- 4-Hydroxy-1,2,3-triazole moiety as bioisostere of the carboxylic acid function: a novel scaffold to probe the orthosteric γ-aminobutyric acid receptor binding site
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The correct application of bio(iso)steric replacement, a potent tool for the design of optimized compounds, requires the continuous development of new isosters able to respond to specific target requirements. Among carboxylic acid isosters, as the hydroxy
- Giraudo, Alessandro,Krall, Jacob,Nielsen, Birgitte,S?rensen, Troels E.,Kongstad, Kenneth T.,Rolando, Barbara,Boschi, Donatella,Fr?lund, Bente,Lolli, Marco L.
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Read Online
- Sustainable Route Toward N-Boc Amines: AuCl3/CuI-Catalyzed N-tert-butyloxycarbonylation of Amines at Room Temperature
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N-tert-butoxycarbonyl (N-Boc) amines are useful intermediates in synthetic/medicinal chemistry. Traditionally, they are prepared via an indirect phosgene route with poor atom economy. Herein, a step- and atom-economic synthesis of N-Boc amines from amines, t-butanol, and CO was reported at room temperature. Notably, this N-tert-butyloxycarbonylation procedure utilized ready-made substrates, commercially available AuCl3/CuI as catalysts, and O2 from air as the sole oxidant. This catalytic system provided unique selectivity for N-Boc amines in good yields. More significantly, gram-scale preparation of medicinally important N-Boc amine intermediates was successfully implement, which demonstrated a potential application prospect in industrial syntheses. Furthermore, this approach also showed good compatibility with tertiary and other useful alcohols. Investigations of the mechanisms revealed that gold catalyzed the reaction and copper acted as electron transfer mediator in the catalytic cycle.
- Cao, Yanwei,Huang, Yang,He, Lin
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- Reductive Radical Conjugate Addition of Alkyl Electrophiles Catalyzed by a Cobalt/Iridium Photoredox System
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Alkyl and aryl halides have been studied extensively as radical precursors; however, mild and less toxic conditions for the activation of alkyl bromides toward alkyl radicals are still desirable. Reported here is a reductive radical conjugate addition tha
- Escobar, Randolph A.,Johannes, Jeffrey W.
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supporting information
p. 6046 - 6051
(2021/08/03)
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- Copper-Catalyzed Cross-Coupling between Alkyl (Pseudo)halides and Bicyclopentyl Grignard Reagents
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The development of a copper-catalyzed cross-coupling between primary and secondary (pseudo)halides and bicyclopentyl Grignard reagents is reported. Highly strained bicyclopentanes can be cross-coupled with a large panel of primary alkyl mesylates and secondary alkyl iodides. The catalytic system is simple and cheap, and the reaction is general and chemoselective.
- Andersen, Claire,Bernardelli, Patrick,Cossy, Janine,Daumas, Marc,Ferey, Vincent,Guérinot, Amandine
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- Synthesis of Alkyl Halides from Aldehydes via Deformylative Halogenation
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An unprecedented deformylative halogenation of aldehydes to alkyl halides is presented. Under oxidative conditions, 1,4-dihydropyridine (DHP), derived from an aldehyde, generated a C(sp3)- radical that coupled with a halogen radical that was generated from inexpensive and atom-economical halogen sources (NaBr, NaI, or HCl), to yield an alkyl halide. Because of the mild conditions, a wide range of functional groups were tolerated, and excellent site selectivity was achieved.
- Liang, Shengzong,Kumon, Tatsuya,Angnes, Ricardo A.,Sanchez, Melissa,Xu, Bo,Hammond, Gerald B.
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supporting information
p. 3848 - 3854
(2019/05/24)
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- PROCESS FOR THE PREPARATION OF ORGANIC BROMIDES
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The present invention provides a process for the preparation of organic bromides, by a radical bromodecarboxylation of carboxylic acids with a bromoisocyanurate.
