John Reiner

Design and synthesis of a novel class of thrombin inhibitors incorporating heterocyclic dipeptide surrogates

Abstract Several potent and selective inhibitors of thrombin incorporating novel heterocyclic peptide surrogates in the P3-P2 position of peptidyl argininals have been discovered. Illustrated in this article are three classes of heterocycles: pyridones, uracils, and pyrimidinones. The synthesis and biological activities of these unique aromatic heterocyclic derivatives are reported herein.

Synthesis and biological activity of n-butylphthalide derivatives.

A series of n-butylphthalide derivatives were designed and synthesized. The in vitro activities of these compounds were evaluated by a resting tension of isolated rat thoracic aorta ring assay. Compounds 4g and 4i were found to be more active than n-butylphthalide.

Formation of N-alkoxyindole framework: intramolecular heterocyclization of 3-alkoxyimino-2-arylalkylnitriles mediated by ferric chloride.

A variety of functionalized N-alkoxyindole-3-carbonitrile derivatives are achieved under remarkably mild conditions by applying a FeCl3-mediated intramolecular heterocyclization of 3-alkoxyimino-2-arylalkylnitriles. This novel synthesis allows the N-moiety on the side chain to be annulated to the benzene ring as the final synthetic step, which enables the functionalization of the benzenoid portion of the indole at an early stage of the synthesis.

Asymmetric synthesis of novel quaternary α-hydroxy-δ-lactam dipeptide surrogates

Application of the Sharpless AD protocol to a series of α-(E)-benzylidene-δ-lactam precursors followed by selective deoxygenation provided efficient synthetic routes to the chiral quaternary α-hydroxy-γ-lactam derivatives 4 and 5. These functionalized intermediates and the diol precursors 3 are regarded as novel types of D-Phe-Pro dipeptide surrogates that are useful as enzyme active site probes.

Investigation of the S3 site of thrombin: design, synthesis and biological activity of 4-substituted 3-amino-2-pyridones incorporating P1-argininals.

A novel scaffold for P4-P2 dipeptide mimics containing a rigid pyridone spacer was designed based on a virtual library strategy. Several selected nonpeptidic 4-aralkyl or 4-alkylpyridones incorporating a P1-argininal sequence were prepared. The modeling studies, synthesis and biological activities of these unique pyridone derivatives are reported herein.

Guanylpiperidine peptidomimetics: potent and selective bis-cation inhibitors of factor Xa

A novel series of rigid P3-guanylpiperidine peptide mimics 3-14 was designed as potential factor Xa and prothrombinase inhibitors. Incorporation into a P2-gly-P1-argininal motif led to highly potent and selective inhibitors. The synthesis and biological activities of these derivatives are reported herein.

One facile preparation of N-aroyl-N'-arylsulfonylhydrazines by oxidation of aromatic aldehyde N-arylsulfonylhydrazones with bis(trifluoroacetoxy)iodobenzene

Abstract N‐aroyl‐N′‐arylsulfonylhydrazines can be obtained by oxidation of aromatic aldehyde N‐arylsulfonylhydrazones with bis(trifluoroacetoxy)iodobenzene in acetone at room temperature in mild to good yields.

Facile determination of the Optical Purity of α-N-Boc-Amino Aldehydes

Abstract A facile 1 H NMR spectroscopic method is presented for the determination of the optical purity of α-amino aldehydes, via derivatization with optically pure semicarbazides.