174022-42-5

Basic information

• Product Name: Bevirimat
• Synonyms: Bevirimat;FH 11327;O-(3,3-Dimethylsuccinyl)betulinic acid;Bevirimat(PA-457)
• CAS NO: 174022-42-5
• Molecular Formula: C36H56O6
• Molecular Weight: 584.832
• Mol File: 174022-42-5.mol

Chemical Properties

• Boiling Point: 662.7±40.0 °C(Predicted)
• Appearance: /
• Density: 1.13±0.1 g/cm3(Predicted)
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility: Acetonitrile (Slightly), Methanol (Very Slightly, Heated, Sonicated)
• PKA: 4.48±0.28(Predicted)
• Stability: Hygroscopic
• CAS DataBase Reference: Bevirimat(CAS DataBase Reference)
• NIST Chemistry Reference: Bevirimat(174022-42-5)
• EPA Substance Registry System: Bevirimat(174022-42-5)

Safety Data

• Hazardous Substances Data: 174022-42-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Bevirimat is used as an HIV-1 maturation inhibitor for targeting the Gag CA-SP1 cleavage site. It is employed to inhibit the replication of both drug-sensitive and drug-resistant clinical isolates of HIV-1 in isolated human peripheral blood mononuclear cells (PBMCs), with mean IC50s of 10.3 and 7.8 nM, respectively.
Additionally, Bevirimat is used in HIV treatment:
In vivo, Bevirimat prevents the replication of HIV-1 in SCID-hu Thy/Liv mice when administered at a dose of 100 mg/kg. Despite its potential as a potent HIV drug candidate, the development of Bevirimat into a new drug has been hindered by numerous resistance-related problems.

Enzyme inhibitor

This first-in-class, natural product-based antiviral (FW = 584.83 g/mol; CAS 174022-42-5; Abbreviation: BVM), also known as 3-O-(3',3'- dimethylsuccinyl)betulinate (DSB), 3β-(3-carboxy-3-methyl-butanoyloxy)- lup-20(29)-en-28-oic acid, PA-457, and MPC-4326, is a novel HIV-1 maturation inhibitor that blocks proteolytic processing of the Gag capsid precursor (CA-SP1) into mature capsid (CA) protein. Bevirimat binds to the Gag polypeptide at the CA/SP1 cleavage site. The net result of BVM treatment is the release of immature, noninfectious viral particles. Despite its promising mode of action, about half of all patients have viruses containing genetic polymorphisms in the Gag SP1 (at positions 6 to 8) protein do not respond to BVM treatment.

Upstream product

• 1189176-34-8 4-chloro-2,2-dimethyl-4-oxobutanoic acid 
• 472-15-1 Betulinic acid 
• 4481-62-3 betulonic acid 
• 473-98-3 betulin 
• 17347-61-4 2,2-dimethylsuccinic anhydride 
• 911140-87-9 (3β)-3-hydroxylup-20(29)-en-28-al 3-(1-hydrogen 2,2-dimethylbutanedioate) 

Relevant articles and documents

Anti-AIDS agents 88. Anti-HIV conjugates of betulin and betulinic acid with AZT prepared via click chemistry

In the present study, a new strategy to link AZT with betulin/betulinic acid (BA) by click chemistry was designed and achieved. This conjugation via a triazole linkage offers a new direction for the modification of anti-HIV triterpenes. Click chemistry provides an easy and productive way for linking two molecules, even when one of them is a large natural product. Among the newly synthesized conjugates, compounds 15 and 16 showed potent anti-HIV activity with EC50 values of 0.067 and 0.10 μM, respectively, which are comparable to that of AZT (EC50: 0.10 μM) in the same assay.

Design and synthesis of basic ionic liquids for the esterification of triterpenic acids

Abstract: We present the design and synthesis of Br?nsted-basic ionic liquids and investigate their application in the microwave-assisted esterification of betulinic acid, aiming towards a benign and pyridine-free manufacturing process of the anti-HIV drug, bevirimat. Graphical abstract: [Figure not available: see fulltext.]

Heterocycle-fused lupane triterpenoids inhibit Leishmania donovani amastigotes

The synthesis of heterocyclic betulin derivatives and their activity against Leishmania donovani is reported. Betulonic acid was used as a versatile intermediate. Several different fused heterocycles were introduced at the 2,3-position of the lupane skeleton including isoxazole, pyrazine, pyridine, indole and pyrazole rings. Also the 28-position was modified. Three compounds, 5, 8 and 25, showed low micromolar activity with IC50 values of 13.2, 4.3 and 7.2 μM, respectively. Compound 8 showed the best activity and selectivity, and its activity was tested on infected macrophages using a concentration, 5 μM, where no macrophage toxicity was exhibited. Interestingly, the activity of compound 8 on axenic amastigotes and Leishmania-infected macrophages was similar.