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Paragraph 00169; 00180; 00205
(2017/07/28)
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- Palladium-Catalyzed Alkoxycarbonylation of Unactivated Secondary Alkyl Bromides at Low Pressure
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Catalytic carbonylations of organohalides are important C-C bond formations in chemical synthesis. Carbonylations of unactivated alkyl halides remain a challenge and currently require the use of alkyl iodides under harsh conditions and high pressures of CO. Herein we report a palladium-catalyzed alkoxycarbonylation of secondary alkyl bromides that proceeds at low pressure (2 atm CO) under mild conditions. Preliminary mechanistic studies are consistent with a hybrid organometallic-radical process. These reactions efficiently deliver esters from unactivated alkyl bromides across a diverse range of substrates and represent the first catalytic carbonylations of alkyl bromides with carbon monoxide.
- Sargent, Brendon T.,Alexanian, Erik J.
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supporting information
p. 7520 - 7523
(2016/07/06)
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- Cobalt-Catalyzed Cross-Coupling of 3- and 4-Iodopiperidines with Grignard Reagents
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A cobalt-catalyzed cross-coupling between 3- and 4-iodopiperidines and Grignard reagents is disclosed. The reaction is an efficient, cheap, chemoselective, and flexible way to functionalize piperidines. This coupling was used as the key step to realize a short synthesis of (±)-preclamol. Some mechanistic investigations were conducted that highlight the formation of radical intermediates. Scaffold synthesis: A cobalt-catalyzed cross-coupling between iodopiperidines and Grignard reagents is reported (see scheme; PG=protecting group). A large variety of 3- and 4-substituted piperidines were synthesized and the method was applied to a short synthesis of (±)-preclamol. This work constitutes one of the rare examples of cross-couplings involving 3-halogeno piperidines.
- Gonnard, Laurine,Gurinot, Amandine,Cossy, Janine
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p. 12797 - 12803
(2015/09/01)
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- Iron-catalyzed borylation of alkyl, allyl, and aryl halides: Isolation of an iron(I) boryl complex
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Activation of B2pin2 with tBuLi facilitates the Fe-catalyzed borylation of alkyl, allyl, benzyl, and aryl halides via the formation of Li[B2pin2(tBu)] (1). The reaction of 1 with a representative iron phosphine precatalyst generates the unique iron(I) boryl complex [Fe(Bpin)(dpbz)2] (2).
- Bedford, Robin B.,Brenner, Peter B.,Carter, Emma,Gallagher, Timothy,Murphy, Damien M.,Pye, Dominic R.
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supporting information
p. 5940 - 5943
(2015/01/08)
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- Compounds Which Selectively Modulate The CB2 Receptor
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Compounds of formula (I) are disclosed. Compounds according to the invention bind to and are agonists, antagonists or inverse agonists of the CB2 receptor, and are useful for treating inflammation. Those compounds which are agonists are additionally useful for treating pain.
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Page/Page column 22; 23
(2011/04/18)
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- Compounds Which Selectively Modulate The CB2 Receptor
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Compounds of formula (I) are disclosed. Compounds according to the invention bind to and are agonists, antagonists or inverse agonists of the CB2 receptor, and are useful for treating inflammation. Those compounds which are agonists are additionally usefu
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Page/Page column 42
(2010/04/23)
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- NOVEL TRICYCLIC DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, PROCESS FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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The present invention relates to novel tricyclic derivatives having an excellent inhibitory activity on poly (ADP-ribose) polymerase, or pharmaceutically acceptable salts thereof, a process for the preparation thereof, and a pharmaceutical composition comprising the same. The tricyclic derivatives of the present invention inhibit the activity of poly (ADP-ribose) polymerase, thereby being used for the prevention or treatment of diseases that are caused by excessive activation of PARP, in particular, neuropathic pain, neurodegenerative diseases, cardiovascular diseases, diabetic neuropathic pain, inflammatory diseases, osteoporosis, and cancer.
