One Step Synthesis of Dihydropyridin-2-imines: Inhibitors of Inducible Nitric Oxide Synthase

Abstract

An exclusive one step synthesis of dihydropyridin-2-imines 2 or 3, both of which are potent inhibitors of inducible nitric oxide (iNOS), from the common starting material 2-aminopyridine 1 was successfully carried out using the Birch reduction followed by the appropriate work-up procedure. The application of this reduction to other substituted 2-aminopyridines 4-8 and 2-hydroxypyridine 9 are reported. The reaction mechanism is also discussed.

One‐Pot Synthesis of Cyclopropane‐Fused Cyclic Amidines: An Oxidative Carbanion Cyclization

“…Moreover, amidines exhibit inducible nitric oxide synthase (iNOS) inhibition and brain penetrant BACE1 inhibition, and also serve as antiresorptive agents and cardiovascular controllers ,. Interestingly, a 3‐azabicyclo[4.1.0]heptane bearing an amide functional group is known to exhibit antiviral activity, whereas the amidine derivative is an inhibitor of iNOS (Figure ) . Amidines are also known to function as ligands, superbases, and organocatalysts, and chiral amidine derivatives have been used as catalysts and ligands in asymmetric catalysis .…”

NOS: Molecular Mechanisms, Clinical Aspects, Therapeutic and Monitoring Approaches

“…3) [84], indicating that iNOS is an important source of the increased exhaled NO in asthma. Recently, a series of 5,6-dihydropyridin-2-imines, new selective inhibitors of human iNOS (hiNOS), have been synthesized and biologically evaluated [85]. We have reported a profound (>90% reduction of NO in patients with asthma), rapid (within 15 minutes) and sustained (longer than 72 hours) reduction in exhaled NO down to, presumably constitutive NO levels, <2 ppb in both normal and asthmatic subjects after a single oral dose of a selective iNOS inhibitor L-NIL [86].…”

α‐Acryloylamidoalkyl Sulfones in a Synthetic Approach for the Preparation of 6‐Alkyltetrahydropyridin‐2‐ones

“…[5] Early methods for the assembly of this heterocyclic system were mostly based on the intramolecular lactamization of δ-amino-α,β-unsaturated carboxylic acid derivatives. [7] Alternative methods based on the Beckmann rearrangement of substituted 2-cyclopenten-1-ones [8] or the hydropyridin-2-ones. [7] Alternative methods based on the Beckmann rearrangement of substituted 2-cyclopenten-1-ones [8] or the hydropyridin-2-ones.…”