- HETEROCYCLIC PAD4 INHIBITORS
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The disclosure generally relates to substituted heterocyclic compounds of Formula (Ia), which are inhibitors of PAD4, method for preparing these compounds, pharmaceutical compositions comprising these compounds and use of these compounds in the treatment of a disease or a disorder associated with PAD4 enzyme activity.
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Page/Page column 323
(2021/08/20)
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- Design, synthesis, in vitro and in silico studies of 2, 3-diaryl benzofuran derivatives as antitubercular agents
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As a part of our drug discovery program for anti-tubercular agents, a total of seventeen 2, 3-diaryl benzofuran hybrids were designed, synthesized and screened for their anti-tubercular potential against Mycobacterium tuberculosis H37Ra avirulent strain. Out of seventeen, four derivatives showed significant activity against M. tuberculosis H37Ra avirulent strain (ATCC 25177) with MIC value ranging from 12.5 to 50 μg/mL but out of four, one derivative (9E) was significantly active (MIC 12.5 μg/mL), which was further supported by the molecular docking energy (?8.4 kcal/mol) with respect to the first line anti-tubercular drug, isoniazid (?6.2 kcal/mol) on the target Polyketide Synthase-13. All the derivatives were also evaluated for their cytotoxicity against the normal lung cell line L-132 by the MTT assay and no toxicity was observed up to 27.4 μg/mL concentration. This report on the antitubercular potential of benzofuran derivatives may be of great help in anti-tubercular drug development.
- Bhukya, Balakishan,Shukla, Aparna,Chaturvedi, Vinita,Trivedi, Priyanka,Kumar, Shailesh,Khan, Feroz,Negi, Arvind S.,Srivastava, Santosh Kumar
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- Total Synthesis of Isohericenone J via a Stille Coupling Reaction
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The first total synthesis of isohericenone J is reported. Key features of this synthetic strategy are a Friedel-Crafts reaction to construct the isobenzofuranone unit and a Pd-catalyzed Stille coupling reaction for the formation of the C5-C1′ bond, generating the natural product, as well as one of its isomers, in 6.0% overall yield in eight steps. This strategy provides a foundation for the synthesis of challenging isobenzofuranone and isoindolinone-type derivatives.
- Cao, Wei,Chen, Ping,Tang, Yu
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p. 1701 - 1705
(2020/06/08)
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- Enantioselective Synthesis of 3-Fluorochromanes via Iodine(I)/Iodine(III) Catalysis
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The chromane nucleus is common to a plenum of bioactive small molecules where it is frequently oxidized at position 3. Motivated by the importance of this position in conferring efficacy, and the prominence of bioisosterism in drug discovery, an iodine(I)/iodine(III) catalysis strategy to access enantioenriched 3-fluorochromanes is disclosed (up to 7:93 e.r.). In situ generation of ArIF2 enables the direct fluorocyclization of allyl phenyl ethers to generate novel scaffolds that manifest the stereoelectronic gauche effect. Mechanistic interrogation using deuterated probes confirms a stereospecific process consistent with a type IIinv pathway.
- Daniliuc, Constantin G.,Gilmour, Ryan,Neufeld, Jessica,Sarie, Jér?me C.,Thiehoff, Christian
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supporting information
p. 15069 - 15075
(2020/06/17)
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- Enantioselective Electrochemical Lactonization Using Chiral Iodoarenes as Mediators
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The enantioselective electrochemical lactonization of diketo acid derivatives using chiral iodoarenes as redox mediators is reported for the first time. Good to high stereoselectivities are observed in the lactonization and also in intermolecular α-alkoxylations of diketo ester derivatives. This enantioselective process was then adapted to an electrochemical flow microreactor where only small amounts of supporting electrolyte were necessary.
- Gao, Wen-Chao,Xiong, Zi-Yue,Pirhaghani, Shafigh,Wirth, Thomas
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supporting information
p. 276 - 284
(2019/01/04)
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- Enantioselective, Catalytic Vicinal Difluorination of Alkenes
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The enantioselective, catalytic vicinal difluorination of alkenes is reported by II/IIII catalysis using a novel, C2-symmetric resorcinol derivative. Catalyst turnover via in situ generation of an ArIIIIF2 species is enabled by Selectfluor oxidation and addition of an inexpensive HF–amine complex. The HF:amine ratio employed in this process provides a handle for regioselective orthogonality as a function of Br?nsted acidity. Selectivity reversal from the 1,1-difluorination pathway (geminal) to the desired 1,2-difluorination (vicinal) is disclosed (>20:1 in both directions). Validation with electron deficient styrenes facilitates generation of chiral bioisosteres of the venerable CF3 unit that is pervasive in drug discovery (20 examples, up to 94:06 e.r.). An achiral variant of the reaction is also presented using p-TolI (up to >95 % yield).
- Scheidt, Felix,Sch?fer, Michael,Sarie, Jér?me C.,Daniliuc, Constantin G.,Molloy, John J.,Gilmour, Ryan
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supporting information
p. 16431 - 16435
(2018/11/23)
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- Protected fluorescent reagent compounds
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Protected fluorescent reagent compounds and their methods of synthesis are provided. The compounds are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The compounds contain fluorescent dye elements, that allow the compounds to be detected with high sensitivity at desirable wavelengths, binding elements, that allow the compounds to be recognized specifically by target biomolecules, and protective shield elements, that decrease undesirable contacts between the fluorescent dye elements and the bound target biomolecules and that therefore decrease photodamage of the bound target biomolecules by the fluorescent dye elements.
