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Your search keyword '"Georgeta Hategan"' showing total 6 results
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6 results on '"Georgeta Hategan"'

1. A general approach to indole-7-yl derivatives of isoxazole, oxadiazole, thiadiazole and pyrazole

Author

Wayne E. Zeller, Alex S. Kiselyov, Jasvinder A. Singh, Alexandre M. Polozov, Georgeta Hategan, and Hua Cao

Subjects
Indole test, Chemistry, Organic Chemistry, Oxadiazole, Phosphoramides, Pyrazole, Biochemistry, chemistry.chemical_compound, Amide, Drug Discovery, Organic chemistry, Molecule, Isoxazole, Derivatization
Abstract

Isosteric replacement of the α,β-unsaturated amide at the C-7 position of indoles with a diverse set of five-membered amino-heterocycles including isoxazole, oxadiazole, thiadiazole and pyrazole followed by subsequent derivatization of the heterocyclic amino group to yield amides, sulfonamides and phosphoramides is described. Distinctive features of these procedures include the versatility and robust nature of the synthetic steps along with the high yields of the targeted molecules.

Published
2010

2. Structure−Activity Relationship Studies Leading to the Identification of (2E)-3-[l-[(2,4-Dichlorophenyl)methyl]-5-fluoro-3-methyl-lH-indol-7-yl]-N-[(4,5-dichloro-2-thienyl)sulfonyl]-2-propenamide (DG-041), a Potent and Selective Prostanoid EP3 Receptor Antagonist, as a Novel Antiplatelet Agent That Does Not Prolong Bleeding

Author

Margret Thorsteinnsdottir, Alex S. Kiselyov, Gudmundur Sigthorsson, Rama K. Mishra, Jose Ramirez, Peng Yu, Nian Zhou, Jun Zhang, Emmanuel Onua, Mark E. Gurney, Georgeta Hategan, Thorkell Andresson, David E. Zembower, Wayne Zeller, Jasbir Singh, and Alex Polozov

Subjects
Sulfonyl, chemistry.chemical_classification, Stereochemistry, Antagonist, Prostanoid, Chemical synthesis, Adenosine diphosphate, chemistry.chemical_compound, chemistry, Drug Discovery, medicine, Molecular Medicine, Structure–activity relationship, lipids (amino acids, peptides, and proteins), Prostaglandin E2, Pharmacophore, medicine.drug
Abstract

The EP3 receptor on the platelet mediates prostaglandin E2 potentiation of thrombogenic coagonists including collagen and adenosine diphosphate (ADP). A pharmacophore driven approach led to the identification of diverse peri-substituted heterocycles as potent and selective EP3 receptor antagonists. A simultaneous chemical optimization and druglike assessment of prioritized molecules converged on a lead compound 50 (DG-041) that displayed favorable in vitro and functional activities as an inhibitor of human platelet aggregation. This agent is currently in human clinical trials for the treatment of atherothrombosis.

Published
2009

3. Heterocyclic 1,7-disubstituted indole sulfonamides are potent and selective human EP3 receptor antagonists

Author

Mark E. Gurney, Guðrún Halldorsdottir, Wayne Zeller, Georgeta Hategan, Hua Cao, Jasbir Singh, Alexandre M. Polozov, Jose Ramirez, Rama K. Mishra, Þorkell Andrésson, and Alex S. Kiselyov

Subjects
Models, Molecular, Indoles, Stereochemistry, Clinical Biochemistry, Pharmaceutical Science, Crystallography, X-Ray, Biochemistry, Structure-Activity Relationship, Heterocyclic Compounds, Drug Discovery, Humans, Receptors, Prostaglandin E, Platelet, Receptor, Molecular Biology, chemistry.chemical_classification, Indole test, Sulfonamides, Dose-Response Relationship, Drug, Molecular Structure, Bicyclic molecule, Organic Chemistry, Stereoisomerism, Ligand (biochemistry), In vitro, Sulfonamide, chemistry, Drug Design, Receptors, Prostaglandin E, EP3 Subtype, Molecular Medicine, Pharmacophore
Abstract

