Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Patent News

Novel Pyrimidin-4-yl-3-amino-pyrrolo[3,4-c]pyrazoles as Protein Kinase C Inhibitors for Treating Diseases

Author(s): Surya K. De*

Volume 31, Issue 8, 2024

Published on: 22 June, 2023

Page: [1036 - 1039] Pages: 4

DOI: 10.2174/0929867330666230531164754

Abstract

This patent describes the series of compounds and their pharmaceutically acceptable salts, such as compound K7 (as a representative potent compound). These protein kinase C selective inhibitors are useful for treating diabetes mellitus and its complications, cancer, ischemia, inflammation, central nervous system disorders, cardiovascular disease, Alzheimer's disease, dermatological disease, virus diseases, inflammatory disorders, or diseases in which the liver is a target organ.

Keywords: Protein kinase C, pyrimidine-pyrrolopyrazoles, cancer, Alzheimer's disease, cardiovascular disease, central nervous system disorders, inflammatory.

Next »
[1]
Sipka, S.; Bíró, T.; Czifra, G.; Griger, Z.; Gergely, P.; Brugós, B.; Tarr, T. The role of protein kinase C isoenzymes in the pathogenesis of human autoimmune diseases. Clin. Immunol., 2022, 241, 109071.
[http://dx.doi.org/10.1016/j.clim.2022.109071] [PMID: 35781096]
[2]
Li, H.; Nukui, S.; Scales, S.A.; Teng, M.; Yin, C. Npyrimidin- 4-yl-3-amino-pyrrolo[3,4-c]pyrazole derivatives as PKC kinase inhibitors. US Patent, US8877761B2, 2014.
[3]
Botrous, I.; Hong, Y.; Li, H.; Liu, K.K.C.; Nukui, S.; Teng, M. 3-amido-pyrrolo[3,4-c]pyrazole-5(1h, 4h,6h) carbaldehyde derivatives as inhibitors of protein kinase c. European Patent, EP2195321B1, 2016.
[4]
Cooke, M.; Kazanietz, M.G. Overarching roles of diacylglycerol signaling in cancer development and antitumor immunity. Sci. Signal., 2022, 15(729), eabo0264.
[http://dx.doi.org/10.1126/scisignal.abo0264] [PMID: 35412850]
[5]
He, S.; Li, Q.; Huang, Q.; Cheng, J. Targeting protein kinase C for cancer therapy. Cancers , 2022, 14(5), 1104.
[http://dx.doi.org/10.3390/cancers14051104] [PMID: 35267413]
[6]
Miao, L.; Pan, D.; Shi, J.; Du, J.; Chen, P.; Gao, J.; Yu, Y.; Shi, D.Z.; Guo, M. Role and mechanism of PKC-δ for cardiovascular disease: Current status and perspective. Front. Cardiovasc. Med., 2022, 9, 816369.
[http://dx.doi.org/10.3389/fcvm.2022.816369] [PMID: 35242825]
[7]
Kawano, T.; Inokuchi, J.; Eto, M.; Murata, M.; Kang, J.H. Activators and inhibitors of protein kinase C (PKC): Their applications in clinical trials. Pharmaceutics, 2021, 13(11), 1748.
[http://dx.doi.org/10.3390/pharmaceutics13111748] [PMID: 34834162]
[8]
Sharifinejad, N.; Azizi, G.; Behniafard, N.; Zaki-Dizaji, M.; Jamee, M.; Yazdani, R.; Abolhassani, H.; Aghamohammadi, A. Protein Kinase C-Delta defect in Autoimmune Lymphoproliferative syndrome-like disease: First case from the national iranian registry and review of the literature. Immunol. Invest., 2022, 51(2), 331-342.
[http://dx.doi.org/10.1080/08820139.2020.1829638] [PMID: 33047643]
[9]
Pilo, C.A.; Newton, A.C. Two sides of the same coin: Protein Kinase C β in cancer and neurodegeneration. Front. Cell Dev. Biol., 2022, 10, 929510.
