- Potent anticancer activity and possible low toxicity of platinum(II) complexes with functionalized 1,1-cyclobutanedicarboxylate as a leaving ligand
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Two platinum(II) complexes, DN603 and DN604, were designed and prepared by using 3-oxocyclobutane-1,1-dicarboxylate as a ligand. The compounds were prepared according to the concept that incorporation of a functionalized moiety in the leaving ligand that
- Zhao, Jian,Gou, Shaohua,Liu, Fengfan
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- Synthesis and anticancer activity of diam(m)ine platinum(II) complexes with 3-oxo-cyclobutane-1,1-dicarboxylate as the leaving group
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Four water-soluble dia(m)mine platinum complexes with 3-oxo-cyclobutane- 1,1-dicarboxylate as the leaving group have been synthesized. These compounds were evaluated for their in vitro anticancer activity against three human A549, SK-OV-3, and HT-29 cance
- Tian, Wen,He, Ling
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- Synthesis and in vitro antitumour activity of carboplatin analogues containing functional handles compatible for conjugation to drug delivery systems
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We describe herein the synthesis of a series of carboplatin derivatives with different functional groups at position 3 of the cyclobutane ring. This pharmacomodulation approach aims at facilitating the vectorisation of these analogues, via their subsequen
- Re?nik, Lisa-Maria,Cantelli, Christophe,Fersing, Cyril,Gongora, Céline,Pouget, Jean-Pierre,Lisowski, Vincent
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- Nitric oxide donor-based platinum complexes as potential anticancer agents
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Joining forces: Platinum complexes containing organic nitrate ligands were investigated as anticancer agents. The complexes, which were stable in aqueous solution, showed cytotoxicity that was superior to that of the corresponding parent compound (carbopl
- Zhao, Jian,Gou, Shaohua,Sun, Yanyan,Yin, Runting,Wang, Zhimei
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- BENZOFURAN DERIVATIVES FOR THE TREATMENT OF HEPATITIS C
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The disclosure provides compounds of formula (I), including their salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV.
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- COMPOUNDS AND COMPOSITIONS AS C-KIT KINASE INHIBITORS
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The invention provides compounds and pharmaceutical compositions thereof, which are useful as protein kinase inhibitors, as well as methods for using such compounds to treat, ameliorate or prevent a condition associated with abnormal or deregulated kinase activity. In some embodiments, the invention provides methods for using such compounds to treat, ameliorate or prevent diseases or disorders that involve abnormal activation of c-kit or c-kit and PDGFR (PDGFRα, PDGFRβ) kinases.
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Paragraph 0543-0551
(2013/03/26)
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- Antitumor platinum(II) complexes containing platinum-based moieties of present platinum drugs and furoxan groups as nitric oxide donors: Synthesis, DNA interaction, and cytotoxicity
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Six novel platinum(II) complexes 1-6 bearing different furoxan moieties as nitric oxide (NO) donors have been designed, synthesized, and characterized by elemental analysis and 1H NMR, IR, and ESI-MS spectroscopy. The furoxan groups were introduced to the platinum complexes to release NO, which may take synergic action with the platinum-based moieties on the tumor cells. It was found that all compounds exhibited considerable cytotoxicity against human HCT-116 and SGC-7901 cell lines via DNA binding together with NO-releasing features, especially for compound 3. This finding is in accordance with the previous reports that NO hybrids show higher cytotoxicity against colon cancer cell lines compared with their parent compounds.
- Zhao, Jian,Gou, Shaohua,Sun, Yanyan,Fang, Lei,Wang, Zhimei
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p. 10317 - 10324
(2013/01/15)
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- CYSTEINE PROTEASE INHIBITORS
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Compounds of the formula (I) wherein One of A1 and A2 is N-CH3 and the other is CH; R1 is C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl or oxetan-3-yl, wherein C3-C6cycloalkyl is optionally substituted with one, two or three fluoro or with CF3; R2a and R2b are independently selected from H, halo, C1-C4alkyl, C1-C4haloalkyl and C1- C4alkoxy; R3 is CH3 or F; n is 1, 2, 3 or 4; or a pharmaceutically acceptable salt, hydrate or N-oxide thereof for the use in the prophylaxis and/or treatment of a disorder characterised by inappropriate expression or activation of cathepsin S.
