Mayumi Hara

Bio: Mayumi Hara is an academic researcher from Nagasaki University. The author has contributed to research in topics: Bicyclic molecule & Phenylhydrazine. The author has an hindex of 3, co-authored 4 publications receiving 112 citations.

Synthesis of Pyrazolo(3,4-d)pyrimidine Derivatives Using Ketene Dithioacetals.

Abstract: The cyclization of 5-amino-3-methylthiopyrazole-4-carbonitriles or 4-carboxamides 3a-j, which were prepared by the reaction of ketene dithioacetals 1a,b [1a: bis(methylthiomethylenemalononitrile; 1b: bis(methylthio)methylenecyanoacetamide] with hydrazines (hydrazine hydrate, phenylhydrazine, p-chlorophenylhydrazine, p-nitrophenylhydrazine), with formamide or carbon disulfide proceeded to give the corresponding 4-amino- or 4-hydroxy-3-methylthiopyrazolo[3,4-d]pyrimidines 6a-h in good yields. 3-Aminopyrazolo[3,4-d]pyrimidine derivatives 6i-1 were also obtained by the application of the cyclization reaction of 3,5-diaminopyrazoles with formamide.

Synthesis of 3-Aminopyrazolo(3,4-d)pyrimidine Derivatives Using N-Bis( methylthio)methylene-p-toluenesulfonamide.

Abstract: N-Bis(methylthio)methylene-p-toluenesulfonamide (1) reacted with active methylene compounds such as malononitrile (2a) and, cyanoacetamide (2b) to give the corresponding 3-methylthio-3-p-toluenesulfonylami-nopropenenitrile derivatives 3a,b which were found to be convenient starting materials for the synthesis of 3,5-diaminopyrazole derivatives. Reaction of 3a and 3b with hydrazines gave the corresponding 3,5-diaminopyrazoles 4a-e, key intermediates for the synthesis of 3-aminopyrazolo[3,4-d]pyrimidine derivatives 5a-d.

The selectivity of protein kinase inhibitors: a further update.

Abstract: The specificities of 65 compounds reported to be relatively specific inhibitors of protein kinases have been profiled against a panel of 70-80 protein kinases. On the basis of this information, the effects of compounds that we have studied in cells and other data in the literature, we recommend the use of the following small-molecule inhibitors: SB 203580/SB202190 and BIRB 0796 to be used in parallel to assess the physiological roles of p38 MAPK (mitogen-activated protein kinase) isoforms, PI-103 and wortmannin to be used in parallel to inhibit phosphatidylinositol (phosphoinositide) 3-kinases, PP1 or PP2 to be used in parallel with Src-I1 (Src inhibitor-1) to inhibit Src family members; PD 184352 or PD 0325901 to inhibit MKK1 (MAPK kinase-1) or MKK1 plus MKK5, Akt-I-1/2 to inhibit the activation of PKB (protein kinase B/Akt), rapamycin to inhibit TORC1 [mTOR (mammalian target of rapamycin)-raptor (regulatory associated protein of mTOR) complex], CT 99021 to inhibit GSK3 (glycogen synthase kinase 3), BI-D1870 and SL0101 or FMK (fluoromethylketone) to be used in parallel to inhibit RSK (ribosomal S6 kinase), D4476 to inhibit CK1 (casein kinase 1), VX680 to inhibit Aurora kinases, and roscovitine as a pan-CDK (cyclin-dependent kinase) inhibitor. We have also identified harmine as a potent and specific inhibitor of DYRK1A (dual-specificity tyrosine-phosphorylated and -regulated kinase 1A) in vitro. The results have further emphasized the need for considerable caution in using small-molecule inhibitors of protein kinases to assess the physiological roles of these enzymes. Despite being used widely, many of the compounds that we analysed were too non-specific for useful conclusions to be made, other than to exclude the involvement of particular protein kinases in cellular processes.

Compounds and methods for kinase modulation, and indications therefor

Abstract: Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof are active on at least one Raf protein kinase. In certain aspects and embodiments, the described compounds are active in inhibiting proliferation of a Ras mutant cell line. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of B-Raf V600E mutant protein kinase, including melanoma, glioma, glioblastoma multiforme, pilocytic astrocytoma, colorectal cancer, thyroid cancer, lung cancer, ovarian cancer, prostate cancer, liver cancer, gallbladder cancer, gastrointestinal stromal tumors, biliary tract cancer, and cholangiocarcinoma. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of c-Raf-1 protein kinase, including acute pain, chronic pain or polycystic kidney disease.

Biologically driven synthesis of pyrazolo[3,4-d]pyrimidines as protein kinase inhibitors: an old scaffold as a new tool for medicinal chemistry and chemical biology studies.

Abstract: Protein Kinase Inhibitors: An Old Scaffold As a New Tool for Medicinal Chemistry and Chemical Biology Studies Silvia Schenone,*,† Marco Radi,‡ Francesca Musumeci,† Chiara Brullo,† and Maurizio Botta †Dipartimento di Farmacia, Universita ̀ degli Studi di Genova Viale Benedetto XV, 3, 16132 Genova, Italy ‡Dipartimento di Farmacia, Universita ̀ degli Studi di Parma Viale delle Scienze, 27/A, 43124 Parma, Italy Dipartimento di Biotecnologie, Chimica e Farmacia, Universita ̀ degli Studi di Siena Via Aldo Moro, 2, 53100 Siena, Italy Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, BioLife Science Building, Suite 333, 1900 N 12th Street, Philadelphia, Pennsylvania 19122, United States