cas 14062-25-0, Ethyl 4-bromophenylacetate

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Identification of two novel RET kinase inhibitors through MCR-based drug discovery: Design, synthesis and evaluation
From an MCR fragment library, two novel chemical series have been developed as inhibitors of RET, which is a kinase involved in the pathology of medullary thyroid cancer (MTC). Structure activity relationship studies (SAR) identified two sub-micromolar tractable leads, 6g and 13g. 6g was confirmed to be a Type-II RET inhibitor. 13g and 6g inhibited RET in cells transformed by RET/C634. A RET DFG-out homology model was established and utilized to predict Type-II inhibitor binding modes.
Frett, Brendan,Moccia, Marialuisa,Carlomagno, Francesca,Santoro, Massimo,Li, Hong-Yu
p. 714 - 723
(2014)
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Photocatalytic acyl azolium-promoted alkoxycarbonylation of trifluoroborates
Despite recent advancements in the selective generation and coupling of organic radical species, the alkoxycarbonyl radical remains underexplored relative to other carbon-containing radical species. Drawing inspiration from new strategies for generating acyl radical equivalents utilizing dual N-heterocyclic carbene catalysis and photocatalysis, we have prepared dimethylimidazolium esters that can function as an alkoxycarbonyl radical surrogate under photocatalytic conditions. We demonstrate the synthetic utility of these azolium-based partners through the preparation of esters arising from the coupling of this radical surrogate with an oxidatively generated alkyl radical.
Scheidt, Karl A.,Zhu, Joshua L.
(2021/06/28)

Enantioselective Desymmetrization of 2-Aryl-1,3-propanediols by Direct O-Alkylation with a Rationally Designed Chiral Hemiboronic Acid Catalyst That Mitigates Substrate Conformational Poisoning
Enantioselective desymmetrization by direct monofunctionalization of prochiral diols is a powerful strategy to prepare valuable synthetic intermediates in high optical purity. Boron acids can activate diols toward nucleophilic additions; however, the design of stable chiral catalysts remains a challenge and highlights the need to identify new chemotypes for this purpose. Herein, the discovery and optimization of a bench-stable chiral 9-hydroxy-9,10-boroxarophenanthrene catalyst is described and applied in the highly enantioselective desymmetrization of 2-aryl-1,3-diols using benzylic electrophiles under operationally simple, ambient conditions. Nucleophilic activation and discrimination of the enantiotopic hydroxy groups on the diol substrate occurs via a defined chairlike six-membered anionic complex with the hemiboronic heterocycle. The optimal binaphthyl-based catalyst 1g features a large aryloxytrityl group to effectively shield one of the two prochiral hydroxy groups on the diol complex, whereas a strategically placed "methyl blocker"on the boroxarophenanthrene unit mitigates the deleterious effect of a competing conformation of the complexed diol that compromised the overall efficiency of the desymmetrization process. This methodology affords monoalkylated products in enantiomeric ratios equal or over 95:5 for a wide range of 1,3-propanediols with various 2-aryl/heteroaryl groups.
Estrada, Carl D.,Ang, Hwee Ting,Vetter, Kim-Marie,Ponich, Ashley A.,Hall, Dennis G.
supporting information

(2021/04/07)

B(C6F5)3-Catalyzed site-selective N1-alkylation of benzotriazoles with diazoalkanes
Alkylation of benzotriazoles is synthetically challenging, often leading to mixtures of N1 and N2 alkylation. Herein, metal-free catalytic site-selective N1-alkylation of benzotriazoles with diazoalkanes is described in the presence of 10 mol% of B(C6F5)3. These reactions provide N1-alkylated benzotriazoles in good to excellent yields and this protocol is successfully adapted to gram-scale syntheses as well as a derivative with antimicrobial activity.
Guo, Jing,Mandal, Dipendu,Stephan, Douglas W.,Wu, Yile,Zhao, Yunbo
supporting information
p. 7758 - 7761
(2021/08/13)

BF3·OEt2-promoted tandem Meinwald rearrangement and nucleophilic substitution of oxiranecarbonitriles
Tandem Meinwald rearrangement and nucleophilic substitution of oxiranenitriles was realized. Arylacetic acid derivatives were readily synthesized from 3-aryloxirane-2-carbonitriles with amines, alcohols, or water in the presence of boron trifluoride under microwave irradiation, and the designed synthetic strategy includes introducing a cyano leaving group into arylepoxides and capturing the in situ generated toxic cyanide with boron trifluoride, making the reaction efficient, safe, and environmentally benign. The reaction occurs through an acid-promoted Meinwald rearrangement, producing arylacetyl cyanides, followed by an addition-elimination process with nitrogen or oxygen-containing nucleophilic amines, alcohols or water. The current method provides a new application of the tandem Meinwald rearrangement.
Xu, Chuangchuang,Xu, Jiaxi
p. 127 - 134
(2019/12/26)

