- USE OF PYRAZOLOPYRIMIDINE DERIVATIVES FOR THE TREATMENT OF PI3K-DELTA RELATED DISORDERS
-
The present application provides methods of treating PI3Kδ related disorders using compounds of Formula I: or pharmaceutically acceptable salts thereof.
- -
-
Paragraph 0368
(2014/09/16)
-
- HETEROCYCLYLAMINES AS PI3K INHIBITORS
-
The present invention provides heterocyclylamine derivatives of Formula I: wherein the variables are defined herein, that modulate the activity of phosphoinositide 3-kinases (PI3Ks) and are useful in the treatment of diseases related to the activity of PI3Ks including, for example, inflammatory disorders, immune-based disorders, cancer, and other diseases.
- -
-
Paragraph 1063
(2013/03/26)
-
- Study of the lanthanide-catalyzed, aqueous, asymmetric Mukaiyama aldol reaction
-
The development of efficient methods for the asymmetric Mukaiyama aldol reaction in aqueous solution has received great attention. We have developed a new series of chiral lanthanide-containing complexes that produce Mukaiyama aldol products with outstanding enantioselectivities. In this paper, we describe an optimized ligand synthesis, trends in stereoselectivity that result from changing lanthanide ions, and an exploration of substrate scope that includes aromatic and aliphatic aldehydes and silyl enol ethers derived from aromatic and aliphatic ketones.
- Mei, Yujiang,Averill, Derek J.,Allen, Matthew J.
-
scheme or table
p. 5624 - 5632
(2012/09/05)
-
- A new class of ligands for aqueous, lanthanide-catalyzed, enantioselective Mukaiyama aldol reactions
-
The development of aqueous methods for generating enantiopure β-hydroxy carbonyl compounds is an important goal because these subunits compose many bioactive compounds and the ability to synthesize these groups in water has environmental and cost benefits. In this communication, we report a new class of ligands for aqueous, lanthanide-catalyzed, asymmetric Mukaiyama aldol reactions for the synthesis of chiral β-hydroxy ketones. Furthermore, we have used luminescence-decay measurements to unveil mechanistic information regarding the catalytic reaction via changes in water-coordination number. The precatalysts presented here yielded β-hydroxy carbonyls from aliphatic and aryl substrates with outstanding syn:anti ratios and enantiometric excesses of up to 49:1 and 97%, respectively.
- Mei, Yujiang,Dissanayake, Prabani,Allen, Matthew J.
-
supporting information; experimental part
p. 12871 - 12873
(2010/11/16)
-
- Enantioselectivity of haloalkane dehalogenases and its modulation by surface loop engineering
-
In the loop: Engineering of the surface loop in haloalkane dehalogenases affects their enantiodiscrimination behavior. The temperature dependence of the enantioselectivity (lnE versus 1/T) of β-bromoalkanes by haloalkane dehalogenases is reversed (red data points) by deletion of the surface loop; the selectivity switches back when an additional single-point mutation is made. This behavior is not observed for -bromoesters.
- Prokop, Zbynek,Sato, Yukari,Brezovsky, Jan,Mozga, Tomas,Chaloupkova, Radka,Koudelakova, Tana,Jerabek, Petr,Stepankova, Veronika,Natsume, Ryo,Van Leeuwen, Jan G. E.,Janssen, Dick B.,Florian, Jan,Nagata, Yuji,Senda, Toshiya,Damborsky, Jiri
-
supporting information; experimental part
p. 6111 - 6115
(2010/11/05)
-
- Enantiodiscrimination of racemic electrophiles by diketopiperazine enolates: asymmetric synthesis of methyl 2-amino-3-aryl-butanoates and 3-methyl-aspartates
-
Enolates of (S)-N,N′-bis-(p-methoxybenzyl)-3-iso-propylpiperazine-2,5-dione exhibit high levels of enantiodiscrimination in alkylations with (RS)-1-aryl-1-bromoethanes and (RS)-2-bromoesters, affording substituted diketopiperazines containing two new stereogenic centres in high de. Deprotection and hydrolysis of the resultant substituted diketopiperazines provides a route to the asymmetric synthesis of homochiral methyl 2-amino-3-aryl-butanoates and 3-methyl-aspartates in high de and ee.
- Bull, Steven D.,Davies, Stephen G.,Epstein, Simon W.,Garner, A. Christopher,Mujtaba, Nadeam,Roberts, Paul M.,Savory, Edward D.,Smith, Andrew D.,Tamayo, Juan A.,Watkin, David J.
-
p. 7911 - 7925
(2007/10/03)
-
- Design and synthesis of aromatic inhibitors of anthranilate synthase
-
Anthranilate synthase catalyses the conversion of chorismate to anthranilate, a key step in tryptophan biosynthesis. A series of 3-(1-carboxy-ethoxy) benzoic acids were synthesised as chorismate analogues, with varying functionality at C-4, the position of the departing hydroxyl group in chorismate. Most of the compounds were moderate inhibitors of anthranilate synthase, with inhibition constants between 20-30 μM. The exception was 3-(1-carboxy-ethoxy) benzoic acid, (C-4 = H), for which K1 = 2.4 μM. These results suggest that a hydrogen bonding interaction with the active site general acid (Glu309) is less important than previously assumed for inhibition of the enzyme by these aromatic chorismate analogues. The Royal Society of Chemistry 2005.
