- Imidazoline- and Benzamidine-Based Trypanosome Alternative Oxidase Inhibitors: Synthesis and Structure-Activity Relationship Studies
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The trypanosome alternative oxidase (TAO), a mitochondrial enzyme involved in the respiration of the bloodstream form trypomastigotes of Trypanosoma brucei, is a validated drug target against African trypanosomes. Earlier series of TAO inhibitors having a 2,4-dihydroxy-6-methylbenzoic acid scaffold ( head ) and a triphenylphosphonium or quinolin-1-ium cation as a mitochondrion-targeting group ( tail ) were shown to be nanomolar inhibitors in enzymatic and cellular assays. We investigated here the effect of different mitochondrion-targeting cations and other scaffold modifications on the in vitro activity of this class of inhibitors. Low micromolar range activities were obtained, and the structure-activity relationship studies showed that modulation of the tail region with polar substituents is generally detrimental to the enzymatic and cellular activity of TAO inhibitors.
- Cisneros, David,Cueto-Diáz, Eduardo J.,Medina-Gil, Tania,Chevillard, Rebecca,Bernal-Fraile, Teresa,López-Sastre, Ramón,Aldfer, Mustafa M.,Ungogo, Marzuq A.,Elati, Hamza A. A.,Arai, Natsumi,Otani, Momoka,Matsushiro, Shun,Kojima, Chiaki,Ebiloma, Godwin U.,Shiba, Tomoo,De Koning, Harry P.,Dardonville, Christophe
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p. 312 - 318
(2022/02/14)
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- From Anilines to Aryl Ethers: A Facile, Efficient, and Versatile Synthetic Method Employing Mild Conditions
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We have developed a simple and direct method for the synthesis of aryl ethers by reacting alcohols/phenols (ROH) with aryl ammonium salts (ArNMe3+), which are readily prepared from anilines (ArNR′2, R′=H or Me). This reaction proceeds smoothly and rapidly (within a few hours) at room temperature in the presence of a commercially available base, such as KOtBu or KHMDS, and has a broad substrate scope with respect to both ROH and ArNR′2. It is scalable and compatible with a wide range of functional groups.
- Wang, Dong-Yu,Yang, Ze-Kun,Wang, Chao,Zhang, Ao,Uchiyama, Masanobu
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p. 3641 - 3645
(2018/03/13)
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- NOVEL ARYLAMIDINE DERIVATIVE OR SALT THEREOF
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An arylamidine derivative represented by a general formula described below or a salt thereof has an excellent antifungal action and high safety, and it is useful as an antifungal agent with good pharmacokinetics and pharmacodynamic properties: wherein X represents an unsubstituted or substituted lower alkylene or alkenylene group; G1 represents an oxygen atom, a sulfur atom, or an imino group; G2 represents a carbon atom or a nitrogen atom; Ra represents at least one group selected from the group consisting of a hydrogen atom, a halogen atom, and unsubstituted or substituted alkyl, cycloalkyl and alkoxy groups; R1 represents an unprotected or protected or unsubstituted or substituted amidino group; and R2 represents a substituted amino or substituted cyclic amino group, or the like.
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- Bispidine compounds useful in the treatment of cardiac arrythmias
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There is provided compounds of formula I, 1 wherein R1, R2, R3, R4, R5, R6, R7, R41, R42, R43 R44, R45, R46, A and B have meanings given in the description, which are useful in the prophylaxis and in the treatment of arrhythmias, in particular atrial and ventricular arrhythmias.
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