Adefovir Dipivoxil

ADEFOVIR · Hepsera · Adefovir Dipivoxi · Preveon · GS 0840 · Ade Vove · adefuweizhi · C20H32N5O8P

https://huagongshe.com/ko/chemical/60871

식별자 및 물리적 특성

CAS No.	142340-99-6
분자식	C20H32N5O8P
평균 분자량	501.5 g/mol
단동위원소 질량	501.19884961 g/mol
SMILES	CC(C)(C)C(=O)OCOP(=O)(COCCn1cnc2c(N)ncnc21)OCOC(=O)C(C)(C)C
InChIKey	WOZSCQDILHKSGG-UHFFFAOYSA-N
PubChem CID	60871
ChEMBL	CHEMBL922
ChEBI	CHEBI:31175
EC No.	634-317-6
DTXSID	DTXSID5046487

화학 및 물리적 성질

XLogP	1.8
극성 표면적	167
수소 결합 공여자 수	1
수소 결합 수용자 수	12
회전 가능 결합 수	15
무거운 원자 수	34
형식 전하	0
복잡도	705
의약품	Pharmaceuticals -> Listed in ZINC15
LogP(분배 계수)	0.82.48
용해도	6.33e-01 g/L에탄올: 용해성50mg/mL
Human Drugs	FDA approved drugs -> Active ingredient
Physical Description	Solid
녹는점	98-102°C
끓는 점	641.0±65.0 °C(Predicted)
밀도	1.35±0.1 g/cm3(Predicted)
저장 조건	Keep in dark place,Inert atmosphere,Store in freezer, under -20°C
pKa(산도 계수)	4.16±0.10(Predicted)
물리적 상태	고체
색상	흰색에서 황백색까지
생물학적 소스	synthetic
Merck	14,151
InChI	InChI=1S/C20H32N5O7P/c1-19(2,3)17(26)29-11-31-33(32-12-30-18(27)20(4,5)6)13-28-8-7-25-10-24-14-15(21)22-9-23-16(14)25/h9-10H,7-8,11-13H2,1-6H3,(H2,21,22,23)
InChIKey	WOZSCQDILHKSGG-UHFFFAOYSA-N
SMILES	P(OCOC(=O)C(C)(C)C)(OCOC(=O)C(C)(C)C)COCCN1C2C(N=C1)=C(N)N=CN=2

화학적 성질

White Solid

안전 및 규제

GHS 분류	WarningH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]P261, P264, P270, P271, P280, P301+P317, P302+P352, P304+P340, P317, P321, P330, P362+P364, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 41 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.Danger
Hazard Classes and Categories	Acute Tox. 4 (100%)
Drug Induced Liver Injury	Drug Induced Liver Injury Rank (DILIrank 2.0)Adefovir dipivoxilvLess-DILI-concernWarnings & precautionsDOI:10.1016/j.drudis.2016.02.015
수질 위해 등급(WGK)	3
RTECS 번호	UA2459362
관세 코드	2933.99.8290
위험 문구(R)	20/21/22
위험 표시	Xn
안전 문구(S)	36/37
위험 등급	Acute Tox. 4 Oral
저장 분류	11 - Combustible Solids

용도

개요

Adefovir dipivoxil is the first nucleotide analog to be launched in the US as an oral treatment for hepatitis B virus (HBV) infections. It can be easily prepared in 4 steps from adenine. Adefovir dipivoxil acts as a bioavailable ester prodrug which is rapidly hydrolyzed to free adefovir and further anabolized to its active form, adefovir diphosphate, by two intracellular phosphotylation steps. The diphosphate competitively inhibits reverse transcriptase and/or causes chain termination when incorporated into growing DNA. Adefovir dipivoxil has a broad antiviral spectrum against retro-, herpes- and hepadnaviruses. The drug inhibits HBV replication, decreases HBV DNA levels and improves liver histology of patients infected with HBV wild type and resistant to other antivirals such as lamivudine. It also demonstrated activity in hepatitis B”e” antigennegative, or precore mutant, patients and in patients co-infected with HIV. To date, no adefovir dipivoxil-associated resistance mutations have been identified in patients up to 136 weeks with the drug. The oral bioavailability of adefovir after oral administration of its dipivoxil prodrug is approximately 30%. It is mainly excreted unchanged in the urine and its plasma elimination half-life is 4.2 h. However, a long intracellular half-life (17 h) of the active bisphosphorylated metabolite enables once-daily dosing. The most prominent adverse effect of adefovir dipivoxil is nephrotoxicity (which has prevented the drug from being marketed for HIV infections where the drug required administration at higher doses).

용도

Adefovir Dipivoxil(Preveon, Hepsera) works by blocking reverse transcriptase, an enzyme that is crucial for the hepatitis B virus (HBV) to reproduce in the body. It is approved for the treatment of chronic hepatitis B in adults with evidence of active vir

일반 설명

Adefovir is an orally active prodrug that is indicated for thetreatment of the chronic form of hepatitis B. The dipivoxil moieties are hydrolyzed by ubiquitous esterases to yieldadefovir, which is phosphorylated by adenylate kinase toyield adefovir diphosphate. This compound is inhibitory atHBV DNA polymerase. In addition, adefovir undergoes incorporationinto viral DNA and causes chain termination.Adefovir is poorly absorbed by the oral route, but the dipivoxilester groups cause the bioavailability to increase toapproximately 60%.