Preparation of Organic Nitrates from Aryldiazoacetates and Fe(NO3)3·9H2O
A thermal protocol is reported for the formal insertion of nitric acid into aryldiazoacetates using Fe(NO3)3·9H2O. This strategy is mild and high yielding and allows the preparation of a large variety of members of an unprecedented family of organic nitrates. The nitrate group can be also readily transformed into other functional groups and heterocyclic moieties and can possibly allow new biological explorations of untapped potential associated with their NO-releasing ability.
Thurow, Samuel,Fernandes, Alessandra A. G.,Quevedo-Acosta, Yovanny,De Oliveira, Matheus F.,De Oliveira, Marcelo G.,Jurberg, Igor D.
p. 6909 - 6913
(2019/09/12)

Ag-Catalyzed Chemoselective Decarboxylative Mono- and gem-Difluorination of Malonic Acid Derivatives
Malonic acid derivatives have been successfully applied in a Ag-catalyzed decarboxylative fluorination reaction, providing an unprecedented route to either gem-difluoroalkanes or α-fluorocarboxylic acids by the judicious selection of base and solvent. This reaction features the use of readily available starting materials, tunable chemoselectivity and good functional group compatibility as well as gram-scale synthetic capability. The advantage of using malonic acid derivatives in this radical decarboxylative functionalization is further highlighted by the facile transformations of the α-fluorocarboxylic acid to valuable fluorine-containing compounds. Preliminary mechanistic studies suggest that an α-carboxylic acid radical is involved in this reaction.
Wang, Zhen,Guo, Cong-Ying,Yang, Cheng,Chen, Jian-Ping
supporting information

(2019/04/16)

Ag-Catalyzed Chemoselective Decarboxylative Mono- and gem-Difluorination of Malonic Acid Derivatives
Malonic acid derivatives have been successfully applied in a Ag-catalyzed decarboxylative fluorination reaction, providing an unprecedented route to either gem-difluoroalkanes or α-fluorocarboxylic acids by the judicious selection of base and solvent. This reaction features the use of readily available starting materials, tunable chemoselectivity and good functional group compatibility as well as gram-scale synthetic capability. The advantage of using malonic acid derivatives in this radical decarboxylative functionalization is further highlighted by the facile transformations of the α-fluorocarboxylic acid to valuable fluorine-containing compounds. Preliminary mechanistic studies suggest that an α-carboxylic acid radical is involved in this reaction.
Wang, Zhen,Guo, Cong-Ying,Yang, Cheng,Chen, Jian-Ping
supporting information
p. 5617 - 5622
(2019/04/17)

Rapid Assembly of Saturated Nitrogen Heterocycles in One-Pot: Diazo-Heterocycle “Stitching” by N–H Insertion and Cyclization
Methods that provide rapid access to new heterocyclic structures in biologically relevant chemical space provide important opportunities in drug discovery. Here, a strategy is described for the preparation of 2,2-disubstituted azetidines, pyrrolidines, pi
Boddy, Alexander J.,Affron, Dominic P.,Cordier, Christopher J.,Rivers, Emma L.,Spivey, Alan C.,Bull, James A.
supporting information
p. 1458 - 1462
(2019/01/04)

Air-Sensitive Photoredox Catalysis Performed under Aerobic Conditions in Gel Networks
In this work, we demonstrate that useful C-C bond-forming photoredox catalysis can be performed in air using easily prepared gel networks as reaction media to give similar results as are obtained under inert atmosphere conditions. These reactions are completely inhibited in homogeneous solution in air. However, the supramolecular fibrillar gel networks confine the reactants and block oxygen diffusion, allowing air-sensitive catalytic activity under ambient conditions. We investigate the mechanism of this remarkable protection, focusing on the boundary effect in the self-assembled supramolecular gels that enhances the rates of productive reactions over diffusion-controlled quenching of excited states. Our observations suggest the occurrence of triplet-sensitized chemical reactions in the gel networks within the compartmentalized solvent pools held between the nanofibers. The combination of enhanced viscosity and added interfaces in supramolecular gel media seems to be a key factor in facilitating the reactions under aerobic conditions.
H?ring, Marleen,Abramov, Alex,Okumura, Keisuke,Ghosh, Indrajit,K?nig, Burkhard,Yanai, Nobuhiro,Kimizuka, Nobuo,Díaz Díaz, David
p. 7928 - 7938
(2018/06/04)

