99198-96-6Relevant articles and documents
Ulotaront: A TAAR1 Agonist for the Treatment of Schizophrenia
Heffernan, Michele L. R.,Herman, Lee W.,Brown, Scott,Jones, Philip G.,Shao, Liming,Hewitt, Michael C.,Campbell, John E.,Dedic, Nina,Hopkins, Seth C.,Koblan, Kenneth S.,Xie, Linghong
supporting information, p. 92 - 98 (2021/12/17)
Ulotaront (SEP-363856) is a trace-amine associated receptor 1 (TAAR1) agonist with 5-HT1A receptor agonist activity in Phase 3 clinical development, with FDA Breakthrough Therapy Designation, for the treatment of schizophrenia. TAAR1 is a G-protein-coupled receptor (GPCR) that is expressed in cortical, limbic, and midbrain monoaminergic regions. It is activated by endogenous trace amines, and is believed to play an important role in modulating dopaminergic, serotonergic, and glutamatergic circuitry. TAAR1 agonism data are reported herein for ulotaront and its analogues in comparison to endogenous TAAR1 agonists. In addition, a human TAAR1 homology model was built around ulotaront to identify key interactions and attempt to better understand the scaffold-specific TAAR1 agonism structure-activity relationships.
A direct route to polythiophenes displaying lateral substituents: Easy one-step synthesis and polymerization of thiophene monomers substituted by a dimethylenecarboxylate (CH2CH2COOR) appendage on the 3-position
Sengmany, Stephane,Ceballos, Claire,Belhadj, Romain,Cachet-Vivier, Christine,Gall, Erwan Le,Brissault, Blandine,Penelle, Jacques,Leonel, Eric
experimental part, p. 900 - 911 (2012/06/01)
Thiophene monomers displaying a dimethylenecarboxylate (CH 2CH2COOR) substituent on the 3-position of the aromatic ring can be easily obtained and in one step from the electrochemically induced reaction of 3-bromothiophene with the corresponding acrylate (CH 2=CHCOOR). The synthesis of the ethyl ester monomer, of related 2,5-dihalogenothiophenes, and their polymerization are reported. Despite the surprisingly low solubilities displayed by the polymers, a full spectroscopic characterization could be performed and the data fully analyzed. Oxidative polymerizations (FeCl3 or electropolymerization) yield a regioirregular polythiophene, with 60-70% of head-to-tail diads. Both experimental and theoretical results suggest that the nonconjugated ester plays a very minor role-if any-in the polymerizations under oxidative conditions, but has a significant influence on the polymer properties. Preliminary attempts to polymerize the dihalogenothiophenes under reductive conditions were hampered by the even lower solubilities exhibited by the regioregular oligomers.
Site-specific hydrogen exchange and hydrogen transfer processes preceding the fragmentation of long-lived radical cations of ethyl dihydrocinnamate and related arylalkanoates
Amick, Aaron W.,Hoegg, Edward,Harrison, Sean,Houston, Katelyn R.,Hark, Richard R.,Reingold, I. David,Barth, Dieter,Letzel, Matthias C.,Kuck, Dietmar
experimental part, p. 206 - 215 (2012/07/01)
An electron ionisation study on the fragmentation of metastable molecular radical cations of ethyl 3-phenylpropanoate (ethyl dihydrocinnamate) and related arylalkanoic acid esters was performed by mass-analysed ion kinetic energy (MIKE) spectrometry. Six deuterium-labelled isotopomers of ethyl dihydrocinnamate were synthesised and studied by MIKE spectrometry. The fragmentation leading to ions C7H7O+ (m/z 107) involving migration of the alkoxycarbonyl group was also observed in the 70-eV mass spectra of related alkyl dihydrocinnamates, but it was found to be a high-energy process that does not compete at low energies in metastable molecular ions. Instead, the metastable ions of ethyl dihydrocinnamate undergo competing losses of carbon monoxide, ethanol and the combined loss of these neutral fragments, giving ionised styrene, C8H8 ?+ (m/z 104). A highly specific H/D interchange involving the four hydrogen atoms at the benzylic α- and ortho-positions was found to precede the losses of ethanol and [ethanol + CO]. This represents another striking case of complete 4H - scrambling that enables the molecular ion to fully equilibrate the interchanging hydrogen atoms prior to fragmentation. A mechanism rationalising these observations and extending previously suggested mechanisms is proposed involving a series of distonic ions and the intermediacy of an ion/neutral complex. The metastable ions of the related esters exhibit in part similar fragmentation behaviour, but the McLafferty reaction turns out to be more favourable with higher alkyl dihydrocinnamates. For example, n-propyl 3-phenylpropanoate and isopropyl 3-phenylpropanoate react through highly distinct fragmentation channels.
