- Distinct CCK-2 receptor conformations associated with β-arrestin-2 recruitment or phospholipase-C activation revealed by a biased antagonist
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Seven-transmembrane receptors (7TMRs), also termed G protein-coupled receptors (GPCRs), form the largest class of cell surface membrane receptors, involving several hundred members in the human genome. Nearly 30% of marketed pharmacological agents target
- Magnan, Rémi,Escrieut, Chantal,Gigoux, Véronique,De, Kavita,Clerc, Pascal,Niu, Fan,Azema, Joelle,Masri, Bernard,Cordomi, Arnau,Baltas, Michel,Tikhonova, Irina G.,Fourmy, Daniel
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supporting information
p. 2560 - 2573
(2013/03/29)
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- Pharmacomodulations around the 4-oxo-1,4-dihydroquinoline-3-carboxamides, a class of potent CB2-selective cannabinoid receptor ligands: Consequences in receptor affinity and functionality
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CB2 receptor selective ligands are becoming increasingly attractive drugs due to the potential role of this receptor in several physiopathological processes. Thus, the development of our previously described series of 4-oxo-1,4-dihydroquinoline-3-carboxamides was pursued with the aim to further characterize the structure-affinity and structure-functionality relationships of these derivatives. The influence of the side chain was investigated by synthesizing compounds bearing various carboxamido and keto substituents. On the other hand, the role of the quinoline central scaffold was studied by synthesizing several 6-, 7-, or 8-chloro-4-oxo-1,4-dihydroquinolines, as well as 4-oxo-1,4-dihydronaphthyridine and 4-oxo-1,4-dihydrocinnoline derivatives. The effect of these modifications on the affinity and functionality at the CB2 receptor was studied and allowed for the characterization of new selective CB2 receptor ligands.
- Stern, Eric,Muccioli, Giulio G.,Bosier, Barbara,Hamtiaux, Laurie,Millet, Régis,Poupaert, Jacques H.,Hénichart, Jean-Pierre,Depreux, Patrick,Goossens, Jean-Fran?ois,Lambert, Didier M.
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p. 5471 - 5484
(2008/03/17)
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- Novel benzodiazepine photoaffinity probe stereoselectively labels a site deep within the membrane-spanning domain of the cholecystokinin receptor
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An understanding of the molecular basis of drug action provides opportunities for refinement of drug properties and for development of more potent and selective molecules that act at the same biological target. In this work, we have identified the active
- Hadac, Elizabeth M.,Dawson, Eric S.,Darrow, James W.,Sugg, Elizabeth E.,Lybrand, Terry P.,Miller, Laurence J.
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p. 850 - 863
(2007/10/03)
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- IMMUNOMODULATING HETEROCYCLIC COMPOUNDS
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Compounds of formula (I) are inhibitors of CD80 and useful in immunomodulation therapy: wherein R1 and R3 independently represent H; F; CI; Br; -NO2; -CN; C1-C6 alkyl optionally substituted by F or Cl; or C1-C6 alkoxy optionally substituted by F; R4 represents a carboxylic acid group (-COOH) or an ester thereof, or -C(=O)NR6R7, -NR7C(=O)R6, -NR7C(=O)OR6, -NHC(=O)NR7R6 or -NHC(=S)NR7R6 wherein R6 represents H, or a radical of formula - (Alk)m-Q wherein m is 0 or 1, Alk is an optionally substituted divalent straight or branched C1-C12 alkylene, or C2-C12 alkenylene, or C2-C12 alkynylene radical or a divalent C3-C12 carbocyclic radical, any of which radicals may contain one or more -O-, -S- or -N(R8)- links wherein R8 represents H or C1-C4 alkyl, C3--C4 alkenyl, C3-C4 alkynyl, or C3-C6 cycloalkyl, and Q represents H; -NR9R10 wherein R9 and R10 independently represents H; C1-C4 alkyl; C3-C4 alkenyl; C3-C4 alkynyl; C3-C6 cycloalkyl; an ester group; an optionally substituted carbocyclic or heterocyclic group; or R9 and R10 form a ring when taken together with the nitrogen to which they are attached, which ring is optionally substituted; and R7 represents H or C1-C6 alkyl; or when taken together with the atom or atoms to which they are attached R6 and R7 form an optionally substituted monocyclic heterocyclic ring having 5, 6 or 7 ring atoms; and X represents a bond or a divalent radical of formula - (Z)n-(Alk)- or - (Alk)-(Z)n- -wherein Z represents -O-, -S- or -NH-, Alk is as defined in relation to R6 and n is 0 or 1.
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- Solid phase synthesis of 6-acylamino-1-alkyl/aryl-4-oxo-1,4- dihydrocinnoline-3-carboxamides
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6-Acylmino-1-alkyl/aryl-4-oxo-1,4-dihydrocinnoline-3-carboxamides were synthesized in parallel from 6-nitro-4-oxo-1,4-dihydrocinnoline-3-carboxylic acid. The latter formed amides with amines bound to polystyrene-based resins via acid-labile linkers. N1 an
- Sereni, Laura,Tató, Marco,Sola, Francesco,Brill, Wolfgang K.-D.
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p. 8561 - 8577
(2007/10/03)
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- Use of 1,5-benzo?b!1,4-diazepines to control gastric emptying
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A method of controlling gastric emptying in patients having an early non-insulin-dependent diabetic condition and exhibiting rapid gastric emptying comprising the administration of an effective gastric emptying controlling amount of a compound of Formula
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- CCK OR GASTRIN MODULATING 5-HETEROCYCLIC-1, 5 BENZODIAZEPINES
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Compounds of general formula (I) and physiologically salts thereof, processes for their preparation and their use as modulators of the effects of gastrin and CCK.
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- Discovery of 1,5-benzodiazepines with peripheral cholecystokinin (CCK-A) receptor agonist activity. 1. Optimization of the agonist "trigger"
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Directed screening of compounds selected from the Glaxo registry file for contractile activity on the isolated guinea pig gallbladder (GPGB) identified a series of 1,5-benzodiazepines with peripheral cholecystokinin (CCK) receptor agonist activity. Agonis
- Aquino, Christopher J.,Armour, Duncan R.,Berman, Judd M.,Birkemo, Larry S.,Carr, Robin A. E.,Croom, Dallas K.,Dezube, Milana,Dougherty Jr., Robert W.,Ervin, Gregory N.,Grizzle, Mary K.,Head, Julie E.,Hirst, Gavin C.,James, Michael K.,Johnson, Michael F.,Miller, Laurence J.,Queen, Kennedy L.,Rimele, Thomas J.,Smith, David N.,Sugg, Elizabeth E.
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p. 562 - 569
(2007/10/03)
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