FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2998839103> ?p ?o ?g. }

• W2998839103 endingPage "113796" @default.
• W2998839103 startingPage "113796" @default.
• W2998839103 abstract "Basic amine substituents provide several pharmacokinetic benefits relative to acidic and neutral functional groups, and have been extensively utilized as substituents of choice in drug design. On occasions, basic amines have been associated with off-target pharmacology via interactions with aminergic G-protein coupled receptors, ion-channels, kinases, etc. Structural features associated with the promiscuous nature of basic amines have been well-studied, and can be mitigated in a preclinical drug discovery environment. In addition to the undesirable secondary pharmacology, α-carbon oxidation of certain secondary or tertiary cycloalkyl amines can generate electrophilic iminium and aldehyde metabolites, potentially capable of covalent adduction to proteins or DNA. Consequently, cycloalkyl amines have been viewed as structural alerts (SAs), analogous to functional groups such as anilines, furans, thiophenes, etc., which are oxidized to reactive metabolites that generate immunogenic haptens by covalently binding to host proteins. Detailed survey of the literature, however, suggests that cases where preclinical or clinical toxicity has been explicitly linked to the metabolic activation of a cycloalkyl amine group are extremely rare. Moreover, there is a distinct possibility for the formation of electrophilic iminium/amino-aldehyde metabolites with numerous cycloalkyl amine-containing marketed drugs, since stable ring cleavage products have been characterized as metabolites in human mass balance studies. In the present work, a critical analysis of the evidence for and against the role of iminium ions/aldehydes as mediators of toxicity is discussed with a special emphasis on often time overlooked detoxication pathways of these reactive species to innocuous metabolites." @default.
• W2998839103 created "2020-01-23" @default.
• W2998839103 creator A5029214116 @default.
• W2998839103 creator A5090896472 @default.
• W2998839103 date "2020-04-01" @default.
• W2998839103 modified "2023-10-16" @default.
• W2998839103 title "Is there enough evidence to classify cycloalkyl amine substituents as structural alerts?" @default.
• W2998839103 cites W1561510118 @default.
• W2998839103 cites W1932664257 @default.
• W2998839103 cites W1978737312 @default.
• W2998839103 cites W1979392432 @default.
• W2998839103 cites W1982712749 @default.
• W2998839103 cites W1987144475 @default.
• W2998839103 cites W1990364993 @default.
• W2998839103 cites W1991853425 @default.
• W2998839103 cites W1992933057 @default.
• W2998839103 cites W1996247719 @default.
• W2998839103 cites W1999587831 @default.
• W2998839103 cites W2002378649 @default.
• W2998839103 cites W2004747801 @default.
• W2998839103 cites W2005087793 @default.
• W2998839103 cites W2020583848 @default.
• W2998839103 cites W2022911097 @default.
• W2998839103 cites W2023922443 @default.
• W2998839103 cites W2025703773 @default.
• W2998839103 cites W2027202120 @default.
• W2998839103 cites W2029390365 @default.
• W2998839103 cites W2029703893 @default.
• W2998839103 cites W2029951339 @default.
• W2998839103 cites W2033935070 @default.
• W2998839103 cites W2035160863 @default.
• W2998839103 cites W2042692588 @default.
• W2998839103 cites W2049814406 @default.
• W2998839103 cites W2053324777 @default.
• W2998839103 cites W2055619480 @default.
• W2998839103 cites W2055659752 @default.
• W2998839103 cites W2058073836 @default.
• W2998839103 cites W2059730101 @default.
• W2998839103 cites W2061209838 @default.
• W2998839103 cites W2064798207 @default.
• W2998839103 cites W2066046379 @default.
• W2998839103 cites W2075221169 @default.
• W2998839103 cites W2075285597 @default.
• W2998839103 cites W2077494042 @default.
• W2998839103 cites W2077696992 @default.
• W2998839103 cites W2079127064 @default.
• W2998839103 cites W2079292156 @default.
• W2998839103 cites W2086319630 @default.
• W2998839103 cites W2099126469 @default.
• W2998839103 cites W2106195907 @default.
• W2998839103 cites W2106551844 @default.
• W2998839103 cites W2115147225 @default.
• W2998839103 cites W2117819606 @default.
• W2998839103 cites W2123226593 @default.
• W2998839103 cites W2124201657 @default.
• W2998839103 cites W2124524221 @default.
• W2998839103 cites W2126345597 @default.
• W2998839103 cites W2130794506 @default.
• W2998839103 cites W2136456223 @default.
• W2998839103 cites W2138045215 @default.
• W2998839103 cites W2145557630 @default.
• W2998839103 cites W2151514200 @default.
• W2998839103 cites W2167182965 @default.
• W2998839103 cites W2168795101 @default.
• W2998839103 cites W2168811254 @default.
• W2998839103 cites W2169463741 @default.
• W2998839103 cites W2176608409 @default.
• W2998839103 cites W2263138261 @default.
• W2998839103 cites W2314375540 @default.
• W2998839103 cites W2314919359 @default.
• W2998839103 cites W2318641107 @default.
• W2998839103 cites W2326139172 @default.
• W2998839103 cites W2344214880 @default.
• W2998839103 cites W2395237281 @default.
• W2998839103 cites W2397695087 @default.
• W2998839103 cites W2536091639 @default.
• W2998839103 cites W2550782658 @default.
• W2998839103 cites W2565073516 @default.
• W2998839103 cites W2595030994 @default.
• W2998839103 cites W2607267818 @default.
• W2998839103 cites W2661763774 @default.
• W2998839103 cites W2707449957 @default.
• W2998839103 cites W2734616715 @default.
• W2998839103 cites W2753925638 @default.
• W2998839103 cites W2767561893 @default.
• W2998839103 cites W2775576435 @default.
• W2998839103 cites W2783510200 @default.
• W2998839103 cites W2803934692 @default.
• W2998839103 cites W2884078845 @default.
• W2998839103 cites W2901139388 @default.
• W2998839103 cites W2903792109 @default.
• W2998839103 cites W2945719805 @default.
• W2998839103 doi "https://doi.org/10.1016/j.bcp.2020.113796" @default.
• W2998839103 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31926938" @default.
• W2998839103 hasPublicationYear "2020" @default.
• W2998839103 type Work @default.
• W2998839103 sameAs 2998839103 @default.
• W2998839103 citedByCount "9" @default.

• next