- 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 0164-0167
(2021/04/17)
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- Methods for treating neisseria gonorrhoeae infection with substituted 1,2-dihydro-2A,5,8A-triazaacenaphthylene-3,8-diones
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The present invention relates to methods for treating Neisseria Gonorrhoeae infection which comprises administering to a subject in need thereof novel 1,2-dihydro-2a,5,8a-triazaacenaphthylene-3,8-dione compounds: or pharmaceutically acceptable salts thereof and/or corresponding pharmaceutical compositions.
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- BICYCLIC HETEROARYL DERIVATIVES AS ECTONUCLEOTIDE PYROPHOSPHATASE PHOSPHODIESTERASE 1 INHIBITORS
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The present disclosure provides certain bicyclic heteroaryl compounds that inhibit ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) enzymatic activity and are therefore useful for the treatment of diseases and conditions modulated at least in part by ENPP1. In some embodiments, the bicyclic heteroaryl compounds includes those of Formula (I). Also provided herein are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
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Paragraph 0329; 0466
(2020/10/21)
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- Benzimidazole derivatives, their preparation and their application in medicine and pharmacology (by machine translation)
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The invention relates to a new control or inhibit indocyanine 2, 3 - dioxygenase (IDO) activity of the benzimidazole derivatives, their preparation and their application in medicine and pharmacology. Specifically, the invention relates to a compound of general formula (I) compound of formula and its pharmaceutically acceptable salt, containing the compound or its pharmaceutically acceptable salt of the pharmaceutical composition, the use of the compound or its pharmaceutically acceptable salts for treating and/or preventing the relevance of the IDO-mediated disease, especially a tumor of the method and the compound or its pharmaceutically acceptable salts thereof. The invention also relates to the compound or its pharmaceutically acceptable salt or containing the compound or its pharmaceutically acceptable salts for the preparation of a pharmaceutical composition for treating and/or preventing the relevance of the IDO-mediated disease, in particular of the use of the drug in the tumor. Wherein the general formula (I) of each substituent is as defined in the specification. (by machine translation)
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Paragraph 0148-0149
(2019/07/16)
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- Potent, Selective, and Cell Active Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor Developed by Structure-Based Virtual Screening and Hit Optimization
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PRMT5 plays important roles in diverse cellular processes and is upregulated in several human malignancies. Besides, PRMT5 has been validated as an anticancer target in mantle cell lymphoma. In this study, we found a potent and selective PRMT5 inhibitor by performing structure-based virtual screening and hit optimization. The identified compound 17 (IC50 = 0.33 μM) exhibited a broad selectivity against a panel of other methyltransferases. The direct binding of 17 to PRMT5 was validated by surface plasmon resonance experiments, with a Kd of 0.987 μM. Kinetic experiments indicated that 17 was a SAM competitive inhibitor other than the substrate. In addition, 17 showed selective antiproliferative effects against MV4-11 cells, and further studies indicated that the mechanism of cellular antitumor activity was due to the inhibition of PRMT5 mediated SmD3 methylation. 17 may represent a promising lead compound to understand more about PRMT5 and potentially assist the development of treatments for leukemia indications.
- Mao, Ruifeng,Shao, Jingwei,Zhu, Kongkai,Zhang, Yuanyuan,Ding, Hong,Zhang, Chenhua,Shi, Zhe,Jiang, Hualiang,Sun, Dequn,Duan, Wenhu,Luo, Cheng
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p. 6289 - 6304
(2017/08/02)
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- Synthesis of carbon-11-labeled imidazopyridine- and purine-thioacetamide derivatives as new potential PET tracers for imaging of nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1)
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The target tracer carbon-11-labeled imidazopyridine- and purine-thioacetamide derivatives, N-(3-[11C]methoxy-4-methoxyphenyl)-2-((5-methoxy-3H-imidazo[4,5-b]pyridin-2-yl)thio)acetamide (3-[11C]4a) and N-(4-[11C]methoxy-3-methoxyphenyl)-2-((5-methoxy-3H-imidazo[4,5-b]pyridin-2-yl)thio)acetamide (4-[11C]4a); 2-((6-amino-9H-purin-8-yl)thio)-N-(3-[11C]methoxy-4-methoxyphenyl)acetamide (3-[11C]8a) and 2-((6-amino-9H-purin-8-yl)thio)-N-(4-[11C]methoxy-3-methoxyphenyl)acetamide (4-[11C]8a), were prepared by O-[11C]methylation of their corresponding precursors with [11C]CH3OTf under basic condition (2 N NaOH) and isolated by a simplified solid-phase extraction (SPE) method in 50-60% radiochemical yields based on [11C]CO2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 185-555 GBq/μmol.
