Nafenodone [LU 39821] is a potent and selective inhibitor of norepinephrine and serotonin uptake. Its development for the treatment of anxiety disorders, major depressive disorder and psychotic disorders has been discontinued.

Dinaciclib (SCH 727965) is a small molecule inhibitor of cyclin-dependent kinases. Dinaciclib demostrates potent and selective inhibition of CDK2, CDK5, CDK1, and CDK9 activity. Dinaciclib inhibits cell cycle progression and proliferation in various tumor cell lines in vitro. Dinaciclib is a product of a drug discovery collaboration between Pharmacopeia (later Ligand Pharmaceuticals) and Schering-Plough (later Merck & Co.) that began in 1998. Dinaciclib showed promising effect in treating haematological malignancies and solid tumors.

Afuresertib (GSK2110183 ) is an orally bioavailable inhibitor of the serine/threonine protein kinase Akt (protein kinase B) with potential antineoplastic activity. Afuresertib binds to and inhibits the activity of Akt, which may result in inhibition of the PI3K/Akt signaling pathway and tumor cell proliferation and the induction of tumor cell apoptosis. Activation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents. Preclinically, AKT inhibition by afuresertib can reverse platinum resistance in ovarian cancer cell lines isolated from patients with platinum-resistant ovarian cancer. Afuresertib is well tolerated and demonstrates clinical activity as monotherapy in heavily pretreated MM patients. Is in phase II clinical trials for Chronic lymphocytic leukaemia; Haematological malignancies; Histiocytosis.

Rezatomidine (AGN 203818) is an alpha adrenergic receptor agonist that was developed for the treatment of chronic pain conditions. Phase II studies have evaluated the safety and effectiveness of rezatomidine in treating the pain in patients with fibromyalgia, irritable bowel syndrome, interstitial cystitis, and diabetic neuropathy. However, three studies were terminated early based on a business decision. Pancreatitis, gastric ulcer, viral infections and dehydration were reported as serious adverse events in patients when administered a 60mg dose.

Volasertib (BI 6727), a dihydropteridinone derivative, is a small-molecule cell cycle inhibitor of polo-like kinase-1 (PLK-1). Volasertib induces G2-M arrest and induction of apoptosis in cancer cells and potently inhibits tumor growth in xenograft models. Boehringer Ingelheim is developing intravenously administered volasertib for the treatment of acute myeloid leukaemia (AML), myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML), non-small cell lung cancer, urogenital cancer, ovarian cancer and solid tumours.

Bremazocine, a kappa-opioid agonist has limited potential as a clinical analgesic, however, possesses a possible utility for the therapy of alcohol and drug addiction. It was shown that bremazocine-like drugs could lower intraocular pressure and to minimize ischemic damage, that could be used in the therapy of glaucoma and cardiovascular disease.

Pracinostat is a pan-histone deacetylase inhibitor being tested in phase II of clinical trials for the treatment of sarcoma, prostate cancer, acute myeloid leukemia, myelofibrosis, myelodysplastic syndrome. The drug was shown to be active in vitro on HCT116 and HL-60 cells.

Betameprodine is an opioid analgesic under international control according to the UN Single Convention 1961. The stereoisomer alphameprodine was more widely used, however, had a similar classification.

Dimoxamine is a memory adjuvant. Dimoxamine hydrochloride has been reported to facilitate the performance of naive rats in a massed trial shuttle box task. At doses that facilitated shuttle box responding, dimoxamine had no effect on unacclimated motor activity of rats nor on the rate of continuous avoidance responding by rats. Dimoxamine has a psychopharmacological profile that is different from other phenylalkylamines such as S-amphetamine and R-DOM. Dimoxamine may prove beneficial in the treatment of individuals having low or deteriorated levels of certain types of associative and psychomotor abilities. Dimoxamine substituted completely for LSD. Dimoxamine can be classified as a partial agonist of 5-HT receptors in sheep umbilical arteries.

There is no much available information related to the biological and pharmacological application of imidoline, but this compound has been found to be as potent as chlorpromazine in increasing striatal DOPA accumulation and prolactin secretion in vivo. Imidoline exhibited only weak inhibitory activity towards dopamine-sensitive adenylate cyclase and 3H-spiroperidol binding to striatal membranes in vitro. A proposed active conformation involves intramolecular hydrogen bonding between the protonated dimethylamino group and the oxygen of the imidazolidinone ring. The spatial relationship between the amine nitrogen and phenyl ring in this conformation allows proper fit of imidoline with key dimensions described for the dopamine receptor.