- Payne, Richard J.,Bulloch, Esther M.M.,Abell, Andrew D.,Abell, Chris
-
p. 3629 - 3635
(2007/10/03)
-
- Enantioselective synthesis of α-bromo acid derivatives and bromohydrins from tartrate derived bromoacetals
-
Bromination of the acetals 4 derived from aryl alkyl ketones, ArCOR, and (2R,3R)-tartaric acid results in bromoacetals 5 with 78-90% de. Hydrolysis of those compounds with Ar = 4-methoxyphenyl or 3-bromo-4-methoxyphenyl results, after recrystallisation, in α-bromoketones 8 with 66-98% ee which are shown to undergo the Baeyer-Villiger oxidation to α-bromoesters 9 with minimal racemisation, α-Bromoketone 8d is shown to undergo carbonyl reduction to threo-bromohydrin 15 with retention of stereochemistry.
- Boyes, Scott A.,Hewson, Alan T.
-
p. 2759 - 2765
(2007/10/03)
-
- Difference in the behavior of methyl (S)-α-bromopropionate in its addition to trimethylvinylsilane depending on the method of initiation
-
The addition of methyl (S)-2-bromopropionate to trimethylvinylsilane initiated by systems based on iron pentacarbonyl affords a racemic adduct and is accompanied by racemization of the unreacted chiral ester. In the presence of benzoyl peroxide, the reaction proceeds similarly, but no racemization of the starting chiral ester occurs.
- Terentiev,Vasilieva,Kuz'mina,Orlova,Ikonnikov,Mysov,Kolehmainen,Laihia,Belokon'
-
p. 676 - 679
(2007/10/03)
-
- Process for the preparation of brominated compounds, especially from alcohols
-
A process for the preparation of a brominated compound which comprises the step of reacting at least one compound selected from the group consisting of a chloroformate, a chlorosulfite and a chlorophosphite with a brominating agent for a time sufficient to obtain at least one brominated compound. In particular, an alcohol is converted into a chloroformate, chlorosulfite or a chlorophosphite, which is then brominated to obtain the desired product. In another embodiment, a brominating agent is reacted with a reactant selected from the group consisting of thionyl chloride, phosgene and phosphorous oxychloride, followed by contacting the reaction product obtained with an alcohol to be brominated.
- -
-
-
- A new simple and industrial process for bromination of alcohols
-
Alcohols treated with thionylchloride, followed by chlorine/bromine exchange using gaseous hydrobromic acid and thermal decomposition in the presence of a tertiary amine give the corresponding brominated compounds. The process is regio/stereo selective.
- Mas,Metivier
-
p. 2187 - 2191
(2007/10/02)
-
- Nucleophilic Substitution Reactions of Alkyl Halides By Using New Polymer-Supported Reagents Containing Hemin
-
A new polymer reagent consisting of hemin, divinylbenzene, and 2-methyl-5-vinylpyridine was synthesized by suspension copolymerization.Substitution reactions of primary, secondary, and tertiary alkyl halides with the hemin copolymer combined with cyanide, azide, and thiocyanate ions were given satisfactory yields.This reaction mechanism was revealed to be a SNi type on the basis of stereochemical study.The hemin copolymer was not only a polymer-supported reagent with functional capabilities, but also served to separate the product from the reaction mixture.
- Saito, Kiyoshi,Harada, Kaoru
-
p. 2562 - 2566
(2007/10/02)
-
- Synthesis and Herbicidal Activity of the D- and L-Methyl 2--propionate Enantiomers
-
The D- and L-enantiomers of the wild oat herbicide diclofop-methyl (title compound) were prepared utilizing resolution operations and by synthetic routes with optically active compounds as starting material.The dextro-rotatory product which the D(R)-configuration can be attributed to, was found to be the herbicidally active species. - Keywords: Phenoxy-phenoxy-propionic Acid Ester, Diclofop-methyl, Stereoisomers, Grass Herbicide
- Nestler, Hans Juergen,Bieringer, Hermann
-
p. 366 - 371
(2007/10/02)
-
- Synthesis of the 2-ethyl-3-methylsuccinic acids via a stereospecific malonic ester alkylation
-
Reaction of (-)-(S)-methyl 2-bromopropionate (4) (obtained from L-alanine) with dibenzyl ethylmalonate gave stereospecifically in four steps (+)-(2R,3S)-2-ethyl-3-methylsuccinic acid (8a) and its diastereoisomer (8b).The malonic ester alkylation proceeded with Walden inversion.The chiroptical properties of the acids and the intermediates are in conformity with the known absolute configurations.
- Leeuwen, F. F. van,Noordam, A.,Maat, L.,Beyerman, H. C.
-
-