MXPA00006107A

MXPA00006107A - Quinolones as serine protease inhibitors

Info

Publication number: MXPA00006107A
Application number: MXPA/A/2000/006107A
Authority: MX
Inventors: Jeremy John Edmunds; Danette Andrea Dudley
Original assignee: Danette Andrea Dudley; Jeremy John Edmunds; Warnerlambert Company
Priority date: 1998-03-31
Filing date: 2000-06-19
Publication date: 2001-07-03

Abstract

This invention discloses quinolinones which display inhibitory effects on serine proteases such as factor Xa, thrombin and/or factor VIIa. The invention also discloses pharmaceutically acceptable salts and prodrugs of the compounds, pharmaceutically acceptable compositions comprising the compounds, their salts or prodrugs, and methods of using them as therapeutic agents for treating or preventing disease states in mammals characterized by abnormal thrombosis.

Description

QJUINOLONAS AS INHIBITORS OF SERINE PROTEASE FIELD OF THE INVENTION In one aspect, this invention describes quinolinones that display inhibitory effects on serine proteases such as factor Xa, thrombin and / or factor Vlla. The invention also discloses pharmaceutically acceptable salts and prodrugs of the compounds, pharmaceutically acceptable compositions comprising the compounds, their salts or prodrugs and methods for using them as therapeutic agents for the treatment or prevention of diseases in mammals characterized by abnormal thrombosis. r.

BACKGROUND OF THE INVENTION In economically developed countries, cardiovascular diseases still represent the main cause of mortality. In particular, abnormal coagulation and inappropriate thrombotic formation in the blood vessels precipitates several acute conditions of cardiovascular diseases. Although it has been recognized that a variety of proteins in plasma such as fibrinogen, serine proteases and cellular receptors are involved in hemostasis, it is abnormal regulation that has emerged as an important contributing factor for cardiovascular diseases. Thrombin can be considered the main regulatory enzyme in the coagulation cascade; plays a pluhnominal role as a negative and positive feedback regulator in normal hemostasis. However, in some pathological conditions, the former is amplified through the catalytic activation of cofactors required for the generation of thrombin such as factor Xa. Factor Xa, as part of the prothrombinase complex composed of the nonenzymatic cofactor Va, calcium ions and a phospholipid membrane surface, regulates the generation of thrombin from its cymogenic prothrombin. In addition, the location of the prothrombinase complex at the convergence of both intrinsic and extrinsic coagulation pathways suggests that factor Xa inhibition ^ i and therefore the generation of thrombin, may be a viable approach to limit the procoagulant activity of thrombin. 10 In fact, there is ample evidence for the role of factor Xa inhibitors as anticoagulants. Antistasin, a potent inhibitor of blood coagulation factor Xa, from the Mexican sucker: Haementeria officinalis, displays antithrombotic activity in various models of arteries and venous thrombosis (Lappato et al., Embo J., 1997: 5151-61) . Other protein or polypeptide inhibitors Factor Xa includes the recombinant label anticoagulant peptide (rTAP), which is known to accelerate the lysis of the plasminogen activator plasmid medium of recombinant tissue and prevent acute reocclusion in the dog, therefore; indicates that factor Xa inhibitors may be useful as an adjunct to thrombolytic therapy (Mellott et al., Fibrínolysis, 1993: 195-202). Also, in an artery canine coronary artery, the rTAP model of electrolytic lesion showed that it reduced thrombus mass and occlusion time in the absence of haemostatic or dramatic hemodynamic changes indicating the primary role for factor Xa in the process of arterial thrombosis (Lynch et al. ., Thromb. Haemostasis, 1995: 640-645, Schaffer et al., Circulation, 1991, 1741-1748). On the venous side, rTAP was also shown to reduce fibrin deposition in a rabbit model of venous thrombosis and to have little involvement in systemic hemostatic parameters (Fioravanti et al., Thromb. Res., 1993.317-324). In addition to these relatively high molecular weight proteins which are not suitable as oral antithrombotic agents, there are also examples of low molecular weight factor Xa inhibitors. In particular, DX9065a, a low molecular weight synthetic factor Xa inhibitor, has also demonstrated antithrombotic potential in several rat models with experimental thrombosis. In both venous stasis and arteriovenous shunt models, inhibition of thrombus formation was achieved at doses that had little effect on APTT indicating that DX9065a is effective in the prevention of thrombosis and therefore has antithrombotic therapeutic potential (Wong et al., Thromb Res., 1996: 117-126). Most of the factor Xa inhibitors known to date have been previously summarized in two reviews (Edmunds et al., Annual Reports in? * 15 Medicinal Chemistry, 1996: 51, Kunitada and Nagahara Curr, Pharm. Des., 1996). : 531 ^ 542). However, it is readily apparent that there is still a need for more effective agents that regulate the proteolytic activity of factor Xa. Some quinolinones have been reported and said compounds have displayed outstanding pharmacological activity- Van den Bogaert, Res. Discl., 1992; 340: 607-608; Qar et al., Lazdunski, Michel, Mol. Pharmacol., 1988; 33 (4) .363-369, Japanese Patent 56125388; Japanese Patent 56049359; Patent of Great Britain 1305278; German Patent 2007468; Petyunin P.A., Ukr. Khim. Zh. 1971; 37 (1): 44-46; United States Patent 3330823; European Patent 797376; Timari et al., Hajos, Gyorgy, Synlett (1997); Issue 9: 1067-1068; World Publication 9707116; López-Alvarado Pilar, J. Chem. Soc, Perkin Trans. 1, 1997; Issue 3: 229-233; European Patent 334135 and European Patent 24638. None of the articles described above suggest compounds of Formula I which are inhibitors of the serine proteases involved in the blood coagulation cascade.

