- 1H-PYRAZOLO[4,3-d]PYRIMIDINE COMPOUNDS AS TOLL-LIKE RECEPTOR 7 (TLR7) AGONISTS AND METHODS AND USES THEREFOR
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Compounds according to formula I are useful as agonists of Toll-like receptor 7 (TLR7). Such compounds can be used in cancer treatment, especially in combination with an anti-cancer immunotherapy agent, or as a vaccine adjuvant.
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Paragraph 0291
(2020/02/19)
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- TRICYCLIC DEGRADERS OF IKAROS AND AIOLOS
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Tricyclic cereblon binders for the degradation of Ikaros or Aiolos by the ubiquitin proteasome pathway for therapeutic applications are described.
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Page/Page column 632-634; 659-660
(2020/10/21)
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- COMPOUNDS AND USES THEREOF
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The present invention features compounds useful in the treatment of neurological disorders and primary brain cancer. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders and primary brain cancer.
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Page/Page column 246
(2020/10/20)
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- COMPOUNDS AND USES THEREOF
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The present invention features compounds useful in the treatment of neurological disorders. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders.
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Page/Page column 239
(2019/10/15)
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- Design, Preparation, and Characterization of Zn and Cu Metallopeptides Based On Tetradentate Aminopyridine Ligands Showing Enhanced DNA Cleavage Activity
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The conjugation of redox-active complexes that can function as chemical nucleases to cationic tetrapeptides is pursued in this work in order to explore the expected synergistic effect between these two elements in DNA oxidative cleavage. Coordination complexes of biologically relevant first row metal ions, such as Zn(II) or Cu(II), containing the tetradentate ligands 1,4-dimethyl-7-(2-pyridylmethyl)-1,4,7-triazacyclononane (Me2PyTACN) and (2S,2S′)-1,1′-bis(pyrid-2-ylmethyl)-2,2′-bipyrrolidine ((S,S′)-BPBP) have been linked to a cationic LKKL tetrapeptide sequence. Solid-phase synthesis of the peptide-tetradentate ligand conjugates has been developed, and the preparation and characterization of the corresponding metallotetrapeptides is described. The DNA cleavage activity of Cu and Zn metallopeptides has been evaluated and compared to their metal binding conjugates as well as to the parent complexes and ligands. Very interestingly, the oxidative Cu metallopeptides 1Cu and 2Cu show an enhanced activity compared to the parent complexes, [Cu(PyTACN)]2+ and [Cu(BPBP)]2+, respectively. Under optimized conditions, 1Cu displays an apparent pseudo first-order rate constant (kobs) of ～0.16 min-1 with a supercoiled DNA half-life time (t1/2) of ～4.3 min. On the other hand, kobs for 2Cu has been found to be ～0.11 min-1 with t1/2 ≈ 6.4 min. Hence, these results point out that the DNA cleavage activities promoted by the metallopeptides 1Cu and 2Cu render ～4-fold and ～23 rate accelerations in comparison with their parent Cu complexes. Additional binding assays and mechanistic studies demonstrate that the enhanced cleavage activities are explained by the presence of the cationic LKKL tetrapeptide sequence, which induces an improved binding affinity to the DNA, thus bringing the metal ion, which is responsible for cleavage, in close proximity.
- Soler, Marta,Figueras, Eduard,Serrano-Plana, Joan,González-Bártulos, Marta,Massaguer, Anna,Company, Anna,Martínez, Ma. ángeles,Malina, Jaroslav,Brabec, Viktor,Feliu, Lidia,Planas, Marta,Ribas, Xavi,Costas, Miquel
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p. 10542 - 10558
(2015/11/27)
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- Redox-Noninnocent Behavior of Tris(2-pyridylmethyl)amine Bound to a Lewis Acidic Rh(III) Ion Induced by C-H Deprotonation
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Rh(III) complexes having tris(2-pyridylmethyl)amine (TPA) and its derivative as tetradentate ligands showed reversible deprotonation at a methylene moiety of the TPA ligands upon addition of a strong base as confirmed by spectroscopic measurements and X-ray crystallography. Deprotonation selectively occurred at the axial methylene moiety rather than equatorial counterparts because of the thermodynamic stability of corresponding deprotonated complexes. One-electron oxidation of the deprotonated Rh(III)-TPA complex afforded a unique TPA radical bound to the Rh(III) center by a ligand-centered oxidation. This is the first example to demonstrate emergence of the redox-noninnocent character of the TPA ligand.