We have developed a pharmacophore model for the EP(3) receptor antagonists based on its endogenous ligand PGE(2). This ligand-based design yielded a series of novel peri-substituted [4.3.0] bicyclic aromatics featuring 1-alklyaryl 7-heterocyclic sulfonamide substituents. The synthesized molecules are potent antagonists of human EP(3) receptor in vitro and show inhibition of rat platelets aggregation. Optimized derivatives display high selectivity over IP, FP, and other EP receptor panels.

Published
2009

4. Design and synthesis of potent, orally active, inhibitors of carboxypeptidase U (TAFIa)

Author

Peng Yu, Aukrust Inger Reidun F, Djordje Musil, Kjetil H. Holm, Marcel Sandberg, Herb Anderson, Carita Nordén, Georgeta Hategan, Neset Siren M, Marcel Linschoten, Susanne Trumpp-Kallmeyer, Louise Tottie, Rune Ringom, John Thurmond, and Polla Magnus

Subjects
Carboxypeptidase B2, Carboxypeptidase U, Stereochemistry, Carboxylic acid, Clinical Biochemistry, Administration, Oral, Biological Availability, Pharmaceutical Science, Biochemistry, Chemical synthesis, Inhibitory Concentration 50, Structure-Activity Relationship, chemistry.chemical_compound, Drug Discovery, Humans, Enzyme Inhibitors, Guanidine, 3-Mercaptopropionic Acid, Molecular Biology, chemistry.chemical_classification, biology, Molecular Mimicry, Organic Chemistry, In vitro, Enzyme, Orally active, chemistry, Enzyme inhibitor, Drug Design, biology.protein, Molecular Medicine
Abstract

A series of 3-mercapto-propionic acid derivatives that function as reversible inhibitors of carboxypeptidase U have been prepared. We present a successful design strategy using cyclic, low basicity guanidine mimetics resulting in potent, selective and bioavailable inhibitors of carboxypeptidase U (TAFIa).

Published
2004

6. Structure-activity relationship studies leading to the identification of (2E)-3-[l-[(2,4-dichlorophenyl)methyl]-5-fluoro-3-methyl-lH-indol-7-yl]-N-[(4,5-dichloro-2-thienyl)sulfonyl]-2-propenamide (DG-041), a potent and selective prostanoid EP3 receptor antagonist, as a novel antiplatelet agent that does not prolong bleeding

Author

Jasbir, Singh, Wayne, Zeller, Nian, Zhou, Georgeta, Hategan, Rama K, Mishra, Alex, Polozov, Peng, Yu, Emmanuel, Onua, Jun, Zhang, José L, Ramírez, Gudmundur, Sigthorsson, Margret, Thorsteinnsdottir, Alex S, Kiselyov, David E, Zembower, Thorkell, Andrésson, and Mark E, Gurney

Subjects
Acrylamides, Molecular Structure, Platelet Aggregation, Hemorrhage, Stereoisomerism, Ligands, Structure-Activity Relationship, Drug Discovery, Receptors, Prostaglandin E, EP3 Subtype, Humans, Receptors, Prostaglandin E, Sulfones, Blood Coagulation, Platelet Aggregation Inhibitors
Abstract

The EP(3) receptor on the platelet mediates prostaglandin E(2) potentiation of thrombogenic coagonists including collagen and adenosine diphosphate (ADP). A pharmacophore driven approach led to the identification of diverse peri-substituted heterocycles as potent and selective EP(3) receptor antagonists. A simultaneous chemical optimization and druglike assessment of prioritized molecules converged on a lead compound 50 (DG-041) that displayed favorable in vitro and functional activities as an inhibitor of human platelet aggregation. This agent is currently in human clinical trials for the treatment of atherothrombosis.

Published
2009

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