2461-35-0Relevant articles and documents
Cytochrome p450 can epoxidize an oxepin to a reactive 2,3-epoxyoxepin intermediate: Potential insights into metabolic ring-opening of benzene
Cote, Noah A.,Fitzgerald, Ryan W.,Greenberg, Arthur,Weaver-Guevara, Holly M.
, (2020)
Dimethyldioxirane epoxidizes 4,5-benzoxepin to form the reactive 2,3-epoxyoxepin intermediate followed by very rapid ring-opening to an o-xylylene that immediately isomerizes to the stable product 1H-2-benzopyran-1-carboxaldehyde. The present study demonstrates that separate incubations of 4,5-benzoxepin with three cytochrome P450 isoforms (2E1, 1A2, and 3A4) as well as pooled human liver microsomes (pHLM) also produce 1H-2-benzopyran-1-carboxaldehyde as the major product, likely via the 2,3-epoxyoxepin. The reaction of 4,5-benzoxepin with cerium (IV) ammonium nitrate (CAN) yields a dimeric oxidized molecule that is also a lesser product of the P450 oxidation of 4,5-benzoxepin. The observation that P450 enzymes epoxidize 4,5-benzoxepin suggests that the 2,3-epoxidation of oxepin is a major pathway for the ring-opening metabolism of benzene to muconaldehyde.
Asymmetric synthesis of azolium-based 1,2,3,4-tetrahydronaphthalen-2-ols through lipase-catalyzed resolutions
Méndez-Sánchez, Daniel,Ríos-Lombardía, Nicolás,Gotor, Vicente,Gotor-Fernández, Vicente
, p. 760 - 767 (2015)
Abstract A series of racemic trans-1,2,3,4-tetrahydronaphthalen-2-ols bearing an azole nucleus at the C-1 or C-3 position has been synthesized by ring opening reactions of the corresponding epoxides using imidazole or 1,2,4-triazole. The kinetic resolutions of these racemates were undertaken through transesterification processes, finding good levels of activities and high to excellent enantiodiscrimination values for the Pseudomonas cepacia lipase immobilized on a ceramic carrier. Investigations into the optimum reaction conditions were carried out by consideration of different organic solvents, temperatures, enzyme loadings, and reaction times. With the best conditions in hand, the experiments were later carried out toward the resolution of the related racemic cis-alcohols, which were previously obtained through a Mitsunobu and deprotection chemical sequence from the trans-stereoisomers.
Crystalline Hetero-Stereocomplexed Polycarbonates Produced from Amorphous Opposite Enantiomers Having Different Chemical Structures
Liu, Ye,Wang, Meng,Ren, Wei-Min,Xu, Yue-Chao,Lu, Xiao-Bing
, p. 7042 - 7046 (2015)
Abstract Stereocomplexation is the stereoselective interaction between two opposite enantiomeric polymers through an interlocked orderly assembly. Most studies focus on the stereocomplex formation from the crystalline opposite enantiomers having the identical structure; nevertheless, rare examples were reported regarding the crystalline stereocomplexes from enantiomeric polymers having different chemical structures. Herein we show a strategy for polymer orderly assembly through the formation of crystalline hetero-stereocomplexed polymeric materials by the cocrystallization of amorphous isotactic polycarbonates with different chemical structures and opposite configurations. The behaviors in the crystalline state are significantly different from that of the component enantiomeric polymers or their homo-stereocomplexes. This study is expected to open up a new way to prepare various semicrystalline materials having a wide variety of physical properties and degradability. Mixed enantiomers: A unique strategy for polymer assembly was demonstrated through the formation of crystalline hetero-stereocomplexed polymeric materials by the cocrystallization of amorphous isotactic polycarbonates with opposite configurations and different chemical structures. This study is expected to open up a new way to prepare various semicrystalline materials with a wide variety of physical properties and degradability.
Self-Masked Aldehyde Inhibitors: A Novel Strategy for Inhibiting Cysteine Proteases
Li, Linfeng,Chenna, Bala C.,Yang, Kai S.,Cole, Taylor R.,Goodall, Zachary T.,Giardini, Miriam,Moghadamchargari, Zahra,Hernandez, Elizabeth A.,Gomez, Jana,Calvet, Claudia M.,Bernatchez, Jean A.,Mellott, Drake M.,Zhu, Jiyun,Rademacher, Andrew,Thomas, Diane,Blankenship, Lauren R.,Drelich, Aleksandra,Laganowsky, Arthur,Tseng, Chien-Te K.,Liu, Wenshe R.,Wand, A. Joshua,Cruz-Reyes, Jorge,Siqueira-Neto, Jair L.,Meek, Thomas D.
, p. 11267 - 11287 (2021/08/16)
Cysteine proteases comprise an important class of drug targets, especially for infectious diseases such as Chagas disease (cruzain) and COVID-19 (3CL protease, cathepsin L). Peptide aldehydes have proven to be potent inhibitors for all of these proteases. However, the intrinsic, high electrophilicity of the aldehyde group is associated with safety concerns and metabolic instability, limiting the use of aldehyde inhibitors as drugs. We have developed a novel class of self-masked aldehyde inhibitors (SMAIs) for cruzain, the major cysteine protease of the causative agent of Chagas disease - Trypanosoma cruzi. These SMAIs exerted potent, reversible inhibition of cruzain (Ki? = 18-350 nM) while apparently protecting the free aldehyde in cell-based assays. We synthesized prodrugs of the SMAIs that could potentially improve their pharmacokinetic properties. We also elucidated the kinetic and chemical mechanism of SMAIs and applied this strategy to the design of anti-SARS-CoV-2 inhibitors.
INHINITORS OF GLI1 AS THERAPEUTIC AGENTS
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Paragraph 0177, (2020/06/10)
This disclosure relates to compounds, pharmaceutical compositions comprising them, and methods of using the compounds and compositions for treating diseases related to glioma- associated oncogene (Gli) expression. More particularly, this disclosure relate