- Discovery of novel DAPY-IAS hybrid derivatives as potential HIV-1 inhibitors using molecular hybridization based on crystallographic overlays
-
Crystallographic overlap studies and pharmacophoric analysis indicated that diarylpyrimidine (DAPY)-based HIV-1 NNRTIs showed a similar binding mode and pharmacophoric features as indolylarylsulfones (IASs), another class of potent NNRTIs. Thus, a novel series of DAPY-IAS hybrid derivatives were identified as newer NNRTIs using structure-based molecular hybridization. Some target compounds exhibited moderate activities against HIV-1 IIIB strain, among which the two most potent inhibitors possessed EC50 values of 1.48?μM and 1.61?μM, respectively. They were much potent than the reference drug ddI (EC50?=?76.0?μM) and comparable to 3TC (EC50?=?2.54?μM). Compound 7a also exhibited the favorable selectivity index (SI?=?80). Preliminary structure-activity relationships (SARs), structure-cytotoxicity relationships, molecular modeling studies, and in silico calculation of physicochemical properties of these new inhibitors were also discussed.
- Huang, Boshi,Wang, Xueshun,Liu, Xinhao,Chen, Zihui,Li, Wanzhuo,Sun, Songkai,Liu, Huiqing,Daelemans, Dirk,De Clercq, Erik,Pannecouque, Christophe,Zhan, Peng,Liu, Xinyong
-
p. 4397 - 4406
(2017/07/22)
-
- TGR5 AGONISTS
-
TGR5 agonists of structural formula VIII(Q), wherein X, R1, R2, and R5 are defined in the specification, pharmaceutically acceptable salts thereof, compositions thereof, and use of the compounds and compositions for treating diseases. The invention also comprises use of the compounds in and for the manufacture of medicaments, particularly for treating diseases.
- -
-
Page/Page column 169
(2011/06/26)
-
- TRIAZOLE AND IMIDAZOLE DERIVATIVES FOR USE AS TGR5 AGONISTS IN THE TREATMENT OF DIABETES AND OBESITY
-
The present invention comprises TGR5 agonists of structural formula I, wherein X, R1, R2, and R5 are defined herein, as well as N-oxides of them and pharmaceutically acceptable salts thereof. The invention further comprise
- -
-
Page/Page column 154-155
(2012/01/30)
-
- Fluorine NMR studies of the human carbonic anhydrase-3,5-difluorobenzenesulfonamide complex
-
Fluorine and nitrogen-15 NMR experiments are described which show that 3,5-difluorobenzene-sulfonamide binds to human carbonic anhydrase I in a 1:1 complex, that the bound inhibitor is present as an anion and that the aromatic ring of the inhibitor underg
- Veenstra,Gerig
-
p. S169-S178
(2007/10/03)
-
