- Five-membered heterocyclic oxo carboxylic acid compound and medical application thereof
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The invention relates to a five-membered heterocyclic oxo carboxylic acid compound and a medical application thereof. Specifically, the invention relates to a compound, a pharmaceutical salt, a prodrug, a hydrate, a solvate or a crystal form as shown in a formula (I), and also relates to a preparation method of the compound, a pharmaceutical composition containing the compound and an application of the pharmaceutical composition as a secretion regulator of interferon type I, especially as an STING agonist in preparation of medicines for preventing and/or treating I-type interferon related diseases.
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Paragraph 0707; 0712-0714
(2021/05/01)
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- Pyrimidine or pyrazino five-membered heterocyclic compound and applications thereof
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The invention discloses a pyrimidine or pyrazino five-membered heterocyclic compound, a pharmaceutically acceptable salt, a hydrate, a prodrug, a stereoisomer or a solvate thereof, and provides a preparation method of the compound, a composition containing the compound, and applications of the compound in preparation of drugs for treating diseases or disorders related to the action mechanism of EED protein and/or PRC2 protein complex.
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- Pyrimidone compound and application thereof
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The invention discloses a pyrimidone compound, pharmaceutically acceptable salt and solvate thereof, and provides a method for preparing the compounds, a composition containing the compounds and medicinal application of the compounds in preparation of medicines for treating diseases or disorders related to EED protein and/or PRC2 protein complex action mechanisms.
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- Pyrido/pyridazocyclic compound and application thereof
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The invention discloses a pyrido/pyridazocyclic compound, a pharmaceutically acceptable salt and a solvent compound thereof. The invention further provides a preparation method of the compound, a composition with the compound and application of the compound for preparing medicines for treating diseases or disorders related to EED (embryonic ectoderm development) protein and/or PRC2 (polycomb repressive complex 2) protein composition action mechanisms.
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- Biocatalytic Strategy for Highly Diastereo- and Enantioselective Synthesis of 2,3-Dihydrobenzofuran-Based Tricyclic Scaffolds
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2,3-Dihydrobenzofurans are key pharmacophores in many natural and synthetic bioactive molecules. A biocatalytic strategy is reported here for the highly diastereo- and enantioselective construction of stereochemically rich 2,3-dihydrobenzofurans in high enantiopurity (>99.9% de and ee), high yields, and on a preparative scale via benzofuran cyclopropanation with engineered myoglobins. Computational and structure-reactivity studies provide insights into the mechanism of this reaction, enabling the elaboration of a stereochemical model that can rationalize the high stereoselectivity of the biocatalyst. This information was leveraged to implement a highly stereoselective route to a drug molecule and a tricyclic scaffold featuring five stereogenic centers via a single-enzyme transformation. This work expands the biocatalytic toolbox for asymmetric C–C bond transformations and should prove useful for further development of metalloprotein catalysts for abiotic carbene transfer reactions.
- Vargas, David A.,Khade, Rahul L.,Zhang, Yong,Fasan, Rudi
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supporting information
p. 10148 - 10152
(2019/07/04)
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- Discovery of Potent Benzofuran-Derived Diapophytoene Desaturase (CrtN) Inhibitors with Enhanced Oral Bioavailability for the Treatment of Methicillin-Resistant Staphylococcus aureus (MRSA) Infections
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Blocking the staphyloxanthin biosynthesis process has emerged as a new promising antivirulence strategy. Previously, we first revealed that CrtN is a druggable target against infections caused by pigmented Staphylococcus aureus (S. aureus) and that naftifine was an effective CrtN inhibitor. Here, we identify a new type of benzofuran-derived CrtN inhibitor with submicromolar IC50 values that is based on the naftifine scaffold. The most potent analog, 5m, inhibits the pigment production of S. aureus Newman and three MRSA strains, with IC50 values of 0.38-5.45 nM, without any impact on the survival of four strains (up to 200 μM). Notably, compound 5m (1 μM) could significantly sensitize four strains to immune clearance and could effectively attenuate the virulence of three strains in vivo. Moreover, 5m was determined to be a weak antifungal reagent (MIC > 16 μg/mL). Combined with good oral bioavailability (F = 42.2%) and excellent safety profiles, these data demonstrate that 5m may be a good candidate for the treatment of MRSA infections.
- Wang, Youxin,Chen, Feifei,Di, Hongxia,Xu, Yong,Xiao, Qiang,Wang, Xuehai,Wei, Hanwen,Lu, Yanli,Zhang, Lingling,Zhu, Jin,Sheng, Chunquan,Lan, Lefu,Li, Jian
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p. 3215 - 3230
(2016/05/19)
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- Visible light-induced monofluoromethylenation of heteroarenes with ethyl bromofluoroacetate
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Visible light-induced monofluoromethylenation of benzofurans and benzothiophenes with ethyl bromofluoroacetate was developed. This method provided a convenient access to novel α-fluoro-α-heteroarylesters under mild reaction conditions.
- Yu, Wei,Xu, Xiu-Hua,Qing, Feng-Ling
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p. 6564 - 6567
(2016/08/09)
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- SPIRO-OXADIAZOLINE COMPOUNDS AS AGONISTS OF α-7-NICOTINIC ACETYLCHOLINE RECEPTORS
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The present invention relates to novel spiro-oxadiazoline compounds that are suitable as agonists or partial agonists of a7-nAChR, and pharmaceutical compositions of the same, methods of preparing these compounds and compositions, and the use of these compounds and compositions in methods of maintaining, treating and/or improving cognitive function. In particular, methods of administering a spiro-oxadiazoline cx7-nAChR agonist or partial agonist, to a patient in need thereof, for example a patient with a cognitive deficiency and/or a desire to enhance cognitive function, that may derive a benefit therefrom.
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- Zeolite-catalyzed synthesis of 2,3-unsubstituted benzo[b]furans via the intramolecular cyclization of 2-aryloxyacetaldehyde acetals
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An efficient and environmentally benign heterogeneous catalytic process for the synthesis of 2,3-unsubstituted benzo[b]furans has been established via the intramolecular cyclization of 2-aryloxyacetaldehyde acetals. By utilizing tin-exchanged H-β zeolite (Sn-β) as catalyst, a wide range of functionalized 2,3-unsubstituted benzo[b]furans could be prepared in good to excellent yields. The Sn-β zeolite catalyst also exhibited excellent shape selectivity on the cyclization of meta-substituted 2-aryloxyacetaldehyde acetals, and 6-substituted isomers were preferably formed up to 97% regio-selectivity. Moreover, Sn-β zeolite could be easily recovered and reused without any noticeable activity loss.
- Sun, Nan,Huang, Peng,Wang, Yifan,Mo, Weimin,Hu, Baoxiang,Shen, Zhenlu,Hu, Xinquan
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p. 4835 - 4841
(2015/07/27)
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- Substituent effects of cis-cinnamic acid analogues as plant growh inhibitors
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1-O-cis-Cinnamoyl-β-d-glucopyranose is one of the most potent allelochemicals that has been isolated from Spiraea thunbergii Sieb by Hiradate et al. It derives its strong inhibitory activity from cis-cinnamic acid (cis-CA), which is crucial for phytotoxicity. By preparing and assaying a series of cis-CA analogues, it was previously found that the key features of cis-CA for lettuce root growth inhibition are a phenyl ring, cis-configuration of the alkene moiety, and carboxylic acid. On the basis of a structure-activity relationship study, the substituent effects on the aromatic ring of cis-CA were examined by systematic synthesis and the lettuce root growth inhibition assay of a series of cis-CA analogues having substituents on the aromatic ring. While ortho- and para-substituted analogues exhibited low potency in most cases, meta-substitution was not critical for potency, and analogues having a hydrophobic and sterically small substituent were more likely to be potent. Finally, several cis-CA analogues were found to be more potent root growth inhibitors than cis-CA.
- Nishikawa, Keisuke,Fukuda, Hiroshi,Abe, Masato,Nakanishi, Kazunari,Taniguchi, Tomoya,Nomura, Takashi,Yamaguchi, Chihiro,Hiradate, Syuntaro,Fujii, Yoshiharu,Okuda, Katsuhiro,Shindo, Mitsuru
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p. 132 - 147
(2014/01/06)
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- Synthesis of piperazino-substituted benzo[b]furans as potential CNS agents
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The synthesis of a series of substituted benzofurans is reported. Selected compounds have been shown to bind strongly and with high selectivity to the serotonin receptor 5-HT2A in the presence of the receptor 5-HT 7 in vitro.
- Klenc, Jeff,Strekowski, Lucjan
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experimental part
p. 249 - 252
(2011/06/10)
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- CARBINOL DERIVATIVES HAVING HETEROCYCLIC LINKER
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[Object] It is to provide a novel LXRβ agonist useful as a preventative and/or therapeutic agent for atherosclerosis; arteriosclerosis such as those resulting from diabetes; dyslipidemia; hypercholesterolemia; lipid-related diseases; inflammatory diseases that are caused by inflammatory cytokines; skin diseases such as allergic skin diseases; diabetes; or Alzheimer's disease. [Solving Means] A carbinol compound represented by the following general formula (I) or salt thereof, or their solvate: (wherein, each V and W independently show N or C—R7; each X and Y independently show CH2, C═O, SO2, etc; Z shows CH or N; each R1, R2 and R7 independently show a hydrogen atom, C1-8 alkyl group, etc.; R3 shows C1-8 alkyl group; R4 shows an optionally substituted C6-10 aryl group or an optionally substituted 5- to 11-membered heterocyclic group; R5 and R6 show a hydrogen atom, etc.; L shows a C1-8 alkyl chain optionally substituted with an oxo group, etc.; and n shows any integer of 0 to 2.)
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Page/Page column 42
(2010/12/29)
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- Aminoalkylbenzofurans as serotonin (5-HT(2c)) agonists
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The present invention provides serotonergic aminoalkylbenzofurans of Formula (I): where R, R1, R2, R3, R4, R4′, R5, R5′, and R12 are as described in the specification.
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Page/Page column 20
(2010/11/08)
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- THIADIAZOLES AS CXC- AND CC- CHEMOKINE RECEPTOR LIGANDS
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Disclosed are novel compounds of Formula (IA) and the pharmaceutically acceptable salts and solvates thereof. Examples of groups comprising Substituent A include heteroaryl, aryl, heterocycloalkyl, cycloalkyl, aryl, alkynyl, alkenyl, aminoalkyl, alkyl or amino. Examples of groups comprising Substituent B include aryl and heteroaryl. Also disclosed is a method of treating a chemokine mediated diseases, such as, cancer, angiogenisis, angiogenic ocular diseases, pulmonary diseases, multiple sclerosis, rheumatoid arthritis, osteoarthritis, stroke and ischemia reperfusion injury, pain (e.g., acute pain, acute and chronic inflammatory pain, and neuropathic pain) using a compound of Formula (IA).
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Page/Page column 209-210
(2010/02/12)
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- 3,4-Di-substituted cyclobutene-1,2-diones as CXC-chemokine receptor ligands
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There are disclosed compounds of the formula or a pharmaceutically acceptable salt or solvate thereof which are useful for the treatment of chemokine-mediated diseases such as acute and chronic inflammatory disorders and cancer.
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- THIADIAZOLEDIOXIDES AND THIADIAZOLEOXIDES AS CXC- AND CC-CHEMOKINE RECEPTOR LIGANDS
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Disclosed are novel compounds of the formula (IA) and the pharmaceutically acceptable salts and solvates thereof. Examples of groups comprising Substituent A include heteroaryl, aryl, heterocycloalkyl, cycloalkyl, aryl, alkynyl, alkenyl, aminoalkyl, alkyl or amino. Examples of groups comprising Substituent B include aryl and heteroaryl. Also disclosed is a method of treating a chemokine mediated diseases, such as, cancer, angiogenisis, angiogenic ocular diseases, pulmonary diseases, multiple sclerosis, rheumatoid arthritis, osteoarthritis, stroke and cardiac reperfusion injury, acute pain, acute and chronic inflammatory pain, and neuropathic pain using a compound of formula (IA).
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Page 240-241
(2008/06/13)
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- SEROTONERGIC BENZOFURANS
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The present invention provides serotonergic benzofurans of Formula (I): where A, R, R, R, R, and R are as described in the specification.
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- Potent and selective non-benzodioxole-containing endothelin-A receptor antagonists
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The benzodioxole ((methylenedioxy)benzene) group is present in a number of endothelin (ET) receptor antagonists thus far reported. As part of our own endothelin antagonist program we have developed (2R*,3R*,4S*)-1-(N,N- dibutylacetamido)-4-(1,3-benzodioxol-5-yl)-2-(4-methoxyphenyl)pyrrolidine-3- carboxylic acid (A-127722). This is a potent antagonist, binding to the ET(A) and ET(B) receptor subtypes with affinities (IC50) of 0.4 and 520 nM, respectively, and also contains the aforementioned benzodioxole. While this compound was seemingly optimized at its N-terminus, no effort had been directed toward understanding the contributions to binding affinity or receptor subtype selectivity conferred by the benzodioxole. Substitution by 1- or 2-naphthyl yielded weak antagonists. Oxygenated benzenes, such as p- anisyl, were potent compounds with IC50s in the low-nanomolar range. Simple deletion of either of the two oxygen atoms (dihydrobenzofurans) yielded extremely potent agents, possessing subnanomolar affinity for the ET(A) receptor. Additionally, the compounds showed enhanced selectivity, binding to the ET(B) receptor subtype in the micromolar range. This paper describes the development of this novel class of compounds.
- Tasker, Andrew S.,Sorensen, Bryan K.,Jae, Hwan-Soo,Winn, Martin,Von Geldern, Thomas W.,Dixon, Douglas B.,Chiou, William J.,Dayton, Brian D.,Calzadila, Samuel,Hernandez, Lisa,Marsh, Kennan C.,WuWong, J. Ruth,Opgenorth, Terry J.
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p. 322 - 330
(2007/10/03)
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- Antitumor compositions and methods of treatment
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This invention provides the use of certain benzofuransulfonamide, benzothiophenesulfonamide, and indolesulfonamide derivatives in the treatment of susceptible neoplasms in mammals. Also provided are certain novel benzofuransulfonamide and benzothiophenesulfonamide derivatives and their pharmaceutical formulations.
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