Roflumilast , ≥99% , 162401-32-3

Synonym(s):
3-(Cyclopropylmethoxy)-N-(3,5-dichloro-4-pyridinyl)-4-(difluoromethoxy)benzamide;3-Cyclopropylmethoxy-4-difluoromethoxy-N-[3,5-dichloropyrid-4-yl]-benzamide

CAS NO.：162401-32-3

Empirical Formula: C17H14Cl2F2N2O3

Molecular Weight: 403.21

MDL number: MFCD00938270

EINECS: 685-382-2

PRODUCT Properties

• Melting point: 158°C
• Boiling point: 430.6±45.0 °C(Predicted)
• Density: 1.471±0.06 g/cm3(Predicted)
• storage temp.: -20°C
• solubility: DMSO: soluble20mg/mL, clear
• pka: 9.89±0.70(Predicted)
• form: powder
• color: white to beige
• Merck: 14,8249
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
• InChI: InChI=1S/C17H14Cl2F2N2O3/c18-11-6-22-7-12(19)15(11)23-16(24)10-3-4-13(26-17(20)21)14(5-10)25-8-9-1-2-9/h3-7,9,17H,1-2,8H2,(H,22,23,24)
• InChIKey: MNDBXUUTURYVHR-UHFFFAOYSA-N
• SMILES: C(NC1C(Cl)=CN=CC=1Cl)(=O)C1=CC=C(OC(F)F)C(OCC2CC2)=C1

Description and Uses

Roflumilast is a selective, orally active PDE4 inhibitor thatwas approved in Germany in July 2010 as an add-on to bronchodilator treatment for maintenance therapy of severe chronic obstructive pulmonary disorder (COPD) associated with chronic bronchitis in adult patients with a history of frequent exacerbations .
Roflumilast and its primary metabolite roflumilast N-oxide are potent and competitive inhibitors of PDE4 and are equipotent against PDE4A, B, andD but inactive against PDE4C and the other ten members of the PDE family (PDEs 1–3, 5–11). Despite its inhibition of PDE4D (IC₅₀=0.80 nM, N-oxide IC₅₀=2.0 nM), roflumilast shows the lowest incidence of nausea (3–5%) among the PDE4 inhibitors investigated in clinical trials.Anti-inflammatory effects of roflumilast have been demonstrated in preclinical cellular and animal models. Roflumilast is synthesized in four steps from 3-(cyclopropylmethoxy)-4-hydroxybenzaldehyde. The difluoromethyl ether is introduced by alkylation of the free phenolic group with chlorodifluoromethane and base. The aldehyde moiety is oxidized to the benzoic acid, which is then converted to an acid chloride and coupled with 3,5-dichloro-4-aminopyridine. Roflumilast is rapidly absorbed and metabolized to its active metabolite, roflumilast N-oxide. Metabolism is mediated by CYP3A4 and CYP1A2.

Selective phosphodiesterase 4(PDE4) inhibitor. Antiasthmatic; in treatment of chronic obstructive pulmonary disease

Safety

• Symbol(GHS): GHS07
• Signal word: Warning
• Hazard statements: H315-H319-H335
• Precautionary statements: P261-P264-P271-P280-P302+P352-P305+P351+P338
• Hazard Codes: Xi
• Risk Statements: 36/37/38
• Safety Statements: 26
• WGK Germany: 3
• RTECS: CV3325600
• HS Code: 2933.39.4100