Nicholas A Magnus

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The design, synthesis, and biological characterization of an orally active prodrug (3) of gemcitabine are described. Additionally, the identification of a novel co-crystal solid form of the compound is presented. Valproate amide 3 is orally bioavailable and releases gemcitabine into the systemic circulation after passing through the intestinal mucosa. The(More)
A practical synthesis of the glycogen synthase kinase-3 (GSK3) inhibitor bisarylmaleimide 1 has been accomplished employing Pictet-Spengler methodology to access the indole 7-position in preparing the benzodiazepine tricyclic fragment. A seven-step linear sequence that starts with commercially available 5-fluoroindole 7 affords the bisarylmaleimide 1 in 33%(More)
The practical and highly diastereoselective syntheses of CF(3)-substituted dihydroquinazolinones via 1,4-additions of nucleophiles to chiral auxiliary substituted 2(3H)-quinazolinones is described. This methodology is applied to the syntheses of the NNRTIs (nonnucleoside reverse transcriptase inhibitors) DPC 961 (1) and DPC 083 (2), which are useful for the(More)
Enantio- and diastereoselective hydrogenation of β-keto-γ-lactams with a ruthenium-BINAP catalyst, involving dynamic kinetic resolution, has been employed to provide a general, asymmetric approach to β-hydroxy-γ-lactams, a structural motif common to several bioactive compounds. Full conversion to the desired β-hydroxy-γ-lactams was achieved with high(More)
The beta-amino alcohol 4 beta-morpholinocaran-3 alpha-ol is prepared by addition of morpholine to alpha-3,4-epoxycarane utilizing anhydrous magnesium bromide as Lewis acid promoter. The enantiopure amino alcohol is uniquely effective as a chiral moderator for the addition of lithium cyclopropylacetylide to an unprotected N-acylketimine. This reaction(More)
A series of 4-alkenyl and 4-alkynyl-3, 4-dihydro-4-(trifluoromethyl)-2-(1H)-quinazolinones were found to be potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) of human immunodeficiency virus type-1 (HIV-1). The 4-alkenyl-3, 4-dihydro-4-(trifluoromethyl)-2-(1H)-quinazolinones DPC 082 and DPC 083 and the 4-alkynyl-3,(More)
An efficient three-step synthesis of a series of fused bicyclic s-[1,2,4]triazolo[1,5-a]pyridines 1 was accomplished utilizing novel intermediates derived from inexpensive, commercially available hydrazides A and methyl coumalate B. A significant feature of this approach was the formation of a dihydrazide intermediate 2, bypassing the need for oxidative N-N(More)
Serotonin norepinephrine reuptake inhibitor (SNRI) pyrrolidinyl ether 2 was synthesized by employing a dynamic kinetic resolution (DKR) with enantio- and diastereoselective hydogenation on β-keto-γ-lactam 8 to afford β-hydroxy-γ-lactam 9 with 96% ee and 94% de. Reduction of 9 and purification via the dibenzoyl-(L)-tartaric acid diastereomeric salt 16(More)
We report the design and discovery of a 2-aminobenzimidazole-based series of potent and highly selective p38alphainhibitors. The lead compound 1 had low-nanomolar activity in both ATP competitive enzyme binding and inhibition of TNFalpha release in macrophages. Compound 18 showed excellent pharmacokinetics properties and oral activity in the rat collagen(More)
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