Experimental solubility profiling of marketed CNS drugs, exploring solubility limit of CNS discovery candidate

Yun W Alelyunas; James R Empfield; Dennis McCarthy; Russell C Spreen; Khanh Bui; Luciana Pelosi-Kilby; Cindy Shen

doi:10.1016/j.bmcl.2010.10.068

Experimental solubility profiling of marketed CNS drugs, exploring solubility limit of CNS discovery candidate

Bioorg Med Chem Lett. 2010 Dec 15;20(24):7312-6. doi: 10.1016/j.bmcl.2010.10.068. Epub 2010 Oct 21.

Authors

Yun W Alelyunas¹, James R Empfield, Dennis McCarthy, Russell C Spreen, Khanh Bui, Luciana Pelosi-Kilby, Cindy Shen

Affiliation

¹ CNS Chemistry and DMPK Department, AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850-5437, USA. yun.alelyunas@astrazeneca.com

PMID: 21055935
DOI: 10.1016/j.bmcl.2010.10.068

Abstract

We determined the experimental solubility of CNS marketed drugs. Of the 98 drugs measured, greater than 90% had solubility >10 μM in pH 7.4 buffer. Only seven drugs had solubility <10 μM. Using these data, we established a solubility criterion to support CNS discovery. The implication of poor solubility with potential safety concerns and undesirable side effects are discussed.

MeSH terms

Central Nervous System Agents / chemistry*
Drug Evaluation, Preclinical
Hydrogen-Ion Concentration
Pharmaceutical Preparations / chemistry*
Solubility

Substances

Central Nervous System Agents
Pharmaceutical Preparations