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... Progress in this area has set the scene for tandem TDA reactions to be attempted. Page 7.Adel... more ... Progress in this area has set the scene for tandem TDA reactions to be attempted. Page 7.Adele, Mum and Jim, Dad, Philip and Greg, Nanna Morris, Nanna Lilly and Grandy. Page 8. It gives me great pleasure to thank the following people for their help! ...
Bioorganic & medicinal chemistry letters, 2014
Previous investigations identified…
Organic & Biomolecular Chemistry, 2005
The Journal of Organic Chemistry, 2003
Type II diabetes mellitus is a chronic metabolic disorder that can lead to serious cardiovascular... more Type II diabetes mellitus is a chronic metabolic disorder that can lead to serious cardiovascular, renal, neurologic, and retinal complications. While several drugs are currently prescribed to treat type II diabetes, their efficacy is limited by mechanism-related side effects (weight gain, hypoglycemia, gastrointestinal distress), inadequate efficacy for use as monotherapy, and the development of tolerance to the agents. Consequently, combination therapies are frequently employed to effectively regulate blood glucose levels. We have focused on the mitochondrial sodium-calcium exchanger (mNCE) as a novel target for diabetes drug discovery. We have proposed that inhibition of the mNCE can be used to regulate calcium flux across the mitochondrial membrane, thereby enhancing mitochondrial oxidative metabolism, which in turn enhances glucose-stimulated insulin secretion (GSIS) in the pancreatic beta-cell. In this paper, we report the facile synthesis of benzothiazepines and derivatives by S-alkylation using 2-aminobenzhydrols. The syntheses of other bicyclic analogues based on benzothiazepine, benzothiazecine, benzodiazecine, and benzodiazepine templates are also described. These compounds have been evaluated for their inhibition of mNCE activity, and the results from the structure-activity relationship (SAR) studies are discussed.
The Journal of Organic Chemistry, 2001
Chemistry - A European Journal, 2005
The stereochemical outcome of the intramolecular Diels-Alder reaction of ester-linked 1,3,8-nonat... more The stereochemical outcome of the intramolecular Diels-Alder reaction of ester-linked 1,3,8-nonatrienes can be controlled by substituents about a stereogenic center attached to C1. The scope and limitations of this approach have been investigated, with variation in substrate structure about the allylic stereocenter and the dienophile. The stereochemical outcomes of these reactions are explained by reference to B3 LYP/6-31G(d) transition structures. New insights into the conformational preferences of allylic alcohol derivatives are reported, results which allow an explanation of the differing levels of pi-diastereofacial selectivity and cis/trans (i.e. endo/exo) selectivity from the reaction.
... Progress in this area has set the scene for tandem TDA reactions to be attempted. Page 7.Adel... more ... Progress in this area has set the scene for tandem TDA reactions to be attempted. Page 7.Adele, Mum and Jim, Dad, Philip and Greg, Nanna Morris, Nanna Lilly and Grandy. Page 8. It gives me great pleasure to thank the following people for their help! ...
Bioorganic & medicinal chemistry letters, 2014
Previous investigations identified…
Organic & Biomolecular Chemistry, 2005
The Journal of Organic Chemistry, 2003
Type II diabetes mellitus is a chronic metabolic disorder that can lead to serious cardiovascular... more Type II diabetes mellitus is a chronic metabolic disorder that can lead to serious cardiovascular, renal, neurologic, and retinal complications. While several drugs are currently prescribed to treat type II diabetes, their efficacy is limited by mechanism-related side effects (weight gain, hypoglycemia, gastrointestinal distress), inadequate efficacy for use as monotherapy, and the development of tolerance to the agents. Consequently, combination therapies are frequently employed to effectively regulate blood glucose levels. We have focused on the mitochondrial sodium-calcium exchanger (mNCE) as a novel target for diabetes drug discovery. We have proposed that inhibition of the mNCE can be used to regulate calcium flux across the mitochondrial membrane, thereby enhancing mitochondrial oxidative metabolism, which in turn enhances glucose-stimulated insulin secretion (GSIS) in the pancreatic beta-cell. In this paper, we report the facile synthesis of benzothiazepines and derivatives by S-alkylation using 2-aminobenzhydrols. The syntheses of other bicyclic analogues based on benzothiazepine, benzothiazecine, benzodiazecine, and benzodiazepine templates are also described. These compounds have been evaluated for their inhibition of mNCE activity, and the results from the structure-activity relationship (SAR) studies are discussed.
The Journal of Organic Chemistry, 2001
Chemistry - A European Journal, 2005
The stereochemical outcome of the intramolecular Diels-Alder reaction of ester-linked 1,3,8-nonat... more The stereochemical outcome of the intramolecular Diels-Alder reaction of ester-linked 1,3,8-nonatrienes can be controlled by substituents about a stereogenic center attached to C1. The scope and limitations of this approach have been investigated, with variation in substrate structure about the allylic stereocenter and the dienophile. The stereochemical outcomes of these reactions are explained by reference to B3 LYP/6-31G(d) transition structures. New insights into the conformational preferences of allylic alcohol derivatives are reported, results which allow an explanation of the differing levels of pi-diastereofacial selectivity and cis/trans (i.e. endo/exo) selectivity from the reaction.