SYNTHESIS OF BETULONIC AND BETULINIC ALDEHYDES

The present invention provides for methods of selectively converting betulin to betulonic aldehyde. The present invention also provides for methods of selectively converting 3-substituted triterpen-28-ols to the corresponding 3-substituted triterpen-28-carboxaldehydes. Additionally, the present invention provides for methods of preparing betulonic aldehyde, betulonic acid, betulinic acid, and corresponding 3-substituted triterpenes.

PREPARATION OF PHARMACEUTICAL SALTS OF 3-O-(3',3'-DIMETHLSUCCINYL) BETULINIC ACID

This invention relates to a novel process for making 3-O-(3',3'- dimethylsuccinyl)betulinic acid ("DSB")- This invention also relates to methods of treating HIV and related diseases using pharmaceutical compositions comprising salt forms of DSB prepared according to the process of the present invention. The invention further relates to dosage forms of pharmaceutical compositions comprising salts of DSB made using the process of this invention.

METHODS OF MANUFACTURING BIOACTIVE 3-ESTERS OF BETULINIC ALDEHYDE AND BETULINIC ACID

The present invention provides a method for preparing a compound of formula (I), the method comprising contacting a compound of formula (II) with an effective amount of a compound of formula (III) or (IV). The present invention also provides a method for preparing a compound of formula (VI), the method comprising contacting a compound of formula (II) with an effective amount of one or more of 2,2-dimethylsuccinic acid, 2,2 dimethylbutanedioyl dichloride, 2,2-dimethylbutanedioyl dibromide, and 2,2 dimethylsuccinic anhydride. The present invention also provides a compound obtained from the method of the present invention.

Anti-AIDS agents - XXVII. Synthesis and anti-HIV activity of betulinic acid and dihydrobetulinic acid derivatives

Two series of lupane-type triterpenoic acid derivatives were synthesized and evaluated for their inhibitory activity against HIV-1 replication in acutely infected H9 cells, based on the fact that betulinic acid (1) and dihydrobetulinic acid (9) were identified as anti-HIV agents. Among the derivatives, 3-O-(3',3'-dimethylsuccinyl)-betulinic acid (3) and 3-O-(3',3'-dimethylsuccinyl)-dihydrobetulinic acid (11) both demonstrated extremely potent inhibitory activity with EC50 values of -4 μM, and remarkable in vitro therapeutic index (TI) values of 20,000 and 14,000, respectively. 3-O-(3',3'-dimethylglutaryl)-betulinic acid (4) and -dihydrobetulinic acid (12), 3-O-diglycolyl-betulinic acid (5) and -dihydrobetulinic acid (13) and 3-O-glutaryl-betulinic acid (6) were also potent inhibitors of HIV replication with EC50 values ranging from 0.04 to 2.3 x 10-3 μM and TI values from 292 to 2344. In addition, compounds 11 and 12 were also active against HIV replication in a monocyte cell line and in peripheral blood mononuclear cells. Our in vitro assay indicated that these compounds are not inhibitors of HIV-1 reverse transcriptase, whereas they inhibited syncytia formation completely in a concentration range of 20-40 μg/mL. However, 3-O-(2',2'-dimethylsuccinyl)-betulinic acid (2) was also found to be an inhibitor of HIV-induced membrane fusion with an IC100 value of 20 μg/mL, though it displayed significantly lower anti-HIV activity than foregoing compounds with an EC50 value of 2.7 μM and TI of 6.7. Further study is underway to determine the mechanisms of action of these compounds.

Betulinic acid and dihydrobetulinic acid derivatives and uses therefor

Some betulinic acid and dihydrobetulinic acid acyl derivatives according to the present invention have been found to have potent anti-HIV activity. Introducing a C2 -C20 substituted or unsubstituted acyl group at the C3 -hydroxy group of betulinic acid and dihydrobetulinic acid produces the corresponding 3-O-acyl derivatives. The compounds of the present invention have the following formulae: STR1 where R may be a mono- or dicarboxylacyl group, substituted or unsubstituted, of from about 2 to about 20 carbon atoms, and R' may be hydrogen or a C2 -C10 substituted and unsubstituted alkyl or aryl group.