- Kotani, Hiroaki,Sugiyama, Takumi,Ishizuka, Tomoya,Shiota, Yoshihito,Yoshizawa, Kazunari,Kojima, Takahiko
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p. 11222 - 11225
(2015/09/21)
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- N-ACYL PYRIDINE BIARYL COMPOUNDS AND THEIR USES
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The present invention provides a compound of general formula:wherein Z2-Z6 include one or two nitrogen atoms as described herein, including pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, or racemates thereof. These compounds inhibit the activity of CDK9 and are thus useful as pharmaceuticals. Also provided are methods of treating a disease or condition mediated by CDK9 using the compounds of Formula I and isomers thereof, and pharmaceutical compositions comprising such compounds.
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Page/Page column 181
(2012/08/08)
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- N-ACYL PYRIMIDINE BIARYL COMPOUNDS AS PROTEIN KINASE INHIBITORS
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The present invention provides a compound of the general formula (1): wherein one of X and Y is N and the other is an optionally substituted carbon atom, and Z2-Z5 represent one or two nitrogen atoms, as further described herein, including pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, or racemates thereof. These compounds inhibit the activity of CDK9 and are thus useful as pharmaceuticals and as components of pharmaceutical compositions. Also provided are methods of treating a disease or condition mediated by CDK9 using the compounds described herein or pharmaceutical compositions comprising such compounds.
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Page/Page column 224
(2012/08/08)
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- PYRAZINYLPYRIDINES USEFUL FOR THE TREATMENT OF PROLIFERATIVE DISEASES
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The present invention provides a compound of Formula (I) and pharmaceutically acceptable salts thereof. Also provided is a method of using a compound of Formula I for treating a disease or condition mediated by a CDK inhibitor.
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Page/Page column 107-108
(2011/04/14)
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- HETEROARYL COMPOUNDS AS KINASE INHIBITORS
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The present invention provides a compound of Formula (I): and pharmaceutically acceptable salts thereof. Also provided is a method of using a compound of Formula I for treating a disease or condition mediated by a CDK inhibitor
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Page/Page column 107-108
(2011/04/14)
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- IMIDAZOLE CARBOXAMIDES
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The present invention provides certain imidazole carboxamide derivatives, pharmaceutical compositions thereof, methods of using the same and processes for preparing the same.
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Page/Page column 16
(2010/02/17)
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- PYRIDINE, BICYCLIC PYRIDINE AND RELATED ANALOGS AS SIRTUIN MODULATORS
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The present invention provides novel sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders relating to aging or stress, diabetes, obesity, neurodegenerative disease, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorder that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent. The compounds are of general formula (III) wherein R1, R2, R", X, Y, W, Z1 and Z2 are as defined in the specification.
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Page/Page column 103
(2010/06/15)
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- New carboxamide compounds having melanin concentrating hormone antagonistic activity, pharmaceutical preparations comprising these compounds and process for their manufacture
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The present invention relates to carboxamide compounds of general formula I wherein the groups and residues A, B, W, X, Y, Z, R1, R2, R3 and k have the meanings given in claim 1. Moreover the invention relates to process for preparing the above mentioned carboxamides as well as pharmaceutical compositions containing at least one carboxamide according to the invention. In view of their MCH-receptor antagonistic activity the pharmaceutical compositions according to the invention are suitable for the treatment of metabolic disorders and/or eating disorders, particularly obesity, bulimia, anorexia, hyperphagia and diabetes.
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Page/Page column 105
(2010/02/09)
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