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Your search keyword '"Halley, Frank"' showing total 11 results
Start Over Author "Halley, Frank" Journal journal of medicinal chemistry
11 results on '"Halley, Frank"'

1. Discovery of 6-(2,4-Dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid (SAR439859), a Potent and Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen-Receptor-Positive Breast Cancer

Author

El-Ahmad, Youssef, primary, Tabart, Michel, additional, Halley, Frank, additional, Certal, Victor, additional, Thompson, Fabienne, additional, Filoche-Rommé, Bruno, additional, Gruss-Leleu, Florence, additional, Muller, Claire, additional, Brollo, Maurice, additional, Fabien, Laurence, additional, Loyau, Véronique, additional, Bertin, Luc, additional, Richepin, Patrick, additional, Pilorge, Fabienne, additional, Desmazeau, Pascal, additional, Girardet, Chrystelle, additional, Beccari, Sylvie, additional, Louboutin, Audrey, additional, Lebourg, Gilles, additional, Le-Roux, Jacques, additional, Terrier, Corinne, additional, Vallée, François, additional, Steier, Valérie, additional, Mathieu, Magali, additional, Rak, Alexey, additional, Abecassis, Pierre-Yves, additional, Vicat, Pascale, additional, Benard, Tsiala, additional, Bouaboula, Monsif, additional, Sun, Fangxian, additional, Shomali, Maysoun, additional, Hebert, Andrew, additional, Levit, Mikhail, additional, Cheng, Hong, additional, Courjaud, Albane, additional, Ginesty, Celine, additional, Perrault, Christelle, additional, Garcia-Echeverria, Carlos, additional, McCort, Gary, additional, and Schio, Laurent, additional

Published
2019
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2. Discovery of 6-(2,4-Dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid (SAR439859), a Potent and Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen-Receptor-Positive Breast Cancer

Author

El-Ahmad, Youssef, Tabart, Michel, Halley, Frank, Certal, Victor, Thompson, Fabienne, Filoche-Rommé, Bruno, Gruss-Leleu, Florence, Muller, Claire, Brollo, Maurice, Fabien, Laurence, Loyau, Véronique, Bertin, Luc, Richepin, Patrick, Pilorge, Fabienne, Desmazeau, Pascal, Girardet, Chrystelle, Beccari, Sylvie, Louboutin, Audrey, Lebourg, Gilles, Le-Roux, Jacques, Terrier, Corinne, Vallée, François, Steier, Valérie, Mathieu, Magali, Rak, Alexey, Abecassis, Pierre-Yves, Vicat, Pascale, Benard, Tsiala, Bouaboula, Monsif, Sun, Fangxian, Shomali, Maysoun, Hebert, Andrew, Levit, Mikhail, Cheng, Hong, Courjaud, Albane, Ginesty, Celine, Perrault, Christelle, Garcia-Echeverria, Carlos, McCort, Gary, and Schio, Laurent

Abstract

More than 75% of breast cancers are estrogen receptor alpha (ERα) positive (ER+), and resistance to current hormone therapies occurs in one-third of ER+ patients. Tumor resistance is still ERα-dependent, but mutations usually confer constitutive activation to the hormone receptor, rendering ERα modulator drugs such as tamoxifen and aromatase inhibitors ineffective. Fulvestrant is a potent selective estrogen receptor degrader (SERD), which degrades the ERα receptor in drug-resistant tumors and has been approved for the treatment of hormone-receptor-positive metastatic breast cancer following antiestrogen therapy. However, fulvestrant shows poor pharmacokinetic properties in human, low solubility, weak permeation, and high metabolism, limiting its administration to inconvenient intramuscular injections. This Drug Annotation describes the identification and optimization of a new series of potent orally available SERDs, which led to the discovery of 6-(2,4-dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid (43d), showing promising antitumor activity in breast cancer mice xenograft models and whose properties warranted clinical evaluation.

Published
2020
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3. Discovery and Optimization of Pyrimidone Indoline Amide PI3Kβ Inhibitors for the Treatment of Phosphatase and Tensin Homologue (PTEN)-Deficient Cancers

