- Identifying new lead structures to enhance tolerance towards drought stress via high-throughput screening giving crops a quantum of solace
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Novel synthetic lead structures interacting with RCAR/(PYR/PYL) receptor proteins were identified based on the results of a high-throughput screening campaign of a large compound library followed by focused SAR studies of the three most promising hit clusters. Whilst indolinylmethyl sulfonamides 8y,z and phenylsulfonyl ethylenediamines 9y,z showed strong affinities for RCAR/ (PYR/PYL) receptor proteins in wheat, thiotriazolyl acetamides 7f,s exhibited promising efficacy against drought stress in vivo (wheat, corn and canola) combined with confirmed target interaction in wheat and arabidopsis thaliana. Remarkably, binding affinities of several representatives of 8 and 9 were on the same level or even better than the essential plant hormone abscisic acid (ABA).
- Frackenpohl, Jens,Schneider, Linn,Decker, Luka J.B.,Dittgen, Jan,Fenkl, Franz,Fischer, Christian,Franke, Jana,Freigang, Joerg,Getachew, Rahel,Gonzalez Fernandez-Nino, Susana M.,Helmke, Hendrik,Hills, Martin J.,Hohmann, Sabine,Kleemann, Jochen,Kurowski, Karoline,Lange, Gudrun,Luemmen, Peter,Meyering, Nicole,Poree, Fabien,Schmutzler, Dirk,Wrede, Sebastian
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- Discovery of Adamantyl Heterocyclic Ketones as Potent 11β-Hydroxysteroid Dehydrogenase Type1 Inhibitors
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11β-Hydroxysteroid dehydrogenase type1 (11β-HSD1) plays a key role in converting intracellular cortisone to physiologically active cortisol, which is implicated in the development of several phenotypes of metabolic syndrome. Inhibition of 11β-HSD1 activity with selective inhibitors has beneficial effects on various conditions, including diabetes, dyslipidemia and obesity, and therefore constitutes a promising strategy to discover novel therapies for metabolic and cardiovascular diseases. A series of novel adamantyl heterocyclic ketones provides potent and selective inhibitors of human 11β-HSD1. Lead compounds display low nanomolar inhibition against human and mouse 11β-HSD1 and are selective with no activity against 11β-HSD2 and 17β-HSD1. Selected potent 11β-HSD1 inhibitors show moderate metabolic stability upon incubation with human liver microsomes and weak inhibition of human CYP450 enzymes.
- Su, Xiangdong,Vicker, Nigel,Thomas, Mark P.,Pradaux-Caggiano, Fabienne,Halem, Heather,Culler, Michael D.,Potter, Barry V.L.
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experimental part
p. 1439 - 1451
(2012/06/30)
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- METHODS OF USING DIHYDROPYRIDOPHTHALAZINONE INHIBITORS OF POLY (ADP-RIBOSE)POLYMERASE (PARP)
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Provided herein are methods of treating cancer comprising administering a topoisomerase inhibitor, temozolomide, or a platin in combination with a Compound of Formula (I) or Formula (II), where the substituents Y, Z, A, B, R1, R2, R3, R4 and R5 are as defined herein.
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Page/Page column 155
(2011/11/01)
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- DIHYDROPYRIDOPHTHALAZINONE INHIBITORS OF POLY(ADP-RIBOSE)POLYMERASE (PARP)
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A compound having the structure set forth in Formula (I) and Formula (II): wherein the substituents Y, Z, A, B, R1, R2, R3, R4 and R5 are as defined herein. Provided herein are inhibitors of poly(ADP-ribose)polymerase activity. Also described herein are pharmaceutical compositions that include at least one compound described herein and the use of a compound or pharmaceutical composition described herein to treat diseases, disorders and conditions that are ameliorated by the inhibition of PARP activity.
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Page/Page column 80-81
(2010/03/02)
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- Synthesis and biological evaluations of sulfanyltriazoles as novel HIV-1 non-nucleoside reverse transcriptase inhibitors
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A novel sulfanyltriazole was discovered as an HIV-1 non-nucleoside reverse transcriptase inhibitor via HTS using a cell-based assay. Chemical modifications and molecular modeling studies were carried out to establish its SAR and understand its interactions with the enzyme. These modifications led to the identification of sulfanyltriazoles with low nanomolar potency for inhibiting HIV-1 replication and promising activities against selected NNRTI resistant mutants. These novel and potent sulfanyltriazoles could serve as advanced leads for further optimization.
