- Polycyclic compound for inhibiting RNA helicase DHX33
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The invention relates to a polycyclic compound for inhibiting RNA helicase DHX33. In particular, the invention relates to a compound shown as a formula I or a pharmaceutically acceptable form thereof, a pharmaceutical composition containing the compound, a preparation method of the compound, and medical application of the compound to prevention and/or treatment of DHX33 related diseases.
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Paragraph 0240-0243
(2021/04/17)
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- SUBSTITUTED BENZIMIDAZOLE CARBOXAMIDES AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS
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The invention provides substituted benzimidazole carboxamides and related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat a medical disorder, e.g., cancer, lysosomal storage disorder, neurodegenerative disorder, inflammatory disorder, in a patient.
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Paragraph 00442
(2021/04/01)
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- A model D - amino acid oxidase inhibitor and its preparation and application
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The invention provides a novel D- amino acid oxidase inhibitor and a preparation and application thereof. In particular, the invention discloses derivatives of quinoxaline-2,3-diketone, which has a novel structure shown in formula A, as well as a preparation method thereof and an application as an inhibitor of D-amino acid oxidase (DAAO). The compound provided by the invention shows excellent effects of analgesia and blocking morphine analgesia tolerance, and has application value for analgesia, treating opiate drug tolerance, and anti-schizophrenia.
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Paragraph 0319; 0320
(2019/02/02)
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- Discovery and analgesic evaluation of 8-chloro-1,4-dihydropyrido[2,3- b ]pyrazine-2,3-dione as a novel potent d -amino acid oxidase inhibitor
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A series of 5-azaquinoxaline-2,3-dione derivatives were synthesized and evaluated on d-amino acid oxidase (DAAO) inhibition as potential α-hydroxylactam-based inhibitors. The potent inhibitory activities in vitro suggested that 5-nitrogen could significantly enhance the binding affinity by strengthening relevant hydrogen bond interactions. The analgesic effects of intrathecal and systemic injection of 8-chloro-1,4-dihydropyrido[2,3-b]pyrazine-2,3-dione, a representative molecule of 5-azaquinoxaline-2,3-dione, were investigated in rodents. This research not only confirmed the analgesic effect of the DAAO inhibitors but provided a new class of chemical entities with oral application potential for the treatment of chronic pain and morphine analgesic tolerance.
- Xie, Dongsheng,Lu, Jun,Xie, Jin,Cui, Junjun,Li, Teng-Fei,Wang, Yan-Chao,Chen, Yuan,Gong, Nian,Li, Xin-Yan,Fu, Lei,Wang, Yong-Xiang
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- 2-(HETERO)ARYL-BENZIMIDAZOLE AND IMIDAZOPYRIDINE DERIVATIVES AS INHIBITORS OF ASPARAGIME EMETHYL TRANSFERASE
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Substituted benzimidazole and 3H-imidazo[4,5-b]pyridines or formula I: where X and Y respectively are selected from: (i) N and N; and (ii) N and CR4; A2 is selected from:, a C5 heteroarylene group, containing 2 or 3 ring heteroatoms, where the bonds to L1 and the core are β to one another; L1 is selected from: (i)A1-O-CH2-A2; (ii)A1-CH2-O-A2; (iii)A1-C(=O)-NH-A2; (iv)A1-CH(OH)-A2; (v)A1-CH2-NH-C(=O)-A2; (vi) A1-S-CH2-A2; (vii)A1- CH2-S-A2; (viii)A1-CH2-A2; and (ix)A1-CH(CH3)-O-A2; A1 is phenyl, optionally substituted by F or CF3; their use as pharmaceuticals, and in particular, in treating cancer and hemoglobinopathies.
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Page/Page column 59
(2014/09/03)
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- PYRIDINE COMPOUNDS AND USES THEREOF
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The present invention is directed to pyridine compounds of Formula (I). Separate aspects of the invention are directed to pharmaceutical compositions comprising said compounds and uses of the compounds as therapeutic agents treating neurological and psych
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Page/Page column 19
(2013/03/26)
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- Inotropic 'A' ring substituted sulmazole and isomazole analogues
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A series of 'A' ring substituted sulmazole and isomazole analogues have been prepared and evaluated as inotropic agents. pK(A)'s, protonation sites, and log P values were measured for selected compounds and their electronic properties were calculated. No simple correlation between inotropic activity and pK(A), protonation site, or log P value was observed. However, in vitro inotropism did correlate with the calculated charge density of the 'B' ring imidazo nitrogen atom. The 6-position of sulmazole appeared to be the most tolerant toward substituents, th 6-amino derivative 7 being a more potent inotrope than sulmazole itself. 4-Methoxyisomazole 13 had comparable in vivo inotropic properties to those of isomazole.
- Barraclough,Black,Cambridge,Collard,Firmin,Gerskowitch,Glen,Giles,Hill,Hull,Iyer,King,Kneen,Lindon,Nobbs,Randall,Shah,Smith,Vine,et al.
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p. 2231 - 2239
(2007/10/02)
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- Kinetic Studies of the Mechanism of the Nitraminopyridine Rearrangement
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Rate data are reported for the rearrangement, in 92percent sulfuric acid at 30 deg C, of a series of 4-X-2-nitraminopyridines (X=H, Me, Br, Cl, MeO, CO2H) and of 4-methyl-2-nitramino(3-D)-pyridine.Values of pKa for second protonation of the corresponding pyridin-2-amines were also measured and rate constants for nitration of the monoprotonated pyridinamines were thereby calculated.The results suggest that the rate-determining step occurs prior to formation of the appropriate 3- and 5-nitro ? complexes.The nature of this step is not clear, however, and a key role for the nitramine itself is not proven by the current evidence
- Deady, Leslie W.,Korytsky, Olga L.
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p. 2035 - 2040
(2007/10/02)
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- Substituent Effects on the Isomer Ratios in the Rearrangement of Some 2- and 4-Nitraminopyridines
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The preparation, and rearrangement in 92percent sulfuric acid, of 4-X-2-nitramino- (1), 2-X-4-nitramino- (2), and 6-X-2-nitramino-pyridines (3) is reported (X=H,Me,MeO,Br,Cl,CO2H).The product isomer ratios can be explained by differential electronic stabilization of the appropriate ? complexes for aromatic nitration and steric effects seem relatively unimportant.Deuteration had no effect on the product distribution
- Deady, Leslie W.,Korytsky, Olga L.,Rowe, Jeffrey E.
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p. 2025 - 2034
(2007/10/02)
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