Author

Certal, Victor, primary, Carry, Jean-Christophe, additional, Halley, Frank, additional, Virone-Oddos, Angela, additional, Thompson, Fabienne, additional, Filoche-Rommé, Bruno, additional, El-Ahmad, Youssef, additional, Karlsson, Andreas, additional, Charrier, Véronique, additional, Delorme, Cécile, additional, Rak, Alexey, additional, Abecassis, Pierre-Yves, additional, Amara, Céline, additional, Vincent, Loïc, additional, Bonnevaux, Hélène, additional, Nicolas, Jean-Paul, additional, Mathieu, Magali, additional, Bertrand, Thomas, additional, Marquette, Jean-Pierre, additional, Michot, Nadine, additional, Benard, Tsiala, additional, Perrin, Marc-Antoine, additional, Lemaitre, Olivier, additional, Guerif, Stephane, additional, Perron, Sébastien, additional, Monget, Sylvie, additional, Gruss-Leleu, Florence, additional, Doerflinger, Gilles, additional, Guizani, Houlfa, additional, Brollo, Maurice, additional, Delbarre, Laurence, additional, Bertin, Luc, additional, Richepin, Patrick, additional, Loyau, Véronique, additional, Garcia-Echeverria, Carlos, additional, Lengauer, Christoph, additional, and Schio, Laurent, additional

Published
2014
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4. Discovery and Optimization of New Benzimidazole- and Benzoxazole-Pyrimidone Selective PI3Kβ Inhibitors for the Treatment of Phosphatase and TENsin homologue (PTEN)-Deficient Cancers

Author

Certal, Victor, primary, Halley, Frank, additional, Virone-Oddos, Angela, additional, Delorme, Cécile, additional, Karlsson, Andreas, additional, Rak, Alexey, additional, Thompson, Fabienne, additional, Filoche-Rommé, Bruno, additional, El-Ahmad, Youssef, additional, Carry, Jean-Christophe, additional, Abecassis, Pierre-Yves, additional, Lejeune, Pascale, additional, Vincent, Loic, additional, Bonnevaux, Hélène, additional, Nicolas, Jean-Paul, additional, Bertrand, Thomas, additional, Marquette, Jean-Pierre, additional, Michot, Nadine, additional, Benard, Tsiala, additional, Below, Peter, additional, Vade, Isabelle, additional, Chatreaux, Fabienne, additional, Lebourg, Gilles, additional, Pilorge, Fabienne, additional, Angouillant-Boniface, Odile, additional, Louboutin, Audrey, additional, Lengauer, Christoph, additional, and Schio, Laurent, additional

Published
2012
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6. Selective ETAAntagonists. 5. Discovery and Structure−Activity Relationships of Phenoxyphenylacetic Acid Derivatives

Author

Astles, Peter C., primary, Brown, Thomas J., additional, Halley, Frank, additional, Handscombe, Caroline M., additional, Harris, Neil V., additional, Majid, Tahir N., additional, McCarthy, Clive, additional, McLay, Iain M., additional, Morley, Andrew, additional, Porter, Barry, additional, Roach, Alan G., additional, Sargent, Carol, additional, Smith, Christopher, additional, and Walsh, Roger J. A., additional

Published
2000
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7. Discovery and Optimizationof Pyrimidone Indoline Amide PI3Kβ Inhibitors for the Treatmentof Phosphatase and Tensin Homologue (PTEN)-Deficient Cancers.

Author

Certal, Victor, Carry, Jean-Christophe, Halley, Frank, Virone-Oddos, Angela, Thompson, Fabienne, Filoche-Rommé, Bruno, El-Ahmad, Youssef, Karlsson, Andreas, Charrier, Véronique, Delorme, Cécile, Rak, Alexey, Abecassis, Pierre-Yves, Amara, Céline, Vincent, Loïc, Bonnevaux, Hélène, Nicolas, Jean-Paul, Mathieu, Magali, Bertrand, Thomas, Marquette, Jean-Pierre, and Michot, Nadine

Published
2014
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8. Selective Endothelin A Receptor Antagonists. 4. Discovery and Structure−Activity Relationships of Stilbene Acid and Alcohol Derivatives

Author

Astles, Peter C., primary, Brown, Thomas J., additional, Halley, Frank, additional, Handscombe, Caroline M., additional, Harris, Neil V., additional, McCarthy, Clive, additional, McLay, Iain M., additional, Lockey, Peter, additional, Majid, Tahir, additional, Porter, Barry, additional, Roach, Alan G., additional, Smith, Christopher, additional, and Walsh, Roger, additional

Published
1998
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10. Discovery and Optimizationof New Benzimidazole- andBenzoxazole-Pyrimidone Selective PI3Kβ Inhibitors for the Treatmentof Phosphatase and TENsin homologue (PTEN)-Deficient Cancers.

