, purified by silica gel column chromatography (eluent: DCM/MeOH, 98/2, v/v). The amine-borane complex 21-BH3 (209 mg; 0.816 mmol) was obtained as beige crystals. Yield 70%; mp 99-100 °C
, H NMR (200 MHz, CDCl3), vol.1, 1027.
, Wiley-Interscience Series in Mass Spectrometry, Proteomic Biology Using LC-MS, pp.255-255
Cristallographic data are available in supporting information ,
, 1044, 981; 1 H NMR (500 MHz, CD3OD) ? 5.11 (dd, 1H, 2 JH-H = 13.5 Hz, 3 JH-P = 7.7 Hz, OCH'), 5.08 (dd, 1H, 2 JH-H = 13.5 Hz, 3 JH-P = 7
,
,
, Conversion table for cholesterol concentration (mg/100 ml ? mmol/l), The Biology of Cholesterol and Related Steroids, vol.3229, p.xiv, 1981.
, CH2CH2Cl)2), 3.17 (s, 9H, CH2N + (CH3)3); 13 C NMR (126 MHz, CD3OD) ? 147.18 (CArNO2), 136.36 (CArCH=CH), 133.17 (d, 3 JC-P = 6.5 Hz, CArCH2O), vol.132
,
, N-dimethylpropan-1-amine borane complex (24a-BH3) was prepared from alcohol 21-BH3 (133 mg, 0.519 mmol) as described for the preparation of 14a-BH3. The crude product was purified by silica gel chromatography (eluent: DCM/EtOH, 96/4, v/v) to yield compound 24a-BH3 (150 mg, 0.629 mmol) as an oil. Yield 63%
, IR (ATR) ? cm -1 3231, 0980.
, 500 MHz, CDCl3) ? 5.14 (dd, 1H, 2 JH-H = 13.4 Hz, 3 JH-P = 7
, 4 Hz, 3 JH-P = 6.4 Hz
The Clinical Approach Towards Chondrosarcoma, The Oncologist, vol.13, pp.320-329, 2008. ,
, Surmounting Chemotherapy and Radioresistance in Chondrosarcoma: Molecular Mechanisms and Therapeutic Targets, 2011.
Increased levels of hypoxia-inducible factor-1? are associated with Bcl-xL expression, tumor apoptosis, and clinical outcome in chondrosarcoma, Journal of Orthopaedic Research, vol.29, issue.1, pp.143-151, 2010. ,
Correlation of hypoxic signalling to histological grade and outcome in cartilage tumours, Histopathology, vol.56, pp.641-651, 2010. ,
Novel therapeutic approaches in chondrosarcoma, Future Oncology, vol.13, pp.637-648, 2017. ,
Biological aspects of chondrosarcoma: Leaps and hurdles, Crit. Rev. Oncol./Hematol, vol.126, pp.32-36, 2018. ,
URL : https://hal.archives-ouvertes.fr/hal-01867855
Proteoglycan form and function: A comprehensive nomenclature of proteoglycans, Matrix Biol, vol.42, pp.11-55, 2015. ,
Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer, Pharmacol. Ther, vol.164, pp.152-169, 2016. ,
Bioreductive prodrugs as cancer therapeutics: targeting tumor hypoxia, Chin. J. Cancer, vol.33, pp.80-86, 2014. ,
AQ4N: a new approach to hypoxia-activated cancer chemotherapy, Br. J. Cancer, vol.83, pp.1589-1593, 2000. ,
Efficacy, pharmacokinetic and pharmacodynamic evaluation of apaziquone in the treatment of non-muscle invasive bladder cancer, Expert Opin. Drug Metab. Toxicol, vol.13, pp.783-791, 2017. ,
EO9 (Apaziquone): from the clinic to the laboratory and back again, Br J Pharmacol, vol.168, pp.11-18, 2013. ,
Pharmacokinetic/pharmacodynamic modeling identifies SN30000 and SN29751 as tirapazamine analogues with improved tissue penetration and hypoxic cell killing in tumors, Clin. Cancer Res, vol.16, pp.4946-4957, 2010. ,
Reductive Metabolism Influences the Toxicity and Pharmacokinetics of the Hypoxia-Targeted Benzotriazine Di-Oxide Anticancer Agent SN30000 in Mice, Front. Pharmacol, vol.8, p.531, 2017. ,
, Molecular and Cellular Pharmacology of the Hypoxia-Activated Prodrug TH-302, vol.11, pp.740-751, 2012.
