- Synthesis and biological evaluation of 7-(aminoalkyl)pyrazolo[1,5-a]pyrimidine derivatives as cathepsin K inhibitors
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A series of novel 7-aminoalkyl substituted pyrazolo[1,5-a]pyrimidine derivatives were synthesized and tested for inhibition of cathepsin K. The synthetic methodology comprises cyclization of 5-aminopyrazoles with N-Boc-α-amino acid-derived ynones followed by transformation of the ester and the Boc-amino functions. It allows for easy diversification of the pyrazolo[1,5-a]pyrimidine scaffold at various positions. Molecular docking studies with pyrazolo[1,5-a]pyrimidine derivatives were also performed to elucidate the binding mode in the active site of cathepsin K. The synthesized compounds exhibited moderate inhibition activity (Ki ≥ 77 μM).
- Petek, Nejc,?tefane, Bogdan,Novinec, Marko,Svete, Jurij
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Read Online
- Synthesis of pyrazolopyrimidinones using a “one-pot” approach under microwave irradiation
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A simple one-pot method for the microwave-assisted synthesis of substituted pyrazolo[1,5-a]pyrimidinones, a core scaffold in many bioactive and pharmaceutically relevant compounds, has been established. A variety of substituents was tolerated at the 2 and 5 positions, including functionalized aryls, heterocycles, and alkyl groups.
- Kelada, Mark,Walsh, John M. D.,Devine, Robert W.,McArdle, Patrick,Stephens, John C.
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supporting information
p. 122 - 1228
(2018/06/13)
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- 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; 0164-0169
(2016/01/12)
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- Discovery of a novel alpha-7 nicotinic acetylcholine receptor agonist series and characterization of the potent, selective, and orally efficacious agonist 5-(4-acetyl[1,4]diazepan-1-yl)pentanoic acid [5-(4-methoxyphenyl)-1H- pyrazol-3-yl] amide (SEN15924, WAY-361789)
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Alpha-7 nicotinic acetylcholine receptors (α7 nAChR) are implicated in the modulation of many cognitive functions such as attention, working memory, and episodic memory. For this reason, α7 nAChR agonists represent promising therapeutic candidates for the treatment of cognitive impairment associated with Alzheimer's disease (AD) and schizophrenia. A medicinal chemistry effort, around our previously reported chemical series, permitted the discovery of a novel class of α7 nAChR agonists with improved selectivity, in particular against the α3 receptor subtype and better ADME profile. The exploration of this series led to the identification of 5-(4-acetyl[1,4] diazepan-1-yl)pentanoic acid [5-(4-methoxyphenyl)-1H-pyrazol-3-yl] amide (25, SEN15924, WAY-361789), a novel, full agonist of the α7 nAChR that was evaluated in vitro and in vivo. Compound 25 proved to be potent and selective, and it demonstrated a fair pharmacokinetic profile accompanied by efficacy in rodent behavioral cognition models (novel object recognition and auditory sensory gating).
- Zanaletti, Riccardo,Bettinetti, Laura,Castaldo, Cristiana,Cocconcelli, Giuseppe,Comery, Thomas,Dunlop, John,Gaviraghi, Giovanni,Ghiron, Chiara,Haydar, Simon N.,Jow, Flora,MacCari, Laura,Micco, Iolanda,Nencini, Arianna,Scali, Carla,Turlizzi, Elisa,Valacchi, Michela
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experimental part
p. 4806 - 4823
(2012/07/28)
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- A convenient synthesis of 3- and 5-amino-1 H -pyrazoles via 3(5)-amino-4-(ethylsulfi nyl)-1 H -pyrazole desulfi nylation
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Syntheses of 5-amino-3-aryl- and 3-amino-5-aryl-1 H -pyrazoles from β -bromo- α -(ethylsulfanyl)cinnamonitrile are described. The β -bromo- α -(ethylsulfanyl)cinnamonitriles were oxidized with H2O 2 to the corresponding β -bromo- α -
- Lassagne, Frederic,Snegaroff, Katia,Roisnel, Thierry,Nassar, Ekhlass,Mongin, Florence
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p. 139 - 145
(2011/12/01)
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- ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR INHIBITORS
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The present invention provides compounds and compositions, methods of making them, and methods of using them to modulate α7 nicotinic acetylcholine receptors and/or to treat any of a variety of disorders, diseases, and conditions. Provided compounds can a
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Page/Page column 91
(2010/04/03)
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- Design, synthesis, and evaluation of 2-aryl-7-(3′,4′-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines as novel PDE-4 inhibitors
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Described herein is design, synthesis, and biological evaluation of novel series of 2-aryl-7-(3′,4′-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines acting as inhibitors of type 4 phosphodiesterase (PDE4) which is known as a good target for the treatment of asthma and COPD. For this purpose, structure optimization was conducted with the aid of structure-based drug design using the known X-ray crystallography. Also, biological effects of these compounds on the target enzyme were evaluated by using in vitro assays, leading to the potent and selective PDE-4 inhibitor (IC50 10 nM).
- Kim, Ikyon,Song, Jong Hwan,Park, Chang Min,Jeong, Joon Won,Kim, Hyung Rae,Ha, Jin Ryul,No, Zaesung,Hyun, Young-Lan,Cho, Young Sik,Sook Kang, Nam,Jeon, Dong Ju
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scheme or table
p. 922 - 926
(2010/06/22)
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- NICOTINIC ACETYLCHOLINE RECEPTOR MODULATORS
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The present invention provides compounds of formula (I) and compositions thereof, methods of making them, and methods of using them to modulate alpha7 nicotinic acetylcholine receptors and/or to treat any of a variety of disorders, diseases, and conditions. Provided compounds can affect, among other things, neurological, psychiatric and/or inflammatory system.
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Page/Page column 62
(2008/12/07)
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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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- 3-(heteroarylamino)methylene-1,3-dihydro-2H-indol-2-ones as kinase inhibitors
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The present invention relates to organic molecules capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and/or inhibit abnormal cell proliferation.
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