- OXALAMIDE HETEROBYCYCLIC COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH STING ACTIVITY
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This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt, and/or hydrate, and/or cocrystal, and/or drug combination of the compound) that inhibit (e.g., antagonize) Stimulator of Interferon Genes (STING). Said chemical entities are useful, e.g., for treating a condition, disease or disorder in which increased (e.g., excessive) STING activation (e.g., STING signaling) contributes to the pathology and/or symptoms and/or progression of the condition, disease or disorder (e.g., cancer) in a subject (e.g., a human). This disclosure also features compositions containing the same as well as methods of using and making the same.
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Page/Page column 146
(2021/04/10)
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- Carbamoyl Radicals via Photoredox Decarboxylation of Oxamic Acids in Aqueous Media: Access to 3,4-Dihydroquinolin-2(1 H)-ones
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The first visible-light-mediated photoredox oxidative approach for generating carbamoyl radicals from oxamic acids is disclosed. Reaction of the generated carbamoyl radicals with electron-deficient alkenes opens efficient access to 3,4-dihydroquinolin-2(1H)-ones under mild conditions through a sequence of intermolecular radical addition, cyclization, and aromatization. The process is compatible with a variety of oxamic acids and electron-deficient alkenes, and a wide variety of 3,4-dihydroquinolin-2(1H)-ones were prepared.
- Bai, Qi-Fan,Jin, Chengan,He, Jing-Yao,Feng, Gaofeng
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supporting information
p. 2172 - 2175
(2018/04/30)
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- Tethered NHC Ligands for Stereoselective Alkyne Semihydrogenations
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A copper(I)-catalyzed semihydrogenation of internal alkynes has been developed. A variety of oxygen- and nitrogen-tethered N-heterocyclic carbene (NHC) complexes have been investigated, leading to a highly Z-selective transformation. The catalyst is generated from inexpensive copper(I) chloride in situ and allows catalytic semihydrogenation down to 10 bar H2.
- Pape, Felix,Teichert, Johannes F.
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supporting information
p. 2470 - 2482
(2017/05/22)
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- Highly efficient dehydrogenative cross-coupling of aldehydes with amines and alcohols
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A common protocol for the synthesis of amides, esters and α-ketoesters via cross dehydrogenative coupling of aldehydes and amines/alcohols has been developed. The method is applicable to a wide variety of alcohols and amines as well as aliphatic and aromatic aldehydes. Also, the use of acetaldehyde for acetylation and ethyl glyoxalate to access 2-oxo-amino esters is presented for the first time.
- Deshidi, Ramesh,Rizvi, Masood Ahmad,Shah, Bhahwal Ali
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p. 90521 - 90524
(2015/11/11)
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- Design, synthesis, and antiviral activity of entry inhibitors that target the CD4-binding site of HIV-1
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The CD4 binding site on HIV-1 gp120 has been validated as a drug target to prevent HIV-1 entry to cells. Previously, we identified two small molecule inhibitors consisting of a 2,2,6,6-tetramethylpiperidine ring linked by an oxalamide to a p-halide-substituted phenyl group, which target this site, specifically, a cavity termed "Phe43 cavity". Here we use synthetic chemistry, functional assessment, and structure-based analysis to explore variants of each region of these inhibitors for improved antiviral properties. Alterations of the phenyl group and of the oxalamide linker indicated that these regions were close to optimal in the original lead compounds. Design of a series of compounds, where the tetramethylpiperidine ring was replaced with new scaffolds, led to improved antiviral activity. These new scaffolds provide insight into the surface chemistry at the entrance of the cavity and offer additional opportunities by which to optimize further these potential-next- generation therapeutics and microbicides against HIV-1.
- Curreli, Francesca,Choudhury, Spreeha,Pyatkin, Ilya,Zagorodnikov, Victor P.,Bulay, Anna Khulianova,Altieri, Andrea,Kwon, Young Do,Kwong, Peter D.,Debnath, Asim K.
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scheme or table
p. 4764 - 4775
(2012/07/28)
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- CD4 mimics targeting the mechanism of HIV entry
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A structure-activity relationship study was conducted of several CD4 mimicking small molecules which block the interaction between HIV-1 gp120 and CD4. These CD4 mimics induce a conformational change in gp120, exposing its co-receptor-binding site. This induces a highly synergistic interaction in the use in combination with a co-receptor CXCR4 antagonist and reveals a pronounced effect on the dynamic supramolecular mechanism of HIV-1 entry.
