pde4 in 4

PDE4-IN-4 is a compound acting as both a potent M3 antagonist (p IC 50 = 10.2) and a PDE4 inhibitor (p IC 50 = 8.8), designed for inhalation-based treatment of pulmonary diseases.

ethyl 1-(4-aminophenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate, also known as EAPT, is a potent and selective PDE4 inhibitor that regulates intracellular cyclic adenosine monophosphate (cAMP) levels. It has been used in a variety of scientific applications, including the study of cAMP-mediated signaling pathways, and has potential as a therapeutic agent for the treatment of inflammatory and immune-related diseases.

PDE4 inhibitor intermediate 1 is a PDE4 inhibitor synthesis intermediate.

PDE4ligand 2 is a CRBN E3 ligase ligand. It is utilized in the synthesis of PROTACs, such as [PDE4degrader-1]. Additionally, PDE4ligand 2 is applicable in the study of autoimmune and anti-inflammatory diseases.

PROTACPDE4 degrader-1 (Compound 9m) is an orally active, selective PDEC4 PROTAC degrader with a DC50 of 41.98 μM. It effectively inhibits the secretion of pro-inflammatory cytokines, such as TNF-α and IL-6, and significantly reduces pulmonary inflammation in a mouse model of LPS-induced acute lung injury (ALI).

M3/PDE4 Modulator-1 (compound 10f) serves as a bifunctional entity functioning both as an M3 mAChR antagonist and a PDE4 inhibitor. When administered intravenously at concentrations ranging from 10 to 1000 nM/kg, this compound effectively diminishes eosinophil influx into cysts within the OVA rat model [1].

(Rac)-PDE4-IN-4 is a diastereomeric mixture of PDE4-IN-4. PDE4-IN-4 acts as an M3 antagonist (pIC50 = 10.2) and a PDE4 inhibitor (pIC50 = 8.8), and it is utilized in inhalation studies related to pulmonary diseases.

PDE IV-IN-1 is a potent phosphodiesterase 4 (PDE4) inhibitor with anti-inflammatory activity for the treatment of asthma, chronic obstructive pulmonary disease and other inflammatory diseases, and is a potential compound for the study of depression.

Oglemilast (GRC 3886) suppresses pulmonary cell infiltration, including eosinophilia and neutrophilia in vitro and in vivo. Oglemilast is an effective and orally active phosphodiesterase-4 (PDE4) inhibitor (IC50: 0.5 nM for PDE4D3). Oglemilast has the potential for inflammatory airway diseases.

AWD 12-281 is a selective phosphodiesterase 4 (PDE4) inhibitor with anti-inflammatory and bronchodilator activity used in the study of chronic obstructive pulmonary disease (COPD).

PF-07038124 HCl is a selective and potent PDE4 inhibitor with an IC50 of 0.5 nM for PDE4B2.PF-07038124 HCl inhibits IL-13, IL-4, and IFNγ, and can be used in the study of skin disorders such as atopic dermatitis and plaque psoriasis.

Dovramilast (CC-11050) is an orally active phosphodiesterase 4 (PDE4) inhibitor that reduces the production of pro-inflammatory mediators and cytokines. Dovramilast is used in the study of Mycobacterium tuberculosis infections and lupus erythematosus.

Lirimilast (IC₅₀ = 49 nM) is a potent, selective, and orally active phosphodiesterase 4 (PDE4) inhibitor with significant anti-inflammatory effects, used in research on asthma and chronic obstructive pulmonary disease (COPD).

PDE4-IN-22 (Compound 2e) is a phosphodiesterase 4 (PDE4) inhibitor with an IC50 value of 2.4 nM. It exhibits anti-inflammatory properties and demonstrates significant anti-psoriatic effects in an Imiquimod-induced psoriasis mouse model.

