- Synthesis and methemoglobinemia-inducing properties of benzocaine isosteres designed as humane rodenticides
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A number of isosteres (oxadiazoles, thiadiazoles, tetrazoles and diazines) of benzocaine were prepared and evaluated for their capacity to induce methemoglobinemia - with a view to their possible application as humane pest control agents. It was found that an optimal lipophilicity for the formation of methemoglobin (metHb) in vitro existed within each series, with 1,2,4-oxadiazole 3 (metHb% = 61.0 ± 3.6) and 1,3,4-oxadiazole 10 (metHb% = 52.4 ± 0.9) demonstrating the greatest activity. Of the 5 candidates (compounds 3, 10, 11, 13 and 23) evaluated in vivo, failure to induce a lethal end-point at doses of 120 mg/kg was observed in all cases. Inadequate metabolic stability, particularly towards hepatic enzymes such as the CYPs, was postulated as one reason for their failure.
- Conole, Daniel,Beck, Thorsten M.,Jay-Smith, Morgan,Tingle, Malcolm D.,Eason, Charles T.,Brimble, Margaret A.,Rennison, David
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supporting information
p. 2220 - 2235
(2014/04/17)
-
- Crystal landscape of primary aromatic thioamides
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The crystal landscape of a series of primary aromatic thioamides is described, displaying similar characteristic intermolecular hydrogen-bonding interactions in the solid state to those observed in their widely studied amide analogues, including R22(8) dimers and C(4) chains. In a number of cases, high Z′ values were observed in the structures. On the basis of the observed solid-state features, the thioamide functional group, which is a strong hydrogen-bond donor and moderate acceptor, offers considerable potential as a key moiety for crystal engineering.
- Eccles, Kevin S.,Morrison, Robin E.,Maguire, Anita R.,Lawrence, Simon E.
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p. 2753 - 2762
(2014/06/23)
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- Agonists for the adenosine A1 receptor with tunable residence time. a case for nonribose 4-amino-6-aryl-5-cyano-2-thiopyrimidines
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We report the synthesis and evaluation of previously unreported 4-amino-6-aryl-5-cyano-2-thiopyrimidines as selective human adenosine A 1 receptor (hA1AR) agonists with tunable binding kinetics, this without affecting their nanomolar affinity for the target receptor. They show a very diverse range of kinetic profiles (from 1 min (compound 52) to 1 h (compound 43)), and their structure-affinity relationships (SAR) and structure-kinetics relationships (SKR) were established. When put in perspective with the increasing importance of binding kinetics in drug discovery, these results bring new evidence of the consequences of affinity-only driven selection of drug candidates, that is, the potential elimination of slightly less active compounds that may display preferable binding kinetics.
- Louvel, Julien,Guo, Dong,Agliardi, Marta,Mocking, Tamara A. M.,Kars, Roland,Pham, Tan Phát,Xia, Lizi,De Vries, Henk,Brussee, Johannes,Heitman, Laura H.,Ijzerman, Adriaan P.
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supporting information
p. 3213 - 3222
(2014/05/20)
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- Evaluation of thiazole containing biaryl analogs as diacylglycerol acyltransferase 1 (DGAT1) inhibitors
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Biphenyl carboxylic acids, exemplified by compound 5, are known potent inhibitors of diacylglycerol acyltransferase, DGAT1, an enzyme involved in the final committed step of triglyceride biosynthesis. We have synthesized and evaluated 2-phenylthiazole, 4-
- Kadam, Kishorkumar S.,Jadhav, Ravindra D.,Kandre, Shivaji,Guha, Tandra,Reddy, M. Mahesh Kumar,Brahma, Manoja K.,Deshmukh, Nitin J.,Dixit, Amol,Doshi, Lalit,Srinivasan, Shaila,Devle, Jayendra,Damre, Anagha,Nemmani, Kumar V. S.,Gupte, Amol,Sharma, Rajiv
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p. 337 - 347
(2013/10/01)
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- Sulfonic acid functionalized nano Γ-Al 2O 3: A new, efficient, and reusable catalyst for synthesis of thioamides
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Sulfonic acid functionalized nano γ-Al2O3 is easily prepared by the reaction of nano γ-Al2O3 with 1,3-propane sulfone. This reagent can be used as an eficient catalyst for the synthesis of thioamides. This new method consistently has the advantages of excellent yields and short reaction times. Further, the catalyst can be recovered for several times.
