prefers the inactive carboxylate form, thereby enhancing the stability of the active lactone structure and resulting in prolonged agent activity.

7-(2-HYDROXY-3-ISOPROPYLAMINOPROPOXY)INDENE HYDROCHLORIDE (1-(7-indenyloxy)3-isopropylaminopropane-2-ol hydrochloride,YB-2) has been reported to possess a potent beta-adrenergic receptor blocking activity with a mild intrinsic beta-sympathomimetic activity and a local anesthetic effect, and to be effective against ouabain-induced and epinephrine-induced arrhythmias.1-(7-indenyloxy)3-isopropylaminopropane-2-ol hydrochloride is a component of Indenolol hydrochloride, which is a mixture of 1-(7-indenyloxy)3-isopropylaminopropane-2-ol hydrochloride and 1-(4-indenyloxy)-3-isopr opylamino-2-propanol monohydrochloride. The antihypertensive effects of indenolol were evaluated in patients with WHO grades I and II essential hypertension (range 160/95 to 200/115 mm Hg) in a double-blind, placebo-controlled study after acute (12 patients) and 2-week treatment (seven patients). Indenolol (30 to 120 mg) reduced blood pressure in a dose-dependent fashion. Maximum reduction was 26 mm Hg for systolic and 17 mm Hg for diastolic pressure. Indenolol did not alter adrenergic reflexes (standing, cold application, and hand-grip) and did not induce any side effect. It possesses an antihypertensive activity associated with reduction of vascular resistance.

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.

Trebenzomine (CI-686) is a centrally acting psychotropic drug structurally distinct from currently available drugs. Preclinical studies indicate that trebenzomine, unlike most psychotropic drugs, has both neuroleptic and stimulant profiles. Stimulant properties of trebenzomine include potentiation of methamphetamine-induced self-stimulation. Neuroleptic properties of trebenzomine include reduction of septal hyperirritability, suppression of conditioned avoidance behavior, blockade of apomorphine-induced emesis in dogs, and elevation of brain homovanillic acid (HVA). Trebenzomine's effect on dopamine (DA) metabolism appears to be related more to the presynaptic release of DA rather than by blockade of postsynaptic DA receptors. Unique preclinical profile suggests a mechanism of action other than dopamine antagonism which could have implications regarding current thinking on the pathophysiology of schizophrenia.

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.