Roflumilast

Roflumilast 속성

Roflumilast C화학적 특성, 용도, 생산

개요

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.

화학적 성질

Crystallin Solid

용도

Roflumilast (Daxas) is a selective inhibitor of PDE4 with IC50 of 0.2-4.3 nM.

정의

ChEBI: 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

Mechanism of action

Roflumilast is the more potent of the two drugs, and along with its active metabolite, roflumilast-N-oxide, it is nonselective in its inhibitory action on PDE4B and PDE4D. The PDE4B appears to be the most closely linked to anti-inflammatory effects, whereas the PDE4D receptor subtype is thought to be linked to nausea, possibly through a central effect. Roflumilast exhibits 80% oral bioavailability and has an elimination half-life of 10 hours, whereas the N-oxide has an elimination half-life of 20 hours and has shown no drug interactions. Clinical trials in patients with asthma or COPD are quite promising.

Pharmacokinetics

Roflumilast is well absorbed on oral administration and has a half-life of 10 hours. Roflumilast is metabolized in the liver to its N-oxide derivative, which also is a PDE4 inhibitor, and it has a plasma half-life of 20 hours.

Clinical Use

Roflumilast is currently undergoing clinical trials in Europe for use in the treatment of both asthma and COPD.

Roflumilast 준비 용품 및 원자재

원자재

준비 용품

Roflumilast 공급 업체

공급자	전화	이메일	국가	제품 수	이점
Hefei TianRui Pharmaceutical Chemical Co., Ltd.	+86-0551-68665055 +86-+86-18616906106	sales@trywchem.com	China	129	58
Shanghai Famo Biotech Co Ltd	+8618550473860	mayan@famobiotech.com	China	505	58
Hebei Mojin Biotechnology Co., Ltd	+8613288715578	sales@hbmojin.com	China	12455	58
Henan Bao Enluo International TradeCo.，LTD	+86-17331933971 +86-17331933971	deasea125996@gmail.com	China	2503	58
Anhui Ruihan Technology Co., Ltd	+8617756083858	daisy@anhuiruihan.com	China	994	58
Henan Tianfu Chemical Co.,Ltd.	+86-0371-55170693 +86-19937530512	info@tianfuchem.com	China	21689	55
Hangzhou FandaChem Co.,Ltd.	008657128800458; +8615858145714	fandachem@gmail.com	China	9344	55
Nanjing ChemLin Chemical Industry Co., Ltd.	025-83697070	product@chemlin.com.cn	CHINA	3012	60
Shanghai Yingrui Biopharma Co., Ltd.	+86-21-33585366 - 03@	sales03@shyrchem.com	CHINA	738	60
ATK CHEMICAL COMPANY LIMITED	+undefined-21-51877795	ivan@atkchemical.com	China	32686	60

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