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Page/Page column 111-112
(2009/06/27)
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- Indole, azaindole and related heterocyclic 4-alkenyl piperidine amides
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This invention provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the invention is concerned with new piperidine 4-alkenyl derivatives that possess unique antiviral activity. More particularly, the present invention relates to compounds useful for the treatment of HIV and AIDS. The compounds of the invention for the general Formula I: wherein: Z is Q is selected from the group consisting of: —W— is
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Page/Page column 17
(2010/02/06)
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- 2-PHENOXY- AND 2-PHENYLSULFOMAMIDE DERIVATIVES WITH CCR3 ANTAGONISTIC ACTIVITY FOR THE TREATMENT OF ASTHMA AND OTHER INFLAMMATORY OR IMMUNOLOGICAL DISORDERS
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The present invention relates to a benzenesulfonamide derivative of formula (I), which is useful as an active ingredient of pharmaceutical preparations. The benzenesulfonamide derivatives of the present invention have CCR3 (CC type chemokine receptor) ant
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Page/Page column 64
(2008/06/13)
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- Sulfone derivatives, process for their production and use thereof
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A compound represented by the formula: 1wherein R is a cyclic hydrocarbon group, or the like; W is a bond, or the like; X is a divalent hydrocarbon group, or the like; Y and Z are each independently —N(R6)— or the like; ring A is a nitrogen-containing heterocyclic ring, or the like; R5 and R6 are independently hydrogen atom, a hydrocarbon group, or the like; Z′ is imidoyl group, or the like; a is 0, 1 or 2; and b is 0 or 1, or a salt thereof.
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- Antagonists of the human CCR5 receptor as anti-HIV-1 agents. Part 4: Synthesis and structure-activity relationships for 1-[N-(methyl)-N-(phenylsulfonyl)amino]-2-(phenyl)-4-(4-(N-(alkyl)-N- (benzyloxycarbonyl)amino)piperidin-1-yl)butanes
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(2S)-2-(3-Chlorophenyl)-1-[N-(methyl)-N-(phenylsulfonyl)amino]-4-[spiro (2,3-dihydrobenzthiophene-3,4′-piperidin-1′-yl)]butane S-oxide (1b) has been identified as a potent CCR5 antagonist having an IC50 = 10 nM. Herein, structure-activity relationship studies of non-spiro piperidines are described, which led to the discovery of 4-(N-(alkyl)-N-(benzyloxycarbonyl)amino)piperidine derivatives (3-5) as potent CCR5 antagonists.
- Finke, Paul E.,Oates, Bryan,Mills, Sander G.,MacCoss, Malcolm,Malkowitz, Lorraine,Springer, Martin S.,Gould, Sandra L.,DeMartino, Julie A.,Carella, Anthony,Carver, Gwen,Holmes, Karen,Danzeisen, Renee,Hazuda, Daria,Kessler, Joseph,Lineberger, Janet,Miller, Michael,Schleif, William A.,Emini, Emilio A.
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p. 2475 - 2479
(2007/10/03)
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- Seleninic Acid Analogues of the Inhibitory Neurotransmitter 7-Aminobutyric Acid
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The first seleninic acid analogues of γ-aminobutyric acid (GABA) and of the specific GABA agonist piperidine-4-carboxylic acid (isonipecotic acid), 1 and 2, respectively, have been synthesized and shown to be potent agonists at the GABA receptors.
- Stuhr-Hansen, Nicolai,Ebert, Bjarke,Krogsgaard-Larsen, Povl,Kehler, Jan
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- 4-N-linked-heterocyclic piperidine derivatives with high affinity and selectivity for human dopamine D4 receptors
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The syntheses of a number of different N-linked heterocyclic pyrazole replacements based on the structure 1 are described (compounds 3-12) as hD4 ligands. After further optimisation the best compound identified was 13 which has high affinity for hD4 (5.2 nM) and >300-fold selectivity for hD4 receptors over hD2 and hD3 receptors.
- Moore, Kevin W.,Bonner, Katrine,Jones, Elizabeth A.,Emms, Frances,Leeson, Paul D.,Marwood, Rosemary,Patel, Shil,Patel, Smita,Rowley, Michael,Thomas, Steven,Carling, Robert W.
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p. 1285 - 1290
(2007/10/03)
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- INDOLE DERIVATIVES AS DOPAMINE D4 ANTAGONISTS
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Compounds of formula (I), or a salt or prodrug thereof, wherein R represent hydrogen or C 1-6 alkyl; Q represents a moiety of formula Qa or Qb; they are antagonists of dopamine receptor subtypes within the brain, having a selective affinity for the dopami
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