Three-Bond Breaking of Cyclic Anhydrides: Easy Access to Polyfunctionalized Naphthalenes and Phenanthrenes

School of Chemistry, College of Science, University of Tehran, 14155-6455 Tehran, Iran
Org. Lett., Article ASAP
Publication Date (Web): July 25, 2013 (Letter)
DOI: 10.1021/ol401318v

Benzannulation of phthalic anhydrides with alkynes to polyfunctionalized naphthalenes and phenanthrenes was confirmed to be straightforward using a palladium catalytic system. Sequential liberation of CO2 and CO occurred via oxidative decomposition of anhydride. In the case of 1,8-naphthalenedicarboxylic anhydrides, both aryls were encompassed in the annulation reaction to afford acenaphthylenes.

Discovery of an HIV integrase inhibitor with an excellent resistance profile

Discovery of an HIV integrase inhibitor with an excellent resistance profile

Med. Chem. Commun., 2013, Advance Article
DOI: 10.1039/C3MD00014A, Concise Article
David C. Pryde, Rob Webster, Scott L. Butler, Edward J. Murray, Kevin Whitby, Chris Pickford, Mike Westby, Michael J. Palmer, David J. Bull, Hannah Vuong, David C. Blakemore, Darren Stead, Christopher Ashcroft, Iain Gardner, Claire Bru, Wai-Yee Cheung, Ieuan O. Roberts, Jennifer Morton, Richard A. Bissell
PFIZER GLOBAL, KENT, UK
Structure-activity relationship studies within a series of N-hydroxy-dihydronaphthyridinone HIV integrase inhibitors led to a candidate compound, of high potency and with an excellent resistance profile.

In the present article, we describe SAR studies within a series of N-hydroxy-dihydronaphthyridinone HIV integrase inhibitors that led to a candidate compound, PF-4776548, of high potency and with an excellent resistance profile. Uncertainties around the human pharmacokinetic predictions for PF-4776548 led to the compound being taken into a human microdose study to confirm its human pharmacokinetics, the results of which are described herein.

Graphical abstract: Discovery of an HIV integrase inhibitor with an excellent resistance profile
DOI: 10.1039/C3MD00014A

Identification of 4,6-diaryl-1,4-dihydropyridines as a new class of neuroprotective agents

Identification of 4,6-diaryl-1,4-dihydropyridines as a new class of neuroprotective agents

Med. Chem. Commun., 2013, 4,590-594
DOI: 10.1039/C3MD20345J, Concise Article
Giammarco Tenti, Javier Egea, Mercedes Villarroya, Rafael Leon, Jose Carlos Fernandez, Juan Fernando Padin, Vellaisamy Sridharan, M a Teresa Ramos, J. Carlos Menendez
MADRID SPAIN
4,6-Diaryl-1,4-dihydropyridines, lacking the structural features needed for vascular activity, were found to prevent calcium overload and behave as neuroprotective agents.

A library of 4,6-diaryl-1,4-dihydropyridines was synthesized using a CAN-catalyzed, Hantzsch-related three component reaction starting from ammonium acetate, β-dicarbonyl compounds and a variety of α,β-unsaturated ketones including chalcones, their vinylogs and heteroanalogues. These compounds lack the structural features needed for vascular activity and were found to prevent calcium overload and behave as neuroprotective agents. One of the compounds, bearing a 2-thienyl substituent at C-4, showed the highest neuroprotective activity and was also a moderate antioxidant, being a good lead compound for further studies in this area.

Graphical abstract: Identification of 4,6-diaryl-1,4-dihydropyridines as a new class of neuroprotective agents