Acylaminothiazole derivatives, their preparation and their therapeutic use
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Page/Page column 10, (2008/06/13)
Compound corresponding to the general formula (I): in which, X represents an oxygen or sulphur atom; R1 represents a C1-10 alkyl group optionally substituted, a C3-7 cycloalkyl, thienyl, pyridinyl or pyrimidinyl group; the thienyl groups being optionally substituted; the phenyl group being optionally substituted; R2 represents a C1-6 alkyl group optionally substituted, a C3-7 cycloalkyl, piperidinyl, phenyl or pyridinyl group; the C3-7 cycloalkyl and piperidinyl groups being optionally substituted; the phenyl and pyridinyl groups being optionally substituted; R3 represents a hydrogen atom or a C1-6 alkyl group optionally substituted with a C3-7 cycloalkyl group; R4 represents a hydrogen atom or a C1-6 alkyl group; R5 and R5′ represent, independently of each other, a hydrogen or halogen atom, a hydroxyl or C1-3 alkyl group; or R5 and R5′ form together an oxo or oxime group such as: where R7 represents a hydrogen atom or a C1-3 alkyl; n represents an integer ranging from 0 to 3; and R6 represents, independently of each other when n=2 or 3, a hydrogen or halogen atom, a hydroxyl, C1-3 alkyl, C1-3 alkoxy, C1-3 fluoroalkyl or C1-3 fluoroalkoxy group; in the form of a base, of an addition salt with an acid, of a hydrate or of a solvate. therapeutic application.
CoBr2(Bpy): An efficient catalyst for the direct conjugate addition of aryl halides or triflates onto activated olefins
Amatore, Muriel,Gosmini, Corinne,Perichon, Jacques
, p. 6130 - 6134 (2007/10/03)
An efficient cobalt-catalyzed method devoted to the direct conjugate addition of functionalized aryl compounds onto Michael acceptors is described. The CoBr2(2,2′-bipyridine) complex appears to be an extremely suitable catalyst for the activation of a variety of aromatic reagents ranging from halides to triflates functionalized by reactive groups. This procedure allows for the synthesis of compounds resulting from 1,4-addition in good to excellent yields. The versatility of this original process represents a simple alternative to most known methods using organometallic reagents.
Synthesis of Thiophene-Substituted Spiropyrans and Spirooxazines, Precursors of Photochromic Polymers
Moustrou, Corinne,Samat, Andre,Guglielmetti, Robert,Dubest, Roger,Garnier, Francis
, p. 1887 - 1893 (2007/10/02)
The synthesis of spiropyrans 11 and 12 and spirooxazines 13-17 containing a thiophene moiety is described.Two different synthetic approaches were used.The spectrokinetic properties of these new compounds are reported.
Structure-Odor Correlation, XXI. Olfactory Properties and Convenient Synthesis of Furans and Thiophenes Related to Rose Furan and Perillene and Their Isomers
Weyerstahl, Peter,Schenk, Anja,Marschall, Helga
, p. 1849 - 1854 (2007/10/03)
Starting from 3-bromofuran (1) or 3-bromothiophene (2) via alkylation in 2-position (-> 3-8) followed by the corresponding second alkylation in 3-position, we obtained rose furan (9), rose thiophene (10), and their analogs 11-16.From the α,β-unsaturated esters 17-20 by hydrogenation (-> 21-24), DIBAH reduction (-> 25-28), and Wittig reaction, perillene (29), thioperillene (30), and their analogs 29-36 were obtained.Olfactory evaluation showed that the difference between the furans and thiophene derivatives is remarkably small, particularly for perillene (29) compared with thioperillene (30), and their analogs.Also the influence of position and structure of the side chain is lower than expected within the compared compounds 9-36. - Keywords: Rose furan / Perillene / Furans / Thiophenes / Structure-odor correlation / Odoriferous substances
New spiropyrans and two spirooxazines compounds with one or two thiophene nuclei. Applications to anticopying protection materials
Moustrou,Campredon,Samat,Garnier,Robillard,Guglielmetti
, p. 29 - 32 (2007/10/02)
The strategy of synthesis of new thiophene-substituted spiroheterocyclic photochromic structures, in spiropyran or spirooxazine series is described. The polymerization of thiophene entity give interesting semi-conductor systems. Such molecular materials prevent the reproduction of documents and could be useful in other applications such as fast optical switches.
SYNTHESE ET ETUDE ELECTROCHIMIQUE D'ALCOOLS ET D'ESTERS DERIVES DE 3-ALKYL THIOPHENES
Blanchetiere, D.,Noyere, C.,Catel, J.,Andrieu, C. G.,Ebel, M.
, p. 93 - 102 (2007/10/03)
Starting from 3-bromothiophene, ω-(3-thienyl)alkan-1-ols and ω-(3-thienyl)alkyl esters are obtained.Electrochemical characteristics and polymerization are described and discussed.Key words: ω-(3-thienyl)alkanols and ω-(3-thienyl)alkyl esters, electrochemical polymerization.