SUMMARY OF THE INVENTION An objective of the present invention is to provide inhibitors of serine protease that display inhibitory activity through the enzymes involved in the coagulation cascade and mainly the white enzymes, factor Xa, thrombin and factor Vlla. A further objective of the present invention is to provide serine protease inhibitors that display inhibitory activity through factor Xa of the target enzyme in a pharmaceutically acceptable state. In addition, a further objective of the present invention is to provide the use of these factor Xa inhibitors and formulations thereof as an anticoagulant and factor Xa inhibiting agents. A further objective of the present invention is to provide the use of these factor Xa inhibitors and formulations thereof for therapeutic treatment of various thrombotic diseases. A further objective of the present invention is a process for the synthesis of these low molecular weight thrombin inhibitors. The enzyme inhibitors of the present invention are included in the structure of the general Formula I shown below.

The present invention meets these objectives and provides novel compounds that display antithrombotic activity. More specifically, the present invention provides novel compounds that display antithrombotic activity via the inhibition of factor Xa as reflected in Formula I, or pharmaceutically acceptable salts of prodrug forms thereof. The present invention also provides acceptable pharmaceutical compositions comprising the novel compounds or their salts or prodrugs and methods of use as therapeutic agents for treating or preventing disease states in mammals characterized by abnormal thrombosis. Therefore, in a first embodiment, the present invention provides novel compounds of Formula I: or stereoisomers or pharmaceutically acceptable salts, esters, amides or prodrugs thereof, wherein: A is selected from CH2, CH, C (alkyl); B is selected from H, alkyl, cycloalkyl, heteroalkyl, cycloalkylalkyl, heteroalkylalkyl, aryl, arylalkyl, heterocycle, heterocycloalkyl, each optionally substituted with Ri and R2; D is selected from H, alkyl, cycloalkyl, heteroalkyl, cycloalkylalkyl, heteroalkylalkyl, aryl, arylalkyl, heterocycle, heterocycloalkyl, each optionally substituted with Ri and R2; E is absent or selected from O, S, NH; F is selected from N, NCH2, CH2N; G is absent or selected from alkyl, alkyl interrupted by one or more heteroatoms, cycloalkyl, cycloalkyl interrupted by one or more heteroatoms; J is absent or selected from aryl or heterocycle each optionally substituted with Ri and R2; K is absent or selected from an alkyl, alkyl interrupted by one or more heteroatoms, cycloalkyl interrupted by one or more heteroatoms, cycloalkyl interrupted by one or more heteroatoms, each optionally substituted with Ri and R2; L is selected from H, chloro, bromo, iodo, OH, O (alkyl), amine, alkyl, fluoroalkyl, amide, N02, SH, S (0) n (alkyl), SO3H, alkyl S03, aldehyde, ketone , acid, ester, urea, O-alkylamide, O-alkyl ester, O-alkyl acid, N-alkyl acid, alkylamine, alkylamide, alkyl ketone, alkyl acid, alkyl ester, alkylurea, N-alkylamide, N-alkyl ester, NC (= O) alkyl, NC (= O) aryl, nitrile, NC (= O) cycloalkyl, NC (= O) cycloalkylalkyl, NC (= O) alkylaryl, R-i, R2; R1 is selected from H, amine, alkylamine, amide, C (= NH) NHNH2, alkylC (= NH) NHNH2, C (= NH) NHOH, alkylC (= NH) NHOH, NHC (= NH) NH2, alkylNHC (= NH) NH2, C (= S) NH2, alkylC (= S) NH2, C (= NH) alkyl, alkylC (= NH) alkyl, C (= NR3) N (R4) (R5), alkylC (= NR3) N (R4) (R5); R 2 is selected from H, chloro, fluoro, bromo, iodo, OH, Oalkyl, amine, alkylaldehyde, alkylamide, alkyl ester, alkyl ketone, alkyl acid, O-alkylamide, O-alkyl acid, alkyl ester, aminalkyl acid, aminalkylamide, aminalkyl ester, NC (= O) alkyl, NC (= O) aryl, NC (= O) cycloalkyl, NC (= O) alkylaryl, alkylamine, amide, aldehyde, ester, ketone, NO2, SH, S (0) p (C?.? Oalkyl), SO3H, SO3alkyl, CHO, acid, alkyl, C (= NH) alkyl , C (= NH) NHNH2l alkylC (= NH) NHNH2, C (= NH) NHOH, alkylC (= NH) NHOH, NHC (= NH) NH2, alkylNHC (= NH) NH2, C (= S) NH2, alkylC (= S) NH2, C ^ alkyl (= NH) alkyl, C (= NR3) N (R4) (R5), C ^ alkyl (= NR3) N (R4) (R5); R3, R4 and R5 are hydrogen atoms, alkyl group having 1 to 4 carbon atoms optionally interrupted by a heteroatom or R4 and R5 are linked to