1350915-26-2Relevant articles and documents
C-3 benzoic acid derivatives of C-3 deoxybetulinic acid and deoxybetulin as HIV-1 maturation inhibitors
Liu, Zheng,Swidorski, Jacob J.,Nowicka-Sans, Beata,Terry, Brian,Protack, Tricia,Lin, Zeyu,Samanta, Himadri,Zhang, Sharon,Li, Zhufang,Parker, Dawn D.,Rahematpura, Sandhya,Jenkins, Susan,Beno, Brett R.,Krystal, Mark,Meanwell, Nicholas A.,Dicker, Ira B.,Regueiro-Ren, Alicia
, p. 1757 - 1770 (2016/04/05)
A series of C-3 phenyl- and heterocycle-substituted derivatives of C-3 deoxybetulinic acid and C-3 deoxybetulin was designed and synthesized as HIV-1 maturation inhibitors (MIs) and evaluated for their antiviral activity and cytotoxicity in cell culture. A 4-subsituted benzoic acid moiety was identified as an advantageous replacement for the 3′3′-dimethylsuccinate moiety present in previously disclosed MIs that illuminates new aspects of the topography of the pharmacophore. The new analogs exhibit excellent in vitro antiviral activity against wild-type (wt) virus and a lower serum shift when compared with the prototypical HIV-1 MI bevirimat (1, BVM), the first MI to be evaluated in clinical studies. Compound 9a exhibits comparable cell culture potency toward wt virus as 1 (WT EC50 = 16 nM for 9a compared to 10 nM for 1). However, the potency of 9a is less affected by the presence of human serum, while the compound displays a similar pharmacokinetic profile in rats to 1. Hence 9a, the 4-benzoic acid derivative of deoxybetulinic acid, represents a new starting point from which to explore the design of a 2nd generation MI.
MODIFIED C-3 BETULINIC ACID DERIVATIVES AS HIV MATURATION INHIBITORS
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, (2011/12/14)
Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, modified C-3 betulinic acid and other structurally related natural products derivatives that possess unique antiviral activity are provided as HIV maturation inhibitors. These compounds are useful for the treatment of HIV and AIDS.
