- DIAGNOSIS, TREATMENT AND PREVENTION OF NEUROTENSIN RECEPTOR-RELATED CONDITIONS
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The present invention describes a compound of formula (I) which can be used in the diagnosis, treatment or prevention of neurotensin receptor-related conditions such as tumors and hematological malignancies.
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Paragraph 0124; 0126
(2018/03/01)
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- Hit-to-Lead Optimization of Mouse Trace Amine Associated Receptor 1 (mTAAR1) Agonists with a Diphenylmethane-Scaffold: Design, Synthesis, and Biological Study
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The trace amine-associated receptor 1 (TAAR1) is a G-protein-coupled receptors (GPCR) potently activated by a variety of molecules besides trace amines (TAs), including thyroid hormone-derivatives like 3-iodothyronamine (T1AM), catechol-O-methyltransferase products like 3-methoxytyramine, and amphetamine-related compounds. Accordingly, TAAR1 is considered a promising target for medicinal development. To gain more insights into TAAR1 physiological functions and validation of its therapeutic potential, we recently developed a new class of thyronamine-like derivatives. Among them compound SG2 showed high affinity and potent agonist activity at mouse TAAR1. In the present work, we describe design, synthesis, and SAR study of a new series of compounds (1-16) obtained by introducing specific structural changes at key points of our lead compound SG2 skeleton. Five of the newly synthesized compounds displayed mTAAR1 agonist activity higher than both SG2 and T1AM. Selected diphenylmethane analogues, namely 1 and 2, showed potent functional activity in in vitro and in vivo models.
- Chiellini, Grazia,Nesi, Giulia,Sestito, Simona,Chiarugi, Sara,Runfola, Massimiliano,Espinoza, Stefano,Sabatini, Martina,Bellusci, Lorenza,Laurino, Annunziatina,Cichero, Elena,Gainetdinov, Raul R.,Fossa, Paola,Raimondi, Laura,Zucchi, Riccardo,Rapposelli, Simona
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supporting information
p. 9825 - 9836
(2016/11/19)
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- Efficient synthesis of heterocyclic neurotensin receptor ligands by microwave-assisted aminocarbonylation
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Marking the heterocyclic neurotensin receptor antagonist SR142948A as a lead compound, the development of an efficient and a practical synthetic route to heterocyclic aryl carboxamides is reported. Thus, a highly efficient and flexible access to these carboxamides was elaborated by taking advantage of microwave-assisted aminocarbonylation reaction mediated by Mo(CO)6, Herrmann's palladacycle, [(t-Bu)3PH]BF4, and DBU.
- Lang, Christopher,Gmeiner, Peter
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p. 2474 - 2480
(2013/09/23)
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- Subtle "supramolecular buttressing effects" in Cucurbit[7]uril/guest assemblies
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Biphenyl derivatives bearing a dimethylsulfonium group at position 3 and three different substituents at position 4 (H, F and CH3) have been prepared as probes to test the validity of the "supramolecular buttressing" concept. We define the latter as the alteration, by a neighboring unit, of a substituent effect on intermolecular recognition. In this case, the 4-substituents exert some pressure on the 3-dimethylsulfonium groups and control the ratio of their syn and anti conformations. As free species, biphenyls bearing 4-H and 4-F substituents are present as approximately equimolar mixtures of syn and anti-conformers, while the biphenyl scaffold with a 4-CH3 group adopts the anti-conformation exclusively. The 3-dimethylsulfonium substituents then interact with one of the carbonylated portals of Cucurbit[7]uril (CB[7]), and their conformations affect the position of the guests inside the cavity of the macrocycle, thereby validating our "supramolecular buttressing" model. Surprisingly however, binding affinities towards CB[7] are barely affected by the nature of the 4-substituents and the conformations of the neighboring sulfonium groups, despite very different electronic densities presented to the CB[7] portal in their syn or anti conformations. Solvation was found to dramatically smoothen host-guest Columbic interactions, although the latter remain important in the recognition process. Replacing the positively charged 3-dimethylsulfonium unit with an isopropyl substituent decreases the affinity of the biphenyl guest by 1000-fold. The Royal Society of Chemistry 2013.
