Hydrogen-Bond-Directed Enantioselective Decarboxylative Mannich Reaction of β-Ketoacids with Ketimines: Application to the Synthesis of Anti-HIV Drug DPC 083

2013 ◽  
Vol 125 (14) ◽  
pp. 3961-3965 ◽  
Author(s):  
Hai-Na Yuan ◽  
Shuai Wang ◽  
Jing Nie ◽  
Wei Meng ◽  
Qingwei Yao ◽  
...  
Keyword(s):  
Hydrogen Bond ◽  
Mannich Reaction ◽  
Anti Hiv

ChemInform Abstract: Hydrogen-Bond-Directed Enantioselective Decarboxylative Mannich Reaction of β-Ketoacids with Ketimines: Application to the Synthesis of anti-HIV Drug DPC 083.

ChemInform ◽  
2013 ◽  
Vol 44 (35) ◽  
pp. no-no
Author(s):  
Hai-Na Yuan ◽  
Shuai Wang ◽  
Jing Nie ◽  
Wei Meng ◽  
Qingwei Yao ◽  
...  
Keyword(s):  
Hydrogen Bond ◽  
Mannich Reaction ◽  
Anti Hiv

scholarly journals Crystal structure of ammonium 3′-azido-3′-deoxythymidine-5′-aminocarbonylphosphonate hemihydrate: an anti-HIV agent

2014 ◽  
Vol 70 (11) ◽  
pp. 396-399
Author(s):  
Maxim V. Jasko ◽  
Galina V. Gurskaya ◽  
Marina K. Kukhanova ◽  
Ivan S. Bushmarinov
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bond ◽  
Hydrogen Bonds ◽  
Water Molecule ◽  
Rotation Axis ◽  
Three Dimensional ◽  
Amide Group ◽  
The Other ◽  
Asymmetric Unit ◽  
Anti Hiv

The asymmetric unit of the title compound, NH4+·C11H14N6O7P−·0.5H2O, contains one 3′-azido-3′-deoxythymidine-5′aminocarbonylphosphonate (ACP–AZT) anion, half of an NH4+cation lying on a twofold rotation axis and in another position, occupied with equal probabilities of 0.5, an NH4+cation and a water molecule. The amide group of the ACP–AZT anion is disordered (occupancy ratio 0.5:0.5), with one part forming an N—H...O (involving C=O...H4N+) hydrogen bond and the other an O—H...N (involving C—NH2...OH2) hydrogen bond with the components of the split NH4+/H2O position. The pseudorotation parameters of ACP–AZT set it apart from previously studied AZT and thymidine. In the crystal, the various components are linked by N—H...O, O—H...O, N—H...N, C—H...O and C—H...N hydrogen bonds, forming a three-dimensional framework.

scholarly journals Insights into the Mechanism of Inhibition of CXCR4: Identification of Piperidinylethanamine Analogs as Anti-HIV-1 Inhibitors

2015 ◽  
Vol 59 (4) ◽  
pp. 1895-1904 ◽  
Author(s):  
Debananda Das ◽  
Kenji Maeda ◽  
Yasuhiro Hayashi ◽  
Navnath Gavande ◽  
Darshan V. Desai ◽  
...  
Keyword(s):  
Hydrogen Bond ◽  
Amino Acid ◽  
Envelope Glycoprotein ◽  
Site Directed Mutagenesis ◽  
Shape Similarity ◽  
Amino Acid Substitutions ◽  
Hydrogen Bond Interactions ◽  
Computational Search ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACTThe cellular entry of HIV-1 into CD4+T cells requires ordered interactions of HIV-1 envelope glycoprotein with C-X-C chemokine receptor type 4 (CXCR4) receptors. However, such interactions, which should be critical for rational structure-based discovery of new CXCR4 inhibitors, remain poorly understood. Here we first determined the effects of amino acid substitutions in CXCR4 on HIV-1NL4-3glycoprotein-elicited fusion events using site-directed mutagenesis-based fusion assays and identified 11 potentially key amino acid substitutions, including D97A and E288A, which caused >30% reductions in fusion. We subsequently carried out a computational search of a screening library containing ∼604,000 compounds, in order to identify potential CXCR4 inhibitors. The computational search used the shape of IT1t, a known CXCR4 inhibitor, as a reference and employed various algorithms, including shape similarity, isomer generation, and docking against a CXCR4 crystal structure. Sixteen small molecules were identified for biological assays based on their high shape similarity to IT1t, and their putative binding modes formed hydrogen bond interactions with the amino acids identified above. Three compounds with piperidinylethanamine cores showed activity and were resynthesized. One molecule, designated CX6, was shown to significantly inhibit fusion elicited by X4 HIV-1NL4-3glycoprotein (50% inhibitory concentration [IC50], 1.9 μM), to inhibit Ca2+flux elicited by stromal cell-derived factor 1α (SDF-1α) (IC50, 92 nM), and to exert anti-HIV-1 activity (IC50, 1.5 μM). Structural modeling demonstrated that CX6 bound to CXCR4 through hydrogen bond interactions with Asp97 and Glu288. Our study suggests that targeting CXCR4 residues important for fusion elicited by HIV-1 envelope glycoprotein should be a useful and feasible approach to identifying novel CXCR4 inhibitors, and it provides important insights into the mechanism by which small-molecule CXCR4 inhibitors exert their anti-HIV-1 activities.

scholarly journals Mannich Bases: An Important Pharmacophore in Present Scenario

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Suman Bala ◽  
Neha Sharma ◽  
Anu Kajal ◽  
Sunil Kamboj ◽  
Vipin Saini
Keyword(s):  
Mannich Reaction ◽  
Ethacrynic Acid ◽  
Mannich Bases ◽  
Unsaturated Ketone ◽  
Bond Forming ◽  
Carbon Carbon Bond ◽  
Nucleophilic Addition Reaction ◽  
Antiviral Activities ◽  
Nitrogen Containing Compounds ◽  
Anti Hiv

Mannich bases are the end products of Mannich reaction and are known as beta-amino ketone carrying compounds. Mannich reaction is a carbon-carbon bond forming nucleophilic addition reaction and is a key step in synthesis of a wide variety of natural products, pharmaceuticals, and so forth. Mannich reaction is important for the construction of nitrogen containing compounds. There is a number of aminoalkyl chain bearing Mannich bases like fluoxetine, atropine, ethacrynic acid, trihexyphenidyl, and so forth with high curative value. The literature studies enlighten the fact that Mannich bases are very reactive and recognized to possess potent diverse activities like anti-inflammatory, anticancer, antifilarial, antibacterial, antifungal, anticonvulsant, anthelmintic, antitubercular, analgesic, anti-HIV, antimalarial, antipsychotic, antiviral activities and so forth. The biological activity of Mannich bases is mainly attributed to α, β-unsaturated ketone which can be generated by deamination of hydrogen atom of the amine group.

Sign in / Sign up

Export Citation Format

Share Document