- Yamada, Yuko,Ochiai, Chihiro,Yoshimura, Kazuhisa,Tanaka, Tomohiro,Ohashi, Nami,Narumi, Tetsuo,Nomura, Wataru,Harada, Shigeyoshi,Matsushita, Shuzo,Tamamura, Hirokazu
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experimental part
p. 354 - 358
(2010/04/05)
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- Chemical hybridizing agents for chickpea (Cicer arietinum L.): Leads from QSAR analysis of ethyl oxanilates and pyridones
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In the self-pollinated crops such as chickpea, induction of male sterility by deployment of chemical hybridizing agents (CHAs) facilitating "two-line" approach holds immense potential in heterosis breeding. A total of 40 test CHAs comprising 20 ethyl oxanilates and 20 pyridones were screened as potential CHAs on chickpea (variety BG 1088) at 500, 800, and 1000 ppm. Three test compounds mostly having either F (4)/Br (5)/CF3 (19) at the para position of the aryl ring from a pool of 20 ethyl oxanilates were identified as the most potent CHAs causing >99% induction of pollen sterility and >90% total flower sterility at 1000-ppm test concentration. Among pyridone derivatives, N-(4-chlorophenyl)-5-carbethoxy-4,6-dimethyl, 1,2-dihydropyrid-2-one (26) was found to be the most active. Quantitative structure activity relationship (QSAR) analysis has revealed a direct involvement of Swain-Lupton field constant, Fp, with the target bioactivity which implied that field rather than resonance effect (R) had a positive effect on the activity. The real guiding principle for selectivity was found out to be the hydrophobic parameter π value. The QSAR models indicated that increased steric bulk at the 4-position on the phenyl ring is associated with enhanced activity. The CHAs appeared to act by mimicking UDP-glucose, the key substrate in the synthesis of callose, or lead to an imbalance in acid-base equilibrium in pollen mother cells resulting in dissolution of callose wall by premature callase secretion.
- Chakraborty, Kajal,Devakumar
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p. 1868 - 1873
(2007/10/03)
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- Rapid microwave-assisted syntheses of derivatives of HIV-1 entry inhibitors
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The direct amidation of esters with 4-amino-2,2,6,6-tetramethylpiperidine was achieved by computer-controlled microwave irradiation in toluene. The microwave protocol allowed the new amides to be prepared in three hours rather than the three days required by traditional thermal methods. Georg Thieme Verlag Stuttgart.
- McFarland, Chris,Vicic, David A.,Debnath, Asim Kumar
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p. 807 - 812
(2007/10/03)
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- N-acylanilines, herbicide-CHA chimera, and amino acid analogues as novel chemical hybridizing agents for wheat (Triticum aestivum L.)
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In the absence of viable alternative technology of hybrid wheat development, chemical induction of male sterility mediated technology based on chemical hybridizing agents (CHAs) holds a great potential. N-Acylaniline derivatives, namely, ethyl 4′-fluoro oxanilate (1) and ethyl 4′-trifluoromethyl oxanilate (2) containing halogen atoms in the para position of the aryl ring and substituted amide linkage (-CO-NH-) in the acyl side chain induced >98% spikelet sterility on three genotypes of wheat, namely, PBW 343, HD 2046 and HD 2733, at 1500 ppm. The active moieties were incorporated in the form of herbicide-CHA chimera and amino acid analogues using glycine and alanine as templates. The target activity was made more selective by synthesizing chimeric structure of herbicide (2,4-dichlorophenoxyacetic acid and dalapon) and the most active CHA templates, namely, 4-fluoroanilinyl and β-ethoxycarbonyl moieties. Among herbicide-CHA chimera ethyl 2′,4′-dichlorophenyl oxalate (14) induced 79.11% male sterility, whereas benzyl methyl 2-oxo-3-azaadipate (20) was the best, inducing 73.87% male sterility in HD 2733, among amino acid analogues. The CHAs were found to modify the reproductive biology to ensure cross-pollination in the cleistogamous wheat flowers, increasing the probability for the development of hybrids.
- Chakraborty, Kajal,Devakumar
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p. 7899 - 7907
(2007/10/03)
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- Synthesis and quantitative structure-activity relationships of oxanilates as chemical hybridizing agents for wheat (Triticum aestivum L.)
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Chemical hybridizing agents (CHAs) can facilitate two-line breeding in heterosis programs of crops. Twenty-seven oxanilates having different aromatic substitutions were synthesized and screened as CHAs on two genotypes of wheat, PBW 343 and HD 2733, during two Rabi (winter) seasons, 2000-01 and 2001-02. The oxanilates prepared by thermal condensation of anilines with diethyl oxalate or by acylation with ethoxycarbonyl methanoyl chloride were sprayed at 1000 and 1500 ppm at the premeiotic stage of wheat, when the length of the emerging spike of the first node was 7-8 mm. Pollen sterility and spikelet sterility were measured in each treatment. Ethyl oxanilates 5, 6, and 25, containing 4-F, 4-Br, and 4-CF3 aromatic substituents, respectively, induced greater than 98% spikelet sterility, the desired level, at 1500 ppm. Quantitative structure-activity relationship analysis revealed a direct relationship between Fp and molecular mass but an inverse relationship between MR, Es, and R in influencing the bioactivity. Several F1 hybrids were developed using 5, and at least one showed heterosis.
- Chakraborty, Kajal,Devakumar, Chakravarthi,Tomar, Shiv M. S.,Kumar, Rajendra
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p. 992 - 998
(2007/10/03)
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- Control of pollen formation
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A method of controlling pollen formation in a hermaphrodite plant, the method comprising applying to the plant, to seed of the plant or to the locus surrounding the plant or seed, a compound of formula: STR1 wherein R1 is hydrogen or alkyl, Rs
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