ACT-281959 (molecular weight 850.9 g/mol), the di-ester prodrug of ACT-246475 (molecular weight 618.6 g/mol), was developed to improve absorption after oral dosing and is rapidly converted by esterases in vivo to ACT-246475 in two-steps via the formation of ACT-409100 (molecular weight 734.7 g/mol), the mono-ester prodrug. ACT-281959 is a novel potent and selective P2Y12 receptor antagonist with a wider therapeutic window. ACT-281959 showed antithrombotic efficacy after oral administration in the rat ferric chloride model. ACT-281959 entered clinical studies in healthy volunteers. ACT-281959 had been in phase I clinical trials by Actelion for the treatment of thrombosis. But there is no development reported for this study recently.

ADX-71149 (JNJ-40411813), a phenylpiperidine-substituted pyridone, is positive allosteric modulator (PAM) metabotropic glutamate type 2 (mGlu2) receptor activity. In fed rats, JNJ-40411813 was rapidly absorbed with an absolute oral bioavailability of 31%. ADX-71149 (JNJ-40411813) demonstrates antipsychotic activity in vivo rodents experiments. ADX-71149 (JNJ-40411813) is being jointly developed by Addex Therapeutics and Janssen Pharmaceuticals, a Johnson & Johnson company, for the treatment of epilepsy. Addex Therapeutics was also developing the candidate for schizophrenia, major depressive disorder and anxiety disorders. However, development in these indications has been discontinued.

PF-03893787 is potent and selective histamine H4 receptor (H4R) antagonist. It has comparable binding affinity to the human histamine H3 receptor. PF-03893787 was found to have significant affinity for the hERG channel. Novartis initiates a phase II extension trial in Atopic dermatitis. Studies exploring the utility of PF-3893787 in patients would be reported in due course, being the potential indications of asthma, pruritus, inflammatory skin diseases and pain, among others.

LX 2931 (LX 3305) is an inhibitor of sphingosine 1-phosphate (S1P) lyase. S1P lyase is an enzyme identified as a promising new target on a pathway associated with regulation of the immune system. Lexicon Pharmaceuticals, Inc. was developing LX 2931 for the treatment of rheumatoid arthritis. LX 2931 has disappeared from the pipeline of Lexicon Pharmaceuticals, Inc. In preclinical studies LX 2931 was effective against experimental cerebral malaria, lung inflammation in a F508del CFTR murine cystic fibrosis model and osteoporosis.

ASC-09 orTMC-310911, a HIV protease inhibitor, participated in phase II clinical for the treatment of Human Immunodeficiency Virus Type 1. However, no recent development has been reported.

AZD9164 was invented by AstraZeneca as a muscarinic M(3) receptor antagonist for evaluation of the potential as a treatment for chronic obstructive pulmonary disease. However, in 2010 studies were discontinued.

LY2300559 is a dual metabotropic glutamate receptor 2 (mGluR2) positive allosteric modulator and cysteinyl leukotriene receptor 1 (CysLTR1) antagonist. Eli Lilly was developing LY2300559 for the prevention of migraine. LY2300559 development has been discontinued.

CMX-2043 is a is an α-lipoic acid analog developed by Ischemix LLC for reduction of cellular injury and organ damage due to ischemia-reperfusion injury (IRI). CMX-2043 was more effective than lipoic acid in antioxidant effect, activation of insulin receptor kinase, soluble tyrosine kinase, and Akt phosphorylation, and activated insulin-like growth factor 1 as effectively as lipoic acid. In a rat model of cardiac ischemia-reperfusion injury, treatment with CMX-2043 reduced myocardial IRI as measured by the myocardial infarction/area at risk ratio, and reduced the incidence of arrhythmia. In a 360-patient Phase 2 trial, CMX-2043 demonstrated safety but did not meet pre-specified endpoints regarding prevention of contrast-induced acute kidney injury or cardiac injury in cardiac catheterization lab subjects, and no further development of the drug was reported.