- Developing pyridazine-3-carboxamides to be CB2 agonists: The design, synthesis, structure-activity relationships and docking studies
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Herein, we described the design and synthesis of a series of pyridazine-3-carboxamides to be CB2-selective agonists via a combination of scaffold hopping and bioisosterism strategies. The compounds were subjected to assessment of their potential activities through calcium mobilization assays. Among the tested derivatives, more than half of these compounds exhibited moderate to potent CB2 agonist activity. Six compounds showed EC50 values below 35 nM, and several derivatives also exhibited significantly enhanced potency and high selectivity at the CB2 receptor over the CB1 receptor. Specifically, compound 26 showed the highest CB2 agonist activity (EC50 = 3.665 ± 0.553 nM) and remarkable selectivity (Selectivity Index > 2729) against CB1. In addition, logPs of some representative compounds were measured to display significantly decreased values in comparison with GW842166X. Furthermore, docking simulations were conducted to explain the interaction mode of this series.
- Qian, Hai-Yan,Wang, Zhi-Long,Xie, Xiao-Yu,Pan, You-Lu,Li, Gang-Jian,Xie, Xin,Chen, Jian-Zhong
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p. 598 - 611
(2017/06/29)
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- Pyridazine derivative and preparation method and application thereof
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The invention provides a pyridazine derivative and a pharmaceutically acceptable salt or hydrate of the pyridazine derivative. The compound is an active ligand of a novel cannabinoid II type receptor CB2. The compound and the pharmaceutically acceptable salt or hydrate of the compound generally have high calcium current activity and quite good selectivity for anthropogenic marijuana receptors CB2. The compound is a specificity agonist of the cannabinoid receptor CB2, and can be used for treating, preventing and inhibiting diseases mediated by CB2 receptors. The compound I has the general formula shown in the description.
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- PYRIDAZINE BASED ALPHA-HELIX MIMETICS
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The synthesis of new α-helix scaffolds mimicking i, i+3 or i+4, i+7 residues, was accomplished. The common pyridazine heterocycle originates from the easily available building block, 6. These scaffolds may be thought of as synthetic counterparts of amphip
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Page/Page column 23; Sheet 2
(2009/04/25)
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- 1-[2-[(Heteroarylmethoxy)aryl]carbamoyl]indolines are selective and orally active 5-HT(2C) receptor inverse agonists
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Bisarylmethoxyethers have been identified with nanomolar 5-HT(2C) affinity and selectivity over both 5-HT(2A) 5-HT(2A) and 5-HT(2B) receptors. Compounds such as 1, 2, 8, 12, 14 and 18 have potent oral activity in a centrally mediated pharmacodynamic model
- Bromidge, Steven M.,Davies, Susannah,Duckworth,Forbes, Ian T.,Jones, Graham E.,Jones, Jerome,King, Frank D.,Blackburn, Thomas P.,Holland, Vicky,Kennett, Guy A.,Lightowler, Sean,Middlemiss, Derek N.,Riley, Graham J.,Trail, Brenda,Wood, Martyn D.
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p. 1867 - 1870
(2007/10/03)
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- Synthesis of 3-chloropyridazine-6-carboxylic acid hydrazide and selective hydrazinolysis of 3,6-substituted pyridazines
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3-Chloropyridazine-6-carboxylic acid hydrazide (5) was synthesized by employing hydrazine monohydrate and methyl levalinate as starting materials through five steps, including hydrazinolysis. Selective hydrazinolysis of 3,6-substituted pyridazines was investigated.
- Morishita,Kobayashi,Yamada,Yajima
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p. 371 - 372
(2007/10/02)
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- Fused pyridazinoquinazolone derivatives as neurotrophic agents
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Fused pyridazinoquinazoline compounds, salts thereof, methods of production, intermediates in their production, pharmaceutical compositions containing said compounds and methods for treating neurodegenerative disorders using said compositions are disclosed.
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- Angiotensin II receptor antagonists
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Compounds are disclosed having the formula: STR1 The compounds of the invention are angiotensin II receptor antagonists.
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