Structures of three (2R,3S)-4-(arylmethyl)-1-(4-pheny1-3-amino-2-hydroxy- butyl)-piperazine derivatives, potential anti-malarial agents

Wilson Cunico, Claudia R.B. Gomes, William T.A. Harrison, Marcele Moreth, James L. Wardell, Solange M.S.V. Wardell

Research output: Contribution to journalArticle

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Abstract

Selected (2R,3S)-4-(arylmethyl)-1-(4-phenyl-3-substituted-amino-2- hydroxybutyl)piperazine derivatives have anti-malarial activity. The crystal structures of active tert-butyl (2S,3R)-4-(4-benzo[d] [1,3]dioxol-5-ylmethyl) piperazin-1 - yl)-3-hydroxy-1-phenylbutan-2-ylcarbamate, (1), nonactive (2S,3R)-4-(4-nitrobenzyl)piperazin-1 -yl)-3-hydroxy-1 -phenyl-2-(4- toluenesulfonamido)butane, (2), and the active dihydrated salt, (2S,3R)-4-(4-(benzo[d]-[1,3]dioxol-5-ylmethyl)piperazin-1 -yl)-3-hydroxy-1 -phenyl-2-(4-toluenesulfonamido)butane.dihydrogen chloride, (3) are reported. Biological studies indicated the importance of the OH, the benzyl group and the methylene substituents, at the piperazinyl nitrogens, for generating activity. The bond distances in 1 and 2 and the two independent dications of 3, involving these units, do not correlate with activities. However, the molecular conformation adopted by 2, was different from that in 1 and the dications of 3. Both 1 and 2 possess O(1)-H(1)-O(1) and N-HN-0 intermolecular H-bonds: in both cases, the O-H-O hydrogen bonds involve the hydroxyl oxygen atom, while the N-H-O interaction for 1 involves the carbonyl oxygen and that for 2, a sulfonyl oxygen. The dications of 3 are not directly connected by H-bonds, but each independent dication is linked via chloride anions and water molecules into chains. Three-dimensional networks are obtained for 1-3 from intermolecular C-H-π and or intermolecular C-H-O and C-H-π interactions.

Original languageEnglish
Pages (from-to)461-470
Number of pages10
JournalZeitschrift fur Kristallographie
Volume224
Issue number9
DOIs
Publication statusPublished - 1 Sep 2009

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Antimalarials
Butane
Oxygen
butanes
Derivatives
Chlorides
chlorides
oxygen
methylene
Hydroxyl Radical
Anions
Conformations
oxygen atoms
Hydrogen bonds
Nitrogen
Negative ions
Salts
Crystal structure
interactions
hydrogen bonds

Keywords

  • Anti-malarial
  • Crystal structure analysis
  • Hydrogen bonding
  • Piperazine derivatives
  • X-ray diffraction

ASJC Scopus subject areas

  • Materials Science(all)
  • Condensed Matter Physics
  • Inorganic Chemistry

Cite this

Structures of three (2R,3S)-4-(arylmethyl)-1-(4-pheny1-3-amino-2-hydroxy- butyl)-piperazine derivatives, potential anti-malarial agents. / Cunico, Wilson; Gomes, Claudia R.B.; Harrison, William T.A.; Moreth, Marcele; Wardell, James L.; Wardell, Solange M.S.V.

In: Zeitschrift fur Kristallographie, Vol. 224, No. 9, 01.09.2009, p. 461-470.

Research output: Contribution to journalArticle

Cunico, Wilson ; Gomes, Claudia R.B. ; Harrison, William T.A. ; Moreth, Marcele ; Wardell, James L. ; Wardell, Solange M.S.V. / Structures of three (2R,3S)-4-(arylmethyl)-1-(4-pheny1-3-amino-2-hydroxy- butyl)-piperazine derivatives, potential anti-malarial agents. In: Zeitschrift fur Kristallographie. 2009 ; Vol. 224, No. 9. pp. 461-470.
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abstract = "Selected (2R,3S)-4-(arylmethyl)-1-(4-phenyl-3-substituted-amino-2- hydroxybutyl)piperazine derivatives have anti-malarial activity. The crystal structures of active tert-butyl (2S,3R)-4-(4-benzo[d] [1,3]dioxol-5-ylmethyl) piperazin-1 - yl)-3-hydroxy-1-phenylbutan-2-ylcarbamate, (1), nonactive (2S,3R)-4-(4-nitrobenzyl)piperazin-1 -yl)-3-hydroxy-1 -phenyl-2-(4- toluenesulfonamido)butane, (2), and the active dihydrated salt, (2S,3R)-4-(4-(benzo[d]-[1,3]dioxol-5-ylmethyl)piperazin-1 -yl)-3-hydroxy-1 -phenyl-2-(4-toluenesulfonamido)butane.dihydrogen chloride, (3) are reported. Biological studies indicated the importance of the OH, the benzyl group and the methylene substituents, at the piperazinyl nitrogens, for generating activity. The bond distances in 1 and 2 and the two independent dications of 3, involving these units, do not correlate with activities. However, the molecular conformation adopted by 2, was different from that in 1 and the dications of 3. Both 1 and 2 possess O(1)-H(1)-O(1) and N-HN-0 intermolecular H-bonds: in both cases, the O-H-O hydrogen bonds involve the hydroxyl oxygen atom, while the N-H-O interaction for 1 involves the carbonyl oxygen and that for 2, a sulfonyl oxygen. The dications of 3 are not directly connected by H-bonds, but each independent dication is linked via chloride anions and water molecules into chains. Three-dimensional networks are obtained for 1-3 from intermolecular C-H-π and or intermolecular C-H-O and C-H-π interactions.",
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AU - Gomes, Claudia R.B.

