- Discovery of 2-(Imidazo[1,2- b]pyridazin-2-yl)acetic Acid as a New Class of Ligands Selective for the γ-Hydroxybutyric Acid (GHB) High-Affinity Binding Sites
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Gabazine, a γ-aminobutyric acid type A (GABAA) receptor antagonist, has previously been reported to inhibit the binding of [3H]NCS-382, a representative ligand of the high-affinity binding site for the neuroactive substance γ-hydroxy
- Krall, Jacob,Bavo, Francesco,Falk-Petersen, Christina B.,Jensen, Claus H.,Nielsen, Julie O.,Tian, Yongsong,Anglani, Valeria,Kongstad, Kenneth T.,Piilgaard, Louise,Nielsen, Birgitte,Gloriam, David E.,Kehler, Jan,Jensen, Anders A.,Harps?e, Kasper,Wellendorph, Petrine,Fr?lund, Bente
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p. 2798 - 2813
(2019/05/09)
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- WNT PATHWAY MODULATORS
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The present invention relates to dihydropyrazolo[l,5-a]pyrimidine compounds of formula I, defined herein, as WNT pathways modulators, processes for making them, and pharmaceutical compositions comprising them. Methods of treatment of conditions mediated by WNT pathway signalling including cancer, fibrosis, stem cell and diabetic retinopathy, rheumatoid arthritis, psoriasis and myocardial infarction, comprising the compounds of formula I are also provided.
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Paragraph 0301; 0302; 0337; 0339
(2015/07/07)
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- Mild and direct access to 7-substituted-4-trifluoromethylpyrimido[1,2- b ]pyridazin-2-one systems
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New and efficient methods for the synthesis of 7-substituted-4- trifluoromethylpyrimido[1,2-b]pyridazin-2-one derivatives using either two-step Suzuki/heterocyclization, or two-step heterocyclization/substitution sequences are developed. A variety of substituted products are obtained in good to excellent yields from 3-amino-6-chloropyridazine and ethyl 4,4,4-trifluorobut-2- ynoate. Georg Thieme Verlag Stuttgart · New York.
- Petrignet, Julien,Thiery, Emilie,Silpa, Laurence,Abarbri, Mohamed
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p. 947 - 954
(2014/04/03)
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- A short and straightforward approach towards 6-amino and 6-aminoalkyl thiazolo[4,5-c]pyridazines
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A facile and efficient synthesis of 6-amino and 6-aminoalkyl thiazolo[4,5-c]pyridazines is reported. The key step for the construction of this novel bicyclic scaffold was the reaction between 3-amino-4-bromopyridazine derivatives and alkylisothiocyanates.
- Stella, Alessandro,De Jonghe, Steven,Segers, Kenneth,Herdewijn, Piet
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supporting information
p. 830 - 833
(2013/02/25)
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- Microwave-enhanced synthesis of 2,3,6-trisubstituted pyridazines: Application to four-step synthesis of gabazine (SR-95531)
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Microwave-enhanced, highly efficient protocols for the synthesis of synthetically and biologically important 2,3,6-trisubstituted pyridazine architectures have been developed by sequential amination/Suzuki coupling/alkylation reactions. This powerful strategy is an economical and highly chemoselective protocol for the synthesis of diversified pyridazines. The total synthesis of gabazine (SR-95531) has been achieved using a versatile strategy in four steps and 73% overall yield.
- Gavande, Navnath,Johnston, Graham A. R.,Hanrahan, Jane R.,Chebib, Mary
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supporting information; experimental part
p. 4131 - 4136
(2010/10/18)
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- Efficient one-step synthesis of 3-amino-6-arylpyridazines
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Starting from the commercially available 3-amino-6-chloropyridazine, 3-amino-6-arylpyridazines were prepared in good yields by means of a Suzuki cross-coupling reaction avoiding the somewhat lengthy four-step classic synthesis.
- Guery, Sébastien,Parrot, Isabelle,Rival, Yveline,Wermuth, Camille G.
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p. 2115 - 2117
(2007/10/03)
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- A new approach towards the synthesis of 3-amino-6- (hetero)arylpyridazines based on palladium catalyzed cross-coupling reactions
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The synthesis of 3-amino-6-(hetero)arylpyridazines via palladium catalyzed cross-coupling reactions (Suzuki, Stille) on 3-amino-6- chloropyridazine (1a) and 3-amino-6-iodopyridazine (1b) has been investigated. Comparison of the results shows that there is
- Maes, Bert U. W.,Lemière, Guy L. F.,Dommisse, Roger,Augustyns, Koen,Haemers, Achiel
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p. 1777 - 1781
(2007/10/03)
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- Synthesis and Structure-Activity Relationships of Series of Aminopyridazine Derivatives of γ-Aminobutyric Acid Acting as Selective GABA-A Antagonists
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We have recently shown that an aryloaminopyridazine derivarive of GABA, SR 95103 , is a selective and competitive GABA-A receptor antagonist.In order to further explore the structural requirements for GABA receptor affinity, we synthesized a series of 38 compounds by attaching various pyridazinic structures to GABA or GABA-like side chains.Most of the compounds displaced GABA from rat brain membranes.All the active compounds antagonized the GABA-elicited enhancement of diazepam binding, strongly suggesting that all these compounds are GABA-A receptor antagonists.None of the compounds that displaced GABA from rat brain membranes interacted with other GABA recognition sites (GABA-B receptor, GABA uptake binding site, glutamate decarboxylase, GABA-transaminase).They did not interact with the Cl- ionophore associated with the GABA-A receptor and did not interact with the benzodiazepine, strychnine, and glutamate binding sites.Thus these compounds appear to be specific GABA-A receptor antagonists.In terms of structure-activity, it can be concluded that a GABA moiety bearing a positive charge is necessary for optimal GABA-A receptor recognition.Additional binding sites are tolerated only if they are part of a charge-delocalized amidinic or guanidinic system.If this delocalization is achieved by linking a butyric acid moiety to the N(2) nitrogen of a 3-aminopyridazine, GABA-antagonistic character is produced.The highest potency (ca.250 times bicuculline) was observed when an aromatic ? system, bearing electron-donating substituents, was present on the 6-position of the pyridazine ring.
- Wermuth, Camille-Georges,Bourguignon, Jean-Jacques,Schlewer, Gilbert,Gies, Jean-Pierre,Schoenfelder, Angele,et al.
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p. 239 - 249
(2007/10/02)
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