- Synthesis and pharmacological evaluation of 6-aminonicotinic acid analogues as novel GABAA receptor agonists
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A series of 6-aminonicotinic acid analogues have been synthesized and pharmacologically characterized at native and selected recombinant GABA A receptors. 6-Aminonicotinic acid (3) as well as 2- and 4-alkylated analogues (9-11, 14-16) display low to mid-micromolar GABAAR binding affinities to native GABAA receptors (Ki 1.1-24 μM). The tetrahydropyridine analogue of 3 (22) shows low-nanomolar affinity (K i 0.044 μM) and equipotency as an agonist to GABA itself as well as the standard GABAA agonist isoguvacine. Cavities surrounding the core of the GABA binding pocket were predicted by molecular interaction field calculations and docking studies in a α1β 2γ2 GABAA receptor homology model, and were confirmed by affinities of substituted analogues of 3. The tight steric requirements observed for the remarkably few GABAAR agonists reported to date is challenged by our findings. New openings for agonist design are proposed which potentially could facilitate the exploration of different pharmacological profiles within the GABAAR area.
- Petersen, Jette G.,S?rensen, Troels,Damgaard, Maria,Nielsen, Birgitte,Jensen, Anders A.,Balle, Thomas,Bergmann, Rikke,Fr?lund, Bente
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p. 404 - 416
(2014/08/05)
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- COMPOUNDS AND COMPOSITIONS FOR COGNITION-ENHANCEMENT, METHODS OF MAKING, AND METHODS OF TREATING
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Muscarinic agonists, which are useful for stimulating muscarinic receptors and treating cognitive disorders, are provided. Methods of synthesizing such agonists also are provided. Also provided are compositions for enhancing cognitive function in subjects such as humans, the compositions comprising a muscarinic agonist or a pharmaceutically suitable form thereof. Also provided are methods of treating animals such as humans by administering such compositions.
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Page/Page column 27
(2010/09/18)
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- THIAZOLYL-DIHYDRO-INDAZOLE
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Disclosed are compounds of general formula (I), wherein the groups R1, R2, Ra and Rb have the meanings given in the claims and specification, the tautomers, racemates, enantiomers, diastereomers and the mixtures thereof, and optionally the pharmacologically acceptable acid addition salts, solvates and hydrates thereof, and processes for preparing these thiazolyl-dihydro-indazoles and the use thereof as pharmaceutical compositions.
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Page/Page column 17-18
(2008/06/13)
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- PYRROLOPYRIDAZINE DERIVATIVES
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The invention relates to compound of the formula (I) or its salt, in which R1, R2, R3 and R4 are as defined in the description, their use of as medicament, the process for their preparation and use for the treatment of PDE-IV or TNF-α mediated diseases.
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- Quinolones as gonadotropin releasing hormone (GnRH) antagonists: Simultaneous optimization of the C(3)-aryl and C(6)-substituents
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A series of 3-arylquinolones was prepared and evaluated for their ability to act as gonadotropin releasing hormone (GnRH) antagonists. A variety of substitution patterns of the 3-aryl substituent are described. The 3,4,5-trimethylphenyl substituent (23h) was found to be optimal. (C) 2000 Elsevier Science Ltd. All rights reserved.
- Young, Jonathan R.,Huang, Song X.,Chen, Irene,Walsh, Thomas F.,DeVita, Robert J.,Wyvratt Jr., Matthew J.,Goulet, Mark T.,Ren, Ning,Lo, Jane,Yang, Yi Tien,Yudkovitz, Joel B.,Cheng, Kang,Smith, Roy G.
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p. 1723 - 1727
(2007/10/03)
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- Synthesis of some β-trichloromethyl-azines and -diazines
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Syntheses of compounds required as substrates for reactions with nucleophiles are reported: 2-trichloromethylquinoxaline 5, 3-trichloromethylquinoline 6, 3,5-bis(trichloromethyl)pyridine 7, 2,5-bis(trichloromethyl)pyrazine 8 and 5-trichloromethylpyrimidine 9.
- Cartwright, David,Ferguson, John R.,Giannopoulos, Thomas,Varvounis, George,Wakefield, Basil J.
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p. 2595 - 2598
(2007/10/02)
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- Optically active pyridylethanol derivative
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A novel optically active pyridylethanol derivative having a high twistability and also a superior temperature characteristic is provided, which derivative is expressed by the formula STR1 wherein R is an alkyl group of alkoxy group each of 1 to 20 carbon atoms or hydrogen atom, m and n each represent 0 or 1, STR2 each independently represent STR3 wherein Y is any one of H, halogen atom or CN and STR4 is a pyridine ring the N atom of which may be present at an optionally chosen site thereof.
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