AU - Harrison, William T.A.

AU - Moreth, Marcele

AU - Wardell, James L.

AU - Wardell, Solange M.S.V.

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N2 - Selected (2R,3S)-4-(arylmethyl)-1-(4-phenyl-3-substituted-amino-2- hydroxybutyl)piperazine derivatives have anti-malarial activity. The crystal structures of active tert-butyl (2S,3R)-4-(4-benzo[d] [1,3]dioxol-5-ylmethyl) piperazin-1 - yl)-3-hydroxy-1-phenylbutan-2-ylcarbamate, (1), nonactive (2S,3R)-4-(4-nitrobenzyl)piperazin-1 -yl)-3-hydroxy-1 -phenyl-2-(4- toluenesulfonamido)butane, (2), and the active dihydrated salt, (2S,3R)-4-(4-(benzo[d]-[1,3]dioxol-5-ylmethyl)piperazin-1 -yl)-3-hydroxy-1 -phenyl-2-(4-toluenesulfonamido)butane.dihydrogen chloride, (3) are reported. Biological studies indicated the importance of the OH, the benzyl group and the methylene substituents, at the piperazinyl nitrogens, for generating activity. The bond distances in 1 and 2 and the two independent dications of 3, involving these units, do not correlate with activities. However, the molecular conformation adopted by 2, was different from that in 1 and the dications of 3. Both 1 and 2 possess O(1)-H(1)-O(1) and N-HN-0 intermolecular H-bonds: in both cases, the O-H-O hydrogen bonds involve the hydroxyl oxygen atom, while the N-H-O interaction for 1 involves the carbonyl oxygen and that for 2, a sulfonyl oxygen. The dications of 3 are not directly connected by H-bonds, but each independent dication is linked via chloride anions and water molecules into chains. Three-dimensional networks are obtained for 1-3 from intermolecular C-H-π and or intermolecular C-H-O and C-H-π interactions.

AB - Selected (2R,3S)-4-(arylmethyl)-1-(4-phenyl-3-substituted-amino-2- hydroxybutyl)piperazine derivatives have anti-malarial activity. The crystal structures of active tert-butyl (2S,3R)-4-(4-benzo[d] [1,3]dioxol-5-ylmethyl) piperazin-1 - yl)-3-hydroxy-1-phenylbutan-2-ylcarbamate, (1), nonactive (2S,3R)-4-(4-nitrobenzyl)piperazin-1 -yl)-3-hydroxy-1 -phenyl-2-(4- toluenesulfonamido)butane, (2), and the active dihydrated salt, (2S,3R)-4-(4-(benzo[d]-[1,3]dioxol-5-ylmethyl)piperazin-1 -yl)-3-hydroxy-1 -phenyl-2-(4-toluenesulfonamido)butane.dihydrogen chloride, (3) are reported. Biological studies indicated the importance of the OH, the benzyl group and the methylene substituents, at the piperazinyl nitrogens, for generating activity. The bond distances in 1 and 2 and the two independent dications of 3, involving these units, do not correlate with activities. However, the molecular conformation adopted by 2, was different from that in 1 and the dications of 3. Both 1 and 2 possess O(1)-H(1)-O(1) and N-HN-0 intermolecular H-bonds: in both cases, the O-H-O hydrogen bonds involve the hydroxyl oxygen atom, while the N-H-O interaction for 1 involves the carbonyl oxygen and that for 2, a sulfonyl oxygen. The dications of 3 are not directly connected by H-bonds, but each independent dication is linked via chloride anions and water molecules into chains. Three-dimensional networks are obtained for 1-3 from intermolecular C-H-π and or intermolecular C-H-O and C-H-π interactions.

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KW - Crystal structure analysis

KW - Hydrogen bonding

KW - Piperazine derivatives

KW - X-ray diffraction

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