Configurationally restricted bismacrocyclic CXCR4 receptor antagonists.
A zinc(II) containing configurationally restricted analogue of bismacrocyclic cyclam-type CXCR4 chemokine receptor antagonists has been synthesized and shown to adopt only one configuration in solution. The single crystal X-ray structure reveals favorable binding to acetate via a bidentate chelation that can be related to the proposed interaction with aspartate on the receptor protein surface. The zinc(II) complex is highly active against HIV infection in vitro.
Valks
Gina C
GC
Department of Chemistry and Clinical Biosciences Institute, University of Hull, Hull, HU6 7RX, United Kingdom.
McRobbie
Graeme
G
Lewis
Elizabeth A
EA
Hubin
Timothy J
TJ
Hunter
Tina M
TM
Sadler
Peter J
PJ
Pannecouque
Christophe
C
De Clercq
Erik
E
Archibald
Stephen J
SJ
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001596:Benzylamines; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D000080027:Cyclams; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D047029:Lactams, Macrocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D019345:Zinc Acetate / Q000737:chemistry*
C515131:5,5'-(1,4-phenylenebis(methylene))bis(1,5,8,12-tetraazabicyclo(10.2.2)hexadecane); D019380:Anti-HIV Agents; D001596:Benzylamines; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002614:Chelating Agents; D000080027:Cyclams; D006571:Heterocyclic Compounds; D047029:Lactams, Macrocyclic; D009942:Organometallic Compounds; D019718:Receptors, CXCR4; D019345:Zinc Acetate; C088327:plerixafor