- Yin, Zhikui,Zheng, Bin,Ai, Fang
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p. 1412 - 1420
(2013/10/08)
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- Nano n -propylsulfonated magnetic γ-Fe2O3 as an efficient and reusable catalyst for the synthesis of thioamides
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One-pot three-component reactions of aldehydes, amines, and sulfur are carried out in the presence of nano n-propylsulfonated magnetic γ-Fe2O3 as a catalyst for the synthesis of biologically interesting thioamide derivatives. The value of this catalytic method lies in its mild reaction catalyst and conditions, good yields, and ease of handling.
- Yin, Zhikui,Zheng, Bin
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p. 527 - 531
(2013/10/21)
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- COMPOSITIONS AND METHODS FOR MODULATING A KINASE
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The invention relates to compounds and methods for modulating one or more components of a kinase signaling cascade
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Page/Page column 167; 168
(2013/02/27)
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- Optimizing thiadiazole analogues of resveratrol versus three chemopreventive targets
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Chemoprevention is an approach to decrease cancer morbidity and mortality through inhibition of carcinogenesis and prevention of disease progression. Although the trans stilbene derivative resveratrol has chemopreventive properties, its action is compromised by weak non-specific effects on many biological targets. Replacement of the stilbene ethylenic bridge of resveratrol with a 1,2,4-thiadiazole heterocycle and modification of the substituents on the two aromatic rings afforded potential chemopreventive agents with enhanced potencies and selectivities when evaluated as inhibitors of aromatase and NF-κB and inducers of quinone reductase 1 (QR1).
- Mayhoub, Abdelrahman S.,Marler, Laura,Kondratyuk, Tamara P.,Park, Eun-Jung,Pezzuto, John M.,Cushman, Mark
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experimental part
p. 510 - 520
(2012/03/10)
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- A thiophosphoryl chloride assisted transformation of arylaldoximes to thioamides
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Primary benzothioamides were accessed from benzaldoximes (benzaldehyde oximes) via benzonitriles in a sequential tandem approach utilizing thiophosphoryl chloride as a dehydrating and thionating agent. Georg Thieme Verlag Stuttgart New York.
- Pandey, Lokesh Kumar,Pathak, Uma,Mathur, Sweta,Suryanarayana
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p. 377 - 379
(2012/03/27)
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- O,O-Diethyl dithiophosphoric acid mediated direct synthesis of thioamides from aldehydes and ketones
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A general and convenient method for a one-pot conversion of aldehydes and ketones into thioamides has been developed. The protocol involves oximation of aldehydes and ketones followed by deoxygenative thioamidation of oximes with O,O-diethyl dithiophosphoric acid which acts as an acid as well a source of sulfur. The method is operationally simple, high yielding, and also applicable to the conversion of amides and nitriles into the corresponding thioamides.
- Yadav, Arvind K.,Srivastava, Vishnu P.,Yadav, Lal Dhar S.
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p. 7113 - 7116
(2013/01/15)
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- Sulfated tungstate: An efficient catalyst for synthesis of thioamides via Kindler reaction
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New application of sulfated tungstate, a mildly acidic solid inorganic acid, as reusable heterogeneous catalyst for efficient Kindler reaction, a three component reactions of aldehydes, amines and sulfur, for synthesis of thioamides is discussed.
- Pathare, Sagar P.,Chaudhari, Pramod S.,Akamanchi, Krishnacharya G.
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experimental part
p. 125 - 129
(2012/07/03)
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- P4S10/dimethicone tandem: Efficient reagent for thionation of various aromatic amides and esters
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Organosulfur compounds are valuable because of their rich and varied chemistry especially in biological field. We report a new and efficient way for thionation of various aromatic amides and esters using P4S 10/ dimethicone tandem. The ease of handling and higher yield makes this protocol economical.
