Thromboembolism is an important cause of morbidity and mortality. It occurs when a blood clot breaks free and is carried by the blood stream to obstruct a blood vessel at another site. Thromboembolic disease includes venous thromboembolism, for example deep vein thrombosis or pulmonary embolism, arterial thrombosis, stroke and myocardial infarction.
Thromboembolic diseases may be treated using anticoagulants. One approach has been to target the inhibition of factor XIa (FXIa). Factor XIa is a plasma serine protease involved in the regulation of blood coagulation. Factor XIa is an activated form of factor XI, which is activated by factor XIIa, thrombin, and it is also autocatalytic. FXIa is a component of the “contact pathway” and activates factor IX by selectively cleaving arg-ala and arg-val peptide bonds. Factor IXa, in turn, activates factor X. The safety of this target is supported by the observations that FXI deficiency in humans (hemophilia C) results in a mild bleeding disorder. In addition to this, the efficacy and side effects of this target have been shown using experimental thrombosis and bleeding models in mice lacking FXI, and in baboons and rabbits treated with anti-FXI neutralizing antibodies. These results suggest that FXIa inhibitors will show a potent anti-thrombotic effect without bleeding. Therefore, factor XIa is an attractive target for anti-thrombotic therapy without the side effect of bleeding.
It has been described in Patent literature 1 that compound of formula (A):

wherein AA represents a 5- to 12-membered heterocycle, etc.; L1A represents —CH═CH—, etc.; R11A represents benzyl, etc.; MA represents imidazolyl, etc; are useful as selective inhibitors of factor XIa or dual inhibitors of FXIa and plasma kallikrein.
Furthermore, it has been described in Patent literature 2 that a compound of formula (B-I):

wherein AB represents a 5- to 12-membered heterocycle, etc.; L1B represents —CH═CH—, etc.; R11B represents benzyl, etc.; R3B represents phenyl, etc.; R4B represents chlorine, etc.; R8aB represents hydrogen, etc; or formula (B-II):

wherein MB represents pyridyl, etc.; and the other symbols have the same meanings as described above; inhibit factor XIa and/or plasma kallikrein.
Furthermore, it has been described in Patent literature 3 that a compound of formula (C):

wherein DC represents C10 cycloalkyl or 10-membered heterocycloalkyl, etc.; -LC-EC-GC-JC-represents —C—C—C—C, etc.; R3C represents hydrogen, etc.; R4C represents mono- or bicyclic heteroaryl, etc.; R5C represents hydrogen, etc.; R13C represents hydrogen, etc.; MC represents phenyl, etc.; are useful as inhibitors of factor Xa.
Furthermore, it has been described in Patent literature 4 that a compound of formula (D):

wherein ring BD represents phenyl, etc.; WD represents —NH2, etc.; Z1D represents 5 to 7-membered monocyclic, etc.; LD represents —NH—CO—, etc.; R1D and R2D independently represents (i) hydrogen or (ii) are taken together to form a five-to-seven membered fully saturated heterocycle, etc.; R5D and R6D independently represents hydrogen, etc.; R7D represents —COOH, etc.; R8D represents hydrogen, etc.; (R27D)mD represents —COOH, etc.; are useful as inhibitors of factor VIIa, factor IXa, factor FXIa, tryptase, and urokinase.
Furthermore, it has been described in Patent literature 5 that a compound of formula (E):

wherein AE represents aryl substituted by carboxyl, etc.; R3E represents hydrogen, etc.; XE represents oxygen, etc.; VE represents nitrogen, etc.; WE represents carbon, etc.; ZE represents —CO—, etc.; RE represents aryl substituted by —C(═NH)NH2, etc.; TE represents C2-6 alkylene, etc.; (Y1E)pE represents heterocyclo substituted by —SO2-Me, etc.; are useful as anti-viral agent, however, it is not reported that the compound represented by formula (E) has factor XIa inhibitory activity.
Furthermore, it has been described in Patent literature 6 that a compound of formula (F):

wherein ring XF represents N-containing ring, etc.; A1F represents a bond, etc.; A2F represents Aryl, etc.; R1F, R2F, R3F, R4F and R5F independently represents hydrogen, etc.; are useful as inhibitors of Apoptosis Proteins.
[Patent literature 1] WO2007070826
[Patent literature 2] WO2008076805
[Patent literature 3] WO2007131982
[Patent literature 4] WO2002037937
[Patent literature 5] WO2008064218
[Patent literature 6] WO2009152824