Dynamic kinetic resolution of bis-aryl succinic anhydrides: Enantioselective synthesis of densely functionalised γ-butyrolactones
The efficient Dynamic Kinetic Resolution (DKR) of disubstituted anhydrides has been shown to be possible for the first time. Using an ad hoc designed organocatalyst and an enantio- and diastereoselective cycloaddition process with aldehydes, stereochemically complex γ-butyrolactone derivatives can be obtained-with control over three contiguous stereocentres, one of which is all carbon quaternary.
Claveau, Romain,Twamley, Brendan,Connon, Stephen J.
supporting information
p. 3231 - 3234
(2018/04/05)

Synthesis of α-alkylated γ-butyrolactones with concomitant anhydride kinetic resolution using a sulfamide-based catalyst
The Kinetic Resolution (KR) of α-alkylated enolisable disubstituted anhydrides has been shown to be possible for the first time. In the presence of an ad hoc designed novel class of bifunctional sulfamide organocatalyst, a regio-, diastereo- and enantioselective cycloaddition reaction between the enolisable anhydride and benzaldehydes provides densely functionalised γ-butyrolactones in one pot (up to 19:1 dr, 94% ee) with control over three contiguous stereocentres. The concomitant resolution of the starting material anhydride, provides access to a range of chiral succinate derivatives with selectivity factors up to S? = 10.5.
Claveau, Romain,Twamley, Brendan,Connon, Stephen J.
supporting information
p. 7574 - 7578
(2018/11/02)

Chromoselective Photocatalysis: Controlled Bond Activation through Light-Color Regulation of Redox Potentials
Catalysts that can be regulated in terms of activity and selectivity by external stimuli may allow the efficient multistep synthesis of complex molecules and pharmaceuticals. Herein, we report the light-color regulation of the redox potential of a photocatalyst to control the activation of chemical bonds. Light-color control of the redox power of a photocatalyst introduces a new selectivity parameter to photoredox catalysis: Instead of changing the catalyst or ligand, alteration of the color of the visible-light irradiation adjusts the selectivity in catalytic transformations. By using this principle, the selective activation of aryl–halide bonds for C?H arylation and the sequential conversion of functional groups with different reduction potentials is possible by simply applying different colors of light for excitation of the photocatalyst.
Ghosh, Indrajit,K?nig, Burkhard
supporting information
p. 7676 - 7679
(2016/07/07)

Controlling the Conformational Energy of a Phenyl Group by Tuning the Strength of a Nonclassical CH···O Hydrogen Bond: The Case of 5-Phenyl-1,3-dioxane
Anancomeric 5-phenyl-1,3-dioxanes provide a unique opportunity to study factors that control conformation. Whereas one might expect an axial phenyl group at C(5) of 1,3-dioxane to adopt a conformation similar to that in axial phenylcyclohexane, a series of studies including X-ray crystallography, NOE measurements, and DFT calculations demonstrate that the phenyl prefers to lie over the dioxane ring in order to position an ortho-hydrogen to participate in a stabilizing, nonclassical CH···O hydrogen bond with a ring oxygen of the dioxane. Acid-catalyzed equilibration of a series of anancomeric 2-tert-butyl-5-aryl-1,3-dioxane isomers demonstrates that remote substituents on the phenyl ring affect the conformational energy of a 5-aryl-1,3-dioxane: electron-withdrawing substituents decrease the conformational energy of the aryl group, while electron-donating substituents increase the conformational energy of the group. This effect is correlated in a very linear way to Hammett substituent parameters. In short, the strength of the CH···O hydrogen bond may be tuned in a predictable way in response to the electron-withdrawing or electron-donating ability of substituents positioned remotely on the aryl ring. This effect may be profound: a 3,5-bis-CF3 phenyl group at C(5) in 1,3-dioxane displays a pronounced preference for the axial orientation. The results are relevant to broader conformational issues involving heterocyclic systems bearing aryl substituents.
Bailey, William F.,Lambert, Kyle M.,Stempel, Zachary D.,Wiberg, Kenneth B.,Mercado, Brandon Q.
p. 12116 - 12127
(2016/12/23)

