152265-57-1Relevant articles and documents
Protein arginine methyltransferase 5 (PRMT5) inhibitor, pharmaceutical products thereof, and methods thereof
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, (2020/11/05)
The present invention provides a PRMT5 inhibitor of formula (I); R1 is a non-hydrogen monovalent group; W is a direct bond or-NH-; T, U and V are independently from each other selected from C and N; R2 is H or halogen; m is 1 or 2; X is carbon, nitrogen or oxygen; Y is C or N; Z is a direct bond or carbon; R3 is H, a non-hydrogen monovalent group, an oxo group, a divalent spiro-forming group or adivalent bridge-forming group; and n is 1 or 2, and represents a single or double bond. The present invention also provides pharmaceutical products comprising the PRMT5 inhibitor and use thereof in the treatment of proliferative disorders such as cancer, metabolic disorders, hematological disorders, autoimmune diseases and inflammatory diseases.
INHIBITORS OF PROTEIN ARGININE METHYLTRANSFERASE 5 (PRMT5), PHARMACEUTICAL PRODUCTS THEREOF, AND METHODS THEREOF
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, (2019/10/01)
The present invention provides PRMT5 inhibitors of Formula (I), wherein R1 is a non-hydrogen monovalent group; W is a direct bond or -NH-; T, U, and V are independently of each other selected from C and N; R2 is H or a halo; m is 1 or 2; X is a carbon, a nitrogen, or an oxygen; Y is C or N; Z is a direct bond or a carbon; R3 is H, a non-hydrogen monovalent group, an oxo group, a bivalent spiro ring-forming group, or a bivalent bridge-forming group; n is 1 or 2; and Formula (II) stands for a single bond or a double bond. Pharmaceutical products comprising the PRMT5 inhibitors and use thereof in treating proliferative disorders such as cancer, metabolic disorders, blood disorders, autoimmune diseases, and inflammatory diseases are also provided.
Protozoan Parasite Growth Inhibitors Discovered by Cross-Screening Yield Potent Scaffolds for Lead Discovery
Devine, William,Woodring, Jennifer L.,Swaminathan, Uma,Amata, Emanuele,Patel, Gautam,Erath, Jessey,Roncal, Norma E.,Lee, Patricia J.,Leed, Susan E.,Rodriguez, Ana,Mensa-Wilmot, Kojo,Sciotti, Richard J.,Pollastri, Michael P.
, p. 5522 - 5537 (2015/08/03)
Tropical protozoal infections are a significant cause of morbidity and mortality worldwide; four in particular (human African trypanosomiasis (HAT), Chagas disease, cutaneous leishmaniasis, and malaria) have an estimated combined burden of over 87 million disability-adjusted life years. New drugs are needed for each of these diseases. Building on the previous identification of NEU-617 (1) as a potent and nontoxic inhibitor of proliferation for the HAT pathogen (Trypanosoma brucei), we have now tested this class of analogs against other protozoal species: T. cruzi (Chagas disease), Leishmania major (cutaneous leishmaniasis), and Plasmodium falciparum (malaria). Based on hits identified in this screening campaign, we describe the preparation of several replacements for the quinazoline scaffold and report these inhibitors' biological activities against these parasites. In doing this, we have identified several potent proliferation inhibitors for each pathogen, such as 4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-6-(4-((4-methyl-1,4-diazepan-1-yl)sulfonyl)phenyl)quinoline-3-carbonitrile (NEU-924, 83) for T. cruzi and N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-7-(4-((4-methyl-1,4-diazepan-1-yl)sulfonyl)phenyl)cinnolin-4-amine (NEU-1017, 68) for L. major and P. falciparum.