- Development of 2-Morpholino-N-hydroxybenzamides as anti-proliferative PC-PLC inhibitors
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Phosphatidylcholine-specific phospholipase C (PC-PLC) is a key enzyme involved in the metabolism of the mammalian phospholipid phosphatidylcholine into secondary messengers diacylglycerol (DAG) and phosphocholine. DAG and phosphocholine have been identifi
- Rees, Shaun W.P.,Leung, Euphemia,Reynisson, Jóhannes,Barker, David,Pilkington, Lisa I.
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- Incorporation of a nitric oxide donating motif into novel pc-plc inhibitors provides enhanced anti-proliferative activity
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Inhibition of phosphatidylcholine-specific phospholipase C (PC-PLC) has previously been shown to be a potential target for novel cancer therapeutics. One downstream consequence of PC-PLC activity is the activation of NF-κB, a nuclear transcription factor
- Rees, Shaun W. P.,Rees, Tayla A.,Leung, Euphemia,Walker, Christopher S.,Barker, David,Pilkington, Lisa I.
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- Development, synthesis and biological investigation of a novel class of potent PC-PLC inhibitors
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Phospholipases are enzymes that are involved in the hydrolysis of acyl and phosphate esters of phospholipids, generating secondary messengers that have implications in various cellular processes including proliferation, differentiation and motility. As such inhibitors of phospholipases have been widely studied for their use as anti-cancer therapeutics. Phosphatidylcholine-specific phospholipase C (PC-PLC) is implicated in the progression of a number of cancer cell lines including aggressing triple-negative breast cancers. Most current studies on PC-PLC have utilised D609 as the standard inhibitor however it is known to have multiple failings, including poor stability in aqueous media. 2-Morpholinobenzoic acids were recently identified using vHTS as a potential class of lead compounds, with improvements over D609. In this work 129 analogues in this class were prepared and their PC-PLC inhibitory activity was assessed. It was found that the majority of these novel compounds had improved activity when compared to D609 with the most potent inhibitors completely inhibiting enzyme activity. It was determined that the best compound/s contained a morpholino and 2-substituted N-benzyl moieties with these findings explained using molecular modelling. The compounds reported here will allow for improved study of PC-PLC activity.
- Barker, David,Langley, Ries J.,Leung, Euphemia,Leung, Ivanhoe K. H.,Paulin, Emily K.,Pilkington, Lisa I.,Rees, Shaun W. P.,Reynisson, Jóhannes,Sparrow, Kevin,Xu, Chris Sun,van Rensburg, Michelle
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- Aryl bithiazole compound and application
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The invention discloses an aryl bithiazole compound and application. A series of aryl bithiazole compounds are prepared in the invention, and application of the compounds is researched. According to biological activity test results, the aryl bithiazole compound provided by the invention has excellent herbicidal activity, has wide herbicide controlling spectrum to wheat, sorghum, barnyard grass, cucumber, oilseed rapes and radish, has a high inhibition rate on broadleaf weeds, and particularly has obvious inhibitory effects on amaranthus retroflexus and eclipta prostrate.
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Paragraph 0033; 0034
(2019/01/06)
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- FORMIMIDAMIDINE COMPOUNDS USEFUL AGAINST PHYTOPATHOGENIC MICROORGANISMS
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The present invention relates to 4-substituted amidine derivatives of the general formula (I), wherein A1-A4, D, L, Q, R7, R7' and integer's v and w have the meanings as defined in description. The invention further relates to methods for their preparation and use of said compounds to fight undesired phytopathogenic microorganisms, and agents for said purpose, comprising said amidine derivatives, all according to the invention. This invention further relates to a method for controlling undesired phytopathogenic microorganisms by application of said 4-substituted amidine derivatives of general formula (I) to such undesired microorganisms and/or to their habitat, according to the invention. (I)
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Page/Page column 77-78
(2018/12/12)
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- Acylhydrazone compounds with anti-tumor activity as well as preparation method and application of acylhydrazone compounds
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The invention belongs to the technical field of medicinal chemistry, and in particular relates to acylhydrazone compounds with anti-tumor activity as well as a preparation method and application of the acylhydrazone compounds. The structures of the acylhydrazone compounds are as shown in a general formula (I) shown in the description, wherein R and R' are independently selected from any one or more of halogen, amino, cyano, alkoxy, 3,4-methylenedioxy, nitro, phenyl or substituted phenyl, and R and R' substituents are mono-substituted, disubstituted or tri-substituted. The preparation method issimple; biological activity test results of the compounds show that the compounds have a very good inhibitory effect on histone methyltransferase SET7, and have good application prospect in the development of anti-tumor aspects.
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Paragraph 0039; 0040; 0041; 0042
(2018/05/16)
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- Dinuclear MoV Complexes with Thiophenolate-oxazoline Ligands: Synthesis, Characterization, and Exceptional Activity in Catalytic Olefin Epoxidation
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The synthesis, characterization, and epoxidation catalysis of two neutral, dinuclear molybdenum(V) complexes [{MoO(Lx)(μ-O)}2] (x = 1: 1; x = 2: 2) bearing S,N-bidentate thiophenolate-oxazoline ligands (L1, L2) are described. Both complexes are
- Peschel, Lydia M.,Belaj, Ferdinand,Schachner, J?rg A.,M?sch-Zanetti, Nadia C.
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p. 2808 - 2817
(2017/06/13)
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- NOVEL COMPOUNDS AS CHLORIDE CHANNEL BLOCKING AGENT
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Disclosed is a novel compound to function as a calcium-dependent chloride channel blocking agent.
