Pinokalant is the isoquinoline derivative. It is a broad-spectrum cation channel blocker which inhibits store-operated cation channels in human endothelial cells, mast cells, HL60 cells and in primary cultures of cortical and hippocampal neurons. Pinokalant inhibits voltage-operated calcium channels of the L- and N-subtypes in primary cultures of cortical neurons and shows some antagonism on the NMDA- and AMPA glutamate receptor subtypes. Pinokalant also acts as an antagonist at the delayed rectifier K+ channel in PC12 cells and cortical neurons. Pinokalant reduced in vivo lesion size as well as post mortem infarct size derived from 2,3,5-triphenyltetrazolium chloride-stained brain slices 24 hr after middle cerebral artery occlusion. Pinokalant has been evaluated as a potential neuroprotectant in rodent models of stroke.

Pincainide is a new beta-amino anilide with local anesthetic properties. It has been shown to be 3 times more potent than lidocaine as a local anaesthetic on desheathed frog sciatic nerve. It was found to be effective against arrhythmias induced in guinea-pigs by ouabain infusion or by administration of adrenaline and chloroform. Pincainide not only inhibited the influx of Ca 2+ and increased 45Ca efflux, thus reducing the contractile responses induced in rat aorta by noradrenaline and high K +, but it also inhibited other effects related to the noradrenaline-induced release of intracellular Ca 2+ stores. Further studies, however, must be performed in experimental models of arrhythmias before the effectiveness of pincainide as an antiarrhythmic drug can be established.

Diflomotecan is an E-ring modified camptothecin analogue, which possesses greater lactone stability in plasma compared with other topoisomerase I inhibitors. Diflomotecan was the first homocamptothecin to enter clinical studies. Phase I data are summarized for both the intravenous and oral schedules. The toxicity is primarily haematological while no severe gastrointestinal toxicity has been observed in contrast to other topoisomerase I inhibitors. Diflomotecan has a high oral bioavailability (72 - 95%) and the oral day 1 - 5 every 3 weeks regimen is recommended for Phase II testing because it is relatively well tolerated. Diflomotecan had been in Phase II clinical trials for the treatment of small cell lung cancer. However, this research has been discontinued.

Cytochlor is a radio-sensitizing pyrimidine nucleoside with potential antineoplastic activity. Cytochlor is metabolized first to a phosphate derivative, CldCMP, by the enzyme deoxycytidine kinase and then to the active uracyl derivative, CldUMP, by the enzyme dCMP deaminase. CldUMP, the active metabolite, incorporates into DNA and, upon exposure to radiation, induces the formation of uracil radicals and double-strand DNA breaks. Cytochlor has been used in trials studying the treatment of Head and Neck Cancer and Brain and Central Nervous System Tumors.

Epothilone D (KOS-862 or BMS-241027) is an intermediary obtained in the synthesis of members of the epothilone family and is a small-molecule microtubule stabilizer. It was investigated in Phase II trials in colorectal, metastatic breast and non-small-cell lung cancers. However, development was discontinued in 2007 in favor of a second-generation analog with a better safety profile. This drug also was studied for the treatment of Alzheimer's disease. The study ended in October 2013, and evaluation of epothilone D for Alzheimer's disease was subsequently discontinued. The mechanism by which epothilones induce microtubule polymerization appears to be similar to that of paclitaxel, in that epothilones compete with paclitaxel for binding to microtubules and suppress microtubule dynamics in a manner similar to that of paclitaxel.

Befetupitant (Ro67-5930) is a high-affinity, competitive, tachykinin 1 receptor (NK1R) antagonist that was initially invented by Hoffmann-La Roche as a potential antiemetic drug. These studies were discontinued, because of the clinical trials with the more suitable drug, netupitant. Befetupitant was also investigated for topical application to reduced corneal neovascularization in the alkali burn model. However, the drug was toxic and was not tested in the suture model.

Eltanolone (pregnanolone) is an endogenous neuro active steroid that is biosynthesized from progesterone. It is a positive allosteric modulator of the GABAA receptor, as well as a negative allosteric modulator of the glycine receptor. There is strong evidence that it is involved in the pathophysiology of premenstrual syndrome, catamenial epilepsy, major depression, and stress-sensitive brain disorders and is known to have sedative, anxiolytic, anesthetic, and anticonvulsant effects. It was investigated for clinical use as a general (intravenous) anesthetic. It produced unwanted side effects such as convulsions on occasion, and for that reason was not marketed. Pregnanolone possesses neuroprotective and neurotrophic properties thus has been through a number of clinical trials including for treatment of traumatic brain injury (TBI), Alzheimer disease, cognitive impairment and fragile X-associated tremor/ataxia syndrome.

ALT-2074 (SYI 2074) is small molecule organoselenium compound which acts as a glutathione peroxidase mimetic. Like native glutathione peroxidase, ALT-2074 catalyzes the reduction of hydroperoxides to less toxic species using glutathione (GSH) as the reducing agent. The hydroperoxides could otherwise lead to the formation of free radicals, which can cause tissue damage. ALT-2074 also down-regulates the gene transcription which leads to the production of a wide array of inflammatory mediators. GPx mimics such as BXT-51072 behave as potent antagonists of TNF-alpha and interleukin-1 through the downregulation of endothelial proinflammatory responses. ALT-2074 was investigated for use/treatment in cardiovascular disorders, diabetes mellitus type 1 and 2, plaque psoriasis, ulcerative colitis.

Glisamuride is a hypoglycemic agent and part of the second-generation sulfonamide derivatives. Sulphonylureas are used as medication to control blood sugar levels in patients with diabetes type 2. Compared to other hypoglycemic agents, glisamuride exerts greater binding affinity for peroxisome proliferator-activated receptor gamma (PPARgamma) agonistic activity. This type of compound has also been studied for effects on tumor growth. In one study, several sulfonyl urea derivates, among which glisamuride, were shown to inhibit the adherence of intravenously injected carcinosarcoma cells to the vascular endothelium of the rat mesentery, and to significantly reduce the rate of instantly occurring terminal tumor cell embolism of the lung.

Glipalamide (Glipolamid) is a hypoglycemic agent and part of the second-generation sulfonamide derivatives. These sulphonylureas are used as medication to control blood sugar levels in patients with diabetes type 2. Like other sulphonylureas, glipalamide exerts extra-pancreatic activity. The antihyperglycemic action of this compound (and other sulphonylureas) may be explained by increased affinity of insulin receptors and the stimulating action of these compounds on peripheral glucose metabolism. Glipalamide was analyzed for its physical-chemical properties. After oral administration in animals, no differences were observed in insulin concentration between experimental and control groups, despite a significant fall in blood glucose level.