7-Azabicycloheptane carboxylic acid: a proline replacement in a boroarginine thrombin inhibitor.
[formula: see text] The synthesis of thrombin inhibitor 3, which incorporates conformationally constrained 7-azabicycloheptane carboxylic acid (1) as a proline replacement, is described. The inhibition constant (Ki(thrombin) = 2.9 nM) indicates that 1 is a reasonable replacement of proline in the formation of a beta-turn tripeptide mimetic.
Han
W
W
Department of Chemical and Physical Sciences, DuPont Pharmaceuticals Company, Experimental Station, Wilmington, Delaware 19880, USA. wei.han@dupontpharma.com
Pelletier
J C
JC
Mersinger
L J
LJ
Kettner
C A
CA
Hodge
C N
CN
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D011392:Proline / Q000737:chemistry*; D013237:Stereoisomerism; D013917:Thrombin / Q000037:antagonists & inhibitors
C410425:7-Azabicycloheptane carboxylic acid; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002264:Carboxylic Acids; D011392:Proline; D013917:Thrombin