Author

Certal, Victor, Halley, Frank, Virone-Oddos, Angela, Delorme, Cécile, Karlsson, Andreas, Rak, Alexey, Thompson, Fabienne, Filoche-Rommé, Bruno, El-Ahmad, Youssef, Carry, Jean-Christophe, Abecassis, Pierre-Yves, Lejeune, Pascale, Vincent, Loic, Bonnevaux, Hélène, Nicolas, Jean-Paul, Bertrand, Thomas, Marquette, Jean-Pierre, Michot, Nadine, Benard, Tsiala, and Below, Peter

Subjects
*CANCER treatment, *BENZIMIDAZOLES, *PYRIMIDINES, *PHOSPHATASE inhibitors, *PHOSPHOINOSITIDE-dependent kinase-1, *CLINICAL trials, *CARCINOGENESIS, *PHARMACOKINETICS, *PHARMACEUTICAL research, *TUMOR growth
Abstract

Most of the phosphoinositide-3 kinase (PI3K) kinase inhibitorscurrently in clinical trials for cancer treatment exhibit pan PI3Kisoform profiles. Single PI3K isoforms differentially control tumorigenesis,and PI3Kβ has emerged as the isoform involved in the tumorigenicityof PTEN-deficient tumors. Herein we describe the discovery and optimizationof a new series of benzimidazole- and benzoxazole-pyrimidones as smallmolecular mass PI3Kβ-selective inhibitors. Starting with compound 5obtained from a one-pot reaction via a novel intermediate 1, medicinal chemistry optimization led to the discovery ofcompound 8, which showed a significant activity and selectivityfor PI3Kβ and adequate in vitro pharmacokinetic properties.The X-ray costructure of compound 8in PI3Kδ showedkey interactions and structural features supporting the observed PI3Kβisoform selectivity. Compound 8achieved sustained targetmodulation and tumor growth delay at well tolerated doses when administeredorally to SCID mice implanted with PTEN-deficient human tumor xenografts. [ABSTRACT FROM AUTHOR]

Published
2012
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11. Discovery of 6-(2,4-Dichlorophenyl)-5-[4-[(3 S )-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7 H -benzo[7]annulene-2-carboxylic acid (SAR439859), a Potent and Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen-Receptor-Positive Breast Cancer.

Author

El-Ahmad Y, Tabart M, Halley F, Certal V, Thompson F, Filoche-Rommé B, Gruss-Leleu F, Muller C, Brollo M, Fabien L, Loyau V, Bertin L, Richepin P, Pilorge F, Desmazeau P, Girardet C, Beccari S, Louboutin A, Lebourg G, Le-Roux J, Terrier C, Vallée F, Steier V, Mathieu M, Rak A, Abecassis PY, Vicat P, Benard T, Bouaboula M, Sun F, Shomali M, Hebert A, Levit M, Cheng H, Courjaud A, Ginesty C, Perrault C, Garcia-Echeverria C, McCort G, and Schio L

Subjects
Animals, Breast Neoplasms metabolism, Crystallography, X-Ray, Dogs, Drug Resistance, Neoplasm, Female, Half-Life, High-Throughput Screening Assays, Humans, Ligands, Mice, Models, Molecular, Rats, Receptors, Estrogen drug effects, Selective Estrogen Receptor Modulators pharmacokinetics, Selective Estrogen Receptor Modulators pharmacology, Structure-Activity Relationship, Xenograft Model Antitumor Assays, Breast Neoplasms drug therapy, Drug Discovery methods, Pyrrolidines chemical synthesis, Pyrrolidines pharmacology, Receptors, Estrogen metabolism, Selective Estrogen Receptor Modulators therapeutic use
Abstract

More than 75% of breast cancers are estrogen receptor alpha (ERα) positive (ER+), and resistance to current hormone therapies occurs in one-third of ER+ patients. Tumor resistance is still ERα-dependent, but mutations usually confer constitutive activation to the hormone receptor, rendering ERα modulator drugs such as tamoxifen and aromatase inhibitors ineffective. Fulvestrant is a potent selective estrogen receptor degrader (SERD), which degrades the ERα receptor in drug-resistant tumors and has been approved for the treatment of hormone-receptor-positive metastatic breast cancer following antiestrogen therapy. However, fulvestrant shows poor pharmacokinetic properties in human, low solubility, weak permeation, and high metabolism, limiting its administration to inconvenient intramuscular injections. This Drug Annotation describes the identification and optimization of a new series of potent orally available SERDs, which led to the discovery of 6-(2,4-dichlorophenyl)-5-[4-[(3 S )-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7 H -benzo[7]annulene-2-carboxylic acid ( 43d ), showing promising antitumor activity in breast cancer mice xenograft models and whose properties warranted clinical evaluation.

Published
2020
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