- Synthesis and Biological Evaluation of 2-substituted-6-(morpholinyl/piperidinyl)pyridazin-3(2H)-ones as Potent and Safer Anti-inflammatory and Analgesic Agents
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A series of 2-substituted-6-(morpholinyl/piperidinyl)pyridazin-3(2H)-ones was synthesized and the structures were established using various spectroscopic techniques. The target compounds were screened for anti-inflammatory and analgesic activities at 20 and 40?mg/kg. The safety of the synthesized derivatives was evaluated by assessing anti-platelet activity and ulcer index. The obtained pharmacological data revealed that 6-morpholinyl derivatives 4a–12a were found to be somewhat more potent than 6-piperidinyl derivatives 4b–6b. The 6-morpholinyl substituted pyridazinone 12a exhibited maximum anti-inflammatory and analgesic activities. Homoveratrylamine substituted compounds 6a and 6b emerged as promising leads in both the series with good anti-inflammatory and analgesic activities without any ulcerogenicity. Anti-platelet activity results of the compounds of both the series showed significantly low bleeding time in comparison with standard drug aspirin indicating the cardiovascular safety of new pyridazinones.
- Singh, Jyoti,Sharma, Deepika,Bansal, Ranju
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p. 2935 - 2945
(2017/09/26)
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- Selective mono-amination of dichlorodiazines
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A mild, easy-to-perform, and versatile method for the formation of aminochlorodiazines from reaction of several types of dichlorodiazines (i.e., pyridazines, pyrimidines, and pyrazines) with primary or secondary amines in ethanol in the presence of trieth
- Sengmany, Stéphane,Lebre, Julie,Le Gall, Ewan,Léonel, Eric
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p. 4859 - 4867
(2015/08/03)
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- Structure-activity relationship studies of SEN12333 analogues: Determination of the optimal requirements for binding affinities at α7 nAChRs through incorporation of known structural motifs
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Alpha7 nicotinic acetylcholine receptors (nAChRs) have implications in the regulation of cognitive processes such as memory and attention and have been identified as a promising therapeutic target for the treatment of the cognitive deficits associated with schizophrenia and Alzheimer's disease (AD). Structure affinity relationship studies of the previously described α7 agonist SEN12333 (8), have resulted in the identification of compound 45, a potent and selective agonist of the α7 nAChR with enhanced affinity and improved physicochemical properties over the parent compound (SEN12333, 8).
- Beinat, Corinne,Reekie, Tristan,Banister, Samuel D.,O'Brien-Brown, James,Xie, Teresa,Olson, Thao T.,Xiao, Yingxian,Harvey, Andrew,O'Connor, Susan,Coles, Carolyn,Grishin, Anton,Kolesik, Peter,Tsanaktsidis, John,Kassiou, Michael
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supporting information
p. 277 - 301
(2015/03/31)
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- An electrochemical nickel-catalyzed arylation of 3-amino-6- chloropyridazines
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3-Amino-6-aryl- and 3-amino-6-heteroarylpyridazines have been obtained in generally good yield using a nickel-catalyzed electrochemical cross-coupling between 3-amino-6-chloropyridazines and aryl or heteroaryl halides at room temperature. Comparative experiments involving classical palladium-catalyzed reactions, such as Suzuki, Stille, or Negishi cross-couplings, reveal that the electrochemical method can constitute a reliable alternative tool for biaryl formation. A possible reaction mechanism is proposed on the basis of electrochemical analyses.
- Sengmany, Stephane,Vitu-Thiebaud, Arnaud,Le Gall, Erwan,Condon, Sylvie,Leonel, Eric,Thobie-Gautier, Christine,Pipelier, Muriel,Lebreton, Jacques,Dubreuil, Didier
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p. 370 - 379
(2013/03/13)
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- 4-Amino-5-aryl-6-arylethynylpyrimidines: Structure-activity relationships of non-nucleoside adenosine kinase inhibitors
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A series of non-nucleoside adenosine kinase (AK) inhibitors is reported. These inhibitors originated from the modification of 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine (ABT-702). The identification of a linker that would approximate the spatial arrangement found between the pyrimidine ring and the aryl group at C(7) in ABT-702 was a key element in this modification. A search of potential linkers led to the discovery of an acetylene moiety as a suitable scaffold. It was hypothesized that the aryl acetylenes, ABT-702, and adenosine bound to the active site of AK (closed form) in a similar manner with respect to the orientation of the heterocyclic base. Although potent acetylene analogs were discovered based on this assumption, an X-ray crystal structure of 5-(4-dimethylaminophenyl)-6-(6-morpholin-4-ylpyridin-3-ylethynyl)pyrimidin-4-ylamine (16a) revealed a binding orientation contrary to adenosine. In addition, this compound bound tightly to a unique open conformation of AK. The structure-activity relationships and unique ligand orientation and protein conformation are discussed.
- Matulenko, Mark A.,Paight, Ernest S.,Frey, Robin R.,Gomtsyan, Arthur,DiDomenico Jr., Stanley,Jiang, Meiqun,Lee, Chih-Hung,Stewart, Andrew O.,Yu, Haixia,Kohlhaas, Kathy L.,Alexander, Karen M.,McGaraughty, Steve,Mikusa, Joseph,Marsh, Kennan C.,Muchmore, Steven W.,Jakob, Clarissa L.,Kowaluk, Elizabeth A.,Jarvis, Michael F.,Bhagwat, Shripad S.
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p. 1586 - 1605
(2008/02/01)
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- INHIBITORS OF HISTONE DEACETYLASE
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The invention relates to a series of compounds useful for inhibiting histone deacetylase (HDAC) enzymatic activity. The invention also provides a method for inhibiting histone descetylase in a cell using said compounds as well as a method for treating cell proliferative diseases and conditions using said HDAC inhibitors. Further, the invention provides pharmaceutical compositions comprising the HDAC inhibiting compounds and a pharmaceutically acceptable carrier.
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Page/Page column 87
(2010/02/14)
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