Solution and solid state properties of a set of procaine and procainamide derivatives

OLIVERA, ME; RIGO, MVR; CHATTAH, AK; LEVSTEIN, PR; BASCHINI, M; MANZO, RH

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2003 vol. 18 p. 337 - 337

font size="2"> A set of potential Class III antiarrhythmic agents of structure p-HOOC-R-CO-NH-C6H4-CO-X-C2H5-N(C2H5)(2) were isolated as crystalline solids of the amide and ester derivatives, I: succinylprocainamide (X=-NH-, R=-C2H4-); II: succinylprocaine (X=-O-, R=-C2H4-); III: maleylprocainamide (X=-NH-, R=-C2H2-) and IV: maleylprocaine (X=-O-, R=-C2H2-). Although compounds I-IV exhibit similar solution properties (i.e. acid-base speciation, with zwitterionic (+-) to neutral (00) form ratios higher than 10(4)), aqueous solubility of -NH- derivatives is significantly higher than that of -O- derivatives and also, solvent effects on solubility (i.e. the change of water by ethanol) is clearly different in both series. Solution and solid-state properties of I-IV were characterized to account for the observed differences. Results indicate that procainamide derivatives I and III crystallizes as (+-)s but procaine derivatives II and IV as (00)(s), Besides, I is anhydrous but II-IV are