- Gao, Mingzhang,Wang, Min,Zheng, Qi-Huang
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p. 1371 - 1375
(2016/02/19)
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- Lithium Hexamethyldisilazane Transformation of Transiently Protected 4-Aza/Benzimidazole Nitriles to Amidines and their Dimethyl Sulfoxide Mediated Imidazole Ring Formation
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Trimethylsilyl-transient protection successfully allowed the use of lithium hexamethyldisilazane to prepare benzimidazole (BI) and 4-azabenzimidazole (azaBI) amidines from nitriles in 58-88% yields. This strategy offers a much better choice to prepare BI/azaBI amidines than the lengthy, low-yielding Pinner reaction. Synthesis of aza/benzimidazole rings from aromatic diamines and aldehydes was affected in dimethyl sulfoxide in 10-15 min, while known procedures require long time and purification. These methods are important for the BI/azaBI-based drug industry and for developing specific DNA binders for expanded therapeutic applications.
- Abou-Elkhair, Reham A. I.,Hassan, Abdalla E. A.,Boykin, David W.,Wilson, W. David
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supporting information
p. 4714 - 4717
(2016/09/28)
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- INHIBITORS OF DNA GYRASE FOR THE TREATMENT OF BACTERIAL INFECTIONS
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The present invention relates to compounds which specifically inhibit bacterial DNA Gyrase and can be used for the treatment of respiratory tract infections.
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- Imidazopyridine- and purine-thioacetamide derivatives: Potent inhibitors of nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1)
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Nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) belongs to the family of ecto-nucleotidases, which control extracellular nucleotide, nucleoside, and (di)phosphate levels. To study the (patho)physiological roles of NPP1 potent and selective inhibitors with drug-like properties are required. Therefore, a compound library was screened for NPP1 inhibitors using a colorimetric assay with p-nitrophenyl 5′-thymidine monophosphate (p-Nph-5′-TMP) as an artificial substrate. This led to the discovery of 2-(3H-imidazo[4,5-b]pyridin-2-ylthio)-N-(3,4-dimethoxyphenyl)acetamide (5a) as a hit compound with a Ki value of 217 nM. Subsequent structure-activity relationship studies led to the development of purine and imidazo[4,5-b]pyridine analogues with high inhibitory potency (Ki values of 5.00 nM and 29.6 nM, respectively) when assayed with p-Nph-5′-TMP as a substrate. Surprisingly, the compounds were significantly less potent when tested versus ATP as a substrate, with Ki values in the low micromolar range. A prototypic inhibitor was investigated for its mechanism of inhibition and found to be competitive versus both substrates.
- Chang, Lei,Lee, Sang-Yong,Leonczak, Piotr,Rozenski, Jef,De Jonghe, Steven,Hanck, Theodor,Müller, Christa E.,Herdewijn, Piet
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p. 10080 - 10100
(2015/02/05)
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- IMIDAZOLE DERIVATIVES
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Described herein are compounds of formula I. The compounds of formula I act as DGAT1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for hyperlipidemia, diabetes mellitus and obesity.
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Page/Page column 39-40
(2012/07/28)
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- Synthesis and biological activity of splitomicin analogs targeted at human NAD+-dependent histone deacetylases (sirtuins)
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Small molecules interfering with posttranslational modification of histones are of interest as tools to study epigenetic regulation of gene transcription. Specifically, drugs that interfere with histone deacetylation could be useful to induce differentiation, growth arrest as well as apoptotic cell death in tumor cells. One class of histone deacetylases is known as sirtuins some of which (Saccharomyces cerevisiae Sir2) are for example inhibited by the lactone splitomicin leading to telomeric silencing in yeast. However, splitomicin is only a micromolar inhibitor of yeast Sir2 and does not inhibit human subtypes and the lactone is prone to hydrolytic ring opening. In preliminary SAR-studies, splitomicin analogs lacking this hydrolytically labile ring were described as inactive while the naphthalene moiety could successfully be replaced by smaller aromatic rings in a fragment-like dihydrocoumarin. Here we report the synthesis and biological activity of a series of hydrolytically stable analogs with activity against human SIRT1 and 2. These comparatively small compounds characterized by high ligand efficiency are used as a starting point toward the development of specific inhibitors of histone deacetylases from the class of sirtuins.
- Freitag, Marcus,Schemies, Joerg,Larsen, Tim,El Gaghlab, Khattab,Schulz, Felix,Rumpf, Tobias,Jung, Manfred,Link, Andreas
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experimental part
p. 3669 - 3677
(2011/08/03)
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- TRICYCLIC NITROGEN COMPOUNDS AND THEIR USE AS ANTIBACTERIAL AGENTS
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Tricyclic nitrogen containing compounds and their use as antibacterials.
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Page/Page column 48
(2009/09/04)
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- COMPOUNDS
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Compounds of Formula (I) or pharmaceutically acceptable salts or N-oxides thereof: (relative chemistry shown) pharmaceutical compositions comprising them, their use in therapy especially against tuberculosis, and methods of preparing them are described.
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Page/Page column 21
(2009/12/24)
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- TRICYCLIC NITROGEN CONTAINING COMPOUNDS AS ANTIBACTERIAL AGENTS
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Tricyclic nitrogen containing compounds and their use as antibacterials. Z1and Z2 are independently selected from CH and N.
