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Second basic pKa: An overlooked parameter in predicting phospholipidosis-inducing potential of diamines.

Authors
  • Sakai, Hiroki1
  • Inoue, Hidekazu2
  • Murata, Kenji2
  • Toba, Tetsuya2
  • Takemoto, Naohiro2
  • Matsumoto, Takahiro2
  • Kawabata, Takeo3
  • 1 Asubio Pharma Co., Ltd., 6-4-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. Electronic address: [email protected] , (Japan)
  • 2 Asubio Pharma Co., Ltd., 6-4-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. , (Japan)
  • 3 Institute for Chemical Research, Kyoto University Uji, Kyoto 611-0011, Japan. , (Japan)
Type
Published Article
Journal
Bioorganic & medicinal chemistry letters
Publication Date
May 01, 2020
Volume
30
Issue
9
Pages
126933–126933
Identifiers
DOI: 10.1016/j.bmcl.2019.126933
PMID: 32044185
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

In this paper, we present the phospholipidosis-inducing potential (PLIP) of forty fragment-sized diamines derived from N-benzyl-4-(methylamino)piperidine and discuss the relationship between their PLIP and the physicochemical properties. Our results demonstrate that the previously reported methods are not suitable for predicting the PLIP of fragment-sized diamines; the second basic pKa can distinguish PLIP-positive diamines from PLIP-negative diamines more accurately than ClogP or most basic pKa. To the best of our knowledge, this is the first report describing the relationship between PLIP and second basic pKa. Copyright © 2019 Elsevier Ltd. All rights reserved.

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