- 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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- An expedient Pd/DBU mediated cyanation of aryl/heteroaryl bromides with K4[Fe(CN)6]
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A practical Pd(PPh3)4/DBU catalytic system for the synthesis of pharmaceutically relevant aminopyridine nitrile intermediates, as well as a variety of other aryl nitriles using non-toxic K4[Fe(CN) 6] has been developed. The key features of our new protocol for cyanation lie in that the reaction can be carried out with readily available Pd(PPh3)4 under mild and green conditions, even without the assistance of other ligands. The Royal Society of Chemistry 2012.
- Zhang, Dengyou,Sun, Haifeng,Zhang, Lei,Zhou, Yu,Li, Chunpu,Jiang, Hualiang,Chen, Kaixian,Liu, Hong
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supporting information; experimental part
p. 2909 - 2911
(2012/03/27)
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- AZAINDOLE DERIVATIVES AS INHIBITORS OF P38 KINASE
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The invention is directed to methods to inhibit p38 kinase, preferably p38-α using compounds which are azaindoles wherein the azaindoles are coupled through an azacyclic linker to another cyclic moiety.
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Page/Page column 73
(2010/11/24)
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- Novel amino acid derivatives, method for production thereof and pharmaceutical compositions comprising said derivative
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Compound of formula (I): wherein: R1 represents aryl, heteroaryl or alkyl which is optionally substituted, or a group of formula —(CO)—CR6R7NR8R9 wherein R6, R7, R8 an
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Page/Page column 4
(2008/06/13)
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- 2,3-methano-amino acid compounds
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Compound of formula (I): wherein: n represents 2 or 3, R1represents optionally substituted alkyl, cycloalkyl or optionally substituted phenyl, R2represents amino, optionally substituted amidino, optionally substituted guanidino or optionally substituted isothioureido, Ar represents aryl or heteroaryl, X1represents hydroxy or optionally substituted amino, isomers thereof, and also salts thereof with a pharmaceutically acceptable acid or base, and which medicinal products containing the same/are useful as trypsin-related serine protease inhibitors.
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- A highly catalytic robust palladium catalyzed cyanation of aryl bromides
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A dependable high yielding palladium catalyzed aryl bromide cyanation procedure has been developed. The optimized cyanation features extremely low levels of palladium and DPPF ligand.
- Maligres, Peter E.,Waters, Marjorie S.,Fleitz, Fred,Askin, David
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p. 8193 - 8195
(2007/10/03)
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- Efficacious, orally bioavailable thrombin inhibitors based on 3- aminopyridinone or 3-aminopyrazinone acetamide peptidomimetic templates
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We have addressed the key deficiency of noncovalent pyridinone acetamide thrombin inhibitor L-374,087 (1), namely, its modest half-lives in animals, by making a chemically stable 3-alkylaminopyrazinone bioisostere for its 3- sulfonylaminopyridinone core.
- Sanderson, Philip E. J.,Lyle, Terry A.,Cutrona, Kellie J.,Dyer, Dona L.,Dorsey, Bruce D.,McDonough, Colleen M.,Naylor-Olsen, Adel M.,Chen, I.-Wu,Chen, Zhongguo,Cook, Jacquelynn J.,Cooper, Carolyn M.,Gardell, Stephen J.,Hare, Timothy R.,Krueger, Julie A.,Lewis, S. Dale,Lin, Jiunn H.,Lucas Jr., Bobby J.,Lyle, Elizabeth A.,Lynch Jr., Joseph J.,Stranieri, Maria T.,Vastag, Kari,Yan, Youwei,Shafer, Jules A.,Vacca, Joseph P.
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p. 4466 - 4474
(2007/10/03)
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- PYRIDINONE THROMBIN INHIBITORS
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Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions and have the following structure: STR1 for example: STR2
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