Chemistry can be defined as the study of matter and the changes it undergoes. You’ll sometimes hear it called the central science because it is the connection between physics and all the other sciences, starting with biology. 112-37-8, Name is Undecanoic acid, molecular formula is , belongs to benzisoxazole compound. In a document, author is Yu, Jian, COA of Formula: C11H22O2.
Elucidation of a Novel Bioactivation Pathway of a 3,4-Unsubstituted Isoxazole in Human Liver Microsomes: Formation of a Glutathione Adduct of a Cyanoacrolein Derivative after Isoxazole Ring Opening
Studies on the biotransformation of isoxazole rings have shown that molecules containing a C3-substituted isoxazole or a 1,2-benzisoxazole can undergo a two-electron reductive ring cleavage to form an imine. In the absence of a C3 substituent, the isoxazole ring opens via deprotonation of the C3 proton followed by N-O bond cleavage to yield an alpha-cyanoenol analog. We report the identification of a novel bioactivation pathway of a 3,4-unsubstituted isoxazole in human liver microsomes. After the enzyme-catalyzed cleavage of the 3,4-unsubstituted isoxazole ring of N-((2-isopropyl-7-methyl-1-oxoisoindolin-5-yl)methyl)isoxazole-5-carboxamide (P) in human liver microsomes, the formed alpha-cyanoenol (M1) condenses with formaldehyde to generate an alpha,beta-unsaturated Michael acceptor intermediate (a cyanoacrolein derivative, VII), which further reacts with the cysteinyl thiol of glutathione to yield a GSH adduct of a cyanoacrolein derivative (M3). The same adduct also is formed when M1, generated in 0.1 N NaOH aqueous solution, reacts with formaldehyde and GSH. (13)C-labeled methanol was used to confirm that methanol from the drug stock solution was oxidized by liver microsomal enzymes to formaldehyde and the carbon atom from methanol was finally incorporated in the corresponding GSH adduct. The formation of isoxazole ring-opened products (M1 and M2) in human liver microsomes is NADPH-dependent. M1 and M2 were found in human liver microsomes preincubated with 1-aminobenzotriazole (1 mM) and NADPH (5 mM) at similar to 10% of the levels found in the samples in the absence of 1-aminobenzotriazole, suggesting that this biotransformation pathway is primarily catalyzed by cytochrome P450. The formation of M3 also was inhibited by 1-aminobenzotriazole at a similar level.
Sometimes chemists are able to propose two or more mechanisms that are consistent with the available data. If a proposed mechanism predicts the wrong experimental rate law, however, the mechanism must be incorrect.Welcome to check out more blogs about 112-37-8, in my other articles. COA of Formula: C11H22O2.
Reference:
Benzisoxazole – Wikipedia,
,Benzisoxazole – an overview | ScienceDirect Topics