form - (CH2) pW- (CH2) q-, where p and q are an integer of 2 or 3, a certain position in the methylene chain is substituted or unsubstituted by an alkyl group having from 1 to 4 carbon atoms, W is a direct bond, -CH2-, -O-, - N (R6) - or -S (O) r wherein R6 is H or alkyl and r is O or 1 or 2; n is selected from 0, 1, 2; X1 is C or N; X2 is C or NI; X3 is C or N; X4 is C or N and - represent an additional optional link. The preferred group of compounds has Formula II: K or stereoisomers or pharmaceutically acceptable salts, esters, amides or prodrugs thereof, wherein B, G, J, K, L and - are as defined above. The most preferred compounds provided by this invention are compounds of Formula III wherein X, Y, R7, R8 and - are as follows: X is selected from (CH2) 5, (CH2) 4, (CH2) 6, CH2C (= O) NHCH2CH2I (CH2) 2NH (CH2) 2, ( CH2) 2O (CH2) 2, C6H4, ChbCeFU, C6H4CH2, CßHio, CH2C6H10, CeH? OCH2, CsHs, CH2CH = CHCH2CH2; And it is selected from 2,6-dimethylpiper? Dinil, piperidinyl, 2,2,6,6-tetramethyl-piperidinyl-4-one, (2-carboxy) piperidinyl, (3-carboxy) piperidinyl, (4-carboxy) piperidinyl, 3,5-dimethylpiperidinyl, (4-hydroxy) piperidinyl, (2-amino) piperidinyl, piperidinyl- 4-one-il, (2-dimethylaminomethyl) -piperidinyl, (4-dimethylamino) -pperidinyl, (4-sulfonyloxy) -piperidinyl, (2-phenyl) piperidinyl, 2,5-dimethylpyrrolidinyl, pyrrolidinyl , (2-carboxy) pyrrolidinyl, (3-N-acetyl-N-methyl) pyrrolidinyl, (3-amino) pyrrolidinyl, (2I5-bis-methoxymethyl) -pyrrolidinyl, 2-bidroxymethyl-pyrrolidinyl, 2-hydroxymethyl- 5-methyl-pyrrolidinyl, diisopropylamino, diethylamino, methylamino, 1-methyl-4,5-dihydro-1 H-imidazol-2-yl, 2,5-dimethyl-1 H-1-imidazolyl, m-polyfolinyl, 2,6- dimethylmorpholinyl, piperazinyl, 2,6-dimethylpiperazinyl, 1H-pyrazolyl, tetrahydro-1 H-pyrazolyl, 2,5-dimethyltetrahydro-1 H-1-pyrazolyl and 1, 2,3,4-tetrahydro-2-oxo-3- phenyl-1-quinolinyl; R is selected from (3-amidino) phenyl, phenyl, 4-methoxyphenyl, 4- (amidino) phenyl, 3- (aminocarbonyl) phenyl, 3- (methoxycarbonyl) phenyl, (3-hydroxy) phenyl, [3-hydroxylamino ( imino) methyl] -phenyl, [3-hydrazine (imino) methyl] -phenyl, (3-aminomethyl) phenyl, (3-amino) phenyl, (3-methylamino) phenyl, (3-dimethylamino) phenyl, (5-amid? No-2-hydroxy) phenyl, (1 -amidino) piperid-3 il, (1-amidino) pyrrolid-3-yl, (5-amidino) thien-2-yl, (5-amidino) furan-2-yl, (5-amidino) -1, 3-oxazol-2-yl , (2-amidino) -1, 3-oxazol-5-yl, 1 H -pyrazol-5-yl, tetrahydro-1 H -pyrazol-3-yl, (1 -amidino) tetrahydro-1 H -pyrazole-3 -il, (2-amidino) -1 H-imidazol-4-yl, (2-amino) -1 H -imidazol-4-yl, (5-amidino) -1 H -imidazol-2-yl, (5-amino) -1 H -imidazol-2-yl, pyridin-3-yl, (4-amino) pyridin-3-yl, (4-dimethylamino) pyridin-3-yl, (6-amino) pyridin- 2-yl, (6-amidino) pyridin-2-yl, (2-amino) pyridin-4-yl, (2-amidino) pyridin-4-yl, (2-amidino) pyrimid-4-yl (2-amino) pyrimidin-4-yl (4-amidino) pyrimid-2-yl (4-amino) pyrimidin-2-yl (6-amidino) pyrazin-2-yl (6-amino) pyrazin-2-yl, (4-amidino) -1, 3,5-triazin-2-yl, (4-amino) -1, 3,5-triazin-2-yl, (3-amidino) -1, 2,4-triazin-5-yl, (3-amino) -1, 2,4-triazin-5-yl, (3-Amidino) benzyl, (3-amino) benzyl, (3-aminomethyl) benzyl, (1 -amidino) p -perid-3-ylmethyl, (1-amidino) pyrrolid-3-ylmethyl, (5-amidino) thien-2-ylmethyl, (5-amidino) furan-2-ylmethyl, (5-amidino) oxazol-2-ylmethyl, (2-amidino) imidazol-5-ylmethyl, (5-amidino) imidazol-2-ylmethyl, (6-amidino) pyridin-2-ylmethyl, (6-amino) pyridin-2-ylmethyl, (2-amidino) pyrimidin-4-ylmethyl-1 (2-amino) pyrimidin-4-ylmethyl, (4-amidino) pyrimidin-2-yl; lmethyl, (4-amino) pyrimidin-2-ylmethyl, (6-amidino) pyrazin-2-methyl, (6-amino) pyrazin-2-ylmethyl, 3-aminociclohexyl, 3-aminidinocyclohexyl, 3-aminocyclohexylmethyl, 3-amidinocyclohexylmethi, 3-aminociclopentyl, 3-amidinocyclopentyl, 3-aminociclopentylmethyl and 3-amidinocyclopentylmethyl and selected from H, Cl, F, SH, SMe, CF3, CH3, CO2H, C02Me, CN, C (= NH) NH2, C (= NH) NHOH, C (= NH) NHNH2, C (= O) NH2, CH2OH, CH2NH2, NO2, OH, OMe, OCH2Ph, OCH2CO2H, O (CH2) 2CO2H, O (CH2) 3CO2H, NHCH2CO2H, NH (CH2) 2CO2H, OCH2CH2OH, OCH2 (1 H-tetrazole) 5-il), NH2, NH Butyl, NMe2, NHPh, NHCH2Ph, NHC (= O) Me, NHC (= O) c-Hexyl, NHC (= O) CH2c-Hexyl, NHC (= O) Ph, NHC (= O) CH2Ph, NHS (= O) 2Me, NHS (= 0) 2c-Hexyl, NHS (= 0) 2CH2c-Hexyl, NHS (= O) Ph and NHS (= O) CH2Ph; or stereoisomers or pharmaceutically acceptable salts, esters, amides or prodrugs thereof. The most preferred compounds provided by this invention are compounds of Formula IV wherein X, Y, R7, R8 and - are as follows: X is selected from (CH2) 5, (CH2) 4, (CH2) 6, CH2CH2NHC (= O) CH2, CH2C6H4, CßHio, And it is selected from 2,6-dimethylpiperidinyl, piperidinyl, 2,2,6,6-tetramethyl-piperidinyl-4-one, (2-carboxy) piperidinyl, (3-carboxy) piperidinyl, (4-carboxy) piperidinyl, 3,5-dimethylpiperidinyl, (4-hydroxy) piperidinyl, (2-imino) piperidinyl, piperidin-4-one- il, (2-d-methmetomethyl) -p -peridinyl, (4-dimethylamino) -piperidinyl, (4-sulfonyloxy) -piperidinyl, (2-phenyl) piperidinyl, 2,5-dimethylpyrrolidinyl, pyrrolidinyl, (2-carboxy) pyrrolidinyl, (3-N-acetyl-N-methyl) pyrrolidinyl, (3-amino) pyrrolidinyl, (2,5-bis-methoxymethyl) -pyrrolidinyl, 2-hydroxymethyl-pyrrolidinyl, 2-hydroxymethyl-5-methyl-pyrrolidinyl, diisopropylamino, diethylamino, methylamino, 1-methyl-4,5-dihydro-1H-imidazol-2-yl, 2,5-dimethyl-1 H-1-imidazolyl, morpholinyl, 2,6-dimethylmorpholinyl, piperazinyl, 2,6-demethylpiperazinyl, 1 H-pyrazolyl, tetrahydro-1 H-pyrazolyl and 2,5-dimethyltetrahydro-1 H- 1-pyrazolyl; R7 is selected from (3-amidino) phenyl, (3-hydroxy) phenyl, [3-hydroxylamino (imino) methyl] -phenyl, [3-hydrazine (imino) methyl] -phenyl, (3-aminomethyl) phenyl, ( 3-amino) phenyl, (3-methylamino) phenyl, (3-dimethylamino) phenyl, (5-amidino-2-hydroxy) phenyl, (-amidino) piperid-3-yl, (1 -amidino) pyrrolid-3- il, (5-amidino) thien-2-yl, (5-amidino) furan-2-yl, (5-amidino) -1, 3-oxazol-2-yl, (2-amidino) -1, 3- oxazol-5-yl, 1 H-pyrazol-5-yl, tetrahydro-1 H -pyrazol-3-yl, (1-amidino) tetrahydro-1 H -pyrazol-3-yl, (2-amidino) -1 H -imidazol-4-yl, (2-amino) -1 H -imidazol-4-yl, (5-amidino) -1 H -imidazol-2-yl, (5-amino) -1 H -imidazole-2- il, pyridin-3-yl, (4-amino) pyridin-3-yl, (4-dimethylamino) pyridin-3-yl, (6-amino) pyridin-2-yl, (6-amidino) pyridin-2-yl, (2-amino) pyridin-4-yl, (2-amidin) pyridin-4-yl, (2-amidino) pyrimid-4-yl, (2-amino) pyrimidin-4-yl, (4-amidino) pyrimid-2-yl, (4-amino) pyrimidn-2-yl, (6-amidino) pyrazin-2-yl, (6-amino) pyrazin-2-yl, (4-amidino) -1, 3,5-triazin-2-yl, (4-amino) -1, 3,5-triazin-2-yl, (3-amidino) -1, 2,4-triazin-5-yl, (3-amino) -1, 2,4-triazin-5-yl, (3-amidino) benzyl, (3-amino) benzyl, (3-aminomethyl) benzyl, (1-amidino) piperid-3-ylmethyl, (1 -amidino) pyrrolid-3-ylmethyl, (5-amidino) thien-2-ylmethyl, (5-amidino) furan-2-ylmethyl, (5-Amidino) oxazol-2-ylmethyl, (2-amidino) imidazol-5-ylmethyl, (5-amidino) imidazol-2-ylmethyl, (6-amidino) pyridin-2-ylmethyl, (6-amino) pyridin-2-ylmethyl, (2-amidino) ) pyrimidin-4-ylmethyl, (2-amino) pyrimidin-4-ylmethyl, (4-amidino) pyrimidin-2-ylmethyl, (4-amino) pyrimidin-2-ylmethyl, (6-amdino) pyrazin-2-ylmethyl, (6-amino) pyrazin-2-ylmethyl, 3-aminociclohexil, 3-amidinociclohexil, 3-aminociclohexilmetil, 3-amidinociclohexilmetil, 3-aminociclopentil, 3-amidinociclopentil, 3-aminociclopentylmethyl and 3-amidinociclopentylmetil and R8 is selected from H, Cl, F, SH, SMe, CF3, CH3, C02H, CO2Me, CN, C (= NH) NH2, C (= NH) NHOH, C (= NH) NHNH2, C (= O) NH2, CH2OH, CH2NH2, NO2, OH, OMe, OCH2Ph, OCH2CO2H, O (CH2) 2CO2H, O (CH2) 3CO2H, NHCH2CO2H, NH (CH2) 2CO2H, NH (CH2) 3CO2H, OCH2CH2OH, OCH2 (1 H-tetrazole-5? L), NH2, NHButil, NMe2, NHPh, NHCH2Ph, NHC (= 0) Me, NHC (= O) c-Hexyl, NHC (= O) CH2c-Hexyl, NHC (= O) Ph, NHC (= O) CH2Ph, NHS (= 0) 2Me, NHS (= 0) 2c-Hexyl, NHS (= O) 2CH2c-Hexyl, NHS (= O) 2Ph and NHS (= O) 2CH2Ph, or steroisomers or pharmaceutically acceptable salts, esters, amides or prodrugs thereof. In one embodiment of Formula IV, Y, R7 and R8 are as above and X is (CH2) 5- In another embodiment of Formula IV, X, R7 and R8 are as above and Y is 2,6-dimethylpiperidinyl. In another embodiment of Formula IV, X, Y and R8 are as above and R is (2-hydroxy-5-amidino) phenyl. In another embodiment of Formula IV, X, Y and R7 are as above and R8 is H. In another embodiment of Formula IV, R7 is as above and X is (CH2) 5, Y is 2,6-dimethylpiperidinyl and R8 it's H.

In another embodiment of Formula IV, R7 is as above and X is (CH2) 5 and Y is 2,5-dimethylpyrrolidinyl. Representative compounds of the present invention include: 3- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 - /) - pyridinyl] pentyl-2-oxo-1,2-dihydro- 3-quinolinyl) benzenecarboximidamide; 1-5 - [(2,6S) -2,6-Dimethyltetrahydro-1 (2 / -) -pyridinyl] pentyl-3- (3-hydroxyphenyl) -2 (fH) -quinolinone; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -N -hydroxybenzenecarboximidamide; 3- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidohydrazide; 3- [3- (Aminomethyl) phenyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridyl] pentyl-2 (7'H) -quinol ninth; 3- (3-Amhonophenyl) -1-5 [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (7H) -quinolinone; 1-5 - [(2R; 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3- [3- (methylamino) pheny] -2 (7 -) -quinol ninth; 3- [3- (Dimethylamino) phenyl] -1-5 - [(2RJ6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (^ / - /) -quinolinone; 3- (1-5 - [(2R; 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -4-hydroxybenzenecarboximidamide; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) tetrahydro-1 (2H) ) -pyridinecarboximidamide; 3- (1-5 - [(2R 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -1-pyrrolidinecarboximidamide; 5- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 -) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -2-thiophenecarboximidamide; 5- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -2-furancarboxyramide; 2- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 - /) - pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) - 1,3-oxazole-5-carboximidamide; 5- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -1, 3- oxazole-2-carboximidamide; 1-5-2R; 6S) -2,6-Dimethyltetrahydro-1 (2 - /) - pyridinyl] pentyl-3- (1H-pyrazol-3-yl) -2 (1 / - /) - quinolinone; 1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 - /) - pyridinyl] pentyl-3-tetrahydro-1 H -pyrazol-3-yl-2 (7?) -quinolinone; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -1-pyrazolidinecarboximidamide; 5-0 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentiol-2-oxo-1,2-dihydro-3-quino-III) -1 / - / - imidazole-2-carboximidamide; 3- (2-Amino-1H-imidazol-5-yl) -1-5 - [(2R, 6S) -2,6-d.methyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1 H) - quinolinone; 2- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -1 - / - imidazole-5-carboximidamide; 3- (5-Amino-1H-imidazol-2-yl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2-) -pyridinyl] pentyl-2 (1 - /) - quinolonone; 1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3- (3-pyridinyl) -2 (1H) -quinolinone; 3- (6-Amino-3-pyridinyl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2 (1H) -quinolinone; 3- [6- (D-methylamino) -3-pyridinyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1 / - /) - quinolinone; 3- (6-Amino-2-pyridinyl) -1-5 - [(2R; 6S) -2,6-dimethyltetrahydro-1 (2 - /) - pyridinyl] pentyl-2 (1 / - / ) -quinolinone; 6- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -2-pyridinecarboximidamide; 3- (2-Amino-4-pyridinyl) -1-5 - [(2R, 6S) -2,6-d.methyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2 (1 / - /) - quinolinone; 4- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -2-pyridinecarboximidamide; 4- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -2- pyrimidnancarboxyramide; 3- (2-Amino-4-pyrimidinyl) -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1 H) -quinolinone; 2- (1-5 - [(2R, 6S) -2,6-D-methyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -4-pyrimidinecarboximidamide; 3- (4-Amino-2-pyrimidinyl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1H) -quinolonone; 6- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -2- pyrazinecarboxyramide; 3- (6-Amino-2-pyrazinyl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1 - /) -quinolinone; 4- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -1, 3,5-triazine-2-carboxamidedamide; 3- (4-Amino) -1, 3,5-triazin-2-yl) -1-5-Y (2R, 6S) -2, dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1 / - /) - quinolinone; 5- (1-5 - [(2R, 6S) -2,6-D-methyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) - 1, 2,4-triazine-3-carboximidamide; 3- (3-Amino-1, 2,4-triazin-5-yl) -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl- 2 (1 - /) - quinolinone; 3 - [(1 -5 - [(2R; 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolineTl) methyl] benzenecarboximidamide; 3- (3-Aminobenzyl) -1-5 - [(2R / 6S) -2,6-d.methyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1 / - /) -quinolinone; 3- [3- (Aminomethyl) benzyl] -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1H) -quinolinone; 3 - [(1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolyl) methyl] tetrahydro- 1 (2 / -) -pyridinecarboximidamide; 3 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) methyl] - 1-pyrrolidinecarboxamidamide; 5 - [(1-5-1 (2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) methyl] -2-thiophenecarboximidamide; - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 - /) - pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) methyl] -2 -furancarboximidamide; 2 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentiol-2-oxo-1,2-dihydro-3-quinolinyl) methylene] -1,3-oxazole-5-carboxamidedamide; 5-f (? -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) methyl] - 1 / - / - midazole-2-carboxylamide; 2 - [(1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) methyl] -1H-imidazole -5-carboximidamide; 6 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) methyl] -2 pyridinecarboximidamide; 3 - [(6-Amino-2-pyridinyl) methyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl- 2 (1 -) -quinolinone; 4 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) methyl] -2-pyrimidinecarboximidamide; 3 - [(2-Amino-4-pyrimidinyl) methyl] -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 * (2 H) -pyridinyl] pentyl-2 (1 -) -quinolinone; 2 - [(1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentiol-2-oxo-1,2-dihydro-3 -quinolinyl) methyl] -4-pyrimidinecarboximidamide; 3 - [(4-Amino-2-pyrimidinyl) methyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1 H) -quinolinone; 6 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) methyl] -2-pyrazinecarboximidamide; 3 - [(6-Amino-2-pyrazinyl) methyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1H) -quinolinone; 3- (3-Aminocyclohexyl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 ('2 / - /) - pyridinyl] pentyl-2 (1 -) -quinolinone; 3- (1-5 - [(2R, 6S) -2,6-D-methyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) cyclohexanecarboximidamide; 3 - [(3-Aminocyclohexyl) methyl] -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1H) -quinolinone; 3 - [(1-5 - [(2R, 6S) -2,6-D-methyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) methyl] cyclohexanecarboximidamide; 3- (3-Aminocyclopentyl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 C2 / - / j-pyridinyl] pentyl-2 (1 / - /) -quinolonone; 3- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) cyclopentanecarboximidamide; 3 - [(3-Aminocyclopentyl) methyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentiI-2 (1 -) -quinolinone; 3 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) methyl] cyclopentanecarboximidamide; 3- (1-4 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] butyl-2-oxo-1,2'-dihydro-3-quinolinyl) benzenecarboximidamide; 3- (1 -6 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] hexyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboxamidamide; 2- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2H) -quinolinyl] -N-2 - [(2Rí6S) -2,6-Dimethyltetrahydro-1 (2 / - /) -pyridinyl] etlacetamide; 3- [3-3- [Amino (imine) methy1] pheny1-2-oxo-1 (2 - /) - quinolinyl] -N - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] methylpropanamide; 3-1- [2- (2 - [(2R; 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] et.lamino) ethyl] -2-oxo- 1,2-dihydro-3-quinol N-benzenecarboxyramide; 3- [1- (2-2 - [(2R, 6S) -2,6-D-methyltetrahydro-1 (2H) -pyridinyl] ethoxyethyl) -2-oxo-1,2-dihydro-3-quinolinyl] benzenecarboximidamide; 3- (1 -4 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] phenyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- (1-4 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] benzyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- [1 - (4 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] methylphenyl) -2-oxo-1,2-dihydro-3-quinolinyl ] benzenecarboximidamide; 3- (1-4 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] cyclohexyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- [1 - (4 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] cyclohexylmethyl) -2-oxo-1,2-dihydro-3-quinolinyl] benzenecarboximidamide; 3- [1- (4 - [(2RJ6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] methylcyclohexyl) -2-oxo-1,2-dihydro-3-quinolinyl] benzenecarboximidamide; 