A5074826873- Chemical Synthesis and Analysis
- Asymmetric Synthesis and Catalysis
- Cancer therapeutics and mechanisms
- Synthesis and pharmacology of benzodiazepine derivatives
- Synthesis and Catalytic Reactions
- Chemical Synthesis and Reactions
- HIV/AIDS drug development and treatment
- Microbial Natural Products and Biosynthesis
- Synthetic Organic Chemistry Methods
- Synthesis and Biological Evaluation
- Cancer Treatment and Pharmacology
- PARP inhibition in cancer therapy
- Asymmetric Hydrogenation and Catalysis
- Synthesis of β-Lactam Compounds
- Pharmacogenetics and Drug Metabolism
- Boron Compounds in Chemistry
- Metabolomics and Mass Spectrometry Studies
- Bioactive Compounds and Antitumor Agents
- Fluorine in Organic Chemistry
- Cyclopropane Reaction Mechanisms
- DNA and Nucleic Acid Chemistry
- Radiopharmaceutical Chemistry and Applications
- Synthesis and biological activity
- Carbohydrate Chemistry and Synthesis
- Click Chemistry and Applications
Star Technology and Research (United States)
2004-2024
Merck & Co., Inc., Rahway, NJ, USA (United States)
1993-2022
University of Bath
2001-2016
Spirogen (United Kingdom)
2009
University of London
2009
Johnson & Johnson (United States)
2008
Johnson Matthey (United States)
2008
University College London
1996-2003
Yorkshire Cancer Research
2003
Cancer Research UK
2003
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDirect conversion of activated alcohols to azides using diphenyl phosphorazidate. A practical alternative Mitsunobu conditionsAndrew S. Thompson, Guy R. Humphrey, Anthony M. DeMarco, David J. Mathre, and Edward GrabowskiCite this: Org. Chem. 1993, 58, 22, 5886–5888Publication Date (Print):October 1, 1993Publication History Published online1 May 2002Published inissue 1 October...
A highly enantioselective and practical synthesis of the HIV-1 reverse transcriptase inhibitor efavirenz (1) is described. The proceeds in 62% overall yield seven steps from 4-chloroaniline (6) to give excellent chemical optical purity. novel, addition Li-cyclopropyl acetylide (4a) p-methoxybenzyl-protected ketoaniline 3a mediated by (1R,2S)-N-pyrrolidinylnorephedrine lithium alkoxide (5a) establishes stereogenic center target with a remarkable level stereocontrol.
Addition of lithium cyclopropylacetylide (RLi) to ArCOCF3 mediated by 1(R),2(S)-R2NCH(CH3)CH(Ph)OLi (ROLi; R2N = pyrrolidino) occurs with 50:1 enantioselectivity (Thompson, A. S. et al. Tetrahedron. Lett. 1995, 36, 8937). Low-temperature 6Li and 13C NMR spectroscopies reveal in THF be a dimer−tetramer mixture the alkoxide complex oligomers. Mixtures RLi ROLi afford stoichiometry-dependent mixtures 3:1, 2:2, 1:3 mixed tetramers. The dramatic improvements stereochemistry 1,2-additions caused...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRational design of a highly efficient irreversible DNA interstrand cross-linking agent based on the pyrrolobenzodiazepine ring systemD. Subhas Bose, Andrew S. Thompson, Jingshan Ching, John A. Hartley, Mark D. Berardini, Terence C. Jenkins, Stephen Neidle, Laurence H. Hurley, and David E. ThurstonCite this: J. Am. Chem. Soc. 1992, 114, 12, 4939–4941Publication Date (Print):June 1, 1992Publication History Published online1 May 2002Published inissue...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTotal synthesis of (-)-laurenyne. Use acetal-initiated cyclizations to prepare functionalized eight-membered cyclic ethersLarry E. Overman and Andrew S. ThompsonCite this: J. Am. Chem. Soc. 1988, 110, 7, 2248–2256Publication Date (Print):March 1, 1988Publication History Published online1 May 2002Published inissue 1 March 1988https://pubs.acs.org/doi/10.1021/ja00215a040https://doi.org/10.1021/ja00215a040research-articleACS PublicationsRequest reuse...
An efficient convergent synthesis of a homologous series C8-linked pyrrolobenzodiazepine dimers with remarkable DNA interstrand cross-linking activity and potent in vitro cytotoxicity is reported. The "amino thioacetal" cyclization procedure was used to produce the electrophilic DNA-interactive N10-C11 imine moiety during final synthetic step. In order construct key A-ring fragments (9a-d), versatile approach has been developed join two units vanillic acid alpha,omega-dihaloalkanes varying...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMilbemycin-avermectin studies. 5. Total synthesis of milbemycin .beta.3 and its C(12) epimerSteven R. Schow, Jonathan D. Bloom, Andrew S. Thompson, Kevin N. Winzenberg, Amos B. SmithCite this: J. Am. Chem. Soc. 1986, 108, 10, 2662–2674Publication Date (Print):May 1, 1986Publication History Published online1 May 2002Published inissue 1 1986https://pubs.acs.org/doi/10.1021/ja00270a027https://doi.org/10.1021/ja00270a027research-articleACS...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTotal synthesis of milbemycin .beta.3Amos B. Smith III, Steven R. Schow, Jonathan D. Bloom, Andrew S. Thompson, and Kevin N. WinzenbergCite this: J. Am. Chem. Soc. 1982, 104, 14, 4015–4018Publication Date (Print):July 1, 1982Publication History Published online1 May 2002Published inissue 1 July 1982https://pubs.acs.org/doi/10.1021/ja00378a045https://doi.org/10.1021/ja00378a045research-articleACS PublicationsRequest reuse permissionsArticle...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPreparation of eight-membered cyclic ethers by Lewis acid promoted acetal-alkene cyclizationsTodd A. Blumenkopf, Matthias Bratz, Armando Castaneda, Gary C. Look, Larry E. Overman, Domingo Rodriguez, and Andrew S. ThompsonCite this: J. Am. Chem. Soc. 1990, 112, 11, 4386–4399Publication Date (Print):May 1, 1990Publication History Published online1 May 2002Published inissue 1...