- Wang, Zhiwei,Wu, Baogen,Kuhen, Kelli L.,Bursulaya, Badry,Nguyen, Truc N.,Nguyen, Deborah G.,He, Yun
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p. 4174 - 4177
(2007/10/03)
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- 4-PIPERAZINYL-PYRIMIDINE COMPOUNDS SUITABLE FOR TREATING DISORDERS THAT RESPOND TO MODULATION OF THE DOPAMINE D3 RECEPTOR
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The present invention relates to novel 4-piperazinylpyrimidine compounds. The compounds possess valuable therapeutic properties and are suitable, in particular, for treating diseases that respond to modulation of the dopamine D3 receptor. The 4- piperzinylpyrimidine compounds have the general formula (I), wherein Ar, X, A, R1 and R 1a are as defined in the claims.
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Page/Page column 47
(2010/10/19)
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- TRIAZOLE COMPOUNDS SUITABLE FOR TREATING DISORDERS THAT RESPOND TO MODULAIONT OF THE DOPAMINE D3 RECEPTOR
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The invention relates to compounds of formula (I), wherein n is 1 or 2, Ar is a C-bound 1,2,4-triazol radical which carries a radical R1 on the remaining carbon atom and a radical R1a on one of the nitrogen atoms; R1 is hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C4 alkoxymethyl, fluorinated C1-C6 alkyl, fluorinated C3-C6 cycloalkyl, fluorinated C1-C4 alkoxymethyl, or optionally substituted phenyl or 5- or 6-membered heteroaryl; R1a is hydrogen or C1-C4 alkyl; and R2 is C1-C6 alkyl, C3-C6 cycloalkyl, fluorinated C1-C6 alkyl or fluorinated C3-C6 cycloalkyl; and to the physiologically tolerated acid addition salts of there compounds. The invention also relates to a pharmaceuticaly composition that comprises at least one triazole compound of the formula (I) and/or at least one physiologically tolerated acid addition salt thereof, and further to a method for treating disorders that respond beneficially to dopamine D3 receptor antagonists or dopamine D3 agonists, said method comprising administering an effective amount of at least one traizole compound or physiologically tolerated acid addition salt of the formula (I) to a subject in need thereof.
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Page/Page column 20
(2010/11/08)
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- Inhibitors of hepatitis C virus RNA-dependent RNA polymerase, and compositions and treatments using the same
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The invention relates to compounds of the formula 1 and to pharmaceutically acceptable salts, solvates, prodrugs and metabolites thereof, wherein W, Z, R1 and R2, are as defined herein. The invention also relates to methods of treating Hepatitis C virus in mammals by administering the compounds of formula 1, and to pharmaceutical compositions for treating such disorders, which contain the compounds of formula 1. The invention also relates to methods of preparing the compounds of formula 1.
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Page/Page column 214
(2008/06/13)
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- Triazole compouds suitable for treating disorders that respond to modulation of the dopamine D3 receptor
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The invention relates to triazole compounds of the general formula I wherein R1 is hydrogen or methyl, and R2 is C3-C4 alkyl or C1-C2 fluoroalkyl, as well as the physiologically tolerated acid addition salts of these compounds. The invention also relates to a pharmaceutical composition that comprises at least one triazole compound of the formula I and/or at least one physiologically tolerated acid addition salt thereof, and further to a method for treating disorders that respond beneficially to dopamine D3 receptor antagonists or dopamine D3 agonists, said method comprising administering an effective amount of at least one triazole compound or physiologically tolerated acid addition salt of the formula I to a subject in need thereof.
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- Triazole compounds suitable for treating disorders that respond to modulation of the dopamine D3 receptor
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The invention relates to triazole compounds of the general formula I wherein R1 is hydrogen or methyl, and R2 is C3-C4 alkyl or C1-C2 fluoroalkyl, as well as the physiologically tolerated acid addition salts of these compounds. The invention also relates to a pharmaceutical composition that comprises at least one triazole compound of the formula I and/or at least one physiologically tolerated acid addition salt thereof, and further to a method for treating disorders that respond beneficially to dopamine D3 receptor antagonists or dopamine D3 agonists, said method comprising administering an effective amount of at least one triazole compound or physiologically tolerated acid addition salt of the formula I to a subject in need thereof.
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- Synthesis and structure-activity relationship of C-3 substituted triazolylthiomethyl cephems
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A series of C-3 substituted triazolylthiomethyl cephems with an aminothiazolemethoxyiminoacetamido side chain at C-7 were synthesized and tested for antimicrobial activity against clinically-relevant isolates. The compound with 3-pyridyl at C-5 and methyl at N-4 of the triazole moiety exhibited good antibacterial activity against both Gram-positive and Gram-negative bacteria, with the exception of pseudomonas spp against which none of the derivatives exhibited favorable activity.
- Singh,Fiakpui,Galpin,Stewart,Singh,Micetich
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p. 301 - 309
(2007/10/03)
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- Cephalosporin displacement reaction
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The present invention is directed to a process for the displacement of the acetoxy group of a cephalosporanic acid by a sulfur nucleophile, in an organic solvent and under essentially anhydrous conditions.
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