Selective synthesis of arylacetic acid esters from ethyl acetoacetate and aryl halides in the presence of copper(II) on 4 ? molecular sieves
A heterogeneous catalyst, copper(II) on 4 ? molecular sieves has successfully been used in the arylation of ethyl acetoacetate, selectively forming arylacetic esters in high yields. The air stable and easily handled catalyst can be simply filtered off during purification thus avoiding significant metal contamination of the product.
Zsolczai, Dávid,Németh, János,Hell, Zoltán
p. 6389 - 6392
(2015/11/16)

MULTIFUNCTIONAL MONOMERS AND THEIR USE IN MAKING CROSS-LINKED POLYMERS AND POROUS FILMS
This invention is a monomer comprising at least two dienophile groups and at least two ring structures which ring structures are characterized by the presence of two conjugated carbon-to-carbon double bonds and the presence of a leaving group L, wherein L is characterized that when the ring structure reacts with a dienophile in the presence of heat or other energy sources, L is removed to form an aromatic ring structure. This invention is also curable oligomers and polymers and highly cross-linked polymers made with such monomers. Moreover, this invention is a method of making porous films by combining such monomers or their oligomers with a porogen, curing the polymer and removing the porogen.
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Paragraph 0053

(2016/01/25)

Synthesis of α-aryl esters and nitriles: Deaminative coupling of α-aminoesters and α-aminoacetonitriles with arylboronic acids
Transition-metal-free synthesis of α-aryl esters and nitriles using arylboronic acids with α-aminoesters and α-aminoacetonitriles, respectively, as the starting materials has been developed. The reaction represents a rare case of converting C(sp3)-N bonds into C(sp3)-C(sp2) bonds. The reaction conditions are mild, demonstrate good functional-group tolerance, and can be scaled up. Touch base: A transition-metal-free protocol for the synthesis of α-aryl esters and nitriles by deaminative coupling is presented. Strong bases and transition-metal catalysts are not needed. The new synthetic method uses readily available starting materials and demonstrates wide substrate scope.
Wu, Guojiao,Deng, Yifan,Wu, Chaoqiang,Zhang, Yan,Wang, Jianbo
supporting information
p. 10510 - 10514
(2016/02/18)

A chemoselective Reformatsky-Negishi approach to α-haloaryl esters
A practical synthesis of α-haloaryl esters has been achieved via a chemoselective Negishi coupling of poly-halogenated aromatics and Reformatsky reagents in the presence of catalytic Pd(dba)2 and Xantphos. This chemistry tolerates a variety of aryl halides and was successfully applied to the synthesis of Ibuprofen. The α-haloaryl ester products, exemplified by ethyl 2-(4-bromo-2-chlorophenyl)acetate (3a), can be further functionalized via palladium or copper catalysis to afford an array of α-aryl esters.
Wong, Brian,Linghu, Xin,Crawford, James J.,Drobnick, Joy,Lee, Wendy,Zhang, Haiming
p. 1508 - 1515
(2014/02/14)

PROCESS FOR SYNTHESIZING PHENYLACETIC ACID BY CARBONYLATION OF TOLUENE
A production process for substituted phenylacetic acids or ester analogues thereof is disclosed. In this process toluene or toluene substituted with various substituents, an alcohol, an oxidant and carbon monoxide are used as raw materials to obtain compounds comprising structure of phenylacetic acid ester or analogues thereof by catalysis of the complex catalyst formed from transition metal and ligand, and such compounds are hydrolyzed to obtain various substituted phenylacetic acid based compounds. This type of compounds and their derivatives serve as important fine chemicals used widely in the industries of pharmaceuticals, pesticides, perfume and the like.
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Paragraph 0064; 0065

(2013/11/19)

Amine Substituted Methanesulfonamide Derivatives as Vanilloid Receptor Ligands
The invention relates to amine substituted methanesulfonamide derivatives as vanilloid receptor ligands, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.
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Paragraph 0473; 0474

(2013/04/10)

AMINE SUBSTITUTED METHANESULFONAMIDE DERIVATIVES AS VANILLOID RECEPTOR LIGANDS
The invention relates to amine substituted methanesulfonamide derivatives of formula (I) as vanilloid receptor ligands, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.
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Paragraph 51

(2013/04/13)

Aryl or N-heteroaryl Substituted Methanesulfonamide Derivatives as Vanilloid Receptor Ligands
The invention relates to aryl or N-heteroaryl substituted methanesulfonamide derivatives as vanilloid receptor ligands, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.
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Paragraph 0554; 0556

(2013/04/10)

