, 94 (s, 6H, C 6 H 6 ) ppm. ESI-MS: (+ mode) m/z = 463, vol.5
, Complex 2 was obtained with [(? 6 -toluene)RuCl 2 ] 2 (53.2 mg, 0.101 mmol) and L1 (50.0 mg, 0.202 mmol) using the same protocol as used for 1 as a red solid, Yield: 100 mg (97%). 1 H NMR
, 1H, quinolinyl), 7.87 (d, 3 J HH = 9 Hz, 2H, CH 4 OH), 7.03 (d, 3 J HH = 9 Hz, 2H, CH 4 OH)
,
, 16 (s, 3H, CH 3 ) ppm. ESI-MS: (+ mode) m/z = 477, vol.2
, 108 mmol) and L2 (50.0 mg, 0.215 mmol) were added to MeOH (15 mL) and stirred at rt over 12 h. The solvent was removed in vacuo and the resulting solid was washed with ether (3 × 10 mL). The final product was dried in vacuo for 1 h to give a yellow solid
, 1H, naphthyl), 7.95 (m, 1H, py), vol.7
, CH 3 ) 2 ), 0.93 (bs, 9H, C(CH 3 ) 2 ) ppm. ESI-MS: (+ mode) m/z = 573 [M] + . Purity (HPLC): 95.5% at 214 nm and 92
, Diethyl ether (40 mL) was than added to precipitate the product. The suspension was filtered and the resulting solid washed with ether (3 × 10 mL). The final product was then dried in vacuo for 1 h to give a reddish brown solid, Yield: 290 mg (71%). 1 H NMR
Synthesis of [(? 6 -Hexamethylbenzene)RuCl(3-chloro-N-(2-quinolinylmethylene)aniline)]Cl (5). 2-Quinolinecarboxaldehyde (78.6 mg, 0.5 mmol) and 3-chloroaniline (52.9 ?L, 0.5 mmol) were added to dry EtOH (8 mL) and stirred at rt over 72 h. The solvent was removed in vacuo and dried. Crude 3-chloro-N -(2-quinolinylmethylene)aniline (135 mg) was treated with, p.16 ,
, 1H, quinolinyl), 8.34 (s, 1H, C 6 H 4 ), 7.99 (d, 3 J HH = 8 Hz, 1H, C 6 H 4 ), 7.88 (t, 3 J HH = 7 Hz, 1H, quinolinyl), 7.79 (t, 3 J HH = 7 Hz, 1H, quinolinyl), vol.7
Chemical Space and Biology, Nature, vol.432, pp.824-828, 2004. ,
Navigating Chemical Space for Biology and Medicine, Nature, vol.432, pp.855-861, 2004. ,
Charting Biologically Relevant Chemical Space, Proc. Natl. Acad. Sci. U. S. A, vol.102, pp.17272-17277, 2005. ,
Structural Diversity of Organic Chemistry. A Scaffold Analysis of the CAS Registry, J. Org. Chem, vol.73, pp.4443-4451, 2008. ,
The Properties of Known Drugs. 1. Molecular Frameworks, J. Med. Chem, pp.39-2887, 1996. ,
Targeting Proteins with Metal Complexes, Chem. Commun, vol.9, 1001. ,
Reputation and Power: Organizational Image and Pharmaceutical Regulation at the FDA, 2010. ,
The Resurgence of Platinum-based Cancer Chemotherapy, Nat. Rev. Cancer, vol.7, pp.573-584, 2007. ,
Non-Platinum Chemotherapeutic Metallopharmaceuticals, Schellens, J. H. M. Phase I and Pharmacological Study with Imidazolium-trans-DMSO-imidazole-tetrachlororuthenate, vol.99, pp.3717-3727, 1999. ,
A New Redox-Active Anticancer Agent?Preclinical Development and Results of a Clinical Phase I Study in Tumor Patients, Chem. Biodiversity, vol.5, pp.2140-2155, 2008. ,
Challenges and Opportunities in the Development of Organometallic Anticancer Drugs, Organometallics, vol.31, pp.5677-5685, 2012. ,
Medicinal Organometallic Chemistry: Designing Metal Arene Complexes as Anticancer Agents, Chem.-Asian J, vol.3, pp.1890-1899, 2008. ,
Organometallic Ruthenium(II) Arene Compounds with Antiangiogenic Activity, J. Med. Chem, vol.54, pp.3895-3902, 2011. ,
The Contrasting Activity of Iodido Versus Chlorido Ruthenium and Osmium Arene Azo-and Imino-pyridine Anticancer Complexes: Control of Cell Selectivity, Cross-Resistance, p53 Dependence, and Apoptosis Pathway, J. Med. Chem, vol.56, pp.1291-1300, 2013. ,