Evofosfamide, a new horizon in the treatment of pancreatic cancer, Anti-Cancer Drugs, vol.27, pp.723-725, 2016. ,
Randomized Phase II Trial of Gemcitabine Plus TH-302 Versus Gemcitabine in Patients With Advanced Pancreatic Cancer, J. Clin. Oncol, vol.33, pp.1475-1481, 2015. ,
Cellular pharmacology of evofosfamide (TH-302): A critical re-evaluation of its bystander effects, Biochem. Pharmacol, vol.156, pp.265-280, 2018. ,
, An Intratumor Pharmacokinetic/Pharmacodynamic Model for the Hypoxia-Activated Prodrug Evofosfamide, vol.21, pp.159-171, 2019.
Potent and Highly Selective Hypoxia-Activated Achiral Phosphoramidate Mustards as Anticancer Drugs, J. Med. Chem, vol.51, pp.2412-2420, 2008. ,
Mechanism of Action and Preclinical Antitumor Activity of the Novel Hypoxia-Activated DNA Cross-Linking Agent PR-104, Clin. Cancer Res, vol.13, pp.3922-3932, 2007. ,
PR-104 a bioreductive pre-prodrug combined with gemcitabine or docetaxel in a phase Ib study of patients with advanced solid tumours, BMC Cancer, vol.12, p.496, 2012. ,
TH-4000, a hypoxia-activated EGFR/Her2 inhibitor to treat EGFR-TKI resistant T790M-negative NSCLC, J. Clin. Oncol, vol.33, pp.13548-13548, 2015. ,
Molecular Pathways: Hypoxia-Activated Prodrugs in Cancer Therapy, Clin. Cancer Res, vol.23, pp.2382-2390, 2017. ,
Targeting the hypoxic fraction of tumours using hypoxia-activated prodrugs, Cancer Chemother. Pharmacol, vol.77, pp.441-457, 2016. ,
Hypoxia-activated prodrugs: paths forward in the era of personalised medicine, Br. J. Cancer, vol.114, pp.1071-1077, 2016. ,
Exploiting tumour hypoxia in cancer treatment, Nat. Rev. Cancer, vol.4, pp.437-447, 2004. ,
The role of hypoxia-activated prodrugs in cancer therapy, Lancet Oncol, vol.1, pp.6-7, 2000. ,
Synthesis and biological evaluation of hypoxia-activated prodrugs of SN-38, Eur. J. Med. Chem, vol.132, pp.135-141, 2017. ,
Synthesis and Biological Evaluation of Paclitaxel and Camptothecin Prodrugs on the Basis of 2-Nitroimidazole, ACS Med. Chem. Lett, 2017. ,
, Targeting a Targeted Drug: An Approach Toward Hypoxia-Activatable Tyrosine Kinase Inhibitor Prodrugs, vol.11, pp.2410-2421, 2016.
Selective radiosensitization of hypoxic cells using BCCA621C: a novel hypoxia activated prodrug targeting DNA-dependent protein kinase, Tumor Microenvironment Therapy, vol.1, 2013. ,
, Proteoglycans as Target for an Innovative Therapeutic Approach in Chondrosarcoma: Preclinical Proof of Concept, vol.15, pp.2575-2585, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01636341
Quaternary ammonium-melphalan conjugate for anticancer therapy of chondrosarcoma: in vitro and in vivo preclinical studies, Invest. New Drugs, vol.30, pp.1782-1790, 2012. ,
Proteoglycan-targeting applied to hypoxia-activated prodrug therapy in chondrosarcoma: first proof-of-concept, Oncotarget, vol.8, pp.95824-95840, 2017. ,
URL : https://hal.archives-ouvertes.fr/inserm-01674377
Structure-activity relationship study of hypoxiaactivated prodrugs for proteoglycan-targeted chemotherapy in chondrosarcoma, Eur. J. Med. Chem, vol.158, pp.51-67, 2018. ,
URL : https://hal.archives-ouvertes.fr/hal-01926337
Hypoxia-directed and activated theranostic agent: Imaging and treatment of solid tumor, Biomaterials, vol.104, pp.119-128, 2016. ,
Reduction Potentials of One?Electron Couples Involving Free Radicals in Aqueous Solution, Journal of Physical and Chemical Reference Data, vol.18, issue.4, pp.1637-1755, 1989. ,
Some reactions and properties of nitro radical-anions important in biology and medicine., Environmental Health Perspectives, vol.64, pp.309-320, 1985. ,
Efficient synthesis of 2-nitroimidazole derivatives and the bioreductive clinical candidate Evofosfamide (TH-302), Organic Chemistry Frontiers, vol.2, issue.9, pp.1026-1029, 2015. ,
Design, synthesis and evaluation of molecularly targeted hypoxia-activated prodrugs, Nat. Protocols, vol.11, pp.781-794, 2016. ,
An Expedient Synthesis of 1-[3-(Dimethylamino)propyl]-5-methyl-3-phenyl-1H-indazole (FS-32) -An Antidepressant, Synthesis, pp.1775-1777, 2001. ,
, Phosphoramidate Alkylator Prodrugs, issue.A2, p.2007002931, 2007.