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- CYSTEINE PROTEASE INHIBITORS
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Compounds of Formula (II) wherein R1a is H; and R1b is C1-C6alkyl, Carbocyclyl or Het; or R1a and R1b together define a saturated cyclic amine with 3-6 ring atoms; R2a and R
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- CYSTEINE PROTEASE INHIBITORS
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Compounds of the formula (I) wherein R1a is H; and R1b is C1-C6alkyl, Carbocyclyl or Het; or R1a and R1b together define a saturated cyclic amine with 3-6 ring atoms; R2a and Rs
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- HETEROARYLOXYCARBOCYCLYL COMPOUNDS AS PDE10 INHIBITORS
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Heteroaryloxycarbocyclyl compounds of formula (I), and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, Huntington's Disease, bipolar disorder, obsessive -compulsive disorder, and the like. Formula (I)
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- NEW CATHEPSIN S PROTEASE INHIBITORS, USEFUL IN THE TREATMENT OF E.G. AUTOIMMUNE DISORDERS, ALLERGY AND CHRONIC PAIN CONDITIONS
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Compounds of the formula (I) wherein R2a and R2b are independently H, halo, C1-C4alkyl, C1-C4haloalkyl or C1-C4alkoxy, or R2a and R2b together wi
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- CYSTEINE PROTEASE INHIBITORS
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Compounds of the formula I wherein R1a is H; and R1b is C1-C6 alkyl, Carbocyclyl or Het; or R1a and R1b together define a saturated cyclic amine with 3-6 ring atoms; R2a and Rsu
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(2010/08/05)
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- Potent ketoamide inhibitors of HCV NS3 protease derived from quaternized P1 groups
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Blood borne hepatitis C infections are the primary cause for liver cirrhosis and hepatocellular carcinoma. HCV NS3 protease, a pivotal enzyme in the replication cycle of HCV virus has been the primary target for development of new drug candidates. Boceprevir and telaprevir are two novel ketoamide derived inhibitors that are currently undergoing phase-III clinical trials. These inhibitors include ketoamide functionality as serine trap and have an acidic alpha-ketoamide center that undergoes epimerization under physiological conditions. Our initial attempts to arrest this epimerization by introducing quaternary amino acids at P1 had resulted in significantly diminished activity. In this manuscript we describe alpha quaternized P1 group that result in potent inhibitors in the enzyme assay and demonstrate cellular activity comparable to boceprevir.
- Venkatraman, Srikanth,Velazquez, Francisco,Wu, Wanli,Blackman, Melissa,Madison, Vincent,Njoroge, F. George
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p. 2151 - 2155
(2010/06/19)
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- AZETIDINE AND CYCLOBUTANE DERIVATIVES AS JAK INHIBITORS
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The present invention relates to azetidine and cyclobutane derivatives, as well as their compositions, methods of use, and processes for preparation, which are JAK inhibitors useful in the treatment of JAK-associated diseases including, for example, inflammatory and autoimmune disorders, as well as cancer.
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(2009/09/28)
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- P1-NONEPIMERIZABLE KETOAMIDE INHIBITORS OF HCV NS3 PROTEASE
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The present invention discloses novel compounds, which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.
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(2009/03/07)
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- A concise synthesis of a novel insulin-like growth factor i receptor (IGF-IR) inhibitor
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An efficient synthesis of a potent insulin-like growth factor I receptor (IGF-IR) inhibitor AEW541 (1) is described. The key step in the synthesis is the cis-selective reductive animation of cyclobutanone, which sets up the desired 1,3-stereochemistry of the cyclobutane ring. The amino group thus generated is used as a handle to build the pyrrolopyrimidine ring. The final step resulting in 1 is accomplished by alkylation of in situ generated mesylate with azetidine.
