- Discovery of CYT997: a structurally novel orally active microtubule targeting agent
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CYT997 was discovered as a potent tubulin polymerization inhibitor possessing potent cytotoxic activity against a range of cancer cells. Details of SAR studies, pharmacokinetic investigations and synthesis of compounds leading to the discovery of CYT997 a
- Burns, Christopher J.,Harte, Michael F.,Bu, Xianyong,Fantino, Emmanuelle,Joffe, Max,Sikanyika, Harrison,Su, Stephen,Tranberg, C. Elisabet,Wilson, Neil,Charman, Susan A.,Shackleford, David M.,Wilks, Andrew F.
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- Co/NHPI-mediated aerobic oxygenation of benzylic C-H bonds in pharmaceutically relevant molecules
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A simple cobalt(ii)/N-hydroxyphthalimide catalyst system has been identified for selective conversion of benzylic methylene groups in pharmaceutically relevant (hetero)arenes to the corresponding (hetero)aryl ketones. The radical reaction pathway tolerates electronically diverse benzylic C-H bonds, contrasting recent oxygenation reactions that are initiated by deprotonation of a benzylic C-H bond. The reactions proceed under practical reaction conditions (1 M substrate in BuOAc or EtOAc solvent, 12 h, 90-100 °C), and they tolerate common heterocycles, such as pyridines and imidazoles. A cobalt-free, electrochemical, NHPI-catalyzed oxygenation method overcomes challenges encountered with chelating substrates that inhibit the chemical reaction. The utility of the aerobic oxidation method is showcased in the multigram synthesis of a key intermediate towards a drug candidate (AMG 579) under process-relevant reaction conditions.
- Hruszkewycz, Damian P.,Miles, Kelsey C.,Thiel,Stahl, Shannon S.
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p. 1282 - 1287
(2017/02/10)
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- RENIN INHIBITORS
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The invention relates to compounds having the formula: STR wherein the variables are as defined herein. The invention further relates to methods of making and using these compounds, intermediates which can be used to make the compounds, and pharmaceutical compositions, kits and articles of manufacture which contain the compounds.
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Page/Page column 151-152
(2010/11/17)
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- ORGANIC COMPOUNDS
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The present invention provides novel organic compounds of Formula (I): methods of use, and pharmaceutical compositions thereof.
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- Palladium-catalyzed synthesis of aryl ketones by coupling of aryl bromides with an acyl anion equivalent
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Palladium-catalyzed couplings of aryl bromides with N-tert-butylhydrazones as acyl anion equivalents to form aryl ketones are reported. The coupling process occurs at the C-position of hydrazones to form N-tert-butyl azo compounds. Isomerization of these azo compounds to the corresponding hydrazones, followed by hydrolysis, gave the desired mixed alkyl aryl ketones. The selectivity of C- versus N-arylation was strongly influenced by the substituent on nitrogen. Arylation at carbon occurred with N-tert-butylhydrazones, whereas N-arylation occurred with N-arylhydrazones. The arylation of hydrazones containing primary and secondary alkyl groups, as well as aryl groups, gave the desired ketones in good yields after hydrolysis. Functional groups on the aromatic ring, such as alkoxy, cyano, trifluoromethyl, carboalkoxy, carbamoyl, and keto groups, were tolerated. This reaction likely occurs by C-C bond-forming reductive elimination from an intermediate containing an η1-diazaallyl ligand. Copyright
- Takemiya, Akihiro,Hartwig, John F.
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p. 14800 - 14801
(2008/02/05)
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- A new and highly efficient water-soluble copper complex for the oxidation of secondary 1-heteroaryl alcohols by tert-butyl hydroperoxide
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The water-soluble copper complex generated in situ from CuCl2 and 2,2′-biquinoline-4,4′-dicarboxylic acid dipotassium salt (BQC), has been revealed as a highly efficient and selective catalyst for the oxidation of secondary 1-heteroaryl alcohols to the corresponding heteroaromatic ketones with aqueous tert-butyl hydroperoxide, under mild conditions. The catalytic system is compatible with different heterocycles such as pyridines, pyrroles, indoles, thiophens, furans, thiazoles, and imidazoles.