ARYL OR N-HETEROARYL SUBSTITUTED METHANESULFONAMIDE DERIVATIVES AS VANILLOID RECEPTOR LIGANDS
The invention relates to aryl or N-heteroaryl substituted methanesulfonamide derivatives of Formula (I) as vanilloid receptor ligands, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.
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(2013/04/13)

SUBSTITUTED PYRIMIDINES
Disclosed are substituted pyrimidines useful as HIF prolyl hydroxylase inhibitors to treat anemia and like conditions.
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Page/Page column 59; 60

(2013/04/10)

SUBSTITUTED PYRIMIDINES
The present invention relates to substituted pyrimidines useful as HIF prolyl hydroxylase inhibitors to treat anemia and like conditions.
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Page/Page column 59; 60

(2013/04/10)

Control of exchange interactions in π dimers of 6-oxophenalenoxyl neutral π radicals: Spin-density distributions and multicentered-two-electron bonding governed by topological symmetry and substitution at the 8-position
The tri-tert-butylphenalenyl (TBPLY) radical exists as a π dimer in the crystal form with perfect overlapping of the singly occupied molecular orbitals (SOMOs) causing strong antiferromagnetic exchange interactions. 2,5-Di-tert-butyl-6-oxophenalenoxyl (6OPO) is a phenalenyl-based air-stable neutral π radical with extensive spin delocalization and is a counter analogue of phenalenyl in terms of the topological symmetry of the spin density distribution. X-ray crystal structure analyses showed that 8-tert-butyl- and 8-(p-XC6H4)-6OPOs (X=I, Br) also form π dimers in the crystalline state. The π-dimeric structure of 8-tert-butyl-6OPO is seemingly similar to that of TBPLY even though its SOMO-SOMO overlap is small compared with that of TBPLY. The 8-(p-XC6H4) derivatives form slipped stacking π dimers in which the SOMO-SOMO overlaps are greater than in 8-tert-butyl-6OPO, but still smaller than in TBPLY. The solid-state electronic spectra of the 6OPO derivatives show much weaker intradimer charge-transfer bands, and SQUID measurements for 8-(p-BrC6H4)-6OPO show a weak antiferromagnetic exchange interaction in the π dimer. These results demonstrate that the control of the spin distribution patterns of the phenalenyl skeleton switches the mode of exchange interaction within the phenalenyl-based π dimer. The formation of the relevant multicenter-two-electron bonds is discussed. Copyright
Nishida, Shinsuke,Kawai, Junya,Moriguchi, Miki,Ohba, Tomohiro,Haneda, Naoki,Fukui, Kozo,Fuyuhiro, Akira,Shiomi, Daisuke,Sato, Kazunobu,Takui, Takeji,Nakasuji, Kazuhiro,Morita, Yasushi
p. 11904 - 11915
(2013/09/23)

Palladium-catalyzed oxidative carbonylation of benzylic C-H bonds via nondirected C(sp3)-H activation
A new strategy for generating benzylpalladium reactive species from toluenes via nondirected C(sp3)-H activation has been developed. This led to construction of an efficient Pd-catalyzed reaction protocol for the oxidative carboxylation of benzylic C-H bonds to form substituted 2-phenylacetic acid esters and derivatives from inexpensive, commercially available starting materials.
Xie, Pan,Xie, Yinjun,Qian, Bo,Zhou, Han,Xia, Chungu,Huang, Hanmin
supporting information; experimental part
p. 9902 - 9905
(2012/08/08)

Dual Bronsted acid/nucleophilic activation of carbonylimidazole derivatives
Carbonylimidazole derivatives have been found to be highly active acylation reagents for esterification and amidation in the presence of pyridinium salts. These reactions are thought to involve both Bronsted acid and nucleophilic catalysis. This mode of activation has been applied to the synthesis of difficult to access oxazolidinones, as well as esters and amides. Finally, the use of pyridinium salts has been shown to accelerate the esterification of carboxylic acids with imidazole carbamates.
Heller, Stephen T.,Fu, Tingting,Sarpong, Richmond
supporting information; experimental part
p. 1970 - 1973
(2012/06/01)

COFERONS AND METHODS OF MAKING AND USING THEM
The present invention is directed to a monomer useful in preparing therapeutic compounds. The monomer includes one or more pharmacophores which potentially binds to a target molecule with a dissociation constant of less than 300 μM and a linker element connected to the pharmacophore. The linker element has a molecular weight less than 500 daltons, is connected, directly or indirectly through a connector, to the pharmacophore.
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(2012/12/13)

