Synthesis of N-acridinyl-N'-alkylguanidines: dramatic influence of amine to guanidine replacement on the physicochemical properties

Walid Zeghida; Julien Debray; Carine Michel; Anne Milet; Pascal Dumy; Martine Demeunynck

doi:10.1016/j.bmcl.2008.07.100

Synthesis of N-acridinyl-N'-alkylguanidines: dramatic influence of amine to guanidine replacement on the physicochemical properties

Bioorg Med Chem Lett. 2008 Sep 1;18(17):4779-82. doi: 10.1016/j.bmcl.2008.07.100. Epub 2008 Jul 30.

Authors

Walid Zeghida¹, Julien Debray, Carine Michel, Anne Milet, Pascal Dumy, Martine Demeunynck

Affiliation

¹ Département Chimie Moléculaire, UMR5250 CNRS-University Joseph Fourier, BP53, 38041 Grenoble Cedex 9, France.

PMID: 18701277
DOI: 10.1016/j.bmcl.2008.07.100

Abstract

Transformation of aminoacridines into N-acridinyl-N'-alkylguanidines is described. The chosen procedure allows introduction of pendent substituents (exemplified by N,N-dimethylaminopropyl chain) into key acridinyl thioureas, thus opening the way to structural diversity. Spectroscopic study and pK(a) determination show that the presence of the strongly basic guanidine has a dramatic influence on the ionization of the acridine nucleus by lowering the pk(a) value down to 4.49.

Publication types

Comparative Study

MeSH terms

Amines / chemistry*
Aminoacridines / chemistry*
Chemical Phenomena
Chemistry, Physical*
Drug Design
Guanidines / chemical synthesis*
Guanidines / chemistry*
Hydrogen-Ion Concentration
Spectrophotometry, Ultraviolet
Structure-Activity Relationship
Thermodynamics

Substances

Amines
Aminoacridines
Guanidines