Regioselective Control of the SNAr Amination of 5-Substituted-2,4-Dichloropyrimidines Using Tertiary Amine Nucleophiles, The Journal of Organic Chemistry, vol.80, issue.15, pp.7757-7763, 2015. ,
, Substituted 6,7-dialkoxy-3-isoquinolinol derivatives as inhibitors of phosphodiesterase 10 (pde10a), pp.2012112946-2012112947, 2012.
Selective reductions. 29. A simple technique to achieve an enhanced rate of reduction of representative organic compounds by borane-dimethyl sulfide, The Journal of Organic Chemistry, vol.47, issue.16, pp.3153-3163, 1982. ,
Intramolecular oxidative phenol coupling. III. Two-electron oxidation with thallium(III) trifluoroacetate, J. Am. Chem. Soc, vol.95, pp.612-613, 1973. ,
Alcaloïdes monoterpéniques: Synthèse stéréospécifique de la ?-7(7a) 4a-?H isotécomanine, Tetrahedron Lett, vol.29, pp.80171-80180, 1988. ,
Metallation of benzylic amines via amine-borane complexes, Tetrahedron, vol.54, issue.98, pp.783-785, 1998. ,
A Convenient Method for the Synthesis of Cyclophosphamide Analogues, Phosphorus Sulfur Silicon Relat. Elem, vol.183, pp.799-803, 2008. ,
Synthesis, activation, and cytotoxicity of aldophosphamide analogs, J. Med. Chem, vol.34, pp.3052-3058, 1991. ,
Synthesis of [3H,33P]-phosphoramide and -isophosphoramide mustards and metabolites [3H]-chloroethylaziridine and -aziridine for studies of DNA alkylation, Journal of Labelled Compounds and Radiopharmaceuticals, vol.50, issue.2, pp.79-84, 2007. ,
Isophosphoramide mustard analogues as prodrugs for anticancer gene-directed enzyme-prodrug therapy (GDEPT)., Acta Biochimica Polonica, vol.49, issue.1, pp.169-176, 2002. ,
Water-Soluble Phosphinothiols for Traceless Staudinger Ligation and Integration with Expressed Protein Ligation, Journal of the American Chemical Society, vol.129, issue.37, pp.11421-11430, 2007. ,
, Hypoxia Activated Prodrugs of Antineoplastic Agents, WO2008151253 (A1), 2008.
Discovery and Optimization of Anthranilic Acid Sulfonamides as Inhibitors of Methionine Aminopeptidase-2: A Structural Basis for the Reduction of Albumin Binding, J. Med. Chem, vol.49, pp.3832-3849, 2006. ,
Reduction with Diimide, in: Organic Reactions, pp.91-155, 2004. ,
Synthesis and Electrochemistry of 2-Ethenyl and 2-Ethanyl Derivatives of 5-Nitroimidazole and Antimicrobial Activity againstGiardia lamblia, Journal of Medicinal Chemistry, vol.52, issue.13, pp.4038-4053, 2009. ,
Nitroaryl Phosphoramides as Novel Prodrugs forE. coliNitroreductase Activation in Enzyme Prodrug Therapy, Journal of Medicinal Chemistry, vol.46, issue.23, pp.4818-4821, 2003. ,
Nitrobenzyl Phosphorodiamidates as Potential Hypoxia-Selective Alkylating Agents, Journal of Medicinal Chemistry, vol.37, issue.11, pp.1610-1615, 1994. ,