On the reactivity of imidazole carbamates and ureas and their use as esterification and amidation reagents
The optimization, substrate scope, and mechanism of esterification and amidation of carboxylic acids mediated by imidazole-based reagents are discussed. The innate reactivity of carbonylimidazole reagents with a range of nucleophiles is also explored. New reagents developed for the synthesis of α,β-unsaturated esters are described, as are reagents for the preparation of tertiary amides directly from carboxylic acids.
Heller, Stephen T.,Sarpong, Richmond
experimental part
p. 8851 - 8859
(2011/12/02)

Discovery and optimization of a biphenylacetic acid series of prostaglandin D2 receptor DP2 antagonists with efficacy in a murine model of allergic rhinitis
Biphenylacetic acid (5) was identified through a library screen as an inhibitor of the prostaglandin D2 receptor DP2 (CRTH2). Optimization for potency and pharmacokinetic properties led to a series of selective CRTH2 antagonists. Compounds demonstrated potency in a human DP2 binding assay and a human whole blood eosinophil shape change assay, as well as good oral bioavailability in rat and dog, and efficacy in a mouse model of allergic rhinitis following oral dosing.
Scott, Jill M.,Baccei, Christopher,Bain, Gretchen,Broadhead, Alex,Evans, Jilly F.,Fagan, Patrick,Hutchinson, John H.,King, Christopher,Lorrain, Daniel S.,Lee, Catherine,Prasit, Peppi,Prodanovich, Pat,Santini, Angelina,Santini, Brian A.
scheme or table
p. 6608 - 6612
(2011/12/04)

4-AMINO-5-OXO-7, 8-DIHYDROPYRIMIDO [5,4-F] [1,4] OXAZEPIN-6 (5H) -YL) PHENYL DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
The invention provides compounds of Formula (I), wherein R1, R2a, R2b, R3, m and A are as defined herein, as well as compositions thereof and methods for treating a disease, condition or disorder that is modulated by the inhibition of the diacylglycerol O-acyltransferase 1 (DGAT-1) enzyme by administering the compounds of the present invention and/or compositions thereof.
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(2010/08/09)

A general method for the synthesis of 3,5-diarylcyclopentenones via Friedel-Crafts acylation of vinyl chlorides
(Chemical Equation Presented) A general approach for the synthesis of 3,5-diarylcyclopentenones was developed. Key aspects of this approach are the intramolecular Friedel-Crafts-type cyclization of vinyl chlorides and subsequent Pd-catalyzed cross-coupling reactions. The requisite vinyl chloride-bearing arylacetic acid precursors are readily available by straightforward alkylation of arylacetic acid esters and undergo cyclization to yield 3-chloro-5-aryl-2- cyclopentenones when treated with AlCl3. The vinylogous acid chloride functionality present in these immediate products allows for further elaboration via Pd-catalyzed cross-coupling chemistry, leading to a diverse array of products.
Xu, Yingju,McLaughlin, Mark,Chen, Cheng-Yi,Reamer, Robert A.,Dormer, Peter G.,Davies, Ian W.
supporting information; experimental part
p. 5100 - 5103
(2009/10/17)

Design, synthesis, and structure-affinity relationships of novel series of sialosides as CD22-specific inhibitors
Sialosides incorporating substituted amides or amines at 9-position of sialic acid moiety have been synthesized and evaluated as CD22 inhibitors. Several derivatives exhibited inhibitory potency in sub- to low micromolar range (e. g., 80, 9d, 9g, and 9k s
Abdu-Allah, Hajjaj H. M.,Tamanaka, Taichi,Yu, Jie,Zhuoyuan, Lu,Sadagopan, Magesh,Adachi, Takahiro,Tsubata, Takeshi,Kelm, Soerge,Ishida, Hideharu,Kiso, Makoto
body text
p. 6665 - 6681
(2009/11/30)

