Roflumilast

한글명:Roflumilast

카스 번호162401-32-3

상품명:Roflumilast

CBNumberCB7412688

분자식C17H14Cl2F2N2O3

포뮬러 무게403.21

MOL 파일162401-32-3.mol

화학적 성질

녹는점	158°C
끓는 점	430.6±45.0 °C(Predicted)
밀도	1.471±0.06 g/cm3(Predicted)
저장 조건	-20°C
용해도	DMSO: 용해성20mg/mL, 투명
산도 계수 (pKa)	9.89±0.70(Predicted)
물리적 상태	가루
색상	흰색에서 베이지색
Merck	14,8249
안정성	제공된 대로 구매일로부터 1년 동안 안정적입니다. DMSO 용액은 -20°C에서 최대 3개월 동안 보관할 수 있습니다.
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
CAS 데이터베이스	162401-32-3(CAS DataBase Reference)

위험 및 안전 성명

위험품 표기

위험 카페고리 넘버

36/37/38

안전지침서

WGK 독일

RTECS 번호

CV3325600

HS 번호

2933.39.4100

NFPA 704:

	0
2		0

그림문자(GHS)

Roflumilast 화학적 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.
부작용
Common side effects of Roflumilast include: diarrhoea, nausea, dizziness, headache, back pain, muscle cramps, loss of appetite and weight loss. Severe can lead to persistent diarrhoea, acute pancreatitis, significant weight loss and psychiatric symptoms (such as anxiety, depression, insomnia and suicidal tendencies). In addition, the incidence of prostate, lung and colorectal cancer is significantly higher.

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