672323-74-9Relevant academic research and scientific papers
Structural Insights into the Inhibition of Undecaprenyl Pyrophosphate Synthase from Gram-Positive Bacteria
Workman, Sean D.,Day, Jonathan,Farha, Maya A.,El Zahed, Sara S.,Bon, Chris,Brown, Eric D.,Organ, Michael G.,Strynadka, Natalie C. J.
supporting information, p. 13540 - 13550 (2021/09/20)
The polyprenyl lipid undecaprenyl phosphate (C55P) is the universal carrier lipid for the biosynthesis of bacterial cell wall polymers. C55P is synthesized in its pyrophosphate form by undecaprenyl pyrophosphate synthase (UppS), an essentialcis-prenyltransferase that is an attractive target for antibiotic development. We previously identified a compound (MAC-0547630) that showed promise as a novel class of inhibitor and an ability to potentiate β-lactam antibiotics. Here, we provide a structural model for MAC-0547630’s inhibition of UppS and a structural rationale for its enhanced effect on UppS fromBacillus subtilisversusStaphylococcus aureus. We also describe the synthesis of a MAC-0547630 derivative (JPD447), show that it too can potentiate β-lactam antibiotics, and provide a structural rationale for its improved potentiation. Finally, we present an improved structural model of clomiphene’s inhibition of UppS. Taken together, our data provide a foundation for structure-guided drug design of more potent UppS inhibitors in the future.
Reactivity of the -C(Cl){double bond, long}C-C{double bond, long}N- moiety towards AlCl3-induced C-C bond forming reactions: a new synthesis of 7-(hetero)aryl-substituted pyrazolo[1,5-a]pyrimidines
Kodimuthali, Arumugam,T. C., Nishad,Prasunamba, Padala Lakshmi,Pal, Manojit
supporting information; experimental part, p. 354 - 358 (2009/04/19)
The reactivity of the -C(Cl){double bond, long}C-C{double bond, long}N- moiety towards an AlCl3-induced C-C bond forming reaction was investigated through the reaction of 7-chloro-5-phenyl-pyrazolo[1,5-a]pyrimidine with arenes and heteroarenes.
Versatile templates for the development of novel kinase inhibitors: Discovery of novel CDK inhibitors
Dwyer, Michael P.,Paruch, Kamil,Alvarez, Carmen,Doll, Ronald J.,Keertikar, Kerry,Duca, Jose,Fischmann, Thierry O.,Hruza, Alan,Madison, Vincent,Lees, Emma,Parry, David,Seghezzi, Wolfgang,Sgambellone, Nicole,Shanahan, Frances,Wiswell, Derek,Guzi, Timothy J.
, p. 6216 - 6219 (2008/03/18)
A series of four bicyclic cores were prepared and evaluated as cyclin-dependent kinase-2 (CDK2) inhibitors. From the in-vitro and cell-based analysis, the pyrazolo[1,5-a]pyrimidine core (represented by 9) emerged as the superior core for further elaboration in the identification of novel CDK2 inhibitors.
PYRAZOLOPYRIMIDINES AS CYCLIN-DEPENDENT KINASE INHIBITORS
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Page 71-72, (2008/06/13)
In its many embodiments, the present invention provides a novel class of pyrazolo[1,5-a]pyrimidine compounds as inhibitors of cyclin dependent kinases, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.
PYRAZOLOPYRIMIDINES AS CYCLIN DEPENDENT KINASE INHIBITORS
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Page/Page column 44, (2008/06/13)
In its many embodiments, the present invention provides a novel class of pyrazolo[1,5-a]pyrimidine compounds as inhibitors of cyclin dependent kinases, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.
PYRAZOLOPYRIMIDINES AS CYCLIN DEPENDENT KINASE INHIBITORS
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Page 42; 44, (2008/06/13)
In its many embodiments, the present invention provides a novel class of pyrazolo[1,5-a]pyrimidine compounds as inhibitors of cyclin dependent kinases, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.