4-Amino-5-aryl-6-arylethynylpyrimidines: Structure-activity relationships of non-nucleoside adenosine kinase inhibitors
A series of non-nucleoside adenosine kinase (AK) inhibitors is reported. These inhibitors originated from the modification of 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine (ABT-702). The identification of a linker that would approximate the spatial arrangement found between the pyrimidine ring and the aryl group at C(7) in ABT-702 was a key element in this modification. A search of potential linkers led to the discovery of an acetylene moiety as a suitable scaffold. It was hypothesized that the aryl acetylenes, ABT-702, and adenosine bound to the active site of AK (closed form) in a similar manner with respect to the orientation of the heterocyclic base. Although potent acetylene analogs were discovered based on this assumption, an X-ray crystal structure of 5-(4-dimethylaminophenyl)-6-(6-morpholin-4-ylpyridin-3-ylethynyl)pyrimidin-4-ylamine (16a) revealed a binding orientation contrary to adenosine. In addition, this compound bound tightly to a unique open conformation of AK. The structure-activity relationships and unique ligand orientation and protein conformation are discussed.
Matulenko, Mark A.,Paight, Ernest S.,Frey, Robin R.,Gomtsyan, Arthur,DiDomenico Jr., Stanley,Jiang, Meiqun,Lee, Chih-Hung,Stewart, Andrew O.,Yu, Haixia,Kohlhaas, Kathy L.,Alexander, Karen M.,McGaraughty, Steve,Mikusa, Joseph,Marsh, Kennan C.,Muchmore, Steven W.,Jakob, Clarissa L.,Kowaluk, Elizabeth A.,Jarvis, Michael F.,Bhagwat, Shripad S.
p. 1586 - 1605
(2008/02/01)

Novel ligands for the human histamine H1 receptor: Synthesis, pharmacology, and comparative molecular field analysis studies of 2-dimethylamino-5-(6)-phenyl-1,2,3,4-tetrahydronaphthalenes
This paper reports the synthesis of a novel series of (±)-2-dimethylamino- 5- and 6-phenyl-1,2,3,4-tetrahydronaphthalene derivatives (5- and 6-APTs), and, corresponding affinity, functional activity, and, molecular modeling studies with regard to drug des
Ghoneim, Ola M.,Legere, Jacqueline A.,Golbraikh, Alexander,Tropsha, Alexander,Booth, Raymond G.
p. 6640 - 6658
(2007/10/03)

Novel thiophene derivatives, their process of preparation and the pharmaceutical compositions which comprise them
A compound of formula (I) selected from: wherein: X represents oxygen or sulphur, Y represents oxygen, —NH— or —N(C1-C6)alkyl-, Ra represents hydrogen, halogen, (C1-C3)alkyl, hydroxyl or (C1-C3)alkoxy, Rb represents hydrogen, halogen or (C1-C3)alkyl, A represents phenyl, pyridyl, (C5-C6)cycloalkyl or (C5-C6)cycloalkenyl, R1 and R2 each represent a group selected from hydrogen, halogen, cyano, nitro, haloalkyl, haloalkoxy, alkyl, alkenyl, alkynyl, —OR4, —NR4R5, —S(O)nR4, —C(O)R4, —CO2R4, —O—C(O)R4, —C(O)NR4R5, —NR5—C(O)R4, —NR5—SO2R4, -T-CN, -T-OR4, -T-OCF3, -T- NR4R5, -T-S(O)nR4, -T-C(O)R4, -T-CO2R4, -T-O—C(O)R4, -T-C(O)NR4R5, -T-NR4—C(O)R5, -T-NR4—SO2R5, —R6 and -T-R6 in which n, T, R4, R5 and R6 are as defined in the description, R3 represents an —R7 or —U—R11 group in which R7 represents hydrogen, alkyl, aryl, cycloalkyl or heterocycle, U represents a linear or branched alkylene chain and R11 is defined in the description, their optical isomers or their addition salts with a pharmaceutically acceptable acid or base, and their use as inhibitor of metalloproteinase and more specifically of metalloproteinase-12.
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(2010/11/30)

Unusual Tethering Effects in the Schmidt Reaction of Hydroxyalkyl Azides with Ketones: Cation-π and Steric Stabilization of a Pseudoaxial Phenyl Group
The Lewis acid-promoted reactions of chiral 2-aryl-3-azido-1-propanols with 4-substituted cyclohexanones lead to iminium ethers and ultimately caprolactams (following a hydrolysis step). In this study, it is shown that these reactions afford variable ratios of products, depending on the electronic nature of the phenyl group. These results are interpreted in the context of a cation?π stabilizing effect in the product-determining reaction intermediate. Remarkably, the best selectivity was obtained when an azidopropanol reagent containing a quaternary center was used; a control experiment showed that the high selectivity observed in this result depended upon the free rotation of the pseudoaxial aromatic group in the intermediate that affords the major product. Copyright
Katz, Christopher E.,Aube, Jeffrey
p. 13948 - 13949
(2007/10/03)

1,2-disubstituted-6-oxo-3-phenyl-piperidine-3-carboxamides and combinatorial libraries thereof
The invention relates to combinatorial libraries containing two or more novel piperidine-3-carboxamide derivative compounds, methods of preparing the piperidine-3-carboxamide derivative compounds and piperidine-3-carboxamide derivative compounds bound to a resin
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(2008/06/13)