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Paragraph 0365; 0366; 0367; 0368; 0369
(2015/06/03)
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- PREPARATION AND METHODS OF USE FOR ORTHO-ARYL 5- MEMBERED HETEROARYL-CARBOXAMIDE CONTAINING MULTI-TARGETED KINASE INHIBITORS
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The present disclosure relates to compounds of the Formula (I): and pharmaceutically acceptable salts, as kinase modulators, compatible with the Type-II inhibition of kinases.
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Page/Page column 90
(2013/03/26)
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- Mechanistic insights into a copper-disulfide interaction in oxidation of imines by disulfides
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The concept of using disulfides as an oxidant for Cu(i) is introduced as part of a Cu-catalyzed process leading to the formation of benzothiazole from an iminodisulfide under an inert atmosphere.
- Srogl, Jiri,Hyvl, Jakub,Revesz, Agnes,Schroeder, Detlef
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supporting information; experimental part
p. 3463 - 3465
(2009/12/26)
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- NPY ANTAGONISTS, PREPARATION AND USES
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The present invention concerns novel compounds, their preparation and their uses, therapeutic uses in particular. More specifically it concerns derivative compounds having at least two aromatic cycles, their preparation and their uses, in particular in the area of human or animal health. These compounds have an affinity for the biological receptors of neuropeptide Y, NPY, present in the central and peripheral nervous systems. The compounds of the invention are preferably NPY antagonists, and more particularly antagonists of sub-type NPY Y1, and can therefore be used for the therapeutic or prophylactic treatment of any disorder involving NPY. The present invention also concerns pharmaceutical compositions containing said compounds, their preparation and their uses, as well as treatment methods using said compounds.
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Page/Page column 86
(2009/09/28)
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- Kinetics of amide formation through carbodiimide/N-hydroxybenzotriazole (HOBt) couplings
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(Chemical Equation Presented) The kinetics of formation of amide, 4, from the corresponding carboxylic acid by reaction with the isopropyl ester of methionine (MIPE), mediated by carbodiimide EDCI, 1, and HOBt, 2, have been studied in 1-methyl-2-pyrrolidi
- Chan, Lai C.,Cox, Brian G.
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p. 8863 - 8869
(2008/03/12)
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- 5-5-MEMBERED FUSED HETEROCYCLIC COMPOUND AND USE THEREOF AS HCV POLYMERASE INHIBITOR
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The present invention relates to a fused ring compound represented by the following formula [I] wherein each symbol is as defined in the specification, or a pharmaceutically acceptable a salt thereof, and a hepatitis C virus (HCV) polymerase inhibitor and
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Page/Page column 119
(2008/06/13)
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- Enzyme kinetics and substrate selectivities of rat glutathione S-transferase isoenzymes towards a series of new 2-substituted 1-chloro-4-nitrobenzenes
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1. Four different rat glutathione S-transferase (GST) isoenzymes, belonging to three different classes, were examined for their GSH conjugating capacity towards 11 2-substituted 1-chloro-4-nitrobenzene derivatives. Significant differences were found in their enzyme kinetic parameters K(m), k(cat) and k(cat)/K(m). 2. Substrates with bulky substituents on the ortho-position appeared to have high affinities (low K(m)'s) for the active site of the GST-isoenzymes, suggesting that there is sufficient space in this area of the active site. A remarkably high K(m) (low affinity) was found for 2-chloro-5-nitropyridine towards all GST-isoenzymes examined. 3. GST 3-3 catalysed the reaction between GSH and the substrates most efficiently (high k(cat)) compared with the other GST-isoenzymes. Moreover, GST 3-3 showed clear substrate selectivities towards the substrates with a trifluoromethyl-, chlorine- and bromine-substituent. 1-Chloro-2,4-dinitrobenzene and 2-chloro-5-nitrobenzonitrile were most efficiently conjugated by all four GST-isoenzymes examined. 4. When the rate of the conjugation reactions was followed, a linear increase of formation of GS-conjugate could be seen for 2-chloro-5-nitrobenzonitrile during a much longer period of time than for 1-chloro-2,4-dinitrobenzene with all GST-isoenzymes examined. Therefore, it is suggested that 2-chloro-5-nitrobenzonitrile might be recommended as an alternative model substrate in GST-research.
- Van Der Aar,Buikema,Commandeur,Te Koppele,Van Ommen,Van Bladeren,Vermeulen
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p. 143 - 155
(2007/10/03)
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- N-phenyl-N-acetamidoglycinamides, their preparation and medicaments containing them
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Compounds of formula: STR1 in which R1 represents a hydrogen atom or an alkyl, alkoxycarbonyl or an unsubstituted or substituted phenyl radical, R2 represents a hydrogen atom or an unsubstituted or substituted alkyl radical, R3 represents an alkyl, phenylalkyl, indanyl, cycloalkylalkyl or an unsubstituted or substituted phenyl radical, or R2 and R3 form a heterocycle together with the nitrogen atom to which they are attached, and R4 represents an unsubstituted or substituted phenyl radical, a naphthyl, indolyl or quinolyl radical or a phenylamino radical in which the phenyl ring is unsubstituted or substituted, their preparation and medicaments containing them.
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- Aniline derivatives
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N-formyl anilino aromatic compounds containing two electronegative groups in the benzene ring, their manufacture from formanilides and aromatic halogen compounds and their use as intermediates for the manufacture of the corresponding diphenylamine compounds. The compounds are useful as pesticides.
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