- Joseph, Roymon,Masson, Eric
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p. 3116 - 3127
(2013/06/05)
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- Donor-substituted distyrylpyrazines: Influence of steric congestion on UV-Vis absorption and fluorescence
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Di(p-aminostyryl)pyrazines with voluminous substituents on the nitrogen and in the adjacent positions were prepared via twofold aldol condensation. Absorption and emission spectra are influenced by increasing steric hindrance because the orbital overlap between nitrogen and π-system is modulated by voluminous groups. Strong solvatochromism of the fluorescence and huge Stokes shifts result from amplified donor-acceptor interaction in the excited state. Protonation occurs at the terminal amino groups first, followed by protonation of the central pyrazine. With increasing strength of acid, absorption and emission spectra are first shifted to the blue followed by a redshift. Copyright
- Wink, Christoph,Detert, Heiner
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supporting information
p. 144 - 150
(2013/03/13)
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- Mild, efficient, and regioselective monobromination of arylamines and phenols using [BBIm]Br3 as a new reagent
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We report here an efficient method for the synthesis and characterization of the room-temperature ionic liquid 1,3-di-n-butylimidazolium tribromide ([BBIm]Br3) (2) and its application as an efficient reagent and solvent for regioselective bromination of arylamines and phenols under mild conditions. The bromination was carried out in the absence of organic solvents, and in most cases, the only extraction solvent needed was water. The spent 1,3-di-n-butylimidazolium bromide (1) was easily recycled.
- Borikar, Sanjay P.,Daniel, Thomas,Paul, Vincent
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experimental part
p. 647 - 653
(2011/02/27)
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- NOVEL RAR RECEPTOR AGONIST LIGANDS AND USE THEREOF IN HUMAN MEDICINE AND COSMETICS
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The invention relates to compounds corresponding to general formula (I) below: to the compositions containing same, to methods for the preparation thereof and to the use thereof in pharmaceutical compositions for use in human or veterinary medicine, or else in cosmetic compositions.
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Page/Page column 8
(2010/11/03)
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- An efficient, rapid, and regioselective bromination of anilines and phenols with 1-butyl-3-methylpyridinium tribromide as a new reagent/solvent under mild conditions
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1-Butyl-3-methylpyridinium tribromide, [BMPy]Br3 proves to be a highly efficient, regioselective reagent/solvent for nuclear bromination of various anilines and phenols. The synthesis and characterization of the room temperature ionic liquid [BMPy]Br3 (2) is described. The bromination was carried out in the absence of organic solvents and in most cases the only extraction solvent needed was water. The spent 1-butyl-3-methylpyridinium bromide (1) was easily recycled.
- Borikar, Sanjay P.,Daniel, Thomas,Paul, Vincent
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scheme or table
p. 1007 - 1009
(2009/05/11)
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- Novel Phosphinic Acid-Containing Thyromimetics
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The present invention relates to compounds of phosphonic acid-containing T3 mimetics and monoesters thereof, stereoisomers, pharmaceutically acceptable salts, co-crystals, and prodrugs thereof and pharmaceutically acceptable salts and co-crystals of the prodrugs, as well as their preparation and uses for preventing and/or treating metabolic diseases such as obesity, NASH, hypercholesterolemia and hyperlipidemia, as well as associated conditions such as atherosclerosis, coronary heart disease, impaired glucose tolerance, metabolic syndrome x and diabetes.
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Page/Page column 103
(2009/02/11)
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- NOVEL PHOSPHORUS-CONTAINING THYROMIMETICS
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The present invention relates to compounds of phosphonic acid containing T3 mimetics, stereoisomers, pharmaceutically acceptable salts, co-crystals, and prodrugs thereof and pharmaceutically acceptable salts and co-crystals of the prodrugs, as well as their preparation and uses for preventing and/or treating metabolic diseases such as obesity, NASH, hypercholesterolemia and hyperlipidemia, as well as associated conditions such as atherosclerosis, coronary heart disease, impaired glucose tolerance, metabolic syndromex and diabetes.
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Page/Page column 237
(2008/06/13)
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- Para-bromination of ortho-alkyl anilines
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A process of selectively preparing p-bromo-o-alkylanilines (e.g. 4-bromo-2-methylaniline) by reacting o-alkylanilines (e.g., 2-methylaniline) with unadsorbed bromine in a solvent selected from the group consisting of an inert di- tri- or tetrahaloaliphatic hydrocarbon (e.g., dichloromethane and dibromomethane), an alkyl nitrile (e.g., acetonitrile) and mixtures thereof.
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