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- COMPOUNDS
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Bicyclic nitrogen containing compounds and their use as antibacterials.
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- HETEROCYCLIC-SUBSTITUTED PIPERDINE COMPOUNDS AND THE USES THEREOF
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The invention relates to Heterocyclic-Substituted Piperidine Compounds, compositions comprising an effective amount of a Heterocyclic-Substituted Piperidine Compound and methods to treat or prevent a condition, such as pain, comprising administering to an animal in need thereof an effective amount of a Heterocyclic-Substituted Piperidine Compound
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Page/Page column 254
(2008/12/07)
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- Process for producing 2,3-diamino-6-methoxypyridine
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The present invention relates to a novel process for producing 2,3-diamino-6-methxoypyridine. The process comprises neutralizing 2,3-diamino-6-methoxy pyridine dihydrochloride, which, in turn, is prepared by the reduction of 2-amino-6-methoxy-3-nitropyridine. The 2-amino-6-methoxy-3-nitropyridine is further prepared by methoxylation of 2-amino-6-chloro-3-nitropyridine by sodium methoxide in methanol.
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Page/Page column 3
(2008/06/13)
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- CGRP RECEPTOR ANTAGONISTS
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The present invention is directed to compounds of Formula (I) and Formula (II) (where variables R1, R2, R3, R4, A, B, G, J, Q, T, U, V, W, X and Y are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.
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- Novel α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor antagonists: Synthesis and structure-activity relationships of 6-(1H- imidazol-1-yl)-7-nitro-2,3(1H,4H)-pyrido[2,3-b]pyrazinedione and related compounds
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We have synthesized and evaluated azaquinoxalinediones 3a-c for their activity in inhibiting [3H]AMPA binding from rat whole brain. It was found that the azaquinoxalinedione nucleus functions as a bioisostere for quinoxalinedione in AMPA receptor binding. The detailed structure-activity relationships of 6- and/or 7-substituted 2,3(1H,4H)-pyrido[2,3- b]pyrazinedione derivatives 4, 7-10, 13, 15, and 16 showed some differences in comparison with those of the corresponding substituted quinoxalinediones, including 6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione (1) (YM90K). The X-ray study exhibited that conformation of the 7-nitro group of 1 · HCl was nearly coplanar with the quinoxaline ring, whereas the 6- imidazol1-yl group was rotated with respect to the aromatic ring. From the glycine site on NMDA receptor binding study, it is indicated that bulkiness of 6-substituents on pyridopyrazinediones may be responsible for the selectivity against the glycine site. Among the series of azaquinoxalinediones, 6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-pyrido[2,3- b]pyrazinedione (8c) exhibited a combination of the best affinity to the AMPA receptors with a K(i) value of 0.14 μM and selectivity against the glycine site (no affinity at 10 μM). In vivo, 8c also protected against sound- induced seizure in DBA/2 mice (minimum effective dose, 10 mg/kg ip).
- Ohmori,Kubota,Shimizu-Sasamata,Okada,Sakamoto
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p. 1331 - 1338
(2007/10/03)
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- Hair dye compositions and process comprising and utilizing a combination of isatin and aminopyridine derivatives
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The invention relates to a process for dyeing keratinous fibers, comprising the simultaneous or sequential application of a component (A) containing at least one compound of formula (I): STR1 in which: R1 denotes hydrogen, alkyl, acetyl, benzoyl, phenyl or carboxyalyl; R2 and R3 denote a hydrogen, alkyl, hydroxyl, halogen, nitro, alkylphenyl, phenyl or alkoxy; and a component (B) containing at least one compound of formula (II): STR2 in which: R4 denotes a hydrogen atom or a β-hydroxyethyl group; n=0, 1 or 2, and m=0 or 1; as well as its cosmetically acceptable salts; or one compound of formula (III): STR3 in which: R5 denotes a hydrogen atom, a hydroxyl group or a group STR4 R6 denotes a hydroxyl group or a group N STR5 R7 denotes H or NH2, R8 denotes a group STR6 R9 and R10, independently of one another, representing a hydrogen atom, a C1 -C4 alkyl, a group (CH2)p --Z, where p=1 to 4 and Z represents OH, halogen, NH2, NHR' or NHR'R", where R' and R" denote a C1 -C4 alkyl or form a heterocycle with the nitrogen atom to which they are attached; with the proviso that one of R5 to R8 denotes NH2 ; and its cosmetically acceptable salts, as well as to the dyeing agents employed.
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- Diaminopyridine compounds and methods of use
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The present invention relates to compositions and method for inhibiting nonenzymatic cross-linking (protein aging) which contain diaminopyridines and derivates thereof. Accordingly, a composition is disclosed which comprises an agent capable of inhibiting the formation of advanced glycosylation endproducts of target proteins by reacting with the carbonyl moiety of the early glycosylation product of such target proteins formed by their initial glycosylation. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.
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