- Cho, Dongho,Ahn, Jiyoung,De Castro, Kathlia A.,Ahn, Hyunseok,Rhee, Hakjune
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supporting information; experimental part
p. 5583 - 5588
(2010/10/02)
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- 2-ARYL- AND 2-HETEROARYLTHIAZOLYL COMPOUNDS, METHODS FOR THEIR PREPARATION AND USE THEREOF
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The present invention discloses fused bicyclic 2-aryl- or 2-heteroarylthiazolyl compounds and their pharmaceutically acceptable salts and esters thereof, which are useful for inhibiting the growth of cancerous cells, inhibiting human breast carcinoma tumo
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Page/Page column 49
(2009/10/22)
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- The BF3·OEt2-assisted conversion of nitriles into thioamides with Lawesson's reagent
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A method for the thiolysis of nitriles by applying Lawesson's reagent and facilitated by the addition of boron trifluoride-diethyl ether complex is reported. The method opens an easy access to primary thioamides. Aromatic, benzylic, and aliphatic nitriles were converted into the corresponding thioamides in high to quantitative yields (even in unfavorable cases, e.g., ortho-substitut-ed benzonitriles). The reaction was performed in 1,2-dimethoxyethane-tetrahydrofuran or toluene-diethyl ether solvent mixtures at 20-50°C, and exhibited considerable selectivity in the case of multifunctional nitrile substrates, such as cyanomethyl N-acetylphenylalaninate, benzoylacetonitrile, 4-cyanobenzamide, 4-acetylbenzonitrile, or pent-3-enenitrile. Georg Thieme Verlag Stuttgart.
- Nagl, Michael,Panuschka, Claudia,Barta, Andrea,Schmid, Walther
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experimental part
p. 4012 - 4018
(2009/05/27)
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- Substituted 2-[(4-aminomethyl)phenoxy]-2-methylpropionic acid PPARα agonists. 1. Discovery of a novel series of potent HDLc raising agents
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The peroxisome proliferator activated receptors PPARα, PPARγ, and PPARδ are ligand-activated transcription factors that play a key role in lipid homeostasis. The fibrates raise circulating levels of high-density lipoprotein cholesterol and lower levels of triglycerides in part through their activity as PPARα agonists; however, the low potency and restricted selectivity of the fibrates may limit their efficacy, and it would be desirable to develop more potent and selective PPARα agonists. Modification of the selective PPARδ agonist 1 (GW501516) so as to incorporate the 2-aryl-2-methylpropionic acid group of the fibrates led to a marked shift in potency and selectivity toward PPARα agonism. Optimization of the series gave 25a, which shows EC50 = 4 nM on PPARα and at least 500-fold selectivity versus PPARγ and PPARγ. Compound 25a (GW590735) has been progressed to clinical trials for the treatment of diseases of lipid imbalance.
- Sierra, Michael L.,Beneton, Véronique,Boullay, Anne-Bénédict,Boyer, Thierry,Brewster, Andrew G.,Donche, Frédéric,Forest, Marie-Claire,Fouchet, Marie-Hélène,Gellibert, Fran?oise J.,Grillot, Didier A.,Lambert, Millard H.,Laroze, Alain,Le Grumelec, Christelle,Linget, Jean Michel,Montana, Valerie G.,Nguyen, Van-Loc,Nicodème, Edwige,Patel, Vipul,Penfornis, Annie,Pineau, Olivier,Pohin, Danig,Potvain, Florent,Poulain, Géraldine,Ruault, Cécile Bertho,Saunders, Michael,Toum, Jér?me,Xu, H. Eric,Xu, Robert X.,Pianetti, Pascal M.
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p. 685 - 695
(2007/10/03)
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- Phosphorus pentasulfide: A mild and versatile reagent for the preparation of thioamides from nitriles
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A simple, efficient, and new method has been developed for the synthesis of thioamides from nitriles. The reaction of a variety of aromatic and aliphatic nitriles in the presence of phosphorus pentasulfide afforded the corresponding thioamides in high yields. This method is easy, rapid, and high-yielding for the synthesis of thioamides from nitriles. Georg Thieme Verlag Stuttgart.
