- Intramolecular Formal anti-Carbopalladation/Heck Reaction: Facile Domino Access to Carbo- and Heterooligocyclic Dienes
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An intramolecular domino process consisting of a formal anti-carbopalladation followed by Heck reaction is realized. Complex oligo(hetero)cyclic scaffolds are efficiently obtained in one synthetic step from easily obtainable enyne precursors. In contrast to common syn-carbopalladation reactions of alkyne units, the carbopalladation employed here is designed to afford an anti-arrangement of the two new substituents across the emerging double bond. A prerequisite is that the residues next to the alkyne should lack any β-hydrogen atoms. The method paves the way to tri- and tetrasubstituted double-bond systems that have not been accessible by conventional Pd catalysis.
- Pawliczek, Martin,Milde, Bastian,Jones, Peter G.,Werz, Daniel B.
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- Synthesis and pharmacological evaluation of N-benzyl substituted 4-bromo-2,5-dimethoxyphenethylamines as 5-HT2A/2C partial agonists
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N-Benzyl substitution of phenethylamine 5-HT2A receptor agonists has dramatic effects on binding affinity, receptor selectivity and agonist activity. In this paper we examine how affinity for the 5-HT2A/2C receptors are influenced by N-benzyl substitution of 4-bromo-2,5-dimethoxyphenethylamine derivatives. Special attention is given to the 2′ and 3′-position of the N-benzyl as such compounds are known to be very potent. We found that substitutions in these positions are generally well tolerated. The 2′-position was further examined using a range of substituents to probe the hydrogen bonding requirements for optimal affinity and selectivity, and it was found that small changes in the ligands in this area had a profound effect on their affinities. Furthermore, two ligands that lack a 2′-benzyl substituent were also found to have high affinity contradicting previous held notions. Several high-affinity ligands were identified and assayed for functional activity at the 5-HT2A and 5-HT2C receptor, and they were generally found to be less efficacious agonists than previously reported N-benzyl phenethylamines.
- Hansen, Martin,Jacobsen, Stine Engesgaard,Plunkett, Shane,Liebscher, Gudrun Eckhard,McCorvy, John D.,Br?uner-Osborne, Hans,Kristensen, Jesper Langgaard
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supporting information
p. 3933 - 3937
(2015/01/30)
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- INHIBITORS OF THE KYNURENINE PATHWAY
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The present application provides novel inhibitors of indoleamine 2,3-dioxygenase-1 and/or indoleamine 2,3-dioxygenase-2 and/or tryptophan 2,3-dioxygenase, metabolites thereof, and phannaceutically acceptable salts or prodrugs thereof. Also provided are methods for preparing these compounds. A therapeutically effective amount of one or more of the compounds of formula (I) is useful in treating diseases resulting from dysregulation of the kynurenine pathway. Compounds of formula (I) act by inhibiting the enzymatic activity or expression of indoleamine 2,3-dioxygenase-1 and/or indoleamine 2,3-dioxygenase-2 and/or tryptophan 2,3-dioxygenase.
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Page/Page column 216
(2014/12/12)
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- OLIGOMERISATION OF ETHYLENE TO MIXTURES OF 1-HEXENE AND 1-OCTENE
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A process for the otigomerisation of ethylene to predominantly 1-hexene or 1-octene or mixtures of 1-hexene and 1-octene includes contacting ethylene with a catalyst under ethylene oligomerisation conditions. The catalyst comprises a source of chromium, a diphosphine ligating compound, and optionally an activator. The diphosphine ligating compound includes at least one optionally substituted fused cyclic structure including at least two rings, the optionally substituted fused cyclic structure including a 5- to 7- membered aromatic first ring bonded to a phosphorus atom, the aromatic first ring being fused to a 4- to 8-membered heterocyclic second ring, the heterocyclic second ring including a heteroatom which is separated by two ring atoms along the shortest connecting path from the phosphorous atom that is bonded to the first aromatic ring.
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Page/Page column 26-27
(2014/12/09)
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- Piperidine derivatives having effects on serotonin related systems
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The present invention provides the compounds of the following formula: Wherein the variables are as defined in the specification and a method for inhibiting the reuptake of seretonin, antagonizing the 5-HT1Areceptor and antagonizing the 5-HT2Areceptor which comprises administering to a subject in need of such treatment an effective amount of the compound of above formula.
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- Azepine derivatives having effects on serotonin related systems
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The present invention provides compounds of formula I and a method of inhibiting the reuptake of serotonin, antagonizing the 5-HT1Areceptor and antagonizing the 5-HT2Areceptor which comprises administering to a subject in need of suc
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- Pyrrolidine and pyrroline derivatives having effects on serotonin related systems
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The present invention provides the compounds of the following formula (I): and a method for inhibiting the reuptake of seretonin, antagonizing the 5-HT1Areceptor and antagonizing the 5-HT2Areceptor which comprises administering to a subject in need of such treatment an effective amount of formula (I).
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Page column 25-26
(2010/02/05)
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- Rotenoid Synthesis by Wadsworth-Emmons Coupling and Mukaiyama Cyclisation: Application to 5-Thiorotenoids
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A new synthesis of general applicability to rotenoid structures is described, through its specific objectives were 5-thiorotenoids.The synthons carrying the A/B- and the B/C-ring components are coupled by Wadsworth-Emmons synthesis and the ring B chromene is formed by Mukaiyama directed aldol cylisation: Michael addition completes the formation of the rotenoid at its correct oxidation state and in its stable cis-form.Examples with, and without 2,3-dimethoxylation in ring A are described.
- crombie, Leslie,Josephs, Jonathan L.
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p. 2599 - 2604
(2007/10/02)
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- Electrophilic Aromatic Substitution. Part 33. Partial Rate Factors for Protiodetritiation of Benzothiophen; the Resonance-dependent Reactivity of the Ring Positions
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Rate coefficients for detriation of benzothiophen, specifically labelled with tritium at each position, have been measured in anhydrous trifluoroacetic acid, and, for benzothiophen, in a range of trifluoroacetic acid-acetic acid mixtures, all at 70 deg C.The dependence of rate upon acidity is consistent with the effect of hydrogen bonding between sulphur and trifluoroacetic acid, as found previously for other sulphur-containing heterocycles.Partial rate factors, corrected for the effect of hydrogen bonding are (positions in parentheses): 8.84 * 105 (2); 1.18 * 106 (3); 360 (4); 13200 (5); 16200 (6); and 26.2 (7); the corresponding ?+ values are -0.68, -0.695, -0.29, -0.47, -0.48, and -0.16.The positional reactivity order is the same as found in pyrolysis of 1-arylethyl acetates, and solvolysis of 1-arylethyl chlorides, but the ?+ values are more negative due to the greater demand for resonance stabilization of the transition states in hydrogen exchange.Comparison of the 2- : 3-isomer ratios in various substitutions leads to the unexpected conclusion that substitution at the 2-position is subject to steric effects, probably due to the proximity of the sulphur d-orbitals.
- Amin, Hassan B.,Awad, Amin A.,Archer, William J.,Taylor, Roger
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p. 1489 - 1492
(2007/10/02)
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