Asymmetric Synthesis of a Potent HIV-1 Integrase Inhibitor.

J Org Chem

Department of Process Chemistry, Merck & Co., Inc. P.O. Box 2000, Rahway, New Jersey 07065, United States.

Published: November 2016

The development of a practical asymmetric total synthesis of the potent HIV-1 integrase inhibitor 5 is described. Key transformations include construction of the naphthridine core in a highly efficient manner followed by cyclization of the 8-membered ring. Control of the atropisomers of intermediates and final compound 5 is also described.

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.joc.6b01229DOI Listing

Publication Analysis

Top Keywords

synthesis potent
8
potent hiv-1
8
hiv-1 integrase
8
integrase inhibitor
8
asymmetric synthesis
4
inhibitor development
4
development practical
4
practical asymmetric
4
asymmetric total
4
total synthesis
4

Similar Publications

1,3,4-Oxadiazole-based heterocyclic analogs (3a-3m) were synthesized cyclization of Schiff bases with substituted aldehydes in the presence of bromine and acetic acid. The structural clarification of synthesized molecules was carried out with various spectroscopic techniques such as FT-IR,H and C-NMR, UV-visible spectroscopy, and mass spectrometry. antifungal activity was performed against , and and analogs 3g, 3i, and 3m showed potent MIC at 200 µg/ml and excellent ZOI measurements of 17-21 nm.

View Article and Find Full Text PDF

The polyketide specialized metabolites of bacteria are attractive targets for generating analogues, with the goal of improving their pharmaceutical properties. Here, we aimed to produce C-26 derivatives of the giant anti-cancer stambomycin macrolides using a mutasynthesis approach, as this position has been shown previously to directly impact bioactivity. For this, we leveraged the intrinsically broad specificity of the acyl transferase domain (AT) of the modular polyketide synthase (PKS), which is responsible for the alkyl branching functionality at this position.

View Article and Find Full Text PDF

Palladium-catalyzed reactions between imidazo[1,2-]pyridine derivatives and 4-bromo-2,2-dialkyl-substituted 2-chromenes under microwave irradiation at 100 W, 120 °C for 20-30 min provided a series of new 3-(2,2-dialkyl-2-chromen-4-yl)-2-phenylimidazo[1,2-]pyridine derivatives in good to excellent yields. The structures of the synthesized compounds were confirmed through spectroscopic techniques (NMR and HRMS). The X-ray single-crystal structure of compound 16e was also determined.

View Article and Find Full Text PDF

A large set of antimalarial molecules (N ~ 15k) was employed from ChEMBL to build a robust random forest (RF) model for the prediction of antiplasmodial activity. Rather than depending on high throughput screening (HTS) data, molecules tested at multiple doses against blood stages of Plasmodium falciparum were used for model development. The open-access and code-free KNIME platform was used to develop a workflow to train the model on 80% of data (N ~ 12k).

View Article and Find Full Text PDF

Previous studies showed that the female genital tract microbiome plays a crucial role in regulating the host's immune defense mechanisms. Our previous research has shown that Lactobacillus gasseri LGV03 (L. gasseri LGV03) isolated from cervico-vagina of HPV-cleared women contributes to clearance of HPV infection and beneficially regulate immune response.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!