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.
Glaxo Wellcome Research and Development, Stevenage, Herts, United Kingdom. mp8073@glaxowellcome.co.uk
M
M
Pass
S
S
Abu-Rabie
A
A
Baxter
R
R
Conroy
S J
SJ
Coote
A P
AP
Craven
H
H
Finch
S
S
Hindley
H A
HA
Kelly
A W
AW
Lowdon
E
E
McDonald
W L
WL
Mitchell
N A
NA
Pegg
P A
PA
Procopiou
N G
NG
Ramsden
R
R
Thomas
D A
DA
Walker
N S
NS
Watson
H
H
Jhoti
C J
CJ
Mooney
C M
CM
Tang
P J
PJ
Thomas
S
S
Parry
C
C
Patel
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