84346-43-0Relevant academic research and scientific papers
N′-(Arylsulfonyl)pyrazoline-1-carboxamidines as novel, neutral 5-hydroxytryptamine 6 receptor (5-HT6R) antagonists with unique structural features
Van Loevezijn, Arnold,Venhorst, Jennifer,Iwema Bakker, Wouter I.,De Korte, Cor G.,De Looff, Wouter,Verhoog, Stefan,Van Wees, Jan-Willem,Van Hoeve, Martijn,Van De Woestijne, Rob P.,Van Der Neut, Martina A. W.,Borst, Alice J. M.,Van Dongen, Maria J. P.,De Bruin, Natasja M. W. J.,Keizer, Hiskias G.,Kruse, Chris G.
experimental part, p. 7030 - 7054 (2011/12/15)
The 5-HT6 receptor (5-HT6R) has been in the spotlight for several years regarding CNS-related diseases. We set out to discover novel, neutral 5-HT6R antagonists to improve off-target selectivity compared to basic amine-con
SULFONYLPYRAZOLE AND SULFONYLPYRAZOLINE CARBOXAMIDINE DERIVATIVES AS 5-HT6 ANTAGONISTS
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Page/Page column 43, (2008/06/13)
This invention concerns sulfonylpyrazoline carboxamidine derivatives as antagonists of 5-HT6 receptors, to methods for the preparation of these compounds and to novel intermediates useful for their synthesis. The invention also relates to the uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in Parkinson's disease, Huntington's chorea, schizophrenia, anxiety, depression, manic depression, psychoses, epilepsy, obsessive compulsive disorders, mood disorders, migraine, Alzheimer's disease, age related cognitive decline, mild cognitive impairment, sleep disorders, eating disorders, anorexia, bulimia, binge eating disorders, panic attacks, akathisia, attention deficit hyperactivity disorder, attention deficit disorder, withdrawal from abuse of cocaine, ethanol, nicotine or benzodiazepines, pain, disorders associated with spinal trauma or head injury, hydrocephalus, functional bowel disorder, Irritable Bowel Syndrome, obesity and type-2 diabetes. The compounds have the general formula (1), wherein the symbols have the meanings given in the description.
Synthesis, Biological Properties, and Molecular Modeling Investigations of Novel 3,4-Diarylpyrazolines as Potent and Selective CB1 Cannabinoid Receptor Antagonists
Lange, Jos H. M.,Coolen, Hein K. A. C.,Van Stuivenberg, Herman H.,Dijksman, Jessica A. R.,Herremans, Arnoud H. J.,Ronken, Eric,Keizer, Hiskias G.,Tipker, Koos,McCreary, Andrew C.,Veerman, Willem,Wals, Henri C.,Stork, Bob,Verveer, Peter C.,Den Hartog, Arnold P.,De Jong, Natasja M. J.,Adolfs, Tiny J. P.,Hoogendoorn, Jan,Kruse, Chris G.
, p. 627 - 643 (2007/10/03)
A series of novel 3,4-diarylpyrazolines was synthesized and evaluated in cannabinoid (hCB1 and hCB2) receptor assays. The 3,4-diarylpyrazolines elicited potent in vitro CB1 antagonistic activities and in general exhibited high CB1 vs CB2 receptor subtype selectivities. Some key representatives showed potent pharmacological in vivo activities after oral dosing in both a CB agonist-induced blood pressure model and a CB agonist-induced hypothermia model. Chiral separation of racemic 67, followed by crystallization and an X-ray diffraction study, elucidated the absolute configuration of the eutomer 80 (SLV319) at its C4 position as 4S. Bioanalytical studies revealed a high CNS-plasma ratio for the development candidate 80. Molecular modeling studies showed a relatively close three-dimensional structural overlap between 80 and the known CB1 receptor antagonist rimonabant (SR141716A). Further analysis of the X-ray diffraction data of 80 revealed the presence of an intramolecular hydrogen bond that was confirmed by computational methods. Computational models and X-ray diffraction data indicated a different intramolecular hydrogen bonding pattern in the in vivo inactive compound 6. In addition, X-ray diffraction studies of 6 revealed a tighter intermolecular packing than 80, which also may contribute to its poorer absorption in vivo. Replacement of the amidine -NH2 moiety with a -NHCH3 group proved to be the key change for gaining oral biovailability in this series of compounds leading to the identification of 80.
Synthesis of Pyrrazoles and Pyrazolopyrimidines from 3-Arylsulfonylaminoacrylates
McFadden, Helen G.,Huppatz, John L.,Halladay, Peter K.
, p. 873 - 886 (2007/10/02)
3-Arylsulfonylaminopyrazole-4-carboxamides and -carboxylates were synthesized from 3-arylsulfonylamino-3-methylthiocyanoacrylate derivatives as potential herbicidal inhibitors of the enzyme acetohydroxyacetic acid synthase (AHAS). Some of these compounds
Fused [1,2,4]oxadiazolylidenebenzenesulfonamides and their use as herbicides and plant growth regulants
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, (2008/06/13)
Fused [1,2,4]oxadiazolylidenebenzenesulfonamides such as 2-chloro-N-(5,7-dimethyl-2H-[1,2,4]oxadiazolo-[2,3-a]pyrimidin-2-ylidene)benzenesulfonamide and 2-chloro-N-(7-methoxy-5-methyl-2H-[1,2,4]oxadiazolo-[2,3-a][1,3,5]triazin-2-ylidene)benzenesulfonamide
