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Your search keyword '"Herranz, Rosario"' showing total 15 results
Start Over Author "Herranz, Rosario" Journal journal of medicinal chemistry
15 results on '"Herranz, Rosario"'

1. Combination of Molecular Modeling, Site-Directed Mutagenesis, and SAR Studies To Delineate the Binding Site of Pyridopyrimidine Antagonists on the Human CCK1 Receptor

Author

Martín-Martínez, Mercedes, primary, Marty, Anne, additional, Jourdan, Maud, additional, Escrieut, Chantal, additional, Archer, Elodie, additional, González-Muñiz, Rosario, additional, García-López, M. Teresa, additional, Maigret, Bernard, additional, Herranz, Rosario, additional, and Fourmy, Daniel, additional

Published
2005
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2. Synthesis, Conformational Analysis, and Cytotoxicity of Conformationally Constrained Aplidine and Tamandarin A Analogues Incorporating a Spirolactam β-Turn Mimetic

Author

Gutiérrez-Rodríguez, Marta, primary, Martín-Martínez, Mercedes, additional, García-López, M. Teresa, additional, Herranz, Rosario, additional, Cuevas, Félix, additional, Polanco, Concepción, additional, Rodríguez-Campos, Ignacio, additional, Manzanares, Ignacio, additional, Cárdenas, Francisco, additional, Feliz, Miguel, additional, Lloyd-Williams, Paul, additional, and Giralt, Ernest, additional

Published
2004
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4. 5-(Tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-Based Potent and Selective CCK1 Receptor Antagonists: Structure−Activity Relationship Studies on the Central 1,3-Dioxoperhydropyrido[1,2-c]pyrimidine Scaffold

Author

Bartolomé-Nebreda, José M., primary, García-López, M. Teresa, additional, González-Muñiz, Rosario, additional, Cenarruzabeitia, Edurne, additional, Latorre, Miriam, additional, Del Río, Joaquín, additional, and Herranz, Rosario, additional

Published
2001
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5. 5-(Tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-Based Potent and Selective CCK1 Receptor Antagonists: Structure−Activity Relationship Studies on the Substituent at N2-Position

Author

Bartolomé-Nebreda, José M., primary, Patiño-Molina, Rosario, additional, Martín-Martínez, Mercedes, additional, Gómez-Monterrey, Isabel, additional, García-López, M. Teresa, additional, González-Muñiz, Rosario, additional, Cenarruzabeitia, Edurne, additional, Latorre, Miriam, additional, Río, Joaquín Del, additional, and Herranz, Rosario, additional

Published
2001
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7. 5-(Tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-Based Potent and Selective CCK1 Receptor Antagonists: Structural Modifications at the Tryptophan Domain

Author

Bartolomé-Nebreda, José M., primary, Gómez-Monterrey, Isabel, additional, García-López, M. Teresa, additional, González-Muñiz, Rosario, additional, Martín-Martínez, Mercedes, additional, Ballaz, Santiago, additional, Cenarruzabeitia, Edurne, additional, LaTorre, Miriam, additional, Del Río, Joaquín, additional, and Herranz, Rosario, additional

Published
1999
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8. Synthesis and Stereochemical Structure−Activity Relationships of 1,3-Dioxoperhydropyrido[1,2-c]pyrimidine Derivatives: Potent and Selective Cholecystokinin-A Receptor Antagonists

Author

Martín-Martínez, Mercedes, primary, Bartolomé-Nebreda, José M., additional, Gómez-Monterrey, Isabel, additional, González-Muñiz, Rosario, additional, García-López, M. Teresa, additional, Ballaz, Santiago, additional, Barber, Ana, additional, Fortuño, Ana, additional, Del Río, Joaquín, additional, and Herranz, Rosario, additional

Published
1997
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14. Synthesis, conformational analysis, and cytotoxicity of conformationally constrained aplidine and tamandarin A analogues incorporating a spirolactam beta-turn mimetic.

