- cGAS ANTAGONIST COMPOUNDS
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Disclosed are novel compounds of Formula (I) that are cGAS antagonists, methods of preparation of the compounds, pharmaceutical compositions comprising the compounds, and their use in medical therapy.
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- Chemoselective zinc/HCl reduction of halogenated β-nitrostyrenes: Synthesis of halogenated dopamine analogues
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A detailed account regarding the synthesis of 2- and 5-halogenated dopamine is given. The key step is a chemoselective reduction of a nitrostyrene by Zn/HCl at 0 °C. These conditions represent a simple, low-cost alternative to reduction by water-sensitive hydride donors and two-step procedures. Under these conditions, aryl fluoride, chloride, and bromide groups are stable. However, iodine undergoes significant reductive dehalogenation.
- Maresh, Justin J.,Ralko, Arthur A.,Speltz, Tom E.,Burke, James L.,Murphy, Casey M.,Gaskell, Zachary,Girel, Joann K.,Terranova, Erin,Richtscheidt, Conrad,Krzeszowiec, Mark
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p. 2891 - 2894
(2015/02/02)
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- Efficient Co(OAc)2-catalyzed aerobic oxidation of EWG-substituted 4-cresols to access 4-hydroxybenzaldehydes
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We reported an efficient ligand-free Co(OAc)2·4H 2O/NaOH/O2/ethylene glycol reaction system that enables selective aerobic oxidation of a wide range of substrates covering 2,6-di-EWG-, 2,3,6-tri-EWG-, 2-EWG-, and 2-EWG-6-EDG-substituted 4-cresols into the corresponding 4-hydroxybenzaldehydes. Based on the experimental investigations and well-defined p-benzoquinone methides, a plausible reaction mechanism was proposed. Considering the simplicity of the procedure and importance of the products, the methodology was expected to become a favorable and practical tool in related benzylic C(sp3)-H functionalization chemistry.
- Jiang, Jian-An,Du, Jia-Lei,Liao, Dao-Hua,Wang, Zhan-Guo,Ji, Ya-Fei
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supporting information
p. 1406 - 1411
(2014/03/21)
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- A highly efficient approach to vanillin starting from 4-cresol
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A highly efficient approach to the famous flavor and fragrance compound vanillin has been developed starting from 4-cresol with the attention focused on improving the sustainability of all the reactions. The approach involves a three-step sequence of the quasi-quantitative selective clean oxybromination of 4-cresol, the high-yield selective aerobic oxidation of 2-bromo-4-cresol, and the quantitative methoxylation of 3-bromo-4-hydroxybenzaldehyde with the recovery of pure methanol. Herein, the pivotal oxidation and methoxylation reactions are logically investigated and developed into two concise methodologies. As a green alternative, the approach holds significant value for the sustainable manufacturing of vanillin. the Partner Organisations 2014.
- Jiang, Jian-An,Chen, Cheng,Guo, Ying,Liao, Dao-Hua,Pan, Xian-Dao,Ji, Ya-Fei
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supporting information
p. 2807 - 2814
(2014/05/06)
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- Cu(OAc)2-catalyzed remote benzylic C(sp3)-H oxyfunctionalization for C=O formation directed by the hindered para-hydroxyl group with ambient air as the terminal oxidant under ligand- and additive-free conditions
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A hindered para-hydroxyl group-directed remote benzylic C(sp3)-H oxyfunctionalization has been developed for the straightforward transformation of 2,6-disubstituted 4-cresols, 4-alkylphenols, 4-hydroxybenzyl alcohols and 4-hydroxybenzyl alkyl ethers into various aromatic carbonyl compounds. The ligand- and additive-free Cu(OAc)2-catalyzed atmospheric oxidation mediated by ethylene glycol unlocks a facile, atom-economical, and environmentally benign C=O formation for the functionalization of primary and secondary benzyl groups. Due to the pharmaceutical importance of 4-hydroxybenzaldehydes and 4-hydroxyphenones, the methodology is expected to be of significant value for both fundamental research and practical applications.
- Jiang, Jian-An,Chen, Cheng,Huang, Jian-Gang,Liu, Hong-Wei,Cao, Song,Ji, Ya-Fei
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supporting information
p. 1248 - 1254
(2014/03/21)
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- The carbonate analogues of 5′-halogenated resiniferatoxin as TRPV1 ligands
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A series of carbonate analogues of 5′-halogenated RTX have been investigated in order to examine the effect of the carbonate group as a linker and the role of halogens in the reversal of activity from agonism to antagonism for rat and human TRPV1 heterologously expressed in Chinese hamster ovary cells. The carbonate analogues showed similar activities to the corresponding RTX derivatives in rat TRPV1 but lower potency in human TRPV1. 5-Halogenation converted the agonists to partial agonists or full antagonists and the extent of antagonism reflected the order of I > Br > Cl > F, with a somewhat greater extent of antagonism for the derivatives of the 4-amino RTX surrogates compared to the corresponding derivatives of RTX itself. The carbonate analogues of I-RTX (60) and 5-bromo-4-amino-RTX (66) were potent and full antagonists with Ki(ant) = 2.23 and 2.46 nM, respectively, for rat TRPV1, which were ca. 5-fold more potent than I-RTX (2) under our conditions. The conformational analysis of the I-RTX-carbonate (60) indicated that its bent conformation was similar to that of I-RTX, consistent with compound 60 and I-RTX showing comparable potent antagonism.
- Lim, Kwang Su,Lee, Hobin,Kim, Sung Eun,Ha, Tae-Hwan,Ann, Jihyae,Son, Karam,Choi, Sun,Sun, Wei,Pearce, Larry V.,Deandrea-Lazarus, Ian A.,Blumberg, Peter M.,Lee, Jeewoo
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p. 233 - 243
(2013/10/01)
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- CEPHEM COMPOUND HAVING CATECHOL GROUP
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A compound of the formula: wherein X is -N=, -CH=, or the like; W is -CH2- or the like; U is -S- or the like; R1 and R2 are each independently hydrogen, halogen, optionally substituted lower alkyl, or the like; R3/su
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Paragraph 0343; 0345
(2013/03/26)
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- Receptor activity and conformational analysis of 5′-halogenated resiniferatoxin analogs as TRPV1 ligands
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A series of 5′-halogenated resiniferatoxin analogs have been investigated in order to examine the effect of halogenation in the A-region on their binding and the functional pattern of agonism/antagonism for rat TRPV1 heterologously expressed in Chinese hamster ovary cells. Halogenation at the 5-position in the A-region of RTX and of 4-amino RTX shifted the agonism of parent compounds toward antagonism. The extent of antagonism was greater as the size of the halogen increased (I > Br > Cl > F) while the binding affinities were similar, as previously observed for our potent agonists. In this series, 5-bromo-4-amino RTX (39) showed very potent antagonism with K i (ant) = 2.81 nM, which was thus 4.5-fold more potent than 5′-iodo RTX, previously reported as a potent TRPV1 antagonist. Molecular modeling analyses with selected agonists and the corresponding halogenated antagonists revealed a striking conformational difference. The 3-methoxy of the A-region in the agonists remained free to interact with the receptor whereas in the case of the antagonists, the compounds assumed a bent conformation, permitting the 3-methoxy to instead form an internal hydrogen bond with the C4-hydroxyl of the diterpene.
- Lim, Kwang Su,Kang, Dong Wook,Kim, Yong Soo,Kim, Myeong Seop,Park, Seul-Gi,Choi, Sun,Pearce, Larry V.,Blumberg, Peter M.,Lee, Jeewoo
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scheme or table
p. 299 - 302
(2011/02/27)
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