- Kaboudin, Babak,Elhamifar, Dawood
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p. 224 - 226
(2007/10/03)
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- AMINO ACIDS
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Compounds of formula (I): Z’ -CO-A-B-NH-Z (I) wherein: Z is H or an amino protecting group; Z’ is OH, a protected or activated hydroxyl group or C1; A is an optionally substituted C5-6 arylene group; and B is an optionally substituted C5-6 arylene group.
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Page/Page column 39
(2008/06/13)
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- Derivatives of 2-(iminomethyl)amino-phenyl, their preparation, their use as medicaments and the pharmaceutical compositions containing them
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The invention relates to new derivatives of 2-(iminomethyl)amino-phenyl which are NO synthase inhibitors and can trap reactive oxygen species. These compounds can notably be used for the treatment of stroke, of neurodegenerative diseases and of ischemic or hemorragic cardiac or cerebral infarctions. These compounds include: N-{4-[({[4-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,3-thiazol-2-yl]methyl}amino)methyl]phenyl}thiophene-2-carboximidamide; N-{3-[({[4-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,3-thiazol-2-yl]methyl}amino)methyl]phenyl}thiophene-2-carboximidamide; N-(4-{[{[4-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,3-thiazol-2-yl]methyl}(methyl)amino]methyl}phenyl)thiophene-2-carboximidamide; N-[3-({[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propyl]amino}methyl)phenyl]thiophene-2-carboximidamide; N-(3-{[(3,5-di-tert-butyl-4-hydroxybenzyl)amino]methyl}phenyl)thiophene-2-carboximidamide; N-[3-({[2-(3,5-di-tert-butyl-4-hydroxyphenyl)ethyl]amino}methyl)phenyl]thiophene-2-carboximidamide; N-[3-({[3-(4-hydroxy-3,5-diisopropylphenyl)propyl]amino}methyl)phenyl]thiophene-2-carboximidamide; N-(3-{[(4-hydroxy-3,5-diisopropylbenzyl)amino]methyl}phenyl) thiophene-2-carboximidamide; N-[3-({[2-(4-hydroxy-3,5-diisopropylphenyl)ethyl]amino}methyl)phenyl]thiophene-2-carboximidamide; N-2-(3,5-di-tert-butyl-4-hydroxybenzoyl)-N-1-(4-{[imino(thien-2-yl)methyl]amino}phenyl)-L-leucinamide; and pharmaceutically acceptable salts thereof.
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-
-
- New derivatives of 2-(iminomethyl)amino-phenyl, their preparation, their use as medicaments and the pharmaceutical compositions containing them
-
The invention relates to new derivatives of 2-(iminomethyl)amino-phenyl which are NO synthase inhibitors and can trap reactive oxygen species. These compounds can notably be used for the treatment of stroke, of neurodegenerative diseases and of ischemic or hemorragic cardiac or cerebral infarctions. These compounds include: N-{4-[({[4-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,3-thiazol-2-yl]methyl}amino)methyl]phenyl}thiophene-2-carboximidamide; N-{3-[({[4-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,3-thiazol-2-yl]methyl}amino)methyl]phenyl}thiophene-2-carboximidamide; N-(4-{[{[4-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,3-thiazol-2-yl]methyl}(methyl)amino]methyl}phenyl)thiophene-2-carboximidamide; N-[3-({[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propyl]amino}methyl) phenyl]thiophene-2-carboximidamide; N-(3-{[(3,5-di-tert-butyl-4-hydroxybenzyl)amino]methyl}phenyl) thiophene-2-carboximidamide; N-[3-({[2-(3,5-di-tert-butyl-4-hydroxyphenyl)ethyl]amino}methyl) phenyl]thiophene-2-carboximidamide; N-[3-({[3-(4-hydroxy-3,5-diisopropylphenyl)propyl]amino}methyl) phenyl]thiophene-2-carboximidamide; N-(3-{[(4-hydroxy-3,5-diisopropylbenzyl)amino]methyl}phenyl) thiophene-2-carboximidamide; N-[3-({[2-(4-hydroxy-3,5-diisopropylphenyl)ethyl]amino}methyl) phenyl]thiophene-2-carboximidamide; N-2-(3,5-di-tert-butyl-4-hydroxybenzoyl)-N-1-(4-{[imino(thien-2-yl)methyl]amino}phenyl)-L-leucinamide; and pharmaceutically acceptable salts thereof.
