- Living Cyclocopolymerization through Alternating Insertion of Isocyanide and Allene via Controlling the Reactivity of the Propagation Species: Detailed Mechanistic Investigation
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Living cyclocopolymerization through the alternating insertion of an isocyanide and allene into palladium-carbon bond was developed based on the controlling the reactivity of the propagation species using bidentate ligands. We revealed that the rate of the presented cyclocopolymerization was depended on the ligands of Pd-initiator. When the palladium-methyl complexes having appropriate cis-chelating ligand, such as 1,3-bis(diphenylphosphino)propane (dppp), were used as initiator, the cyclocopolymerization of bifunctional aryl isocyanides (1) that contain both isocyano and allenyl moieties polymerized to afford poly(quinolylene-2,3-methylene)s with controlled molecular weight and narrow molecular weight distributions. The resulting polymer was characterized by 1H and 13C NMR analyses, which clearly showed that the terminal moiety of the polymer formed well-defined organopalladium complex as the resting state for the polymerization, which could undergo further polymerization; not only cyclocopolymerization with 1 but also homopolymerization of simple aryl isocyanide. In the analysis of the cyclocopolymerization mechanism, we conclusively demonstrated that the insertion reaction of isocyanide is the rate-determination step in the cyclocopolymerization, which proceeds via a five-coordinate intermediate with a geometrical change. The cis-chelating ligand controls the site interchange reaction, which dominates the reactivity of propagation species.
- Kanbayashi, Naoya,Okamura, Taka-Aki,Onitsuka, Kiyotaka
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Read Online
- Novel multitarget-directed ligands targeting acetylcholinesterase and σ1 receptors as lead compounds for treatment of Alzheimer's disease: Synthesis, evaluation, and structural characterization of their complexes with acetylcholinesterase
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Pleiotropic intervention may be a requirement for effective limitation of the progression of multifactorial diseases such as Alzheimer's Disease. One approach to such intervention is to design a single chemical entity capable of acting on two or more targets of interest, which are accordingly known as Multi-Target Directed Ligands (MTDLs). We recently described donecopride, the first MTDL able to simultaneously inhibit acetylcholinesterase and act as an agonist of the 5-HT4 receptor, which displays promising activities in vivo. Pharmacomodulation of donecopride allowed us to develop a novel series of indole derivatives possessing interesting in vitro activities toward AChE and the σ1 receptor. The crystal structures of complexes of the most promising compounds with Torpedo californica AChE were solved in order to further understand their mode of inhibition.
- Lalut, Julien,Santoni, Gianluca,Karila, Delphine,Lecoutey, Cédric,Davis, Audrey,Nachon, Florian,Silman, Israel,Sussman, Joel,Weik, Martin,Maurice, Tangui,Dallemagne, Patrick,Rochais, Christophe
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p. 234 - 248
(2018/11/24)
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- SPIROCYCLE COMPOUNDS AND METHODS OF MAKING AND USING SAME
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Provided herein are compounds and compositions useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain.
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Paragraph 00232
(2019/03/17)
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- PYRAZOLE MAGL INHIBITORS
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Provided herein are pyrazole compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain.
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Paragraph 00291
(2018/12/13)
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- Synthesis of carbazoles based on gold-copper tandem catalysis
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An efficient synthetic method for carbazoles has been developed employing diazo anilinoalkynes as substrates. Sequential activation of the orthogonal functional groups embedded in diazo anilinoalkyne substrates by tandem gold-copper catalysis leads to the formation of highly substituted carbazoles. Substrate scope reveals a broad tolerability toward the substitution on aryl groups.
- Choi, Subin,Srinivasulu, Vunnam,Ha, Sujin,Park, Cheol-Min
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supporting information
p. 3481 - 3484
(2017/03/29)
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- Gold(I)-catalyzed iodination of arenes
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A wide variety of electron-rich arenes were efficiently converted into the corresponding iodinated compounds via a gold(I)-catalyzed reaction under mild conditions. Georg Thieme Verlag Stuttgart. New York.
- Leboeuf, David,Ciesielski, Jennifer,Frontier, Alison J.
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supporting information
p. 399 - 402
(2014/03/21)
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- Tuneable radical cyclisations: A tin-free approach towards tricyclic and spirocyclic heterocycles via a common precursor
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A novel common precursor approach towards both tricyclic and spirocyclic heterocycles is described. Cyclisations are based on thiyl radical/isocyanide methodology and avoid the use of tin.