GPD-1116 is an orally active inhibitor of phosphodiesterase (PDE)4 and PDE1. The compound effectively reduces smoke-induced apoptosis in lung cells. Additionally, GPD-1116 has shown efficacy in various animal disease models, including emphysema, acute lung injury, chronic obstructive pulmonary disease (COPD), asthma, and pulmonary arterial hypertension.

Eggmanone (EGM1) is a potent, selective phosphodiesterase 4 (PDE4) antagonist, exhibiting an IC50 of 72 nM specifically for PDE4D3. It shows 40- to 50-fold greater selectivity for PDE4D3 over other phosphodiesterases. The mechanism of action involves PDE4 selective antagonism by Eggmanone, which activates protein kinase A, culminating in the blockade of the Hedgehog (Hh) signaling pathway [1].

O-Demethyl apremilast is an active metabolite of the phosphodiesterase 4 (PDE4) inhibitor apremilast .1It inhibits the activity of PDE4 isolated from U937 cells and LPS-induced TNF-α production in isolated human peripheral blood mononuclear cells (PBMCs; IC50s = 8.3 and 5.6 μM, respectively). O-Demethyl apremilast is also an oxidative degradation product of apremilast.2,3 1.Hoffmann, M., Kumar, G., Schafer, P., et al.Disposition, metabolism and mass balance of [14C]apremilast following oral administrationXenobiotica41(12)1063-1075(2011) 2.Lu, Y., Shen, X., Hang, T., et al.Identification and characterization of process-related substances and degradation products in apremilast: Process optimization and degradation pathway elucidationJ. Pharm. Biomed. Anal.14170-78(2017) 3.Bhole, R.P., Naksakhare, S.R., and Bonde, C.G.A stability indicating HPTLC method for apremilast and identification of degradation products using MS/MSJ. Pharm. Sci. & Res.11(5)1861-1869(2019)

LEO 39652, a dual-soft PDE4 inhibitor, demonstrates potent inhibition of PDE4 subtypes A, B, C, and D with respective IC50 values of 1.2 nM, 1.2 nM, 3.0 nM, and 3.8 nM. Additionally, it inhibits TNF-α with an IC50 of 6.0 nM, indicating its potential for topical Atopic dermatitis (AD) research [1].

Tetomilast (OPC-6535) is a phosphodiesterase-4 (PDE4) inhibitor, potentially effective for treating inflammatory bowel disease (IBD) and chronic obstructive pulmonary disease (COPD).

PDE4-IN-3 is a newly developed oral compound that acts as a potent inhibitor of the enzyme phosphodiesterase 4 (PDE4), displaying a high affinity for inhibition with an IC50 value of 4.2 nM.

PDE4-IN-8 (Example 5) is a potent Phosphodiesterase 4 (PDE4) inhibitor with an IC50 value of 0.93 nM for PDE4B2. However, it has minimal effects on IL13, IL4, and IFNy, with IC50 values of 4.04 nM, 36.33 nM, and 2394 nM, respectively [1].

PDE4-IN-11 is a potent phosphodiesterase isoenzyme 4 (PDE4) inhibitor, exhibiting remarkable bronchodilatory and anti-inflammatory characteristics. It is specifically designed for studying obstructive or inflammatory airway diseases [1] [2] [3].

(S)-(+)-Rolipram ((+)-Rolipram) inhibits human monocyte cyclic AMP-specific PDE4 with an IC50 of 0.75 μM and exhibits anti-inflammatory and anti-depressant activity in the central nervous system, though it is less potent than its R enantiomer.

AWD 12-281 is a selective phosphodiesterase 4 (PDE4) inhibitor for the treatment of lung inflammation using inhalative administration. AWD 12-281 Is Active in a New Guinea-Pig Model of Allergic Skin Inflammation Predictive of Human Skin Penetration and Suppresses Both Th1 and Th2 Cytokines in Mice. AWD 12-281 is a very promising drug candidate not only for the treatment of lung inflammation using inhalative administration but also for the treatment of atopic dermatitis.