156022-15-0Relevant articles and documents
ML212: A small-molecule probe for investigating fluconazole resistance mechanisms in Candida albicans
Youngsaye, Willmen,Hartland, Cathy L.,Morgan, Barbara J.,Ting, Amal,Nag, Partha P.,Vincent, Benjamin,Mosher, Carrie A.,Bittker, Joshua A.,Dandapani, Sivaraman,Palmer, Michelle,Whitesell, Luke,Lindquist, Susan,Schreiber, Stuart L.,Munoz, Benito
supporting information, p. 1501 - 1507 (2013/10/22)
The National Institutes of Health Molecular Libraries and Probe Production Centers Network (NIH-MLPCN) screened >300,000 compounds to evaluate their ability to restore fluconazole susceptibility in resistant Candida albicans isolates. Additional counter screens were incorporated to remove substances inherently toxic to either mammalian or fungal cells. A substituted indazole possessing the desired bioactivity profile was selected for further development, and initial investigation of structure-activity relationships led to the discovery of ML212.
Diminished reactivity of ortho-substituted phenacyl bromides toward nucleophilic displacement
Kalendra, Diane M.,Sickles, Barry R.
, p. 1594 - 1596 (2007/10/03)
A systematic increase of substitution rates by tert-butylamine on α-bromopropiophenones is observed with meta or para substituents with increasing electron-withdrawing ability (k x 103 L M-1 min-1 = 12.7 (p-CH3), 15.7 (o-F), 20.5 (H), 20.0 (p-Cl), 23.6 (m-Cl), 27.3 (p-CF3)). Within an ortho-substituted series, the reactivities decrease (k x 103 L M-1 min-1 = 7.64 (o-OCH3), 5.31 (o-CH3), 2.85 (o-Cl), 2.40 (o-CF3)). Ortho-substitution results occur from rotational barrier effects and an Aδσ + Bδσ + repulsion. The major bonding contribution between reaction and α-substituent centers (A-B) is only the σ bond. When π bonding is allowed between A and B (meta/para-substitution), delocalization and stabilization of the reacting center occurs.
