Dexbudesonide (22R- Budesonide) is an epimer R of Budesonide, last is used as a mixture of 22R and 22S epimers for the topical treatment of asthma, rhinitis, and inflammatory bowel disease

Cipemastat (Ro 32-3555, tentative trade name Trocade) is a dipeptide, potent, competitive inhibitor of matrix metalloproteinases (MMP) 1, 8 and 13, which was under development by Roche for the potential treatment of rheumatoid arthritis. Cipemastat is a selective inhibitor of metalloproteinases 1, 8 and 13 over the related human matrix metalloproteinases stromelysin 1, and gelatinases A and B. Cipemastat mediated MMP inhibition leads to block the final common event in the destructive cascade resulting in the breakdown of cartilage and bone. Trocade has also been shown to inhibit cartilage destruction in vivo and to prevent structural joint damage in animal models of rheumatoid and osteoarthritis. Cipemastat was in phase II clinical trials for the treatment of rheumatoid arthritis. However, Roche discontinued the development of cipemastat because of an unfavorable risk-benefit profile.

Brolamfetamine (also known as DOB, bromo-DMA, and 4-bromo-2,5-dimethoxyphenylisopropylamine) is one of a vast number of compounds used recreationally to achieve hallucinogenic effects. Brolamfetamine is one of the most potent hallucinogens, with its hallucinogenic potency directly linked to its abuse potential. Brolamfetamine acts as a partial agonist of 5HT2A, 5HT2B, 5HT2C, and TAAR1 receptors, but it’s psychedelic effects are mainly mediated by its agonistic properties at the 5-HT2A receptor. Animal studies have shown physiologic effects including hypertension, tachycardia, hyperpyrexia, pupillary dilatation, and peripheral vasoconstriction. In general, Brolamfetamine having a similar effect to LSD, with slower onset (up to 3–4 h to peak intoxication) and longer duration of effect (up to 36 h). Brolamfetamine is not commonly available, through periods of higher circulation were reported in Australia in 1983, Ireland in 2003, and in Italy in 2015. Brolamphetamine, as well as many other synthetic hallucinogens, are increasingly being sold as LSD. Internationally Brolamfetamine is a Schedule I drug under the Convention on Psychotropic Substances. Due to its selectivity, Brolamfetamine is often used in scientific research when studying the 5-HT2 receptor subfamily.

Levisoprenaline (l-isoproterenol) is beta1- and beta2-adrenoreceptor agonist. In Japan, continuous inhalation of levisoprenaline is a recommended treatment for pediatric patients with acute severe exacerbation. Compared with salbutamol, l-isoproterenol reduced modified pulmonary index score more rapidly. But in most countries do not recommend continuous inhalation of l-isoproterenol to treat pediatric patients with acute severe exacerbation of asthma due to worsening asthma control. Levisoprenaline was used to cause experimental chronic heart failure in rats.

Indiplon is a nonbenzodiazepine, hypnotic sedative that was proposed for the treatment of insomnia. It is a high-affinity allosteric potentiator of GABAA responses that demonstrates preference for α1 subunit-containing GABAA receptors. There is minimal potential for adverse effects, residual daytime sedation, tolerance, respiratory depression. The simultaneous administration of indiplon and alcohol did not result in any significant pharmacokinetic changes. There is little risk of pharmacokinetic interaction between indiplon and any co-administered drugs. Developer (Neurocrine) decided to discontinue all clinical and marketing development of Indiplon in the United States.

Metamfepramone (dimethylcathinone, dimethylpropion, and dimepropion) was synthesized by various routes in the 1930s and 1940s and clinically evaluated as anorectic as well as a treatment of hypotension and symptoms of the common cold. It was widely used for the treatment of the common cold or hypotonic conditions. Due to its stimulating properties and its rapid metabolism resulting in major degradation products such as methylpseudoephedrine and methcathinone, it has been considered relevant for doping controls by the World Anti-Doping Agency (WADA). Metamfepramone was marketed as an appetite suppressant, but was made illegal in 2006.

Normorphine is an opiate analog, specifically the N-demethylated derivative of morphine. It was first described in the 1953 as part of an effort to characterize N-substituted morphine analogs. Normorphine has relatively little opioid activity, but it is a useful intermediate for the production of more potent morphine analogs. It is also a major metabolite of morphine.

Plevitrexed is a rationally designed, orally bioavailable, nonpolyglutamatable quinazoline antifolate that is a selective inhibitor of thymidylate synthase with potent antineoplastic activity and the ability to overcome antifolate resistance due to decreased folylpolyglutamate synthetase activity. It also features a lower toxicity than polyglutamatable thymidylate synthase inhibitors, presumably due to a lesser cellular retention. Plevitrexed is primarily transported into the cells via reduced folate carrier and selectively binds to the folate-binding site of thymidylate synthase with high affinity. Plevitrexed was assessed and in preclinical studies against a panel of human ovarian cancer cell lines and in several phase II clinical studies for the treatment of various solid cancers including colorectal, gastric, pancreatic and ovarian cancer. The combination of plevitrexed and carboplatin is well tolerated with no significant pharmacokinetic interaction between the two drugs - antitumor activity in platinum-pretreated gynecological malignancy was demonstrated.

Quinacainol (also known as PK 10139 or RP 54272) is a quinolinemethanol derivative patented by Pharmindustrie as an antiarrhythmic agent. Quinacainol acts as a sodium channel antagonist and demonstrated both class Ia and Ic antiarrhythmic properties. Quinacainol blocked sodium currents in a concentration-dependent manner and with a potency similar to that of quinidine. Quinacainol produces a slowing of action potential conduction, consistent with a block of sodium channels, and a slight prolongation of action potential duration, consistent with a block of potassium currents.

Darusentan is an orally active, propanoic acid-based endothelin receptor antagonist (ERA) that selectively blocks endothelin-1 (ET-1) binding to the endothelin type-A (ETA) receptor. Darusentan exhibited subnanomolar binding affinity and approximately 1000-fold selectivity for the ETA receptor in binding experiments conducted in vitro under steady-state conditions. Darusentan is orally bioavailable and, when administered to humans, maximum plasma concentrations are observed within 1–2 h post dosing. The mean elimination half-life is relatively long (>15 h), which is consistent with once-daily dosing. Darusentan is primarily glucuronidated by Phase II enzymes in the liver, and the major route of elimination of Darusentan and its metabolites is via the bile. Some glucuronidated metabolites of Darusentan are also excreted in the urine. Darusentan doses up to 300 mg/day were well tolerated and associated with a manageable safety profile in patients with resistant hypertension (RHTN). The most frequently reported adverse events in Ddarusentan-treated subjects were peripheral edema (17%) and headache (11%), which were mostly mild or moderate in severity. Other commonly reported adverse events in the Darusentan treatment group were sinusitis (8%), dizziness (7%), upper respiratory tract infection (5%) and gastroenteritis (5%). In phase III clinical trial the mean reductions in clinic systolic and diastolic blood pressures were 9/5 mm Hg with placebo, 17/10 mm Hg with Darusentan 50 mg, 18/10 mm Hg with Darusentan 100 mg, and 18/11 mm Hg with Darusentan 300 mg. Unfortunately, phase III clinical trial evaluating Darusentan did not achieve its co-primary efficacy endpoints of achieving a change in systolic and diastolic blood pressure after 14 weeks compared to a placebo. Perhaps for this reason, shortly after the top-line results of this study became known, the sponsor announced that Darusentan would not be developed further for resistant hypertension.