- Protein arginine methyltransferase 5 (PRMT5) inhibitor, pharmaceutical products thereof, and methods thereof
-
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.
- -
-
Paragraph 0276; 0281-0283
(2020/11/05)
-
- ALLOSTERIC EGFR INHIBITORS AND METHODS OF USE THEREOF
-
The disclosure relates to compounds that act as an allosteric inhibitors of epidermal growth factor receptor (EGFR); pharmaceutical compositions comprising the compounds; and methods of treating or preventing kinase-mediated disorders, including cancer and other proliferation diseases.
- -
-
Page/Page column 62; 77
(2021/01/22)
-
- INHIBITORS OF PROTEIN ARGININE METHYLTRANSFERASE 5 (PRMT5), PHARMACEUTICAL PRODUCTS THEREOF, AND METHODS THEREOF
-
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.
- -
-
Paragraph 0166; 0168; 0169
(2019/10/01)
-
- CONDENSED RING DERIVATIVE, AND PREPARATION METHOD, INTERMEDIATE, PHARMACEUTICAL COMPOSITION AND USE THEREOF
-
Disclosed are a condensed ring derivative, and a preparation method, an intermediate, a pharmaceutical composition and a use thereof. The condensed ring derivative of the present invention has a significant inhibitive effect on URAT1, which can effectively alleviate or treat hyperuricemia and other related diseases.
- -
-
Paragraph 0332; 0335
(2018/02/28)
-
- PROTOZOAN PARASITE GROWTH INHIBITORS
-
Compounds and methods for inhibiting growth of a protozoan parasite. Methods of treating a protozoan parasite infection in a subject by administering a therapeutically effective amount of a compound as disclosed herein. The compounds and methods can be us
- -
-
Paragraph 0197
(2015/11/10)
-
- Protozoan Parasite Growth Inhibitors Discovered by Cross-Screening Yield Potent Scaffolds for Lead Discovery
-
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.
- 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)
-
- 2-METHYLMORPHOLINE PYRIDO-, PYRAZO- AND PYRIMIDO-PYRIMIDINE DERIVATIVES AS MTOR INHIBITORS
-
There is provided a compound of Formula (I), or a pharmaceutically acceptable salt thereof. There are also provided processes for the manufacture of a compound of Formula (1), and the use of a compound of Formula (1) as a medicament and in the treatment of cancer
- -
-
Page/Page column 115
(2008/06/13)
-