Roflumilast

Crystallin SolidChEBI: A benzamide obtained by formal condensation of the carboxy group of 3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic acid with the amino group of 3,5-dichloropyridin-4-amine. Used for treatment of bronchial asthma and chronic obstructive pulmonary diseaseRoflumilast is a selective, orally active PDE4 inhibitor thatwas approvedin Germany in July 2010 as an add-on to bronchodilator treatment formaintenance therapy of severe chronic obstructive pulmonary disorder(COPD

Roflumilast is a benzamide obtained by formal condensation of the carboxy group of 3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic acid with the amino group of 3,5-dichloropyridin-4-amine. Used for treatment of bronchial asthma and chronic obstructive pulmonary disease. It has a role as a phosphodiesterase IV inhibitor and an anti-asthmatic drug. It is a member of benzamides, a chloropyridine, an aromatic ether, an organofluorine compound and a member of cyclopropanes.|Roflumilast is a phosphodiesterase-4 (PDE-4) inhibitor. Due to its selective inhibition of the PDE4 isoenzyme in lung cells, roflumilast is indicated for the management of chronic obstrtuctive pulmonary disease (COPD) exacerbations. Treatment with Roflumilast is associated with an increase in psychiatric adverse reactions, including suicide and suicidal attempts.|Roflumilast is a Phosphodiesterase 4 Inhibitor. The mechanism of action of roflumilast is as a Phosphodiesterase 4 Inhibitor.|Roflumilast is a selective inhibitor of phosphodiesterase-4 (PDE-4) that has unique antiinflammatory activity and is used to treat and prevent exacerbations of chronic obstructive pulmonary disease (COPD). Roflumilast has not been linked to significant serum enzyme elevations during therapy or to instances of clinically apparent acute liver injury.|Roflumilast is an orally available, long-acting inhibitor of phosphodiesterase (PDE) type 4 (PDE4), with anti-inflammatory and potential antineoplastic activities. Upon administration, roflumilast and its active metabolite roflumilast N-oxide selectively and competitively bind to and inhibit PDE4, which leads to an increase of both intracellular levels of cyclic-3',5'-adenosine monophosphate (cAMP) and cAMP-mediated signaling. cAMP prevents phosphorylation of spleen tyrosine kinase (SYK) and abrogates activation of the PI3K/AKT/mTOR signaling pathway, which may result in the induction of apoptosis. PDE4, a member of the PDE superfamily that hydrolyses cAMP and 3',5'-cyclic guanosine monophosphate (cGMP) to their inactive 5' monophosphates, is upregulated in a variety of cancers and may contribute to chemoresistance; it also plays a key role in inflammation, especially in inflammatory airway diseases.

N, N-dimethylformamide, N-(3, 5-dichloro-4-pyridyl)-4-(difluoromethoxy)-3-hydroxybenzoyl, potassium carbonate, Mix bromomethylcyclopropane, After stirring for 5 minutes, Slowly warm to 80 C, keep warm for 2 h, cool to room temperature, add ice water, The organic phase is extracted with ethyl acetate, dried over anhydrous sodium sulfate and concentrated.Recrystallization from a mixed solvent of 95:5 by volume of isopropanol and water gives General procedure: To a microwave vial equipped with a stir bar was added the substrate(1.0 equiv, 0.4-1.0 mmol), sulfoximine (2.0 equiv), photocatalyst(0.05 equiv), and TEMPO (0.2 equiv), then the vial wasclosed with a septum cap. DCE or MeCN (0.1 M) was added, andthe mixture was sparged with oxygen. The reaction mixturewas subsequently irradiated in a Hepatochem PhotoRedOx Duophotoreactor and two Kessil LED lamps (each 40 W, A160WE) ora PennOC photoreactor m1 (450 nm). For the reaction workup, the mixture was either directly evaporated or half-saturatedaqueous NaHCO3 solution was added followed by extraction (5 ×EtOAc, Na2SO4). Purification was performed using an automatedIsolera Spektra System or preparative HPLC as described inthe Supporting Information.General procedure: To a microwave vial equipped with a stir bar was added the substrate(1.0 equiv, 0.4-1.0 mmol), sulfoximine (2.0 equiv), photocatalyst(0.05 equiv), and TEMPO (0.2 equiv), then the vial wasclosed with a septum cap. DCE or MeCN (0.1 M) was added, andthe mixture was sparged with oxygen. The reaction mixturewas subsequently irradiated in a Hepatochem PhotoRedOx Duophotoreactor and two Kessil LED lamps (each 40 W, A160WE) ora PennOC photoreactor m1 (450 nm). For the reaction workup, the mixture was either directly evaporated or half-saturatedaqueous NaHCO3 solution was added followed by extraction (5 ×EtOAc, Na2SO4). Purification was performed using an automatedIsolera Spektra System or preparative HPLC as described inthe Supporting Information.General procedure: To a microwave vial equipped with a stir bar was added the substrate(1.0 equiv, 0.4-1.0 mmol), sulfoximine (2.0 equiv), photocatalyst(0.05 equiv), and TEMPO (0.2 equiv), then the vial wasclosed with a septum cap. DCE or MeCN (0.1 M) was added, andthe mixture was sparged with oxygen. The reaction mixturewas subsequently irradiated in a Hepatochem PhotoRedOx Duophotoreactor and two Kessil LED lamps (each 40 W, A160WE) ora PennOC photoreactor m1 (450 nm). For the reaction workup, the mixture was either directly evaporated or half-saturatedaqueous NaHCO3 solution was added followed by extraction (5 ×EtOAc, Na2SO4). Purification was performed using an automatedIsolera Spektra System or preparative HPLC as described inthe Supporting Information.

A selective inhibitor of phosphodiesterase 4.Roflumilast is a drug which acts as a selective,long-acting inhibitor of the enzyme PDE-4. It has anti-inflammatory effects and is under development as an orally administered drug for the treatment of inflammatory conditions of the lungs such as asthma, and chronic obstructive pulmonary disease(COPD)。

Molecular Weight:403.2
XLogP3:4.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:7
Exact Mass:402.0349540
Monoisotopic Mass:402.0349540
Topological Polar Surface Area:60.4
Heavy Atom Count:26
Complexity:475
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes