- Novel amide and imidazole compounds as potent hematopoietic prostaglandin D2 synthase inhibitors
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In seeking novel and potent small molecule hematopoietic prostaglandin D2 synthase (H-PGDS) inhibitors as potential therapies for PGD2-mediated diseases and conditions, we explored a series comprising multiple aryl/heteroaryl rings attached in a linear arrangement. Each compound incorporates an amide or imidazole “linker” between the pyrimidine or pyridine “core” ring and the “tail” ring system. We synthesized and screened twenty analogs by fluorescence polarization binding assay, thermal shift assay, glutathione S-transferase inhibition assay, and a cell-based assay measuring suppression of LPS-induced PGD2 stimulation. Amide analogs show ten-fold greater shift in the thermal shift assay in the presence of glutathione (GSH) versus the same assay run in the absence of GSH. The imidazole analogs did not produce a significant change in thermal shift between the two assay conditions, suggesting a possible stabilization effect of the amide linker in the synthase-GSH-inhibitor complex. Imidazole analog 23, (KMN-010034) demonstrates superior potency across the in vitro assays and good in vitro metabolic stability in both human and guinea pig liver microsomes.
- Olson, Kirk L.,Holt, Melissa C.,Ciske, Fred L.,Kramer, James B.,Heiple, Paige E.,Collins, Margaret L.,Johnson, Carrie M.,Ho, Chi S.,Morano, M. Ines,Barrett, Stephen D.
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supporting information
(2021/01/19)
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- Preparation method of 5-bromo-2-substituted pyrimidine compound
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The invention discloses a preparation method of a 5-bromo-2-substituted pyrimidine compound. The 5-bromo-2-substituted pyrimidine compound is obtained through a one-step reaction by using 2-bromomalonaldehyde and an amidine compound as raw materials. The
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Paragraph 0036; 0037; 0038; 0039; 0040
(2020/01/12)
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- Material for organic light-emitting device and organic light-emitting device thereof
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The invention provides a material for an organic light-emitting device and the organic light-emitting device thereof, and relates to the technical field of organic photoelectric materials. According to the invention, C site substitution of carbazole is carried out with an aryl-substituted pyrimidinyl, and N site substitution of carbazole is carried out with a specific heteroaryl; finally, the dendritic-structure material for the organic light-emitting device is formed. The glass transition temperature is high, the thermal stability is good, the film-forming property is good, the refractive index is high, the water and oxygen corrosion resistance is realized, and the synthesis is simple; the material can be applied to the organic light-emitting device as a covering layer, can effectively solve the problems of low refractive index, poor thermal stability, poor water and oxygen resistance stability, low luminous efficiency and short service life of the organic light-emitting device, and the organic light-emitting device has the advantages of high luminous efficiency and long service life.
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Paragraph 0096-0098
(2020/06/16)
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- A arylpyrimidines and its derivatives preparation method (by machine translation)
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This invention has offered a kind of arylpyrimidines and process for preparing derivatives thereof, comprising the following steps: S1) shown in the formula (II) 2 the iminium salts dial two substituted propionic [...], shown in formula (III) compound with a nitrile group of alkaline catalyst 1st reaction in the organic solvent, get mixed solution; S2) in the mixed solution is added with ammonium salt and 2nd alkaline catalyst, for the reaction, formula (I) shown in the arylpyrimidines and its derivatives. Compared with the prior art, this invention is in the presence of the alkaline catalyst, 2 the iminium salts dial two substituted propionic [...], of nitrile compounds and ammonium salt [3+2 + 1] ternary cyclization reaction to construct a pyrimidine ring, in order to get arylpyrimidines and its derivatives, this method does not use the noble metal catalyst, line is simple, low cost, high controllability of the process, easy industrialization, reduces the waste of relatively high yield and emissions. (by machine translation)
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Paragraph 0071; 0072; 0074; 0075
(2016/11/14)
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- ORGANOMETALLIC IRIDIUM COMPLEX, LIGHT-EMITTING ELEMENT, LIGHT-EMITTING DEVICE, ELECTRONIC DEVICE, AND LIGHTING DEVICE
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PROBLEM TO BE SOLVED: To provide a long-lifetime organometallic iridium complex exhibiting yellow light emission with high emission efficiency as a novel substance. SOLUTION: The organometallic iridium complex includes a ligand in which an unsubstituted phenyl group is bonded to each of the 2-position and the 5-position of pyrimidine. The organometallic iridium complex has a structure represented by General Formula (G1). COPYRIGHT: (C)2016,JPO&INPIT
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Paragraph 0250; 0251-0253
(2017/02/23)
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- Organometallic Iridium Complex, Light-Emitting Element, Light-Emitting Device, Electronic Device, and Lighting Device
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To provide a long-lifetime organometallic iridium complex exhibiting yellow light emission with high emission efficiency as a novel substance. The organometallic iridium complex includes a ligand in which an unsubstituted phenyl group is bonded to each of
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- HEPATITIS B CORE PROTEIN ALLOSTERIC MODULATORS
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ABSTRACT The present disclosure provides, in part, compounds having allosteric effector properties against Hepatitis B virus Cp. Also provided herein are methods of treating viral infections, such as hepatitis B, comprising administering to a patient in need thereof a disclosed compound.
