Comparisons of pKa and log P values of some carboxylic and phosphonic acids: Synthesis and measurement
Journal Title: The AAPS Journal - Year 2001, Vol 3, Issue 2
Abstract
The changes in the physiochemical properties accompanying the substitution of a phosphonic acid group for a carboxylic acid group on various heterocyclic platforms was determined. A series of low molecular weight heterocyclic carboxylic and phosphonic acids was prepared, and the acid dissociation content (pKa) and log P values were measured potentiometrically. These values were compared to those of substituted benzene phosphonic acids, carboxylic acids, sulfonamides, and tetrazoles. The carboxylic acids included 3 pyrazoles, an imidazole, a triazole, 2 pyrimidine, and 6 aryl compounds. The phosphonic acids included a triazole, 2 pyrazoles, 4 pyrimidines, a thiophene, and 6 aryl compounds. Most of the compounds synthesized had adequate water solubility, although a simple methyl substituent in 2 series had a great effect, completely changing the properties. Log P values for the synthesized carboxylic and phosphonic acid compounds were below 2, and pK1 values for the heterocyclic phosphonic acids were generally 2 to 3 log units lower than for the heterocyclic carboxylic acids.
Authors and Affiliations
Robert G. Franz
Keywords
Related Articles
- EP ID EP682031
- DOI 10.1208/ps030210
- Views 81
- Downloads 0
The cytoplasmic escape and nuclear accumulation of endocytosed and microinjected HPMA copolymers and a basic kinetic study in hep G2 cells
The development of macromolecules as drugs and drug carriers requires knowledge of their fate in cells. To this end, we studied the internalization and subcellular fate of N-(2-hydroxypropyl)methacrylamide (HPMA) copolym...
Nanosystems for simultaneous imaging and drug delivery to T cells
The T-cell response defines the pathogenesis of many common chronic disease states, including diabetes, rheumatoid arthritis, and transplant rejection. Therefore, a diagnostic strategy that visualizes this response can p...
Stability of Amorphous Pharmaceutical Solids: Crystal Growth Mechanisms and Effect of Polymer Additives
We review recent progress toward understanding and enhancing the stability of amorphous pharmaceutical solids against crystallization. As organic liquids are cooled to become glasses, fast modes of crystal growth can eme...
What is the Likelihood of an Active Compound to Be Promiscuous? Systematic Assessment of Compound Promiscuity on the Basis of PubChem Confirmatory Bioassay Data
Compound promiscuity refers to the ability of small molecules to specifically interact with multiple targets, which represents the origin of polypharmacology. Promiscuity is thought to be a widespread characteristic of p...
Is Extrapolation of the Safety and Efficacy Data in One Indication to Another Appropriate for Biosimilars?
CT-P13, the world’s first biosimilar monoclonal antibody to infliximab, was approved for marketing in South Korea for all the six indications of infliximab, which Europe may follow, although the product was teste...