Synthesis and in vitro anticoagulant activity of 3-(1H-
Received: 21 October 2014 / Accepted: 9 January 2015 / Published online: 6 February 2015
Ó Springer Science+Business Media Dordrecht 2015
Abstract A series of 3-(1H-imidazo[4,5-c]pyridin-2-yl)-1,5-diarylpyridin-2(1H)-
one derivatives were designed and synthesized as potential anticoagulant agents.
The 1,5-diarylpyridin-2(1H)-ones, key intermediates of these anticoagulants, were
synthesized by a simple reaction of 2-aryl vinamidinium salts with ethyl 3-oxo-3-
(arylamino)propanoate derivatives. The prothrombin time in canine blood showed
that amino and hydroxymethyl derivatives therein possess obvious anticoagulant
abilities (PT = 17.07 s).
Keywords Anticoagulant Á Factor VIIa Á Prothrombin time Á Pyridin-2(1H)-one Á
[3 ? 3] annulation
Thrombosis-related diseases, such as myocardial infarction, stoke, deep venous
thrombosis (DVT), and pulmonary embolism (PE), are the principal causes of
mortality and morbidity in the developed world [1, 2]. Therefore, the inhibition of
thrombus formation is important to prevent these diseases.
Coagulation factor VIIa (FVIIa) belongs to the family of trypsin-like serine
proteases . The complex of tissue factor (TF) and factor VIIa (TF/FVIIa) plays a
‘‘trigger’’ role in the extrinsic pathway of blood coagulation cascade [4–6].
Therefore, inhibition of FVIIa may be an effective method for the prevention and
J. Yang Á Y. Chen (&)
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering,
Southeast University, Nanjing 210096, Jiangsu, People’s Republic of China
G. Su Á Y. Ren
Nanjing Zhongrui Pharmaceutical Co., Ltd., Nanjing 211100, Jiangsu, People’s Republic of China
Res Chem Intermed (2015) 41:8773–8783