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-
-
- Derivatives of 2-(iminomethyl)amino-phenyl, their preparation, their use as medicaments and the pharmaceutical compositions containing them
-
A compound selected from the group consisting of a compound of the formula wherein A is selected from the group consisting of and the other substituents are defined in the specification having an inhibitory activity of NO-synthase enzymes producing nitrogen mono-oxide and/or an activity which traps the reactive oxygen species.
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-
Page column 98
(2008/06/13)
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- Novel thiazole derivatives as inhibitors of superoxide production by human neutrophils: Synthesis and structure-activity relationships
-
Neutrophils have an important role in the self-defense systems of organisms through the production of superoxide. On the other hand, it has been proposed that abnormal amounts of superoxide produced by neutrophils are a serious factor in tissue injury. A series of novel thiazole derivatives was prepared and evaluated inhibitory effect on superoxide production by human neutrophils in vitro. Among these compounds, 6-[2-(3,4- diethoxyphenyl)thiazol-4-yl]-pyridine-2-carboxylic acid (OPC-6535) was selected as one of the most promising compounds. The synthesis and structure- activity relationships of these compounds are reported herein.
- Chihiro,Nagamoto,Takemura,Kitano,Komatsu,Sekiguchi,Tabusa,Mori,Tominaga,Yabuuchi
-
p. 353 - 358
(2007/10/02)
-
- THE REACTION OF NITRILES WITH O,O-DIALKYL-DITHIOPHOSPHORIC ACIDS
-
Nitriles react with dialkyldithiophosphoric acids 2a-c to give a mixture of corresponding thioamides and O,O-dialkyl-N-thioacetyl-phosphoroamidothioates 3a-e.The structure of compounds 3 are elucidated chemically and from electronic spectra.The yield of thioamides are improved from the reaction of nitriles with compound 2b in presence of water.Mechanistic consideration on the formation of the products are discussed.
- Yousif, N. M.
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p. 4599 - 4604
(2007/10/02)
-
- STUDIES ON ORGANOPHOSPHORUS COMPOUNDS PART 55 THE TRANSFORMATION OF NITRILES TO THIOAMIDES WITH O,O-DIALKYLDITHIOPHOSPHORIC ACID
-
The reaction between nitriles and O,O-dialkyldithiophosphoric acid (2) under anhydrous conditions produces O,O-diethyl-N-thiobenzoylamidophosphate (5), contrary to literature.When water is present the same reaction gives the corresponding thioamides in reasonable to good yields.Mechanistic considerations and spectral data are presented for the products.
- Shabana, R.,Meyer, H.J.,Lawesson, S.-O.
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p. 297 - 306
(2007/10/02)
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- Correlation pKa - activitee catalitique des thiols dans la reeaction d'hydrolyse de l'aceetate de p-nitropheenyle
-
The kinetic study of the hydrolysis of p-nitrophenylacetate in the presence of primary thiols indicates the thiolate anion as the sole catalytic species.Comparison of the true second order constants (kRS-) reveals that purely aliphatic primary thiols behave differently from aromatic α-substituted primary thiols.In the latter group a correlation can be established between the true second order rate constants and the pKSH values by means of the Broensted equation log kRS- = βpKSH + C, with β equal to 0.40 and C equal to -0.85.
- Brembilla, Alain,Roizard, Denis,Schoenleber, Jacqueline,Lochon, Pierre
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p. 2330 - 2336
(2007/10/02)
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- DIPHENYLPHOSPHINODITHIOIC ACID: A REAGENT FOR THE CONVERSION OF NITRILES TO THIOAMIDES
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Diphenylphosphinodithioic acid is a reagent useful for a sequence effecting the hydrolysis of nitriles under mild conditions.
- Benner, Steven A.
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p. 1851 - 1854
(2007/10/02)
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- MECHANISM OF THE REACTION OF DIPHENYLPHOSPHINODITHIOIC ACID WITH NITRILES
-
Kinetic studies of the reaction of diphenylphosphinodithioic acid with nitriles support a two step mechanism, the first step being an "ene" reaction.
- Benner, Steven A.
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p. 1855 - 1858
(2007/10/02)
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