کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10584371 | 981330 | 2013 | 30 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Discovery and optimization of pyrrolo[1,2-a]pyrazinones leads to novel and selective inhibitors of PIM kinases
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موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Discovery and optimization of pyrrolo[1,2-a]pyrazinones leads to novel and selective inhibitors of PIM kinases Discovery and optimization of pyrrolo[1,2-a]pyrazinones leads to novel and selective inhibitors of PIM kinases](/preview/png/10584371.png)
چکیده انگلیسی
A novel series of PIM inhibitors was derived from a combined effort in natural product-inspired library generation and screening. The novel pyrrolo[1,2-a]pyrazinones initial hits are inhibitors of PIM isoforms with IC50 values in the low micromolar range. The application of a rational optimization strategy, guided by the determination of the crystal structure of the complex in the kinase domain of PIM1 with compound 1, led to the discovery of compound 15a, which is a potent PIM kinases inhibitor exhibiting excellent selectivity against a large panel of kinases, representative of each family. The synthesis, structure-activity relationship studies, and pharmacokinetic data of compounds from this inhibitor class are presented herein. Furthermore, the cellular activities including inhibition of cell growth and modulation of downstream targets are also described.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 21, Issue 23, 1 December 2013, Pages 7364-7380
Journal: Bioorganic & Medicinal Chemistry - Volume 21, Issue 23, 1 December 2013, Pages 7364-7380
نویسندگان
Francesco Casuscelli, Elena Ardini, Nilla Avanzi, Elena Casale, Giovanni Cervi, Matteo D'Anello, Daniele Donati, Daniela Faiardi, Ronald D. Ferguson, Gianpaolo Fogliatto, Arturo Galvani, Aurelio Marsiglio, Danilo G. Mirizzi, Marisa Montemartini,