878804-63-8Relevant academic research and scientific papers
Discovery and Characterization of Selective and Ligand-Efficient DYRK Inhibitors
Ashall-Kelly, Alexander,Bennett, James,Elkins, Jonathan M.,Fedorov, Oleg,Godoi, Paulo H.,Hanley, Marcus T.,Henderson, Scott H.,Hopkins Navratilova, Iva,Robinson, Sean,Ruela De Sousa, Roberta,Sorrell, Fiona,Walter, Daryl S.,Ward, Simon E.
supporting information, p. 11709 - 11728 (2021/08/24)
Dual-specificity tyrosine-regulated kinase 1A (DYRK1A) regulates the proliferation and differentiation of neuronal progenitor cells during brain development. Consequently, DYRK1A has attracted interest as a target for the treatment of neurodegenerative diseases, including Alzheimer's disease (AD) and Down's syndrome. Recently, the inhibition of DYRK1A has been investigated as a potential treatment for diabetes, while DYRK1A's role as a mediator in the cell cycle has garnered interest in oncologic indications. Structure-activity relationship (SAR) analysis in combination with high-resolution X-ray crystallography leads to a series of pyrazolo[1,5-b]pyridazine inhibitors with excellent ligand efficiencies, good physicochemical properties, and a high degree of selectivity over the kinome. Compound 11 exhibited good permeability and cellular activity without P-glycoprotein liability, extending the utility of 11 in an in vivo setting. These pyrazolo[1,5-b]pyridazines are a viable lead series in the discovery of new therapies for the treatment of diseases linked to DYRK1A function.
DERIVATIVES OF 4-(IMIDAZO[L,2-A]PYRIDIN-3-YL)-N-(PYRIDINYL)PYRIMIDIN- 2-AMINE AS THERAPEUTIC AGENTS
-
Paragraph 0083; 0085; 00107, (2021/01/29)
A novel class of heteroaryl compounds for use in the prevention and/or treatment of proliferative diseases and conditions including cancers. The compounds are considered to be capable of inhibiting cell proliferation by inhibiting the activity of FLT3 and its mutant forms and/or other protein kinases such as CDKs. The compounds have the general structure I:
NOVEL SUBSTITUTED IMIDAZOLE DERIVATIVES
-
Page/Page column 44-45, (2010/11/27)
The present invention relates to a compound represented by Formula [I] or a pharmaceutically acceptable salt or ester thereof: wherein: X1, X2, X3, and X4, which may be identical or different, are each C or N, provided that none to two of X1, X2, X3, and X4 is/are N; Y is CH or N; R1, R1', R2, R2', R3, R3', R4, and R4', which may be identical or different, are each a hydrogen atom, a lower alkyl group, or the like; R5 is a hydrogen atom or a methyl group; R6 and R7, which may be identical or different, are each a hydrogen atom, a lower alkyl group, or the like; R8 and R8', which may be identical or different, are each a hydrogen atom, a lower alkyl group, or the like; R9 is an aryl group or a heteroaryl group which may be substituted; and n is an integer from 1 to 3, and a PLK1 inhibitor or an anticancer agent containing the same.
Imidazo[1,2-a]pyridines. Part 2: SAR and optimisation of a potent and selective class of cyclin-dependent kinase inhibitors
Byth, Kate F.,Culshaw, Janet D.,Green, Stephen,Oakes, Sandra E.,Thomas, Andrew P.
, p. 2245 - 2248 (2007/10/03)
Exploration of SAR and optimisation of the imidazo[1,2-a]pyridine CDK inhibitors has lead to the discovery of novel, potent and selective inhibitors of the cyclin-dependent kinase CDK2. Understanding of SAR has identified positions of substitution, which allow modification of physical properties and offer the potential for in vivo optimisation.
