- Highly efficient asymmetric bioreduction of 1-aryl-2-(azaaryl)ethanones. Chemoenzymatic synthesis of lanicemine
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Different ketoreductases (KREDs) have been used to promote a highly selective reduction of several 1-aryl-2-(azaaryl)ethanones (azaaryl = pyridinyl, quinolin-2-yl), the corresponding secondary alcohols being obtained with very high yields and enantiomeric excesses (ee > 99%). The absolute configuration of each optically active alcohol has been assigned by means of modified Mosher and Kelly methods, two shielding effects being evaluated: (1) the Mosher phenyl ring effect on the azaaryl protons and (2) the one of the azaaryl ring on the Mosher methoxy group. In addition, the biologically active amine lanicemine has been synthesized from (R)-1-phenyl-2-(pyridin-2-yl)ethanol, thus proving the utility of the secondary alcohols here prepared.
- Liz, Ramón,Liardo, Elisa,Rebolledo, Francisca
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supporting information
p. 8214 - 8220
(2019/09/19)
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- Synthesis of functionalised 4H-quinolizin-4-ones via tandem Horner-Wadsworth-Emmons olefination/cyclisation
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4H-Quinolizin-4-ones are a unique class of heterocycle with valuable physicochemical properties and which are emerging as key pharmacophores for a range of biological targets. A tandem Horner-Wadsworth-Emmons olefination/cyclisation method has been developed to allow facile access to substituted 4H-quinolizin-4-ones encoded with a range of functional groups.
- Muir, Calum W.,Kennedy, Alan R.,Redmond, Joanna M.,Watson, Allan J. B.
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supporting information
p. 3337 - 3340
(2013/06/05)
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- The application of flow microreactors to the preparation of a family of casein kinase i inhibitors
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In this article we demonstrate how a combination of enabling technologies such as flow synthesis, solid-supported reagents and scavenging resins utilised under fully automated software control can assist in typical medicinal chemistry programmes. In particular automated continuous flow methods have greatly assisted in the optimisation of reaction conditions and facilitated scale up operations involving hazardous chemical materials. Overall a collection of twenty diverse analogues of a casein kinase I inhibitor has been synthesised by changing three principle binding vectors.
- Venturoni, Francesco,Nikbin, Nikzad,Ley, Steven V.,Baxendale, Ian R.
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experimental part
p. 1798 - 1806
(2010/08/07)
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- Synthesis and SAR of 2,3-diarylpyrrole inhibitors of parasite cGMP-dependent protein kinase as novel anticoccidial agents
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Several analogs of 2,3-diaryl pyrroles were synthesized and evaluated as inhibitors of Eimeria tenella cGMP-dependent protein kinase and in in vivo anticoccidial assays. A 4-fluorophenyl group enhances both in vitro and in vivo activities. The most potent
- Biftu, Tesfaye,Feng, Dennis,Ponpipom, Mitree,Girotra, Narindar,Liang, Gui-Bai,Qian, Xiaoxia,Bugianesi, Robert,Simeone, Joseph,Chang, Linda,Gurnett, Anne,Liberator, Paul,Dulski, Paula,Leavitt, Penny Sue,Crumley, Tami,Misura, Andrew,Murphy, Terence,Rattray, Sandra,Samaras, Samantha,Tamas, Tamas,Mathew, John,Brown, Christine,Thompson, Don,Schmatz, Dennis,Fisher, Michael,Wyvratt, Matthew
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p. 3296 - 3301
(2007/10/03)
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- Pyrazolopyridines
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The invention provides the compounds of formula (I) wherein: R0and R1are independently selected from H, halogen, C1-6alkyl, C1-6alkoxy, or C1-6alkoxy substituted by one or more fluorine atoms; R2
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- Identification of novel inhibitors of the transforming growth factor β1 (TGF-β1) type 1 receptor (ALK5)
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Screening of our internal compound collection for inhibitors of the transforming growth factor β1 (TGF-β1) type I receptor (ALK5) identified several hits. Optimization of the dihydropyrroloimidazole hit 2 by introduction of a 2-pyridine and 3,4-methylenedioxyphenyl group gave 7, a selective ALK5 inhibitor. With this information, optimization of the triarylimidazole hit 8 gave the selective inhibitor 14, which inhibits TGF-β1-induced fibronectin mRNA formation while displaying no measurable cytotoxicity in the 48 h XTT assay.
- Callahan, James F.,Burgess, Joelle L.,Fornwald, James A.,Gaster, Laramie M.,Harling, John D.,Harrington, Frank P.,Heer, Jag,Kwon, Chet,Lehr, Ruth,Mathur,Olson, Barbara A.,Weinstock, Joseph,Laping, Nicholas J.
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p. 999 - 1001
(2007/10/03)
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- Substituent and temperature controlled tautomerism of 2-phenacyl-pyridine: The hydrogen bond as a configurational lock of (Z)-2-(2-hydroxy-2-phenylvinyl)pyridine
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2-Phenacylpyridines substituted in the benzene ring are in equilibrium with (Z)-2-(2-hydroxy-2-phenylvinyl)pyridines when dissolved in chloroform. The substituent affects significantly the tautomeric equilibrium [the amount of the enolimine form stabilized by the intramolecular hydrogen bond is 1 and 92% for R = p-N(CH2)4 and p-NO2, respectively]. The negative logarithm of the tautomeric equilibrium constant, KT, is linearly dependent on the Hammett σ substituent constants. The dependence of KT vs. temperature is exponential in character: the more electron-withdrawing is the substituent, the more distinct is the influence of temperature. Unexpectedly, the tautomer present in the crystalline state is not the same for all compounds studied (it is the ketimine one for those carrying strong electron-donor groups). Among the different ab initio methods used to calculate the enthalpy of the proton transfer in chloroform solution, MP2/6-31G** gives the best results.
- Kolehmainen, Erkki,Osmiaowski, Borys,Nissinen, Maija,Kauppinen, Reijo,Gawinecki, Ryszard
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p. 2185 - 2191
(2007/10/03)
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