209224-91-9Relevant academic research and scientific papers
Synthesis and biological evaluation of 7-(aminoalkyl)pyrazolo[1,5-a]pyrimidine derivatives as cathepsin K inhibitors
Petek, Nejc,?tefane, Bogdan,Novinec, Marko,Svete, Jurij
, p. 226 - 238 (2018/12/04)
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).
Structure-based design, synthesis and crystallization of 2-arylquinazolines as lipid pocket ligands of p38α MAPK
Bührmann, Mike,Wiedemann, Bianca M.,Müller, Matthias P.,Hardick, Julia,Ecke, Maria,Rauh, Daniel
, (2017/09/23)
In protein kinase research, identifying and addressing small molecule binding sites other than the highly conserved ATP-pocket are of intense interest because this line of investigation extends our understanding of kinase function beyond the catalytic phosphotransfer. Such alternative binding sites may be involved in altering the activation state through subtle conformational changes, control cellular enzyme localization, or in mediating and disrupting protein-protein interactions. Small organic molecules that target these less conserved regions might serve as tools for chemical biology research and to probe alternative strategies in targeting protein kinases in disease settings. Here, we present the structure-based design and synthesis of a focused library of 2-arylquinazoline derivatives to target the lipophilic C-terminal binding pocket in p38α MAPK, for which a clear biological function has yet to be identified. The interactions of the ligands with p38α MAPK was analyzed by SPR measurements and validated by protein X-ray crystallography.
Synthesis of Aminopyrazoles from Isoxazoles: Comparison of Preparative Methods by in situ NMR Analysis
Kallman, Neil J.,Cole, Kevin P.,Koenig, Thomas M.,Buser, Jonas Y.,McFarland, Adam D.,McNulty, LuAnne M.,Mitchell, David
, p. 3537 - 3543 (2016/10/18)
A single-step method and a two-step method for the synthesis of aminopyrazoles from isoxazoles are presented and compared. Based on in situ NMR monitoring, both processes proceed through a ketonitrile. In the single-step process, hydrazine serves to both open the isoxazole to the unisolated ketonitrile intermediate and form the aminopyrazole. The two-step process involves ring opening of the isoxazole by deprotonation with hydroxide to generate the ketonitrile followed by the addition of acetic acid and hydrazine to form the aminopyrazole.
A new, one-pot, multicomponent synthesis of 5-aza-9-deaza-adenines under microwave irradiation
Lim, Felicia Phei Lin,Luna, Giuseppe,Dolzhenko, Anton V.
, p. 5159 - 5163 (2014/12/10)
A new, practical, three-component method for the synthesis of 5-aza-9-deaza-adenines is developed. Aminopyrazoles react in a one-pot fashion with triethyl orthoformate and cyanamide under microwave irradiation affording 5-aza-9-deaza-adenines in good yiel
Design, synthesis, and evaluation of 2-aryl-7-(3′,4′-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines as novel PDE-4 inhibitors
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
scheme or table, p. 922 - 926 (2010/06/22)
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).
Botulinum neurotoxin serotype A inhibitors: Small-molecule mercaptoacetamide analogs
Moe, Scott T.,Thompson, Andrew B.,Smith, Genessa M.,Fredenburg, Ross A.,Stein, Ross L.,Jacobson, Alan R.
experimental part, p. 3072 - 3079 (2009/09/25)
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.
Pyrazole derivatives
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, (2008/06/13)
The present invention relates to a compound represented by the general formula [I]: wherein A and B rings are ortho-condensed to each other, A ring represents an aromatic carbocyclic or heterocyclic ring and B ring represents an aliphatic four- to seven-m
