- Pyrazolotriazines as inhibitors of nucleases
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The invention provides compounds represented by the structural formula (1): wherein R1, R2, R3 and R4 are as defined in the claims. The compounds are inhibitors of nucleases, and are useful in particular in a method of treatment and/or prevention of proliferative diseases, neurodegenerative diseases, and other genomic instability associated diseases.
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Paragraph 0122; 0123; 0124; 0125; 0126; 0127; 0158-0163
(2016/01/12)
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- Botulinum neurotoxin serotype A inhibitors: Small-molecule mercaptoacetamide analogs
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Botulinum neurotoxin elicits its paralytic activity through a zinc-dependant metalloprotease that cleaves proteins involved in neurotransmitter release. Currently, no drugs are available to reverse the effects of botulinum intoxication. Herein we report the design of a novel series of mercaptoacetamide small-molecule inhibitors active against botulinum neurotoxin serotype A. These analogs show low micromolar inhibitory activity against the isolated enzyme. Structure-activity relationship studies for a series of mercaptoacetamide analogs of 5-amino-3-phenylpyrazole reveal components essential for potent inhibitory activity.
- Moe, Scott T.,Thompson, Andrew B.,Smith, Genessa M.,Fredenburg, Ross A.,Stein, Ross L.,Jacobson, Alan R.
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experimental part
p. 3072 - 3079
(2009/09/25)
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- Development of two synthetic routes to CE-178,253, a CB1 antagonist for the treatment of obesity
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CE-178,253 benzenesulfonate (1) is a CB1 antagonist discovered by Pfizer medicinal chemists. Two syntheses of this compound are described. The first, based on the discovery synthesis, involves assembly of an aryl-substituted pyrazolotriazine core onto which the second aryl moiety is installed by a Suzuki coupling; this route has been scaled to provide up to 6 kg of API. A second, more convergent route is also described, which installs the pyrazolotriazine containing both aryl substituents by condensation of a bromoketone with a substituted thiosemicarbazide. This route has been demonstrated on laboratory scale and is viewed as the preferred bond-forming sequence.
- Brandt, Thomas A.,Caron, Stéphane,Damon, David B.,DiBrino, Joseph,Ghosh, Arun,Griffith, David A.,Kedia, Sandeep,Ragan, John A.,Rose, Peter R.,Vanderplas, Brian C.,Wei, Lulin
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experimental part
p. 3292 - 3304
(2009/08/08)
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- Novel potent neuropeptide Y Y5 receptor antagonists: Synthesis and structure-activity relationships of phenylpiperazine derivatives
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A series of phenylpiperazine derivatives were synthesized and evaluated for their neuropeptide Y (NPY) Y5 receptor antagonistic activities. The benzindane portion of 2 was replaced by 1-phenylpiperazine, resulting in novel urea derivative 3f. Subsequent optimization of the phenylpiperazine template by substitution of the phenyl moiety resulted in a series of (2-methanesulfonamidephenyl)piperazine derivatives that showed potent binding affinity and antagonistic activity for the Y5 receptor.
- Takahashi, Toshiyuki,Sakuraba, Aya,Hirohashi, Tomoko,Shibata, Takunobu,Hirose, Masaaki,Haga, Yuji,Nonoshita, Katsumasa,Kanno, Tetsuya,Ito, Junko,Iwaasa, Hisashi,Kanatani, Akio,Fukami, Takehiro,Sato, Nagaaki
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p. 7501 - 7511
(2007/10/03)
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- PYRAZOLO`1,5-A!`1,3,5! TRIAZIN -4-ONE DERIVATIVES AS CB1 RECEPTOR ANTAGONISTS
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Compounds of Formula (I) are described herein. The compounds have been shown to act as cannabinoid receptor ligands and are therefore useful in the treatment of diseases linked to the mediation of the cannabinoid receptors in animals.
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Page/Page column 43
(2010/02/12)
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- PYRAZOLO [1,5-A] PYRIMIDIN-7-ONE COMPOUNDS AND USES THEREOF
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The compounds of Formula (I) and (II) are described herein. The compounds have been shown to act as cannabinoid receptor ligands and are therefore useful in the treatment of diseases linked to the mediation of the cannabinoid receptors in animals.
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Page/Page column 41
(2008/06/13)
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- CANNABINOID RECEPTOR LIGANDS AND USES THEREOF
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Compounds of Formula (I) that act as cannabinoid receptor ligands and their uses in the treatment of diseases linked to the mediation of the cannabinoid receptors in animals are described herein.
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- Cannabinoid receptor ligands and uses thereof
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Compounds of Formula (I) that act as cannabinoid receptor ligands and their uses in the treatment of diseases linked to the mediation of the cannabinoid receptors in animals are described herein.
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