142217-69-4 Usage
Description
Entecavir is a cyclopentyl guanosine analog launched for the once-daily oral treatment of chronic hepatitis B virus (HBV) infection, and it is the third nucleoside or nucleotide analog to be marketed for this indication. Lamivudine, a deoxythiacytosine analog, and adefovir dipivoxil, a nucleotide analog, have been marketed since 1998 and 2002, respectively. Entecavir and adefovir are specifically indicated for HBV, whereas lamivudine is indicated for both HBV and HIV infections.
Chemical Properties
White to Off-White/Yellow Crystalline Powder
Originator
BMS (US)
Uses
Entecavir is a new generation of guanine nucleoside analogues oral medicine for treatment of hepatitis B virus infection in, mainly for the treatment of adult patients with viral replication activity and serum transaminase continued to increase, or liver tissue for pathological activity of chronic hepatitis B, is currently down virus the fastest and the most powerful, the mutation rate lowest nucleoside analogues.
Definition
ChEBI: Guanine substituted at the 9 position by a 4-hydroxy-3-(hydroxymethyl)-2-methylidenecyclopentyl group. A synthetic analogue of 2'-deoxyguanosine, it is a nucleoside reverse transcriptase inhibitor with selective antiviral activity against hepatitis B virus
Entecavir is phosphorylated intracellularly to the active triphosphate form, which competes with deoxyguanosine triphosphate, the natural substrate of hepatitis B virus reverse transcriptase, inhibiting every stage of the enzyme's activity, although it ha
no activity against HIV. It is used for the treatment of chronic hepatitis B.
Mechanism of action
Entecavir is a nucleoside analog, or more specifically, a deoxyguanosine analogue that belongs to a class of carbocyclic nucleosides and inhibits reverse transcription, DNA replication and transcription in the viral replication process.
Pharmacokinetics
Entecavir had a mean terminal half-life ranging from 128 to 149 hours and an effective half-life of approximately 24 hours. Elimination was predominantly through renal excretion, with mean urinary recovery ranging from 62% to 73%.
Clinical Use
Treatment of chronic hepatitis B virus infection in patients >16 years of age.Entecavir comes as a tablet and solution (liquid) to take by mouth. It is usually taken once a day on an empty stomach, at least 2 hours after a meal and at least 2 hours before the next meal. Take entecavir at around the same time every day.
Side effects
The most common side effects of entecavir: the increase of ALT, fatigue, dizziness, nausea, abdominal pain, abdominal discomfort, abdominal discomfort, liver, muscle, insomnia, rubella and indigestion, also be found in neutrophils decreased slightly. These adverse reactions were mild to moderate. It also found that, as the same type of antiviral drugs, entecavir and the first generation of antiviral drugs have similar side effects, such as acid poisoning, hepatomegaly, liver fatty degeneration in the withdrawal will appear rebound phenomenon.
Synthesis
Entecavir is synthesized from 4-trimethylsilyl-3-butyn-2-one and acrolein. The key features of its preparation are: (1) a stereoselective boron–aldol reaction to afford the acyclic carbon skeleton of the methylenecylopentane moiety; (2) its cyclization by a Cp2TiCl-catalyzed intramolecular radical addition of an epoxide to an alkyne; and (3) the coupling with a purine derivative by a Mitsunobu reaction.
Check Digit Verification of cas no
The CAS Registry Mumber 142217-69-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,4,2,2,1 and 7 respectively; the second part has 2 digits, 6 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 142217-69:
(8*1)+(7*4)+(6*2)+(5*2)+(4*1)+(3*7)+(2*6)+(1*9)=104
104 % 10 = 4
So 142217-69-4 is a valid CAS Registry Number.
InChI:InChI=1/C12H15N5O3/c1-5-6(3-18)8(19)2-7(5)17-4-14-9-10(17)15-12(13)16-11(9)20/h4,6-8,18-19H,1-3H2,(H3,13,15,16,20)/t6-,7-,8+/m0/s1
142217-69-4Relevant articles and documents
A novel and efficient synthesis of Entecavir
Liu, Xiaoyu,Jiao, Xiaozhen,Wu, Qian,Tian, Chengsen,Li, Renze,Xie, Ping
, p. 3805 - 3807 (2012)
A practical synthesis of Entecavir (1) has been accomplished in 10 steps with 21% overall yield. The key steps to construct the five-membered carbocyclic framework 2 are a ring-closing metathesis and a diethyl-aluminum 2,2,6,6-tetramethyl piperidide (DA-TMS) mediated epoxide isomerization. Furthermore, the guanine was introduced by modified Mitsunobu reaction.
Novel preparation method and intermediates of entecavir
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, (2021/04/10)
The invention provides novel intermediates used for entecavir synthesis, compounds shown as a formula II and a formula III in the description, and a novel method for synthesizing entecavir by using the novel intermediates. When the novel intermediates are used for synthesizing entecavir, not only can the synthesis yield be remarkably improved, but also the production cost can be reduced.
Entecavir intermediate, synthetic method thereof and synthetic method of entecavir
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, (2020/07/29)
The invention belongs to the technical field of organic synthesis, and provides an entecavir intermediate, a synthesis method thereof and a method for synthesizing entecavir by using the entecavir intermediate. The intermediate and the methods have the advantages of easily available raw materials, low price, shortest synthesis steps, mild reaction conditions, easiness in control, simple equipmentrequirements, high total yield of products and easiness in industrial production.
Method for synthesizing entecavir
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Paragraph 0040; 0060-0062; 0069, (2019/04/27)
The invention provides a method for synthesizing entecavir. The method comprises the steps of carrying out condensation ring-closure reaction, bromination addition reaction, reduction reaction, Witting reaction and the like. The method has the beneficial effects that the reaction raw material is easy to obtain, the reaction process is simple in operation, the requirement on reaction equipment is low, the reaction condition is relatively mild and the yield and the content are high.