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AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity.
The mammalian target of rapamycin (mTOR) kinase forms two multiprotein complexes, mTORC1 and mTORC2, which regulate cell growth, cell survival, and autophagy. Allosteric inhibitors of mTORC1, such asExpand
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  • Open Access
Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: the discovery of AZD8055 and AZD2014.
The optimization of a potent and highly selective series of dual mTORC1 and mTORC2 inhibitors is described. An initial focus on improving cellular potency whilst maintaining or improving other keyExpand
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Key aspects of the Novartis compound collection enhancement project for the compilation of a comprehensive chemogenomics drug discovery screening collection.
The NIBR (Novartis Institutes for BioMedical Research) compound collection enrichment and enhancement project integrates corporate internal combinatorial compound synthesis and external compoundExpand
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The discovery and optimisation of pyrido[2,3-d]pyrimidine-2,4-diamines as potent and selective inhibitors of mTOR kinase.
We describe a novel series of potent inhibitors of the kinase activity of mTOR. The compounds display good selectivity relative to other PI3K-related kinase family members and, in cellular assays,Expand
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Identification and optimisation of novel and selective small molecular weight kinase inhibitors of mTOR.
A pharmacophore mapping approach, derived from previous experience of PIKK family enzymes, was used to identify a hit series of selective inhibitors of the mammalian target of rapamycin (mTOR).Expand
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Synthesis of C-19-functionalized 1alpha-hydroxyvitamin D(2) analogues via ring-closing metathesis.
A heteroatom-tethered regioselective ring-closing metathesis reaction was used for the C-19 functionalization of 1alpha-hydroxy-5,6-trans-vitamin D(2) analogues. Applications of the reaction to formExpand
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Abstract 917: AZD2014, a dual mTORC1 and mTORC2 inhibitor is differentiated from allosteric inhibitors of mTORC1 in ER+ breast cancer
The mammalian target of rapamycin (mTOR) is a major sensor of nutrients and energy and is part of two multiprotein complexes mTORC1 and mTORC2. mTOR activation is widely reported in cancer and isExpand
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Reactions of Allenyltri-n-butylstannane with Halides of Phosphorus, Arsenic, Antimony, Germanium, Tin, and Boron. Preparation of Propargylic and/or Allenic Derivatives
The reaction of allenyltri-n-butylstannane with a phosphorus or arsenic trihalide and with germanium tetrachloride gave the corresponding propargylic halophosphine, arsine, or germane. When they wereExpand
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Preparation of soluble polymeric supports with a functional group for liquid-phase organic synthesis
Soluble copolymers of styrene with functional groups were prepared by radical co-polymerization of styrene with various substituted styrenes. They were characterized by NMR spectroscopy and theirExpand
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Directed ring-closing metathesis of trienes by silyl substitution
Abstract A synthetic strategy for ‘disarming’ a terminal alkene by substitution with a bulky silyl blocking group has been developed. In a series of model studies, sequential selective ring-closingExpand
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