Roflumilast

Daliresp · Daxas · BY 217 · Roster · CS-1960 · Roflost · BYK 20869 · APTA 2217

https://huagongshe.com/ko/chemical/449193

식별자 및 물리적 특성

CAS No.	162401-32-3
분자식	C17H14Cl2F2N2O3
평균 분자량	403.2 g/mol
단동위원소 질량	402.03495411 g/mol
SMILES	O=C(Nc1c(Cl)cncc1Cl)c1ccc(OC(F)F)c(OCC2CC2)c1
InChIKey	MNDBXUUTURYVHR-UHFFFAOYSA-N
PubChem CID	449193
ChEMBL	CHEMBL193240
ChEBI	CHEBI:47657
EC No.	685-382-2
DTXSID	DTXSID8044123

화학 및 물리적 성질

XLogP	4.6
극성 표면적	60.5
수소 결합 공여자 수	1
수소 결합 수용자 수	6
회전 가능 결합 수	7
무거운 원자 수	26
형식 전하	0
복잡도	475
의약품	Pharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Respiratory system -> Nasal preparations
용해도	Sparingly solubleDMSO: 용해성20mg/mL, 투명
Human Drugs	Breast FeedingLactationMilk, HumanPhosphodiesterase 4 InhibitorsFDA approved drugs -> Active ingredientEMA approved medicines: Human medicine
Dissociation Constants	8.74
녹는점	158°C
끓는 점	430.6±45.0 °C(Predicted)
밀도	1.471±0.06 g/cm3(Predicted)
저장 조건	-20°C
pKa(산도 계수)	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

화학적 성질

Crystallin Solid

안전 및 규제

GHS 분류	WarningH315 (91.1%): Causes skin irritation [Warning Skin corrosion/irritation]P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 45 reports by companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Hazard Classes and Categories	Skin Irrit. 2 (91.1%)
Hepatotoxicity	In preregistration studies, roflumilast was not associated with serum enzyme elevations or with episodes of clinically apparent liver injury. Since approval of roflumilast, there have been no published reports of hepatotoxicity, and the product label does not mention liver injury as an adverse event.
Drug Induced Liver Injury	Drug Induced Liver Injury Rank (DILIrank 2.0)RoflumilastvNo-DILI-concernNo matchDOI:10.1016/j.drudis.2016.02.015
Effects During Pregnancy and Lactation	◉ Summary of Use during Lactation
수질 위해 등급(WGK)	3
RTECS 번호	CV3325600
관세 코드	2933.39.4100
위험 문구(R)	36/37/38
위험 표시	Xi
안전 문구(S)	26
위험 등급	Eye Irrit. 2Skin Irrit. 2STOT SE 3
저장 분류	11 - Combustible Solids

용도

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.

용도

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