- Slade, Joel,Bajwa, Joginder,Liu, Hui,Parker, David,Vivelo, James,Chen, Guang-Pei,Calienni, John,Villhauer, Edwin,Prasad, Kapa,Repic, Oljan,Blacklock, Thomas J.
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p. 825 - 835
(2012/12/30)
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- NOVEL INTERMEDIATES AND THEIR USE
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The invention is directed to novel acyloxy imidazole intermediates useful for making certain C- 14 oxycarbonyl carbamate pleuromutilin derivatives. The invention is further directed to a process for making such acyloxy imidazole intermediates and to a pro
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(2010/11/27)
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- NEW PLEUROMUTILIN DERIVATIVE AND ITS USE
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The invention is directed to the L-tartrate salt of trans-3-aminocyclobutyl (lS,2R,3S,4S:,6R,7R,8R-,14R)-4-ethenyl-3-hydroxy-2,4,7, 14-tetramethyl-9- oxotricyclo[5.4.3.01,8]tetradec-6-yl imidodicarbonate (Compound IA.) Compound IA is useful for the treatment of a variety of diseases and conditions, such as respiratory tract and skin and skin structure infections. Accordingly, the invention is further directed to pharmaceutical compositions comprising Compound IA. The invention is still further directed to methods of treating respiratory tract and skin and skin structure infections using Compound IA or a pharmaceutical composition comprising Compound IA.
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(2010/11/27)
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- CARBOPLATIN-TYPE PLATINUM (II) COMPLEXES
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The invention relates to carboplatinum derivatives, medicaments containing said derivatives and to the use of the carboplatinum derivatives in the production of medicaments for tumour therapy.
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(2008/06/13)
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- SOLID-PHASE PREPARATION OF 18F-LABELLED AMINO ACIDS
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A process for the production of an 18F-labelled tracer which comprises treatment of a solid support-bound precursor of formula (I): SOLID SUPPORT-LINKER-SO2-O -TRACER (I) with 18F- to produce the labelled tracer of formula (II).
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- Pyrimidine compound and anti-rotavirus composition
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A pyrimidine compound of the formula [I]wherein R1 is H, C1-C4 lower alkyl, halogen atom, -OH, C1-C4 lower alkoxy, C1-C6 hydroxy(lower)alkoxy or -NH2; R2 is H, -NH2 or -NHCOCH3; R3 is -NR5(CH2)i-CH2OH; R4 is H, halogen atom, -NH2, -CN, -CHO, -CH2OH, -COOH
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- Diastereoselective synthesis of hydantoin- and isoxazoline-substituted dispirocyclobutanoids
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Synthetic strategies for constructing novel achiral cyclobutanoid isoxazolidinoimidazolidinedione heterocycles, with a generalized structure of II, have been developed via 1,3-dipolar cycloaddition and carbanilide cyclization transformations from methylenecyclobutane 13. The exo methylene cyclobutane system has made the realization of some diasteroselectivity possible, such that the H-bond (Boc-NH) directed product (i.e., 14) was obtained with 3:1 selectivity relative to the non-H-bond directed product (i.e., 15).
- Park, Kyung-Ho,Kurth, Mark J.
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p. 3520 - 3524
(2007/10/03)
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- Synthesis of [F-18]-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC): A pet tracer for tumor delineation
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Fluorine-18 labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC), a new tumor-avid amino acid, was synthesized for positron emission tomography. [18F]FACBC was prepared with high specific activity by nucleophilic displacement with an o
- Shoup, Timothy M.,Goodman, Mark M.
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p. 215 - 225
(2007/10/03)
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- Amino acid analogs for tumor imaging
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The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is ?18 F!-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an α-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of α-aminoisobutyric acid.
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- Amino acid analogs for tumor imaging
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The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is ?18 F!-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an α-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of α-aminoisobutyric acid.
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- Hydroxymethyl cyclobutyl purines
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Antiviral activity is exhibited by compounds having the formula STR1 and their pharmaceutically acceptable salts. R1 is STR2 R2 is hydrogen, --PO3 H2, STR3 wherein R3 is hydrogen, alkyl, substituted a
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