150840-29-2Relevant academic research and scientific papers
Synthesis and anti-HIV activity of bi-functional betulinic acid derivatives
Huang, Li,Ho, Phong,Lee, Kuo-Hsiung,Chen, Chin-Ho
, p. 2279 - 2289 (2006)
Betulinic acid (BA) derivatives with a side chain at C-3 can inhibit HIV-1 maturation. On the other hand, BA derivatives with a side chain at C-28 can block HIV-1 entry. In order to combine the anti-maturation and anti-entry activities in a single molecul
New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1
Dang, Zhao,Ho, Phong,Zhu, Lei,Qian, Keduo,Lee, Kuo-Hsiung,Huang, Li,Chen, Chin-Ho
, p. 2029 - 2037 (2013/05/08)
Bevirimat (1, BVM) is an anti-HIV agent that blocks HIV-1 replication by interfering with HIV-1 Gag-SP1 processing at a late stage of viral maturation. However, clinical trials of 1 have revealed a high baseline drug resistance that is attributed to naturally occurring polymorphisms in HIV-1 Gag. To overcome the drug resistance, 28 new derivatives of 1 were synthesized and tested against compound 1-resistant (BVM-R) HIV-1 variants. Among them, compound 6 exhibited much improved activity against several HIV-1 strains carrying BVM-R polymorphisms. Compound 6 was at least 20-fold more potent than 1 against the replication of NL4-3/V370A, which carries the most prevalent clinical BVM-R polymorphism in HIV-1 Gag-SP1. Thus, compound 6 merits further development as a potential anti-AIDS clinical trial candidate.
Betulinic acid derivatives as human immunodeficiency virus type 2 (HIV-2) inhibitors
Dang, Zhao,Lai, Weihong,Qian, Keduo,Ho, Phong,Lee, Kuo-Hsiung,Chen, Chin-Ho,Huang, Li
experimental part, p. 7887 - 7891 (2010/04/30)
Wepreviously reported that [[N-[3β-hydroxyllup-20(29)-en-28-oyl]-7- aminoheptyl]carbamoyl]methane (A43D, 4) was a potent HIV-1 entry inhibitor. However, 4 was inactive against HIV-2 virus, suggesting the structural requirements for targeting these two ret
Anti-AIDS agents. 78. Design, synthesis, metabolic stability assessment, and antiviral evaluation of novel betulinic acid derivatives as potent anti-human immunodeficiency virus (HIV) agents
Qian, Keduo,Yu, Donglei,Chen, Chin-Ho,Huang, Li,Morris-Natschke, Susan L.,Nitz, Theodore J.,Salzwedel, Karl,Reddick, Mary,Allaway, Graham P.,Lee, Kuo-Hsiung
experimental part, p. 3248 - 3258 (2010/03/25)
In a continuing study of potent anti-HIV agents, seventeen 28,30-disubstituted betulinic acid (BA, 1) derivatives and seven novel 3,28-disubstituted BA analogues were designed, synthesized, and evaluated for in vitro antiviral activity. Among them, compound 21 showed an improved solubility and equal anti-HIV potency (EC50 = 0.09 μM) when compared to HIV entry inhibitors 3b (IC9564, (3R,4S)-N′-[N-[3β-hydroxylup-20(29)-en- 28-oyl]-8-aminooctanoyl]-4-amino-3-hydroxy-6-methylheptanoic acid) and 4 (A43-D, [[N-[3β-O-(3′,3′-dimethylsuccinyl)-lup-20(29)-en-28-oyl]-7- aminoheptyl]carbamoyl]methane). Using a cyclic secondary amine to form the C-28 amide bond increased the metabolic stability of the derivatives significantly in pooled human liver microsomes. The most potent compounds 47 and 48 displayed potent anti-HIV activity with EC50 values of 0.007 and 0.006 μM, respectively. These results are slightly better than that of bevirimat (2, 3′,3′-dimethylsuccinylbetulinic acid), which is currently in phase IIb clinical trials. Compounds 47 and 48 should serve as attractive promising leads to develop next generation, metabolically stable, 3,28-disubstituted bifunctional HIV-1 inhibitors as clinical trials candidates.
Anti-AIDS agents 49. Synthesis, anti-HIV, and anti-fusion activities of IC9564 analogues based on betulinic acid
Sun, I-Chen,Chen, Chin-Ho,Kashiwada, Yoshiki,Wu, Jiu-Hong,Wang, Hui-Kang,Lee, Kuo-Hsiung
, p. 4271 - 4275 (2007/10/03)
The betulinic acid derivative IC9564 inhibits human immunodeficiency virus (HIV)-1 entry. Among a series of IC9564 derivatives, 5 and 20 were the most promising compounds against HIV infection with EC50 values of 0.33 and 0.46 μM, respectively.
Betulinic acid derivatives: A new class of specific inhibitors of human immunodeficiency virus type 1 entry
Soler, Fran?oise,Poujade, Christèle,Evers, Michel,Carry, Jean-Christophe,Hénin, Yvette,Bousseau, Anne,Huet, Thierry,Pauwels, Rudi,De Clercq, Erik,Mayaux, Jean-Fran?ois,Le Pecq, Jean-Bernard,Dereu, Norbert
, p. 1069 - 1083 (2007/10/03)
A novel series of ω-aminoalkanoic acid derivatives of betulinic acid were synthesized and evaluated for their activity against human immunodeficiency virus (HIV). The anti-HIV-1 activity of several members of this new series was found to be in the nanomolar range in CEM 4 and MT-4 cell cultures. The optimization of the ω-aminoalkanoic acid side chain is described. The presence of an amide function within the side chain was found important for optimal activity. RPR 103611 (14g), a statine derivative, was found to be inactive against HIV-1 protease, reverse transcriptase, and integrase as well as on gp120/CD4 binding. 'Time of addition' experiments suggested interaction with an early step of HIV-1 replication. As syncytium formation, but not virus-cell binding, seems to be affected, betulinic acid derivatives are assumed to interact with the postbinding virus-cell fusion process.