3- (1-3 - [(2R; 6S) -2,6-Dimethyltetrahydro-1 (2 - /) - pyridinyl] cyclopentyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- [1- (3 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] cyclopentylmethyl) -2-oxo-1,2-dihydro-3-quinoiinyl] benzenecarboximidamide; 3- [1- (3 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] methylcyclopentyl) -2-oxo-1,2-dihydro-3-quinolinyl] benzenecarboximidamide; 3- (1- (E) -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] -2-pentenyl-2-oxo-1,2-dihydro-3- quinolinyl) benzenecarboximidamide; 3- [2-Oxo-1 - (5-piperidinapentyl) -1,2-dihydro-3-quinolinylj-benzenecarboximidamide; 3-2-Oxo-l - [5- (2,2,6,6-tetramethylpiperidine) pentyl] -1,2-dihydro-3-quinolinylbenzenecarboximidamide; acid-1-5- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2 / - /) -quinolinyl] pentiyl-2-piperidinecarboxylic acid; acid-1-5- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2 -) -quinolinyl] pentyl-3-piperidinecarboxylic acid; acid-1 -5- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2 / - /) -quinolinyl] pentyl-4-piperidinecarboxylic acid; 3-1 - [5- (3,5-Dimethylpiperidine) pentyl) -2-oxo-1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3-1- [5- (4-Hydroxypiperidine) pentyl] -2-oxo-1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3-1 - [5- (2-lminopiperidine) pentyl-2-oxo-1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3-2-Oxo-1 - [5- (4-oxopiperidine) pentyl] -1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3- [1- (5-2 - [(Dimethylamino) methyl] piperidinapentyl) -2-oxo-1,2-dihydro-3-quinolinylj-benzenecarboximydamide; 3- (1 -5- [4- (Dimethylamino) piperidine] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboxyimide; acid-1-5- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2H) -quinolinyl] pentyl-4-piperidinesulfonic acid; 3-2-Oxo-1 - [5- (2-phenylpiperidine) pentyl] -1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3-1 - [5- (2,5-Dimethyl-1-pyrrolidinyl) pentyl] -2-oxo-1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3-2-Oxo-l - [5- (1-pyrrolidinyl) pentyl] -1,2-dihydro-3-quinolinylbenzenecarboximidamide; acid- -5- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2H) -quinolinyl] pentyl-2-pyrrolidinecarboxylic acid; N- (1-5- [3-3- [Amino (im!) Methyl] phenyl-2-oxo-1 (2H) -quinolinyl] pentyltetrahydro-1H-pyrrol-3-yl) -N-methylacetamide; 3-f- [5- (3-Amino-1-pyrrolidinyl) pentyl] -2-oxo-1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3- (1 -5- [2,5-bis (Methoxymethyl) -1-pyrrolidinyl] pentyl-2-oxo-1,2-dihydro-3-quino-inyl) benzenecarboximidamide; 3- (1 -5- [2- (Hydroxymethyl) -1-pyrrolidinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- (1 -5- [2- (Hydroxymethyl) -5-methyl-1-pyrrolidinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3-1 - [5- (Diisopropylamino) pentyl] -2-oxo-1,2-dihydro-3-quinounylbenzenecarboximidamide; 3-1- [5- (Diethylamino) pentyl] -2-oxo-1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3-1 - [5- (Methylamino) pentyl-2-oxo-1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3-1 - [5- (1-methyl-1-imidazol-2-yl) pentyl-2-oxo-1,2-dihydro-3-quinolinyl-benzenecarboximidamide; 3-1- [5- (2,5-Dimethyl-1H-imidazol-1-yl) pentyl] -2-oxo-1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3- [1 - (5-Morpholinopentyl) -2-oxo-1,2-dihydro-3-quinolinyl-benzenecarboximidamide; 3-1 - [5- (3,5-Dimethylmorpholino) pentyl] -2-oxo-1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3- [2-oxo-1- (5-Piperazinylpentyl) -1,2-dihydro-3-quinolinyl-benzenecarboximidamide; 3-1 - [5- (2,6-Dimethyl-piperazine) pentyl] -2-oxo-1,2-dihydro-3-quinolinyl-benzenecarboximidamide; 3-2-Oxo-1 - [5- (1 H -pyrazol-1 -yl) pentyl] -1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3- [2-Oxo-1 - (5-tetrahydro-1 H -pyrazol-1-ylpentyl) -1,2-dihydro-3-quinolinylj-benzenecarboxyimide; 3-1 - [5- (2,5-Dimethyltetrahydro-1 / - / - pyrazol-1 -yl) pentyl] -2-oxo-1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3- (7-Chloro-1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboxylamide; 3- (1 -5 - [(2R, 6S) -2,6-D-methyltetrahydro-1 (2H) -pyridinyl] pentyl-7-fluoro-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-7-sulfanyl-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- [1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-7- (methylsulfanyl) -2-oxo-1,2-dihydro-3-quinolinyl] benzenecarbox