SJG-136 (1) is a sequence-selective DNA-interactive agent that about to enter phase II clinical trials. Using HPLC/MS-based methodology developed evaluate the binding of agents oligonucleotides varying length and sequence, we have demonstrated that, in addition previously known interstrand cross-link at Pu-GATC-Py sequences, 1 can form longer Pu-GAATC-Py an intrastrand both shorter Pu-GATG-Py Pu-GAATG-Py and, addition, monoalkylated adducts suitable PBD sites where neither intra- or...
Maclura pomifera agglutinin is a tetrameric plant seed lectin with high affinity for the tumor-associated T-antigen disaccharide, Galbeta1,3GalNAcalpha, and hence many O-linked glycopeptide structures. Unlike members of most families, it lacks both metal ions Cys residues. The structure its complex Galbeta1,3GalNAc was determined to 2.2 by first using multiwavelength anomalous diffraction lead derivative native protein, then molecular replacement unrefined as model solve complex. subunits...
Poly (ADP‐ribose) synthetase (PARP) is a nuclear enzyme activated by strand breaks in DNA, which are caused inter alia reactive oxygen species (ROS). Here we report on (i) new synthesis of water‐soluble and potent PARP inhibitor, 5‐aminoisoquinolinone (5‐AIQ) (ii) investigate the effects 5‐AIQ circulatory failure organ injury/dysfunction haemorrhage resuscitation anaesthetized rat. Exposure human cardiac myoblasts (Girardi cells) to hydrogen peroxide (H 2 O , 3 m M for 1 h, n =9) substantial...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEfficient preparations of 8- and 9-membered cyclic ethersLarry E. Overman, Todd A. Blumenkopf, Armando. Castaneda, Andrew S. ThompsonCite this: J. Am. Chem. Soc. 1986, 108, 12, 3516–3517Publication Date (Print):June 1, 1986Publication History Published online1 May 2002Published inissue 1 June 1986https://pubs.acs.org/doi/10.1021/ja00272a062https://doi.org/10.1021/ja00272a062research-articleACS PublicationsRequest reuse permissionsArticle...
An efficient synthesis of a homologous series C8-linked pyrrolobenzodiazepine dimers is reported; compounds with an odd number methylenes (n= 3 or 5) in the linker show higher affinity for DNA, enhanced cross-linking efficiency, and are more cytotoxic compared either n= 4 6.
PARP-2 is a member of the poly(ADP-ribose) polymerase family, with some activities similar to those PARP-1 but other distinct roles. Two series isoquinolin-1-ones were designed, synthesized, and evaluated as selective inhibitors PARP-2, using structures catalytic sites isoforms. A new efficient synthesis 5-aminoisoquinolin-1-one was developed, acylation acyl chlorides gave 5-acylaminoisoquinolin-1-ones. By examination carboxylates tethered 5-position, Heck coupling 5-iodoisoquinolin-1-one...
Tankyrases (TNKSs) are poly(ADP-ribose)polymerases (PARPs) that overexpressed in several clinical cancers. They regulate elongation of telomeres, the Wnt system, and essential for function mitotic spindle. A set 2-arylquinazolin-4-ones has been designed identified as potent selective TNKS inhibitors, some being more than lead inhibitor XAV939, with IC50 = 3 nM vs. TNKS-2. Methyl was preferred at 8-position modest bulk 4-position 2-phenyl group; electronic effects H-bonding were irrelevant,...
Members of a homologous series pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimers with C8-O-(CH(2))(n)-O-C8' diether linkages (n = 3-6 for 2a-d, respectively) have been studied their ability to interact oligonucleotide duplexes containing potential target binding sites. The results confirm earlier predictions that the n 3 analogue (2a, DSB-120) will covalently bind 5'-Pu-GATC-Py sequence by cross-linking opposite-strand guanines separated 2 bp. Preference this DNA is shown using oligonucleotides...
Two methylotrophic bacterial strains, TR3 and PSCH4, capable of growth on methanesulfonic acid as the sole carbon source were isolated from marine environment. Methanesulfonic metabolism in these strains was initiated by an inducible NADH-dependent monooxygenase, which cleaved into formaldehyde sulfite. The presence hydroxypyruvate reductase absence ribulose monophosphate-dependent hexulose monophosphate synthase indicated serine pathway for assimilation. Cell suspensions bacteria grown...
Metabolic chiral inversion of 2-arylpropanoic acids (2-APAs; 'profens'), such as ibuprofen, is important for pharmacological activity. Several 2-APA-CoA esters were good racemisation substrates human AMACR 1A, suggesting a common pathway all 2-APAs and an additional mechanism their anti-cancer properties.