TY - JOUR
T1 - Structures of three (2R,3S)-4-(arylmethyl)-1-(4-pheny1-3-amino-2-hydroxy- butyl)-piperazine derivatives, potential anti-malarial agents
AU - Cunico, Wilson
AU - Gomes, Claudia R.B.
AU - Harrison, William T.A.
AU - Moreth, Marcele
AU - Wardell, James L.
AU - Wardell, Solange M.S.V.
PY - 2009/9/1
Y1 - 2009/9/1
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.
KW - Anti-malarial
KW - Crystal structure analysis
KW - Hydrogen bonding
KW - Piperazine derivatives
KW - X-ray diffraction
UR - http://www.scopus.com/inward/record.url?scp=70350153289&partnerID=8YFLogxK
U2 - 10.1524/zkri.2009.1161
DO - 10.1524/zkri.2009.1161
M3 - Article
AN - SCOPUS:70350153289
SN - 0044-2968
VL - 224
SP - 461
EP - 470
JO - Zeitschrift fur Kristallographie
JF - Zeitschrift fur Kristallographie
IS - 9
ER -