Synthetic [5,5] trans-fused indane lactones as inhibitors of thrombin.
Synthesis of trans-fused lactones containing the indane nucleus has resulted in a series of potent acylating inhibitors of thrombin. As an example compound 11e has an apparent second order rate constant of 11 x 10(6) M(-1)sec(-1) for the inhibition of thrombin. The anticoagulant activity of these compounds is discussed.
Pass
M
M
Glaxo Wellcome Research and Development, Stevenage, Herts, United Kingdom. mp8073@glaxowellcome.co.uk
Bolton
R E
RE
Coote
S J
SJ
Finch
H
H
Hindley
S
S
Lowdon
A
A
McDonald
E
E
McLaren
J
J
Owen
M
M
Pegg
N A
NA
Mooney
C J
CJ
Tang
C M
CM
Parry
S
S
Patel
C
C
D000925:Anticoagulants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000991:Antithrombins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007189:Indans / Q000737:chemistry*; D007700:Kinetics; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010314:Partial Thromboplastin Time
D000925:Anticoagulants; D000991:Antithrombins; D007189:Indans; D007783:Lactones