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Page/Page column 295-296
(2018/05/16)
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- MODIFIED NUCLEOTIDE REAGENTS
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Labeled nucleotide analogs comprising at least one avidin protein, at least one dye-labeled compound, and at least one nucleotide compound are provided. The analogs are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The analogs are detectable with high sensitivity at desirable wavelengths. They contain structural components that modulate the interactions of the analogs with DNA polymerase, thus decreasing photodamage and improving the kinetic and other properties of the analogs in sequencing reactions. Also provided are nucleotide and dye-labeled compounds of the subject analogs, as well as intermediates useful in the preparation of the compounds and analogs. Compositions comprising the compounds, methods of synthesis of the intermediates, compounds, and analogs, and mutant DNA polymerases are also provided.
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Paragraph 0228
(2017/11/29)
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- Enantioselective total syntheses of Kuwanon X, Kuwanon Y, and Kuwanol A
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The first enantioselective total syntheses of (a)-kuwanon X, (+)-kuwanon Y, and (+)-kuwanol A have been accomplished by using asymmetric Diels-Alder cycloaddition promoted by chiral VANOL or VAPOL/boron Lewis acid. The biosynthesis-inspired asymmetric Diels-Alder cycloaddition shows high exo selectivity (exo/endo = 13/1), which was unprecedented in the previous total syntheses of related prenylflavonoid Diels-Alder natural products. An acid catalyzed intramolecular ketalization process enabled a biomimetic transformation to construct the polycyclic skeleton of kuwanol A efficiently.
- Gao, Lei,Han, Jianguang,Lei, Xiaoguang
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supporting information
p. 360 - 363
(2016/02/19)
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- MULTIMERIC PROTECTED FLUORESCENT REAGENTS
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Multimeric protected fluorescent reagents and their methods of synthesis are provided. The reagents are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The reagents contain fluorescent dye elements, that allow the compounds to be detected with high sensitivity at desirable wavelengths, binding elements, that allow the compounds to be recognized specifically by target biomolecules, and protective shield elements, that decrease undesirable contacts between the fluorescent dye elements and the bound target biomolecules and that therefore decrease photodamage of the bound target biomolecules by the fluorescent dye elements. The reagents also contain coupling elements connect monomeric compounds into multimeric forms, thereby increasing brightness.
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Paragraph 0281-0282
(2016/09/12)
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- PROTECTED FLUORESCENT REAGENT COMPOUNDS
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Protected fluorescent reagent compounds and their methods of synthesis are provided. The compounds are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The compounds contain fluorescent dye elements, that allow the compounds to be detected with high sensitivity at desirable wavelengths, binding elements, that allow the compounds to be recognized specifically by target biomolecules, and protective shield elements, that decrease undesirable contacts between the fluorescent dye elements and the bound target biomolecules and that therefore decrease photodamage of the bound target biomolecules by the fluorescent dye elements.
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Page/Page column
(2015/02/25)
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- Concise total synthesis of permethylated anigopreissin a, a new benzofuryl resveratrol dimer
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The versatile preparation of permethylated anigopreissin A (1) has been accomplished from methyl 3,5-dihydroxybenzoate. The key steps of the synthesis are sequential Sonogashira and Suzuki cross-couplings for the construction of the 2,3-diarylbenzo[b]furan moiety and Wittig olefination for the introduction of the styryl group.
- Chiummiento, Lucia,Funicello, Maria,Lopardo, Maria Teresa,Lupattelli, Paolo,Choppin, Sabine,Colobert, Francoise
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experimental part
p. 188 - 192
(2012/01/15)
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- Rhodium-catalyzed regioselective carboacylation of olefins: A C-C bond activation approach for accessing fused-ring systems
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Cut and sew: A rhodium-catalyzed regioselective carboacylation reaction of benzocyclobutenones was developed (see scheme). Directed by the pendant olefins, the C1-C2 bond is selectively cleaved rather than the C1-C8 bond. Subsequent alkene insertion leads to complex fused-ring systems. This reaction provides facile access to natural-product-like polycyclic structures in a chemoselective and atom-economic fashion. Copyright
- Xu, Tao,Dong, Guangbin
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scheme or table
p. 7567 - 7571
(2012/09/22)
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- Sonogashira reactions with propyne: Facile synthesis of 4-Hydroxy-2-methylbenzofurans from Iodoresorcinols
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The Sonogashira reaction of terminal alkynes and ortho-halophe- nols with subsequent cyclization is a well-precedented method for the synthesis of substituted benzofurans. Here we describe the extension of this method to the coupling of 2-iodoresorcinols and terminal alkynes, including propyne, to give 4-hydroxy-2-substi- tuted benzofurans. In particular, we describe the screening, method development, and scaleup of the reaction with propyne using standard hydrogenation equipment.
- Berliner, Martin A.,Cordi, Eric M.,Dunetz, Joshua R.,Price, Kristin E.
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experimental part
p. 180 - 187
(2010/04/28)
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