Author

Gutiérrez-Rodríguez M, Martín-Martínez M, García-López MT, Herranz R, Cuevas F, Polanco C, Rodríguez-Campos I, Manzanares I, Cárdenas F, Feliz M, Lloyd-Williams P, and Giralt E

Subjects
Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Depsipeptides chemistry, Depsipeptides pharmacology, Drug Screening Assays, Antitumor, Humans, Lactams chemistry, Lactams pharmacology, Magnetic Resonance Spectroscopy, Models, Molecular, Peptides, Cyclic, Protein Structure, Secondary, Structure-Activity Relationship, Antineoplastic Agents chemical synthesis, Depsipeptides chemical synthesis, Lactams chemical synthesis
Abstract

With the aim of studying the contribution of the beta II turn conformation at the side chain of didemnins to the bioactive conformation responsible for their antitumoral activity, conformationally restricted analogues of aplidine and tamandarin A, where the side chain dipeptide Pro8-N-Me-d-Leu7 is replaced with the spirolactam beta II turn mimetic (5R)-7-[(1R)-1-carbonyl-3-methylbutyl]-6-oxo-1,7-diazaspiro[4.4]nonane, were prepared. Additionally, restricted analogues, where the aplidine (pyruvyl9) or tamandarin A [(S)-Lac9] acyl groups are replaced with the isobutyryl, Boc, and 2-methylacryloyl groups, were also prepared. These structural modifications were detrimental to cytotoxic activity, leading to a decrease of 1-2 orders of magnitude with respect to that exhibited by aplidine and tamandarin A. The conformational analysis of one of these spirolactam aplidine analogues, by NMR and molecular modeling methods, showed that the conformational restriction caused by the spirolactam does not produce significant changes in the overall conformation of aplidine, apart from preferentially stabilizing the trans rotamer at the pyruvyl9-spirolactam amide bond, whereas in aplidine both cis and trans rotamers at the pyruvyl9-Pro8 amide bond are more or less equally stabilized. These results seem to indicate a preference for the cis form at that amide bond in the bioactive conformation of aplidine. The significant influence of this cis/trans isomerism upon the cytotoxicity suggests a possible participation of a peptidylprolyl cis/trans isomerase in the mechanism of action of aplidine.

Published
2004
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15. 5-(tryptophylamino)-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-based cholecystokinin receptor antagonists: reversal of CCK1 receptor subtype selectivity toward CCK2 receptors.

Author

Muñoz-Ruiz P, García-López MT, Cenarruzabeitia E, Del Río J, Dufresne M, Foucaud M, Fourmy D, and Herranz R

Subjects
Amylases metabolism, Animals, Binding, Competitive, COS Cells, Cerebral Cortex drug effects, Cerebral Cortex metabolism, Humans, In Vitro Techniques, Pancreas drug effects, Pancreas metabolism, Pyridines chemistry, Pyridines pharmacology, Pyrimidines chemistry, Pyrimidines pharmacology, Radioligand Assay, Rats, Receptors, CCR1, Stereoisomerism, Structure-Activity Relationship, Pyridines chemical synthesis, Pyrimidines chemical synthesis, Receptor, Cholecystokinin B antagonists & inhibitors, Receptors, Chemokine antagonists & inhibitors
Abstract

With the aim of reversing selectivity or antagonist/agonist functionality in the 5-(tryptophylamino)-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-derived potent and highly selective CCK(1) antagonists, a series of 4-benzyl and 4-methyl derivatives have been synthesized. Whereas the introduction of the benzyl group led, in all cases, to complete loss of the binding affinity, the incorporation of the methyl group gave a different result depending on the stereochemistry of the 1,3-dioxoperhydropyrido[1,2-c]pyrimidine scaffold. Thus, the introduction of the methyl group into the (4aS,5R)-diastereoisomers, giving a (4S)-configuration, produced a 3-fold increase in the CCK(1) binding potency and selectivity. However, the same structural manipulation in the opposite (4aR,5S)-stereochemistry, leading to a (4R,4aR,5S)-configuration, produced reversal of the selectivity for CCK(1) to the CCK(2) receptors. The replacement of the Boc group at the tryptophan moiety by a 2-adamantyloxycarbonyl group also contributed to that reversal. The resulting compounds displayed moderate CCK(2) antagonist activity in rat and human receptors, and a very small partial agonist effect on the production of inositol phosphate in COS-7 cells transfected with the wild-type human CCK(2) receptor.

Published
2004
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