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Your search keyword '"Mordaunt JE"' showing total 6 results
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6 results on '"Mordaunt JE"'

1. Discovery of epigenetic regulator I-BET762: lead optimization to afford a clinical candidate inhibitor of the BET bromodomains.

Author

Mirguet O, Gosmini R, Toum J, Clément CA, Barnathan M, Brusq JM, Mordaunt JE, Grimes RM, Crowe M, Pineau O, Ajakane M, Daugan A, Jeffrey P, Cutler L, Haynes AC, Smithers NN, Chung CW, Bamborough P, Uings IJ, Lewis A, Witherington J, Parr N, Prinjha RK, and Nicodème E

Subjects
Animals, Anti-Inflammatory Agents chemical synthesis, Anti-Inflammatory Agents pharmacokinetics, Anti-Inflammatory Agents pharmacology, Antineoplastic Agents chemical synthesis, Antineoplastic Agents pharmacokinetics, Apolipoprotein A-I biosynthesis, Benzodiazepines chemical synthesis, Benzodiazepines pharmacokinetics, Cell Cycle Proteins, Dogs, Epigenesis, Genetic, Humans, Macaca fascicularis, Mice, Models, Molecular, Permeability, Protein Structure, Tertiary, Rats, Stereoisomerism, Structure-Activity Relationship, Antineoplastic Agents pharmacology, Benzodiazepines pharmacology, Nuclear Proteins antagonists & inhibitors, Transcription Factors antagonists & inhibitors
Abstract

The bromo and extra C-terminal domain (BET) family of bromodomains are involved in binding epigenetic marks on histone proteins, more specifically acetylated lysine residues. This paper describes the discovery and structure-activity relationships (SAR) of potent benzodiazepine inhibitors that disrupt the function of the BET family of bromodomains (BRD2, BRD3, and BRD4). This work has yielded a potent, selective compound I-BET762 that is now under evaluation in a phase I/II clinical trial for nuclear protein in testis (NUT) midline carcinoma and other cancers.

Published
2013
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2. Synthesis and evaluation of novel alpha-amino cyclic boronates as inhibitors of HCV NS3 protease.

Author

Li X, Zhang YK, Liu Y, Ding CZ, Li Q, Zhou Y, Plattner JJ, Baker SJ, Qian X, Fan D, Liao L, Ni ZJ, White GV, Mordaunt JE, Lazarides LX, Slater MJ, Jarvest RL, Thommes P, Ellis M, Edge CM, Hubbard JA, Somers D, Rowland P, Nassau P, McDowell B, Skarzynski TJ, Kazmierski WM, Grimes RM, Wright LL, Smith GK, Zou W, Wright J, and Pennicott LE

Subjects
Boronic Acids pharmacology, Boronic Acids therapeutic use, Catalytic Domain, Drug Design, Hepacivirus enzymology, Molecular Structure, Serine chemistry, Structure-Activity Relationship, Boronic Acids chemical synthesis, Hepacivirus drug effects, Viral Nonstructural Proteins antagonists & inhibitors
Abstract

We have designed and synthesized a novel series of alpha-amino cyclic boronates and incorporated them successfully in several acyclic templates at the P1 position. These compounds are inhibitors of the HCV NS3 serine protease, and structural studies show that they inhibit the NS3 protease by trapping the Ser-139 hydroxyl group in the active site. Synthetic methodologies and SARs of this series of compounds are described., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Published
2010
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3. Structure- and property-based design of factor Xa inhibitors: pyrrolidin-2-ones with acyclic alanyl amides as P4 motifs.

Author

Young RJ, Campbell M, Borthwick AD, Brown D, Burns-Kurtis CL, Chan C, Convery MA, Crowe MC, Dayal S, Diallo H, Kelly HA, King NP, Kleanthous S, Mason AM, Mordaunt JE, Patel C, Pateman AJ, Senger S, Shah GP, Smith PW, Watson NS, Weston HE, and Zhou P

Subjects
Anticoagulants chemical synthesis, Anticoagulants chemistry, Anticoagulants metabolism, Anticoagulants pharmacology, Antithrombin III chemistry, Antithrombin III metabolism, Binding Sites, Crystallography, X-Ray, Factor Xa chemistry, Factor Xa metabolism, Models, Molecular, Molecular Structure, Structure-Activity Relationship, Alanine chemistry, Amides chemistry, Antithrombin III chemical synthesis, Antithrombin III pharmacology, Drug Design, Pyrroles chemistry
Abstract

Structure-based drug design was exploited in the synthesis of 3-(6-chloronaphth-2-ylsulfonyl)aminopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating an alanylamide P4 group with acyclic tertiary amide termini. Optimized hydrophobic contacts of one amide substituent in P4 were complemented by hydrophobicity-modulating features in the second, producing potent fXa inhibitors including examples with excellent anticoagulant properties.

Published
2006
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4. Oxytocin antagonists as potential therapeutic agents for the treatment of preterm labour.

Author

Allen MJ, Livermore DG, and Mordaunt JE

Subjects
Animals, Female, Humans, Obstetric Labor, Premature epidemiology, Oxytocin chemistry, Peptides chemistry, Peptides pharmacology, Pregnancy, Structure-Activity Relationship, Uterus anatomy & histology, Uterus drug effects, Obstetric Labor, Premature drug therapy, Oxytocin antagonists & inhibitors, Oxytocin metabolism
Published
2006
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5. Identification of potent and selective oxytocin antagonists. Part 2: further investigation of benzofuran derivatives.

Author

Wyatt PG, Allen MJ, Chilcott J, Gardner CJ, Livermore DG, Mordaunt JE, Nerozzi F, Patel M, Perren MJ, Weingarten GG, Shabbir S, Woollard PM, and Zhou P

Subjects
Animals, Benzofurans pharmacokinetics, Benzofurans pharmacology, Drug Design, Female, Humans, Kinetics, Models, Molecular, Molecular Conformation, Rats, Receptors, Oxytocin antagonists & inhibitors, Receptors, Oxytocin metabolism, Structure-Activity Relationship, Uterine Contraction drug effects, Benzofurans chemical synthesis, Oxytocin antagonists & inhibitors
Abstract

The paper covers continuing efforts to discover novel, potent and selective oxytocin antagonists. Further benzofuran derivatives with potent oxytocin antagonist activity and good pharmacokinetic parameters are reported. Efforts to improve the in vivo activity of the series are described.

Published
2002
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6. Identification of potent and selective oxytocin antagonists. Part 1: indole and benzofuran derivatives.

Author

Wyatt PG, Allen MJ, Chilcott J, Foster A, Livermore DG, Mordaunt JE, Scicinski J, and Woollard PM

Subjects
Animals, Benzofurans chemistry, Benzofurans pharmacokinetics, Benzofurans pharmacology, Biological Availability, Dogs, Drug Design, Humans, Indoles chemistry, Indoles pharmacokinetics, Indoles pharmacology, Kinetics, Models, Molecular, Molecular Conformation, Structure-Activity Relationship, Benzofurans chemical synthesis, Indoles chemical synthesis, Oxytocin antagonists & inhibitors, Receptors, Oxytocin antagonists & inhibitors
Abstract

Studies to discover novel, potent and selective oxytocin antagonists are reported. Combinatorial libraries designed to find novel replacements of fragments of oxytocin antagonist L-371,257, identified pyrimidine, thiazole, indole and benzofuran as potential alternatives to the benzoic acid moiety of L-371,257. Additional investigations identified indole and benzofuran derivatives with potent oxytocin antagonist activity.

Published
2002
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