Michael J. Hearn

Preparation and antitubercular activities in vitro and in vivo of novel Schiff bases of isoniazid

Structural modification of the frontline antitubercular isonicotinic acid hydrazide (INH) provides lipophilic adaptations (3-46) of the drug in which the hydrazine moiety of the parent compound has been chemically blocked from the deactivating process of N(2)-acetylation by N-arylaminoacetyl transferases. As a class, these compounds show high levels of activity against Mycobacterium tuberculosis in vitro and in tuberculosis-infected macrophages. They provide strong protection in tuberculosis-infected mice and have low toxicity. With some representatives of this class achieving early peak plasma concentrations approximately three orders of magnitude above minimum inhibitory concentration, they may serve as tools for improving our understanding of INH-based treatment modalities, particularly for those patients chronically underdosed in conventional INH therapy.

Preparation and properties of new antitubercular thioureas and thiosemicarbazides

Unsymmetrical thioureas and thiosemicarbazides, valuable as lead compounds for antitubercular drug design and discovery, are prepared by the reactions of isothiocyanates with aromatic amines and acid hydrazides, respectively, in robust procedures that permit considerable structural variety. Occasional isolation of symmetrical thioureas derived wholly from the isothiocyanate components of these reactions may occur by thermal fragmentation of the initial thioureidation products.

Using near Infrared Spectroscopy to Monitor the Preparation of Compounds for Screening as Antituberculosis Drugs

Near infrared (NIR) spectroscopy provides an opportune method for assessing the progress of reactions leading to compounds for evaluation as tuberculostats. The advantages of NIR include convenience of sample handling and ease of quantification. Rate estimates obtained from NIR are useful in categorising reactions and adjusting preparative conditions.

Hydrogenolytic Cleavage Reactions of Phenylhydrazides

Abstract Although phenylhydrazides have been well known for some time as derivatives of carboxylic acids and esters, not much work has been done on the selective reductive cleavage reactions of the nitrogen-nitrogen single bonds of these compounds.[1],[2] Information about this process would be instrumental in the development of new indirect amidation methods for the facile conversion of acids and esters to the corresponding amides under mild conditions, particularly for those instances where direct methods are not successful.[3] In general, the nitrogen-nitrogen single bond is expected to be subject to cleavage. Hydrazine itself has a bond strength of 70 kcal/mole, and more highly subsittuted hydrazines often have weaker bonds. [4], [10], [11] The preparation of amides from simple acid hydrazides by hydrazides by hydrogenoloysis over Raney nickel in alcoholic solvents has been invesitgated. [5], [6] The raction typically requires supstantial quantities of Raney nickel, on th order of 10 grams of catalyst...