Beperidium (also known as SX-810 ) is a competitive antagonist against acetylcholine. Experiments on animal have shown that this compound exhibited spasmolytic and antiulcerative activities without exerting systemic antimuscarinic side effects.

Edonentan (BMS 207940) is a highly selective biphenylsulfonamide endothelin A receptor antagonist. (11)C- and (18)F-labeled analogs of edonentan were evaluated of novel PET radioligands for imaging the endothelin-A receptor. Edonentan was in clinical trials for the treatment of heart failure however its development has been discontinued.

Fedotozine [(1R)-1-phenyl-1-[(3,4,5-trimethoxy) benzyloxymethyl]-N,N- dimethyl-n-propylamine, (2S,3S-tartrate], derived from the arylacetamide series, is an opioid drug which acts as a selective agonist for kappa(1a)-opioid receptor. Pharmacological studies have shown that fedotozine exerts a peripheral antinociceptive action, comparable with that of other kappa-agonists. Results of Phase III trials of fedotozine against irritable bowel syndrome and dyspepsia have ultimately been disappointing and was lack of efficacy in subsequent studies.

Crenolanib is an orally active, highly selective, small molecule, next generation inhibitor of platelet-derived growth factor receptor (PDGFR) tyrosine kinase. Crenolanib, manufactured by Arog Pharmaceuticals in Dallas, is taken orally with chemotherapy. The compound is currently being evaluated for safety and efficacy in clinical trials for various types of cancer, including acute myeloid leukemia (AML), gastrointestinal stromal tumor (GIST), and glioma. Crenolanib is an orally bioavailable, selective small molecule inhibitor of type III tyrosine kinases with nanomolar potencies against platelet-derived growth factor receptors (PDGFR) (isoforms PDGFRα and PDGFRβ) and Fms-related tyrosine kinase 3 (FLT3). Besides PDGFR and FLT3, crenolanib does not inhibit any other known receptor tyrosine kinase (RTK) (e.g. VEGFR and FGFR) or any other serine/threonine kinase (e.g., Abl, Raf) at clinically achievable concentrations. Preclinical trials have shown Crenolanib to be active in inhibiting both wild-type and mutant FLT3. Crenolanib is cytotoxic to the FLT3/ITD-expressing leukemia cell lines Molm14 and MV411, with IC50s of 7 nM and 8 nM, respectively. In immunoblots, crenolanib inhibited phosphorylation of both the wild-type FLT3 receptor (in SEMK2 cells) and the FLT3/ITD receptor (in Molm14 cells) in culture medium with IC50s of 1-3 nM. Importantly, the IC50 of crenolanib against the D835Y mutated form of FLT3 was 8.8 nM in culture medium. Furthermore, crenolanib had cytotoxic activity against primary samples that were obtained from patients who had developed D835 mutations while receiving FLT3 TKIs. In vitro, the IC50 of crenolanib for inhibition of FLT3/ITD in plasma was found to be 34 nM, indicating a relatively low degree of plasma protein binding. From pharmacokinetic studies of crenolanib in solid tumor patients, steady state trough plasma levels of roughly 500 nM were found to be safe and tolerable, suggesting that crenolanib could potentially inhibit the target in vivo. Crenolanib has no significant activity against c-KIT, which may be an advantage in that myelosuppression can be avoided.1Furthermore, there was no evidence of QTc prolongation in patients treated with crenolanib. In summary, crenolanib offers a number of advantages over other FLT3 TKIs. Clinical trials of crenolanib in AML patients with FLT3 activating mutations are being planned.

Diproteverine is a calcium channel blocking agent. Diproteverine provoked a dose-dependent inhibition of LHRH-stimulated luteinizing hormone release. Diproteverine does not modify mean blood pressure. Diproteverine administered with and without pharmacologic autonomic blockade in the conscious dog causes dose-related depressant effects on sinus node function and atrioventricular conduction without producing significant vasodilatation. Diproteverine caused a redistribution of the available coronary blood flow, to the benefit of an ischemic area of the myocardium. The combination of the reduction in heart rate, to lower cardiac oxygen demand, with the beneficial action on coronary blood flow should result in diproteverinebeing particularly beneficial for the treatment of angina pectoris.

CS-834 is a beta-lactam antibiotic of a carbapenem class, developed by the Japanese company Sankyo Co. Ltd. CS-834 is an ester-type prodrug of the active metabolite R-95867. The drug showed potent and well balanced antibacterial activity as well as stability against dehydropeptidase-I. The in vivo efficacy of CS-834 was evaluated in murine systemic infections caused by 16 strains of gram-positive and -negative pathogens. The efficacy of CS-834 was in many cases superior to those of cefteram pivoxil, cefpodoxime proxetil, cefdinir, and cefditoren pivoxil, especially against infections caused by S. aureus, penicillin-resistant S. pneumoniae, E. coli, Citrobacter freundii, and Proteus vulgaris. Pharmacokinetics of CS-834 was evaluated in healthy male volunteers, but no further clinical development of the drug was reported.

Halopenium was studied as an antibacterial and antifungal agent.

Amifloxacin [WIN 49375] is a fluoroquinolone antibacterial with a broad range of activity against aerobic Gram-negative and some aerobic Gram-positive organisms. Amifloxacin is a DNA gyrase inhibitor. The 50% inhibiory concentration for supercoiling activity of E.coli KL16 DNA gyrase of amifloxacin (MIC, 0.10 ug/ml) was 2.47 ug/ml. Amifloxacin was in trials for the treatment of gram-negative infections, septic shock and urinary tract infections. However, development of amifloxacin has been discontinued.

Amotosalen (S-59, psoralen derivative), a chemical capable of binding to nucleic acids is added to platelets. UVA illumination (320 – 400 nm wavelengths) of amotosalen-treated platelet components induces covalent cross-linking of any nucleic acids to which amotosalen is bound; thereby, preventing further replication. Amotosalen is used in the INTERCEPT process to cross-link DNA and RNA. Amotosalen has protective activity against pathogens such as bacteria, viruses, protozoa, and leukocytes. Prior to administration amotosalen is added to plasma and platelets, then in vivo this agent penetrates pathogens and targets DNA and RNA. Upon activation by ultraviolet A light, amotosalen forms interstrand DNA and RNA crosslinks and prevents replication. Thus, the pathogen-inactivation system using amotosalen/ultraviolet A offers the potential to mitigate the risk of ZIKV transmission by plasma and platelet transfusion. Inactivation of leukocytes can prevent graft versus host disease upon transfusion.

Atrasentan (ABT-627, A-127722) is a selective endothelin A receptor antagonist. Atrasentan is being developed by AbbVie as an oral treatment for diabetic nephropathies.Abbott Laboratories was conducting clinical development of atrasentan for the treatment of certain cancers, including phase II trials for prostate cancer. However, no recent development has been reported for cancer indications and development is presumed to be discontinued.