- Boudreau, Josée,Doucette, Mike,Ajjou, Abdelaziz Nait
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p. 1695 - 1698
(2007/10/03)
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- Bismuth-catalyzed benzylic oxidations with tert-butyl hydroperoxide
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(Chemical Equation Presented) Oxidation of alkyl and cycloalkyl arenes with tert-butyl hydroperoxide catalyzed by bismuth and picolinic acid in pyridine and acetic acid gave the corresponding benzylic ketones (48-99%). Alternatively, oxidation of methyl arenes gave the corresponding substituted benzole acids (50-95%). Preliminary mechanistic studies were consistent with a radical mechanism rather than a bismuth(III)-bismuth(V) cycle.
- Bonvin, Yannick,Callens, Emmanuel,Larrosa, Igor,Henderson, David A.,Oldham, James,Burton, Andrew J.,Barrett, Anthony G. M.
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p. 4549 - 4552
(2007/10/03)
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- Catalytic oxidation of alkyl- and benzyl-pyridines using calcined ZnCrCO3-HTlc
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A simple and convenient catalytic methodology for the oxidation of alkyl- and benzyl-pyridines with TBHP to pyridyl ketones in higher yields than the earlier reported methodologies using calcined ZnCrCO3-HTlc is being reported for the first time.
- Choudary,Bhuma,Narender
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p. 281 - 282
(2007/10/03)
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- Sunscreen compositions and compounds for use therein
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The invention relates to sunscreen compositions comprising an effective component at least one compound of formula I STR1 wherein R1 is selected from alkyl, alkenyl, alkynyl substituted alkyl, substituted alkenyl, phenyl, substituted phenyl, substituted benzyl, cycloalkyl, cycloalkenyl, substituted cycloalkyl, substituted cycloalkenyl and polymeric groups; R2 is selected from hydrogen, alkyl and alkoxy; and wherein R1 and R2 may form a carbocyclic ring which may be substituted; R3 is selected from alkyl, sustituted alkyl, alkenyl, substituted alkenyl, alkynyl, phenyl, benzoyl, substituted phenyl, substituted benzyl, substituted benzoyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, alkanyoyl, substituted alkanoyl, polymeric groups, the group OROROR9 wherein R is a bivalent hydrocarbon radical and R9 is alkyl, alkenyl, phenyl benzyl, substituted phenyl, substituted benzyl; R4 is alkyl or alkoxy; n is an integer from 0 to 4; and R5 and R6 are independently selected from alkyl, alkoxy, alkanoyl, alkanoyl substituted by hydroxyl or alkoxycarbonyl and R5 and R6 may form a spiro carbocyclic ring which may be substituted with alkyl; and the invention also relates to novel compounds of formula I and to a method of screening a surface from ultraviolet radiation.
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- Etude de l'action des organomagnesiens sur les derives carboxyliques de la pyridine
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Reactions of Grignard reagents with pyridinecarboxylic esters 1, 2, pyridine-2-carboxylic acid (3), and 2,3-pyridinecarboxylic acid anhydride (5) show regioselectivity at the carbonyl in position 2.This is exemplified by an efficient synthesis of 7,7-dial
- Canonne, P.,Belley, M.
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p. 1885 - 1890
(2007/10/02)
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- A New Simple Synthesis of Fusaric Acid and Other 5-Alkyl-2-pyridinecarboxylic Acids
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Carboxamido groups are introduced into the 6-position of 3-acylpyridines with high regioselectivity via Minisci reaction with formamides, Fe(II) sulfate and tert-butyl hydroperoxide.The isolation procedure is considerably improved by the addition of citric acid for complexation of the Fe ions.Fusaric acid and other 5-alkyl-2-pyridine carboxylic acids are obtained by a following Wolff-Kishner reaction in 20-75percent overall yield.
- Langhals, Elke,Langhals, Heinz,Ruechardt, Christoph
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p. 930 - 949
(2007/10/02)
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- Ligand interaction of sustituted pyridines with cytochrome P-450.
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A series of pyridyl ketones and alkyl pyridines was evaluated as type II ligands for cytochrome P-450. Activity as type II ligands was evaluated in terms of the lipid solubility and the pKa values of the compounds.
- Born,Early
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p. 850 - 851
(2007/10/02)
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