Sulfonamide derivatives
The present invention provides certain sulfonamide derivatives useful for potentiating glutamate receptor function in a mammal and therefore, useful for treating a wide variety of conditions, such as psychiatric and neurological disorders.
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(2008/06/13)

O- or S- substituted tetrahydronaphthalene derivatives having retinoid and/or retinoid antagonist-like biological activity
Compounds of the formula where the symbols have the meaning described in the application, have retinoid-like or retinoid antagonist-like biological activity.
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Page column 70

(2010/11/29)

AROMATIC AMINE DERIVATIVES, PROCESS FOR THE PREPARATION THEREOF AND AGENTS CONTAINING THE SAME
Compounds of a formula: wherein Ring A represents an optionally-substituted aromatic ring; Ring B represents an optionally-substituted cyclic hydrocarbon group; Z represents an optionally-substituted cyclic group; R1 represents a hydrogen atom, an optionally-substituted hydrocarbon group, an optionally-substituted heterocyclic group, or an acyl group; R2 represents an optionally-substituted amino group; D represents a chemical bond or a divalent group; E represents -CO-, -CON(Ra)-, COO-, -N(Ra)CON(Rb)-, -N(Ra)COO-, -N(Ra)SO2-, -N(Ra)-, -O-, -S-,-SO- or -SO2- (in which Ra and Rb each independently represent a hydrogen atom or an optionally-substituted hydrocarbon group); G represents a chemical bond or a divalent group; L represents (1) a chemical bond or (2) a divalent hydrocarbon group optionally having from 1 to 5 substituents selected from;(i) a C1-6 alkyl group,(ii) a halogeno-C1-6 alkyl group,(iii) a phenyl group,(iv) a benzyl group,(v) an optionally-substituted amino group,(vi) an optionally-substituted hydroxy group, and(vii) a carbamoyl or thiocarbamoyl group optionally substituted by: a C1-6 alkyl group, an optionally-substituted phenyl group, or an optionally-substituted heterocyclic group, and optionally interrupted by -O- or -S-; X represents an oxygen atom, an optionally-oxidized sulfur atom, an optionally-substituted nitrogen atom, or an optionally-substituted divalent hydrocarbon group; Y represents two hydrogen atoms, an oxygen atom or a sulfur atom; .... means that R2 may be bonded to the atom on Ring B to form a ring, or their salts, and a method for producing them.
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(2008/06/13)

Sulphonamide derivatives
Glutamate receptor function in a mammal may be potentiated using an effective amount of a compound of formulaR1—L—NHSO2R2??Iin whichR1 represents an unsubstituted or substituted aromatic or heteroaromatic group;R2 represents (1-6C)alkyl, (3-6C)cycloalkyl, (1-6C)fluoroalkyl, (1-6C)chloroalkyl, (2-6C)alkenyl, (1-4C)alkoxy(1-4C)alkyl, phenyl which is unsubstituted or substituted by halogen, (1-4C)alkyl or (1-4C)alkoxy, or a group, of formula R3R4N in which R3 and R4 each independently represents (1-4C)alkyl or, together with the nitrogen atom to which they are attached form an azetidinyl, pyrrolidinyl, piperidinyl, morpholino, piperazinyl, hexahydroazepinyl or octahydroazocinyl group; andL represents a (2-4C)alkylene chain which is unsubstituted or substituted by one or two substituents selected independently from (1-6C)alkyl, aryl(1-6C)alkyl, (2-6C)alkenyl, aryl(2-6C)alkenyl and aryl, or by two substituents which, together with the carbon atom or carbon atoms to which they are attached form a (3-8C)carbocyclic ring;and pharmaceutically acceptable salts thereof.Also disclosed are compounds of formula I, processes for preparing them and pharmaceutical compositions containing them.
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(2008/06/13)

Anti-atherosclerotic diaryl compounds
The present invention is concerned with diaryl compounds of formula (l) and their use in medical therapy, particularly in the prophylaxis or treatment of a clinical condition for which an ACAT inhibitor is indicated, such as hyperlipidaema or atherosclerosis. The invention also relates to pharmaceutical compositions and processes for the preparation of compounds according to the invention. STR1
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(2008/06/13)

Acetylenes disubstituted with a 5-amino or substituted 5-amino substituted tetrahydronaphthyl group and with an aryl or heteroaryl group having retinoid-like biological activity
Compounds of the formula STR1 having retinoid like biological activity.
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(2008/06/13)