Atizoram (CP-80633) is a phosphodiesterase IV inhibitor with bronchodilatory and antiinflammatory properties. It was in phase II trials with Pfizer in the US for the treatment of asthma, atopic dermatitis and psoriasis. Development of atizoram has been discontinued in the asthma indication and no recent development has been reported for the other indications. CP-80633 inhibits PDE4 isozymes (human lung IC50 = 1.27 uM) in the absence of effects on PDE1, PDE2, PDE3 and PDE5 isozymes (IC50 > 100 uM). It exhibits no significant selectivity for any single cloned PDE4A, B, C or D isoform.

Icometasone (CL09) is a synthetic glucocorticoid corticosteroid. It is a metabolite of Mometasone Furoate. The binding on human serum albumin was shown to be non saturable, suggesting that other proteins were involved in CL09 binding. This binding was demonstrated to be reversible. CL09 was extensively metabolized since no unchanged CL09 was recovered in bile or urine and at least nine metabolites have been detected. It was studied in Europe as an anti-asthmatic agent but investigation is discontinued.

Bimosiamose, discovered by Encysive Pharmaceutical and presently being developed by Revotar Biopharmaceuticals, is an 863 g/mol molecular weight dimer with minimal carbohydrate content and is, to date, the leading selectin inhibitor in clinical development. It was developed as anti-inflammatory drug fir the treatment of acute chronic inflammatory disorders including COPD. This compound has shown promise in a phase IIa 'proof of concept' trial in patients with asthma, reducing airway recruitment of eosinophils after intravenous administration. In acute lung injury, neutrophils (a type of white blood cells, thus belonging to the group of cells of the body’s defence system-the immune system) are drawn to the small lung bloodvessels and migrate into the air sacs (alveoli). There they release substances, which cause the inflammation leading to further destruction of the lung tissue. Bimosiamose disodium is expected to hinder the migration of these neutrophils into the alveoli.

MK-0359 (L-454560) is a selective and potent type 4 phosphodiesterases (PDE4) inhibitor, which binds to both the apo-(Mg2+-free) and holoenzyme states of PDE4. This compound successfully has passed the phase II clinical trial for the treatment of asthma, Pulmonary Disease, Chronic Obstructive (COPD) and Rheumatoid Arthritis. However, there is no information about the further research of this drug.

Thiorphan is the first potent synthetic inhibitor of enkephalinase. Thiorphan displays antinociceptive activity after systemic administration. Thiorphan also inhibits to a lesser extent the widely distributed angiotensin-converting enzyme, a carboxydipeptidase implicated in blood pressure regulation. Thiorphan failed to potentiate allergen-induced airway responses in asthma. Thiorphan significantly reduced the castor oil-induced diarrhea in rats when administered intravenously but not when administered intracerebroventricularly. Racecadotril, via its active metabolite thiorphan, was consistently effective in animal models and patients with various forms of acute diarrhea by inhibiting pathologic (but not basal) secretion from the gut without changing gastro-intestinal transit time or motility.

Quiflapon Sodium (MK-0591; (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-yl-methoxy)- indol-2-yl]-2,2-dimethyl propanoic acid, previously L-686,708) had been in phase II clinical studies for the treatment of inflammatory bowel disease, but the study was discontinued later, because in spite of MK-591 markedly inhibited Leukotrienes (LT) biosynthesis, it did not differ significantly from placebo in clinical efficacy. Also was discovered, that MK-0591 may modify the airway changes associated with bronchial hyper responsiveness, as well as offer symptomatic relief in asthma. MK-0591 is a selective and specific 5-Lipoxygenase-activating protein (FLAP) inhibitor with an IC50 value of 1.6 nM in a FLAP binding assay. In additional, recently was discovered, that MK591 possesses all major attributes of a standard anti-metastatic agent with significant cancer-selective effect, and suggest that MK591 may turn out to be an effective agent for therapy of castration-resistant, bone-metastatic prostate cancer. Though details of the molecular underpinnings of the anti-metastatic action of MK591 are unknown at this time, this finding gives an opportunity for further exploration to better understand the signaling mechanisms involved by in vitro and in vivo experiments.

Oglemilast (GRC-3886), is a potent and selective PDE4 inhibitor (IC50: 2.5 nM (PDE4B) and 1.7 nM (PDE4D)). Oglemilast is in phase II clinical trials for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Oglemilast was originally developed by Glenmark Pharmaceuticals, and licensed to Forest (acquired by Actavis in 2014) for the rights in North America in 2004. Teijin Pharma obtained the rights of the compound in Japan in 2005.

Tomelukast (previously known as LY171883), an orally active antagonist of the CysLT1 receptor (leukotriene D4), which was investigated to treat asthma, but this study was discontinued because of adverse gastrointestinal effect.

Piriprost (U-60, 257) is a structural analog of prostaglandin I2 (PGI2) with low IP receptor-mediated activity. It inhibits 5-LO (5-lipoxygenase). Piriprost inhibits the release of histamine and leukotrienes, implicating its role in inflammation and allergic responses. However, it was shown, that piriprost did not influence the airway responses after allergen in asthma. Nevertheless, even more, the drug was irritant to the respiratory tract than was placebo.

UCB35625 is a potential inhibitor of chemokine/eosinophil interactions. UCB35625 is a trans-isomer of a compound J113863, which was originally identified by scientists at Banyu Pharmaceutical Company as a candidate small molecule chemokine receptor antagonist. UCB35625 initially identified as CCR1 and CCR3 antagonists also bind to CCR2 and CCR5 and act as full agonist, partial agonist or antagonist according to the nature of the receptor and the signaling pathway investigated. UCB35625 shows promise as a lead compound for the design of future therapeutics, which may be of use in the treatment of allergic inflammatory diseases such as asthma and also the blockade of viral entry by HIV strains that utilize CCR3.