- Patel,Saviolaki,Ayats,Garcia,Kapadia,Hilton
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p. 18930 - 18932
(2014/05/20)
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- Gold-catalyzed transformation of 2-alkynyl arylazides: Efficient access to the valuable pseudoindoxyl and indolyl frameworks
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An element of surprise: A series of functionalized 2-alkynyl arylazides has beed converted into 3-substituted indoles or 2,2-disubstituted indolin-3-ones in the presence of a gold(I) complex. Various oxygen or aryl nucleophiles can be used in this process to trap the intermediate α-imino gold carbene. The structural motifs of the products are found in a large variety of biologically active compounds and natural products. Copyright
- Wetzel, Alexander,Gagosz, Fabien
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supporting information; experimental part
p. 7354 - 7358
(2011/09/16)
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- Synthesis and evaluation of a series of C5′-substituted duocarmycin SA analogs
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The synthesis and evaluation of a key series of analogs of duocarmycin SA, bearing a single substituent at the C5′ position of the DNA binding subunit, are described.
- Robertson, William M.,Kastrinsky, David B.,Hwang, Inkyu,Boger, Dale L.
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supporting information; experimental part
p. 2722 - 2725
(2011/07/06)
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- METHOD OF TREATMENT
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Method of of preventing or treating myocardial ischemia by inhibiting DGAT1 enzyme with a DGAT1 inhibitor compound.
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Page/Page column 62
(2008/12/06)
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- NOVEL CHEMICAL COMPOUNDS
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This invention relates to newly identified compounds for inhibiting hYAK3 proteins and methods for treating diseases associated with the imbalance or inappropriate activity of hYAK3 proteins.
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Page/Page column 30-31
(2010/11/26)
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- THIAZOLONES FOR USE AS PI3 KINASE INHIBITORS
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Invented is a method of inhibiting the activity/function of PI3 kinases using substituted thiazolones. Also invented is a method of treating one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, ne
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Page/Page column 48
(2008/06/13)
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- Formation of arenes via diallylarenes: Strategic utilization of Suzuki-Miyaura cross-coupling, Claisen rearrangement and ring-closing metathesis
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Two new synthetic strategies for benzoannulation are reported. The first strategy is based on the Suzuki-Miyaura cross-coupling reaction. To this end, various ortho-diallylbenzene derivatives were prepared from the corrresponding diiodo derivatives by an allylation strategy using an allylboronate as coupling partner. These diallyl derivatives were subjected to a ring-closing metathesis (RCM) and one-pot dichlorodicyanoquinone (DDQ) oxidation sequence to deliver 2-substituted naphthalenes. In the second strategy, a double Claisen rearrangement and RCM protocol have been used as key steps to give highly functionalized benzoannulated quinone derivatives.
- Kotha, Sambasivarao,Shah, Vrajesh R.,Mandal, Kalyaneswar
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p. 1159 - 1172
(2008/04/03)
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- 2-PHENYL-5-AMINO-1,3,4-OXADIAZOLES AND THEIR USE AS NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS
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The present invention relates to novel oxadiazole derivatives of formula (1) having pharmacological activity, processes for their preparation, compositions containing them and their use in the treatment of neurological, psychiatric disorders and gastrointestinal disorders through modulation of the nicotinic α7 receptor formula (I).
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Page/Page column 33-34
(2008/06/13)
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- A bioisosteric approach to the discovery of indole carbinol androgen receptor ligands
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Two potential bioisosteres of the nonsteroidal antiandrogen bicalutamide, an imidazolidinone and an indole, were synthesized and tested for their androgen receptor binding. Indole was discovered to be a suitable bioisostere for the acyl anilide moiety in the parent compound. Several analogs in the indole series were found to be 10-fold better than bicalutamide in binding to the recombinant androgen receptor binding domain.
- Lanter, James C.,Fiordeliso, James J.,Allan, George F.,Musto, Amy,Hahn, Do Won,Sui, Zhihua
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p. 5646 - 5649
(2007/10/03)
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- Silicon-directed oxa-Pictet-Spengler cyclization and an unusual dimerization of 2-trimethylsilanyl tryptophols
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(Chemical Equation Presented) The tetrahydro-pyrano[3,4-b]indoles 6 were synthesized from 2-(2-trimethylsilanyl-1H-indol-3-yl)-ethanols 5 and various ketones or aldehydes through silicon-directed oxa-Pictet-Spengler cyclizations. An unusual reaction led to the dimeric products 7 when some of 5 was treated with acetone using BF3 as the catalyst.
- Zhang, Xuqing,Li, Xiaojie,Lanter, James C.,Sui, Zhihua
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p. 2043 - 2046
(2007/10/03)
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- Solid-phase synthesis of an A-B loop mimetic of the Cε3 domain of human IgE: Macrocyclization by Sonogashira coupling
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The solid-phase synthesis of a cyclic peptide containing the 21-residue epitope found in the A-B loop of the Cε3 domain of human immunoglobulin E has been carried out. The key macrocyclization step to form the 65-membered ring is achieved in ~15% yield vi
- Spivey, Alan C.,McKendrick, John,Srikaran, Ratnasothy,Helm, Birgit A.