Opening the Lid on Piano-Stool Complexes: An Account of Ruthenium(II)?Arene Complexes with Medicinal Applications, J. Organomet. Chem, vol.751, pp.251-260, 2014. ,
Organoruthenium Antagonists of Human A3 Adenosine Receptors, Chem.-Eur. J, vol.19, pp.8321-8330, 2013. ,
Rational Design of Selective Organoruthenium Inhibitors of Protein Tyrosine Phosphatase 1B, Inorg. Chem, vol.51, pp.12483-12492, 2012. ,
Organometallic Pyridylnaphthalimide Complexes as Protein Kinase Inhibitors, Organometallics, vol.30, pp.4598-4606, 2011. ,
Organometallic Ruthenium-Based Antitumor Compounds with Novel Modes of Action, J. Organomet. Chem, pp.696-989, 2011. ,
In Vivo Tumour and Metastasis Reduction and in Vitro Effects on Invasion Assays of the Ruthenium RM175 and Osmium AFAP51 Organometallics in the Mammary Cancer Model, J. Inorg. Biochem, vol.104, pp.79-86, 2010. ,
Metal-Based Paullones as Putative CDK Inhibitors for Antitumor Chemotherapy, J. Med. Chem, vol.50, pp.6343-6355, 2007. ,
Combinatorial and Evolution-Based Methods in the Creation of Enantioselective Catalysts, Angew. Chem., Int. Ed, vol.40, pp.284-310, 2001. ,
Combinatorial Libraries of Transition-Metal Complexes, Catalysts and Materials, Curr. Opin. Chem. Biol, vol.2, pp.422-428, 1998. ,
Discovery of a Strongly Apoptotic Ruthenium Complex Through Combinatorial Coordination Chemistry, Dalton Trans, pp.39-8177, 2010. ,
Automated Parallel Solid-Phase Synthesis and Anticancer Screening of a Library of Peptide-Tethered Platinum(II) Complexes, J. Comb. Chem, vol.5, pp.821-825, 2003. ,
Solid-phase Synthesis of Peptide?Platinum Complexes Using Platinum-Chelating Building Blocks Derived From Amino Acids, New J. Chem, p.220, 2005. ,
Synthesis of Ferrocenyl and Ruthenocenyl Thioamide Derivatives Using a Single-Step Three-Component Reaction, Organometallics, vol.32, pp.6098-6105, 2013. ,
Alkali Metal Thioselenophosphinates, M[SeSPR 2 ]: One-Pot Multicomponent Synthesis, DFT Study, and Synthetic Application, Eur. J. Inorg. Chem, pp.415-426, 2013. ,
Metal-Arene Complexes with Indolo[3,2-c]quinolines: Effects of Ruthenium vs Osmium and Modifications of the Lactam Unit on Intermolecular Interactions, Cell Cycle, and Cellular Accumulation, vol.32, pp.903-914, 2013. ,
Benzene Complexes of Ruthenium(II), Can. J. Chem, vol.50, pp.3063-3072, 1972. ,
Preparation and Xray Crystal Structure Analysis of the Hydroxo-Bridged, Dinuclear (?-Arene)ruthenium(II) Cation in, Inorg. Chem, vol.27, pp.2554-2555, 1988. ,
,
Solution Equilibrium Studies on Anticancer Ruthenium(II)?? 6 -p-Cymene Complexes of 3-Hydroxy-2(1H)-pyridones, J. Organomet. Chem, vol.734, pp.38-44, 2013. ,
Evaluation of a Tetrazolium-Based Semiautomated Colorimetric Assay: Assessment of Chemosensitivity Testing, Cancer Res, vol.47, pp.936-942, 1987. ,
Evidence-based Approach To Assess Passive Diffusion and Carrier-Mediated Drug Transport, Drug Discovery Today, vol.17, pp.905-912, 2012. ,
Experimental and Computational Approaches To Estimate Solubility and Permeability in Drug Discovery and Development Settings, Adv. Drug Delivery Rev, vol.23, pp.3-25, 1997. ,
Molecular Properties That Influence the Oral Bioavailability of Drug Candidates, J. Med. Chem, vol.45, pp.2625-2623, 2002. ,
, 107: Partition Coefficient (n-octanol/water): Shake Flask Method, 1995.
