Thrombin inhibitors based on [5,5] trans-fused indane lactams.
A series of trans-fused lactams containing the indane nucleus has been prepared. Compound 19 has much enhanced plasma stability compared with its lactone counterpart and shows appreciable in vitro anticoagulant activity.
Pass
M
M
Glaxo Wellcome Research and Development, Stevenage, Herts, United Kingdom. mp8073@glaxowellcome.co.uk
Abu-Rabie
S
S
Baxter
A
A
Conroy
R
R
Coote
S J
SJ
Craven
A P
AP
Finch
H
H
Hindley
S
S
Kelly
H A
HA
Lowdon
A W
AW
McDonald
E
E
Mitchell
W L
WL
Pegg
N A
NA
Procopiou
P A
PA
Ramsden
N G
NG
Thomas
R
R
Walker
D A
DA
Watson
N S
NS
Jhoti
H
H
Mooney
C J
CJ
Tang
C M
CM
Thomas
P J
PJ
Parry
S
S
Patel
C
C
D000925:Anticoagulants / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D007189:Indans / Q000138:chemical synthesis / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007769:Lactams / Q000138:chemical synthesis / Q000494:pharmacology*; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors*
D000925:Anticoagulants; D004791:Enzyme Inhibitors; D007189:Indans; D007769:Lactams; D013917:Thrombin