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p. 1843 - 1851
(2007/10/03)
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- N-BENZOYLUREIDOCINNAMATE DERIVATIVES, METHOD FOR PRODUCTION AND USE THEREOF
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The invention relates to N-benzoylureidocinnamate derivatives of formula (I), where R1-R11 have the meanings given in the claims, the physiologically acceptable salts and method for production thereof. The compounds are suitable as anti-diabetics, for exa
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- Microwave-assisted synthesis of 5-carboxymethoxy-N-acetyltryptamine derivatives
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The synthesis of the indole core structure was investigated using microwave irradiation. The experimental microwave conditions described allow significant rate enhancements and good yields compared to conventional reaction conditions.
- F?naru, Adriana,Berthault, Aurélie,Besson, Thierry,Guillaumet, Gérald,Berteina-Raboin, Sabine
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p. 787 - 790
(2007/10/03)
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- Cyclization of 1-(2-alkynylphenyl)-3,3-dialkyltriazenes: A convenient, high-yield synthesis of substituted cinnolines and isoindazoles
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A new route to isoindazoles and cinnolines through the cyclization of (2-alkynylphenyl)triazenes under neutral conditions is presented. The products that result from heating the starting triazenes depend on both the type of alkyne ortho to the triazene functionality and the temperature used. Butadiyne moieties ortho to dialkyltriazenes yield bis-isoindazole dimers when heated to 150 °C in MeI. A requirement for cyclization in MeI is that the (2-alkynylphenyl)triazene must contain a suitably electron-withdrawing substituent on the phenyl ring to deactivate the triazene toward methylation-induced decomposition to an iodoarene. Ethynyl moieties ortho to dialkyltriazenes yield both isoindazole dimers as well as 3-formylisoindazoles when subjected to the same conditions. Replacing MeI with 1,2-dichlorobenzene as solvent allows for the general cyclization of (2-ethynylphenyl)dialkyltriazenes. Heating to 170 °C results in a mixture of isoindazole and cinnoline products, whereas the cinnolines are produced exclusively in high yield at 200 °C. Alternatively, the isoindazoles can be obtained in good to excellent yield by stirring a 1,2-dichloroethane solution of the starting triazene with CuCl overnight at 50 °C.
- Kimball, David B.,Weakley, Timothy J. R.,Haley, Michael M.
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p. 6395 - 6405
(2007/10/03)
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- Substituted phenyl farnesyltransferase inhibitors
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Compounds of formula (I) or pharmaceutically acceptable salts thereof, inhibit farnesyltransferase. Methods for making the compounds, pharmaceutical compositions containing the compounds, and methods of treatment using the compounds are disclosed.
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- Stereoselective synthesis of (E)-3-(methoxycarbonyl)methylene-1,3-dihydroindol-2-ones by palladium-catalyzed oxidative carbonylation of 2-ethynylanilines
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A direct synthesis of (E)-3-(methoxycarbonyl)methylene-1,3-dihydroindol-2-ones 2 by palladium-catalyzed oxidative carbonylation of 2-ethynylanilines 1 is reported. Reactions were carried out in MeOH as the solvent at 50-70°C in the presence of catalytic a
- Gabriele, Bartolo,Salerno, Giuseppe,Veltri, Lucia,Costa, Mirco,Massera, Chiara
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p. 4607 - 4613
(2007/10/03)
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- Synthesis of trisubstituted indoles on the solid phase via palladium-mediated heteroannulation of internal alkynes
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Palladium-mediated heteroannulation of internal alkynes with resin-bound o-iodoaniline derivatives 4 or 5a provided diverse trisubstituted indoles 6 in good yields. The facile reaction of trimethylsilylalkynes afforded resin-bound precursors useful for obtaining other 2-substituted indole derivatives, such as 12.
- Zhang, Han-Cheng,Brumfield, Kimberly K.,Maryanoff, Bruce E.
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p. 2439 - 2442
(2007/10/03)
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- Synthesis of I-125 labeled photoaffinity rapamycin analogs
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Two no-carrier-added 125I-labeled photoaffinity rapamycin analogs were prepared: 7-demethoxy-7-(4-azido-3-125I-benzyloxy)rapamycin (2) and its C28-C29 seco analog 3. The key reactions of the synthesis were subst
- Shu, Arthur Y.L.,Yamashita, Dennis S.,Holt, Dennis A.,Heys, J. Richard
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p. 227 - 237
(2007/10/03)
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- TOTAL SYNTHESIS OF THE ANTIVIRAL (+/-)-VIRANTMYCIN
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The total synthesis of the racemic modification of the antiviral metabolite virantmycin is described starting from p-aminobenzoic acid and utilising acetylenic precursors.
- Hill, Malcolm L.,Raphael, Ralph A.
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p. 4587 - 4594
(2007/10/02)
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- TOTAL SYNTHESIS OF THE ANTIVIRAL (+/-) VIRANTMYCIN
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A total synthesis of the antiviral metabolite virantmycin is described.
- Hill, Malcolm L.,Raphael, R. A.
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p. 1293 - 1296
(2007/10/02)
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