Ruthenium?Arene??-Carboline Complexes as Potent Inhibitors of Cyclin-Dependent Kinase 1: Synthesis, Characterization and Anticancer Mechanism Studies, Chem.-Eur. J, vol.19, pp.12152-12160, 2013. ,
Anticancer Activity and DNA Binding of a Bifunctional Ru(II) Arene Aqua-Complex with the 2,4-Diamino-6-(2-pyridyl)-1,3,5-triazine Ligand, Inorg. Chem, vol.52, pp.9962-9974, 2013. ,
In Vitro and in Vivo Activity and Cross Resistance Profiles of Novel Ruthenium (II) Organometallic Arene Complexes in Human Ovarian Cancer, Br. J. Cancer, vol.86, pp.1652-1657, 2002. ,
Roscovitine-based CDK Inhibitors Acting as N-Donor Ligands in the Platinum(II) Oxalato Complexes: Preparation, Characterization and in Vitro Cytotoxicity, Eur. J. Med. Chem, pp.4609-4614, 2010. ,
Organic Cation Transporters are Determinants of Oxaliplatin Cytotoxicity, Cancer Res, vol.66, pp.8847-57, 2006. ,
p53?A Guide to Apoptosis, Curr. Cancer Drug Targets, vol.8, pp.87-97, 2008. ,
Multiple Neurotoxic Stresses Converge on MDMX Proteolysis to Cause Neuronal Apoptosis, Cell Death Differ, vol.14, 2007. ,
Characterization of p53 Wild-Type and Null Isogenic Colorectal Cancer Cell Lines Resistant to 5-Fluorouracil, Oxaliplatin, and Irinotecan. Clin. Cancer Res, vol.10, pp.2158-2167, 2004. ,
, The JNK, ERK and p53 Pathways Play Distinct Roles in Apoptosis Mediated by the Antitumor Agents Vinblastine, Doxorubicin, and Etoposide, vol.66, pp.459-469, 2003.
The Ruthenium(II)?Arene Compound RAPTA-C Induces Apoptosis in EAC Cells Through Mitochondrial and p53-JNK Pathways, J. Biol. Inorg. Chem, vol.13, pp.1149-1155, 2008. ,
Investigation of the Role of Bax, p21/Waf1 and p53 as Determinants of Cellular Responses in HCT116 Colorectal Cancer Cells Exposed to the Novel Cytotoxic Ruthenium(II) Organometallic Agent, RM175, Cancer Chemother. Pharmacol, vol.55, pp.577-583, 2005. ,
Induction of Caspase 8 and Reactive Oxygen Species by Ruthenium-derived Anticancer Compounds with Improved Water Solubility and Cytotoxicity, Biochem. Pharmacol, vol.84, pp.1428-1436, 2012. ,
, Tuning the Activity of Platinum
, Anticancer Complexes Through Asymmetric Acylation, J. Med. Chem, vol.55, pp.7571-7582, 2012.
Controlling Ligand Substitution Reactions of Organometallic Complexes: Tuning Cancer Cell Cytotoxicity, Proc. Natl. Acad. Sci. U. S. A, vol.102, pp.18269-18274, 2005. ,
decane): A Water Soluble Compound that Exhibits pH Dependent DNA Binding Providing Selectivity for Diseased Cells, Chem. Commun, vol.15, pp.1396-1397, 2001. ,
Preparation of New Half Sandwich Ruthenium Arene Complexes with Aminophosphines as Potential Chemotherapeutics, J. Inorg. Biochem, vol.117, pp.171-188, 2012. ,
? 4 -Bonding in (Arene)ruthenium Complexes of Octamethylnapthalene, Organometallics, vol.3, pp.605-613, 1982. ,
6 -Hexamethylbenzene)Ruthenium Complexes, Inorg. Synth, vol.21, pp.74-78, 1982. ,
Arene Ruthenium(II) Complexes Formed by Dehydrogenation of Cyclo-hexadienes with Ruthenium-(III) Trichloride, J. Chem. Soc, pp.223-241, 1974. ,
SAINT+, version 6.22a, 2001. ,
, SHELXTL, version 6.14
, Subcell. Biochem, vol.36, pp.1-25, 2002.