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Paragraph 000296
(2015/10/05)
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- Inverse electron demand diels-alder reactions of 1,2,3-triazines: Pronounced substituent effects on reactivity and cycloaddition scope
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A systematic study of the inverse electron demand Diels-Alder reactions of 1,2,3-triazines is disclosed, including an examination of the impact of a C5 substituent. Such substituents were found to exhibit a remarkable impact on the cycloaddition reactivity of the 1,2,3-triazine without altering, and perhaps even enhancing, the intrinsic cycloaddition regioselectivity. The study revealed not only that the reactivity may be predictably modulated by a C5 substituent (R = CO2Me > Ph > H) but also that the impact is of a magnitude to convert 1,2,3-triazine (1) and its modest cycloaddition scope into a heterocyclic azadiene system with a reaction scope that portends extensive synthetic utility, expanding the range of participating dienophiles. Significantly, the studies define a now powerful additional heterocyclic azadiene, complementary to the isomeric 1,2,4-triazines and 1,3,5-triazines, capable of dependable participation in inverse electron demand Diels-Alder reactions, extending the number of complementary heterocyclic ring systems accessible with implementation of the methodology.
- Anderson, Erin D.,Boger, Dale L.
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supporting information; experimental part
p. 12285 - 12292
(2011/09/16)
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- MULTIHETEROARYL COMPOUNDS AS INHIBITORS OF H-PGDS AND THEIR USE FOR TREATING PROSTAGLANDIN D2 MEDIATED DISEASES
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Multiheteroaryl compounds, their preparation, pharmaceutical compositions comprising these compounds, and their pharmaceutical use in the prevention and treatment of prostaglandin D2 mediated diseases and conditions that may be modulated by the inhibition of hematopoietic prostaglandin D synthase (H-PGDS).
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Page/Page column 21
(2010/04/23)
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- AZABIPHENYLAMINOBENZOIC ACID DERIVATIVES AS DHODH INHIBITORS
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New azabiphenylaminobenzoic acid derivatives having the chemcial structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of the dehydroorotate dihydrogenase (DHODH)
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Page/Page column 52-53
(2009/04/25)
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- PYRIDINE, QUINOLINE AND PYRIMIDINE DERIVATIVES
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This invention is concerned with compounds of the formula wherein A, R1 to R5 are as defined in the specification and G is a pyridine, quinoline or pyrimidine group as defined in the specification, and pharmaceutically acceptable salts thereof. The invention further relates to pharmaceutical compositions containing such compounds, to a process for their preparation and to their use for the treatment and/or prevention of diseases which are associated with the modulation of SST receptors subtype 5.
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Page/Page column 27
(2008/06/13)
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- New pyrimidine- and fluorene-containing oligo(arylene)s: Synthesis, crystal structures, optoelectronic properties and a theoretical study
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New pyrimidine containing oligo(arylene)s, notably the pyrimidine-fluorene hybrid systems 13-16, have been synthesised by Suzuki cross-coupling methodology. An efficient synthesis of the key reagent 9,9-dihexylfluorene-2,7-diboronic acid 10 from 2,7-dibro
- Hughes, Gregory,Wang, Changsheng,Batsanov, Andrei S.,Fern, Michael,Frank, Stephen,Bryce, Martin R.,Perepichka, Igor F.,Monkman, Andrew P.,Lyons, Benjamin P.
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p. 3069 - 3077
(2007/10/03)
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- Suzuki coupling approach for the synthesis of Phenylene - Pyrimidine alternating oligomers for blue light-emitting material
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Conjugated oligomers with an alternating phenylene-pyrimidine structure have been synthesized by the successive Suzuki coupling reaction starting from 2-bromo-5-iodopyrimidine. The photoluminescence properties and quasi-reversible redox behavior of these
- Wong, Ken-Tsung,Hung, Tsung Shi,Lin, Yuting,Wu, Chung-Chih,Lee, Gene-Hsiang,Peng, Shie-Ming,Chou, Chung Hsien,Su, Yuhlong Oliver
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p. 513 - 516
(2007/10/03)
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- A Novel Synthesis of Isoxazolopyrimidine Derivatives
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The title ring system was synthesized through one step reactions starting from the appriopriate pyrimidine derivatives 1 and 2.Key words: isoxazolopyrimidines synthesis
- Wagner, E.,Becan, L.
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