[http://dx.doi.org/10.3389/fcell.2022.929510] [PMID: 35800893]
[10]
Jalil, S.J.; Sacktor, T.C.; Shouval, H.Z. Atypical PKCs in memory maintenance: The roles of feedback and redundancy. Learn. Mem., 2015, 22(7), 344-353.
[http://dx.doi.org/10.1101/lm.038844.115] [PMID: 26077687]
[11]
Kadir, R.R.A.; Alwjwaj, M.; Bayraktutan, U. Protein kinase C-β distinctly regulates blood-brain barrier-forming capacity of brain microvascular endothelial cells and outgrowth endothelial cells. Metab. Brain Dis., 2022, 37(6), 1815-1827.
[http://dx.doi.org/10.1007/s11011-022-01041-1] [PMID: 35763197]
[12]
Zhao, H.; Gong, L.; Wu, S.; Jing, T.; Xiao, X.; Cui, Y.; Xu, H.; Lu, H.; Tang, Y.; Zhang, J.; Zhou, Q.; Ma, D.; Li, X. The inhibition of Protein Kinase Cβ contributes to the pathogenesis of preeclampsia by activating autophagy. EBioMedicine, 2020, 56, 102813.
[http://dx.doi.org/10.1016/j.ebiom.2020.102813] [PMID: 32544612]
[13]
Starosyla, S.A.; Volynets, G.P.; Protopopov, M.V.; Bdzhola, V.G.; Pashevin, D.O.; Polishchuk, V.O.; Kozak, T.O.; Stroi, D.O.; Dosenko, V.E.; Yarmoluk, S.M. Pharmacophore modeling, docking and molecular dynamics simulation for identification of novel human protein kinase C beta (PKCβ) inhibitors. Struct. Chem., 2022, 2022, 1-15.
[http://dx.doi.org/10.1007/s11224-022-02075-y] [PMID: 36248344]
[14]
Melnyk, J.E.; Steri, V.; Nguyen, H.G.; Hwang, Y.C.; Gordan, J.D.; Hann, B.; Feng, F.Y.; Shokat, K.M. Targeting a splicing-mediated drug resistance mechanism in prostate cancer by inhibiting transcriptional regulation by PKCβ1. Oncogene, 2022, 41(11), 1536-1549.
[http://dx.doi.org/10.1038/s41388-022-02179-z] [PMID: 35087237]
[15]
Renkhold, L.; Kollmann, R.; Inderwiedenstraße, L.; Kienitz, M.C. PKC-isoform specific regulation of receptor desensitization and KCNQ1/KCNE1 K+ channel activity by mutant α1B-adrenergic receptors. Cell. Signal., 2022, 91, 110228.
[http://dx.doi.org/10.1016/j.cellsig.2021.110228] [PMID: 34958868]
[16]
von Heydebrand, F.; Fuchs, M.; Kunz, M.; Voelkl, S.; Kremer, A.N.; Oostendorp, R.A.J.; Wilke, J.; Leitges, M.; Egle, A.; Mackensen, A.; Lutzny-Geier, G. Protein kinase C-β-dependent changes in the glucose metabolism of bone marrow stromal cells of chronic lymphocytic leukemia. Stem Cells, 2021, 39(6), 819-830.
[http://dx.doi.org/10.1002/stem.3352] [PMID: 33539629]
[17]
Berardi, D.E.; Ariza Bareño, L.; Amigo, N.; Cañonero, L.; Pelagatti, M.N.; Motter, A.N.; Taruselli, M.A.; Díaz Bessone, M.I.; Cirigliano, S.M.; Edelstein, A.; Peters, M.G.; Diament, M.; Urtreger, A.J.; Todaro, L.B. All-trans retinoic acid and protein kinase C α/β1 inhibitor combined treatment targets cancer stem cells and impairs breast tumor progression. Sci. Rep., 2021, 11(1), 6044.
[http://dx.doi.org/10.1038/s41598-021-85344-w] [PMID: 33723318]
[18]
Isakov, N. Protein kinase C (PKC) isoforms in cancer, tumor promotion and tumor suppression. Semin. Cancer Biol., 2018, 48, 36-52.
[http://dx.doi.org/10.1016/j.semcancer.2017.04.012] [PMID: 28571764]

Rights & Permissions Print Cite
Article Metrics
22
3
© 2024 Bentham Science Publishers | Privacy Policy