Anne-Marie Hogan

The present invention is directed to hemi phorboxazole A: and its stereoisomers, as well as derivatives of hemi phorboxazole A of formula I: wherein ring A is aryl or a 5- or 6-membered heteroaryl optionally substituted with one or more of halogen, —OH, or —C1-6alkyl; and R is —CN, a 5- or 6-membered heteroaryl, or halogen; and the pharmaceutically...

The present invention relates to novel TP receptor antagonists, which optionally cross the blood-brain barrier of a mammal. The invention also provides methods for treating a disorder related to activation of TP receptor utilizing the compounds of the invention.

Neurodegenerative tauopathies, such as Alzheimer's disease (AD), are characterized by insoluble deposits of hyperphosphorylated tau protein within brain neurons. Increased phosphorylation and decreased solubility has been proposed to diminish normal tau stabilization of microtubules (MTs), thereby leading to neuronal dysfunction. Earlier studies ha...

The design, synthesis and biological evaluation of a new phorboxazole analogue, comprising an acetal replacement for the C-ring tetrahdropyran of the natural product and carrying a potency-enhancing C(45-46) vinyl chloride side chain, is described. In addition, the synthesis of (+)-hemi-phorboxazole A and a series of related hemi-phorboxazole A ana...

The ability of bisphosphonates ((HO)(2)P(O)CR(1)R(2)P(O)(OH)(2)) to inhibit bone resorption has been known since the 1960s, but it is only recently that a detailed molecular understanding of the relationship between chemical structures and biological activity has begun to emerge. The early development of chemistry in this area was largely empirical...

Tau, a protein that is enriched in neurons of the central nervous system (CNS), is thought to play a critical role in the stabilization of microtubules (MTs). Several neurodegenerative disorders referred to as tauopathies, including Alzheimer's disease and certain types of frontotemporal lobar degeneration, are characterized by the intracellular ac...

This article addresses the mechanistic features of asymmetric carbolithiation of β-methylstyrenes. While often the presence of functional groups is required to obtain high enantioselectivities in carbolithiation reactions, simple β-methylstyrene also gives high selectivities in (-)-sparteine-mediated addition of alkyl lithium compounds. Computation...

Neurons in the brains of those with Alzheimer's disease (AD) and many frontotemporal dementias (FTDs) contain neurofibrillary tangles comprised of hyperphosphorylated tau protein. Tau normally stabilizes microtubules (MTs), and tau misfolding could lead to a loss of this function with consequent MT destabilization and neuronal dysfunction. Accordin...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Inclusions comprised of fibrils of the microtubule- (MT-) associated protein tau are found in the brains of those with Alzheimer's disease (AD) and other neurodegenerative tauopathies. The pathology that is observed in these diseases is believed to result from the formation of toxic tau oligomers or fibrils and/or from the loss of normal tau functi...

A synthesis providing totally synthetic (+)-hemi-phorboxazole A (1), proceeding in two steps (85% yield) from known vinyl iodide precursor (+)-2, has been achieved in conjunction with the design, synthesis, and biological evaluation of two hemi-phorboxazole analogues [(+)-3 and (-)-4] featuring ring replacements inscribed within the macrolide. Alth...

A stereochemistry-controlled suppression of carbolithiation facilitated a regioselective vinyl C-H lithiation of cis-stilbenes allowing routine regio- and stereoselective access to polysubstituted alkenes and heterocycles. This unique selectivity was obtained for numerous directing groups and could be rationalized with DFT computational studies and...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Carbolithiation reactions are exceptionally versatile transformations which have been utilised in a remarkably diverse and creative manner. In this review we outline the background and scope of these reactions and then focus on their use in organic synthesis with a particular emphasis on literature examples published since 2000.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The enantioselective carbolithiation of ortho-substituted (E)-beta-methylstyrenes provides access to chiral lithiated intermediates with broad synthetic potential. Specifically, beta-methylstyrenes with o-aminomethyl, ether, and oxazoline groups have been employed in the synthesis of chiral aromatics and heteroaromatics such as isoquinolines, isoqu...

The (-)-sparteine-mediated enantioselective intermolecular carbolithiation of (E)-2-propenylarylamines allows for the generation of chiral lithiated intermediates which have broad synthetic potential. These intermediates have been exploited in a series of further in situ reactions with electrophiles to generate a collection of products each contain...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A regioselective carbolithiation of o-amino-(E)-stilbenes has been achieved with a series of alkyllithiums when THF is employed as the reaction solvent. The use of other solvents, such as diethyl ether or hydrocarbons, leads to a pronounced loss in regioselectivity. Moreover, high levels of diastereoselectivity have been obtained following reaction...

[reaction: see text] The vinyl deprotonation of cis-stilbene can be readily achieved using s-BuLi in THF at -25 degrees C. The generated 1-lithio-1,2-diphenylethene undergoes an in situ Z-to-E isomerization, and subsequent reaction with electrophiles results in an efficient stereoselective synthesis of trisubstituted alkenes. A directed vinyl lithi...

[reaction: see text] The regioselective carbolithiation of substituted ortho-amino-(E)-stilbenes can be exploited to initiate cascade reaction sequences that can be utilized as new routes to substituted 3,4-dihydro-1H-quinolin-2-ones, 1,2,3,4-tetrahydroquinolines, 1,4-dihydroquinolines, and quinolines.

Enantioselective cascade reactions are very powerful synthetic protocols for the assembly of complex architectures. Our current approach is to exploit a (-)-sparteine-controlled enantioselective carbolithiation of 2-propenylarylamines to provide chiral intermediates, which depending upon choice of electrophile are subsequently in situ converted int...

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