Anti-AIDS agents 81. Design, synthesis, and structure-activity relationship study of betulinic acid and moronic acid derivatives as potent HIV maturation inhibitors.
Anti-AIDS agents 81. Design, synthesis, and structure-activity relationship study of betulinic acid and moronic acid derivatives as potent HIV maturation inhibitors.
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DOI：
10.1021/jm901782m
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发表时间：
2010-04-22
影响因子：
7.3
通讯作者：
Lee KH
中科院分区：
文献类型：
--
作者：
Qian K;Kuo RY;Chen CH;Huang L;Morris-Natschke SL;Lee KH
在我们继续研究三萜类化合物作为有效的抗HIV药物的过程中，我们设计并合成了不同的C-3构象限制性白桦酸(BA，1)衍生物，以探索C-3药效团的构象空间。3-O-单甲基琥珀酰白桦酸(MSB)类似物的设计也是为了更好地了解Bevirimat(2)的C-3‘二甲基基的贡献，Bevirimat(2)是第一类HIV成熟抑制剂，目前处于IIb期临床试验。此外，还以另一个三萜类骨架--吗啉酸(MA，3)为例，研究了骨架和C-3修饰对该类化合物抗HIV活性的影响。这项研究使我们能够更好地了解三萜类抗艾滋病毒药物的构效关系，并导致设计和合成了化合物12(EC_(50)：0.0006μM)，其作为HIV-1成熟抑制剂的活性略高于2。
In our continuing study of triterpene derivatives as potent anti-HIV agents, different C-3 conformationally restricted betulinic acid (BA, 1) derivatives were designed and synthesized in order to explore the conformational space of the C-3 pharmacophore. 3-O-Monomethylsuccinyl- betulinic acid (MSB) analogs were also designed to better understand the contribution of the C-3′ dimethyl group of bevirimat (2), the first-in-class HIV maturation inhibitor, which is currently in phase IIb clinical trials. In addition, another triterpene skeleton, moronic acid (MA, 3) was also employed to study the influence of the backbone and the C-3 modification towards the anti-HIV activity of this compound class. This study enabled us to better understand the structure-activity relationships (SAR) of triterpene-derived anti-HIV agents, and led to the design and synthesis of compound 12 (EC50: 0.0006 μM), which displayed slightly better activity than 2 as a HIV-1 maturation inhibitor.
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影响因子：
158.5
作者：
Hammer, SM;Katzenstein, DA;Salgo, M
通讯作者：
Salgo, M
影响因子：
5.4
作者：
Kiernan, RE;Ono, A;Freed, EO
通讯作者：
Freed, EO
影响因子：
7.3
作者：
Qian K;Yu D;Chen CH;Huang L;Morris-Natschke SL;Nitz TJ;Salzwedel K;Reddick M;Allaway GP;Lee KH
通讯作者：
Lee KH
影响因子：
2.2
作者：
ROEHM, NW;RODGERS, GH;GLASEBROOK, AL
通讯作者：
GLASEBROOK, AL
影响因子：
7.3
作者：
Kashiwada, Y;Hashimoto, F;Lee, KH
通讯作者：
Lee, KH