Mydamida; 3- [1 -5 - [(2R, 6S) -2,6-D-methyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-7- (trifluoromethyl) -1,2-dihydro-3-quinolinyl ] benzenecarboximidamide; 3- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-7-methyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboxylamide; 3-3- [Amino (imine) methyl] phenyl-1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1, 2-dihydro-7-quinolinecarboxylic acid; Methyl3-3- [amino (imine) methyl] phenyl-1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-7 -quinolinecarboxylate; 3- (7-Cyano-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentiol-2-oxo-1,2-dih dro-3-quinolinyl) benzenecarboximidamide; 3-3- [Amino (imine) methyl] phenyl-1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-7 -quinolinecarboximidamide; 3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-N-hydroxy-2- oxo-, 2-dihydro-7-quinolinecarboximidamide; 3-1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-7- [hydrazine (imine) methyl] -2-oxo-1,2-dihydro -3-quinolinylbenzenecarboximidamide; 3-3- [Amino (imine) methy1] phenyl-1-5 - [(2RJ6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2 -dihydro-7-quinolinecarboxamide; 3-fl-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-7- (hydroxymethyl) -2-oxo-1,2-dihydro-3-quinolinyl] benzenecarboximidamide; 3- (7- (Aminomethyl) -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / -) -pyridinyl-Jpentyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximide gives; 3- (1-5 - [(2R; 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-7-nitro-2-oxo-1,2-dihydro-3- quinolinyl) benzenecarboximidamide; 3- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl) pentyl-7-hydroxy-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboxylamide; 3- (1-5 - [(2R; 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-7-methoxy-2-oxo-1,2-dihydro-3-quinol Nyl) benzenecarboxyramide; 3- (7- (Benzyloxy) -1-5 - [(2RJ6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; acid-2 - [(3-3- [Amino (imine) methyl] phenol-1-5 - [(2R, 6S) -2,6-d-methyl-tetrahydro-1 (2 / - / ) -pyridinyl] pentyl-2-oxo-1,2-dihydro-7-quinolyl) oxy] -acetic; acid-3 - [(3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2- oxo-1, 2-dihydro-7-quinolinyl) oxy] -propanoic acid; acid-4 - [(3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl- 2-oxo-1,2-dihydro-7-quinolinyl) oxy] -butanoic acid; acid-2 - [(3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2- oxo-1, 2-dihydro-7-quinolinyl) amino] -acetic; acid-3 - [(3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-d.methyltetrahydro-1 (2 - /) - pyridinyl] pentyl-2 -oxo-1, 2-dihydro-7-quinolinyl) amino] -propanoic acid; acid-4 - [(3-3- [Amino (imine) methyl] phenyl-1-5 - / '(' 2R; 6Sy) -2,6-dimethyltetrahydro-1 (2 -) -pyridinyl] pentyl-2- oxo-1, 2-dihydro-7-quinolinyl) amino] -butanoic; 3- [1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 - /) - pyridinyl] pentyl-7- (2-hydroxyethoxy) -2-oxo-l, 2-dihydro-3 -quinolinyl] benzenecarboximidamide; 3- [1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-7- (1H-1, 2,3,4-tetraazole- 5-ylmethoxy) -1,2-dihydro-3-quinolinyl] benzenecarboxyramide; 3- (7-Amino-1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1,2-dihydro-3- quinolinyl) benzenecarboximidamide; 3- (7- (Butylamino) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / /) -pyridinyl] pentyl-2-oxo-1,2-d-hydro-3 -quinolinyl) benzenecarboxamidamide; 3- (7- (Dimethylamino) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- (7-Aniline-1-5 - [(2RJ6S) -2,6-dimethyltetrahydro-1 (2 / /) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- (7- (Benzylamine) -1-5 - [(2R; 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1,2-dih dro-3-quinolinyl) benzenecarboximidamide; ? - (3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro -7-quinolinyl) acetamide; ? / - (3-3- [Amino- (mine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-d.methyltetrahydro-1 (2 / - /) - pyridinyl ] pentyl-2-oxo-1,2-dihydro-7-quinolinyl) cyclohexanecarboxamide; / V- (3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2 -dihydro-7-quinolinyl) -2- cyclohexylacetamide; / V- (3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2 -dihydro-7-quinolinyl) benzenecarboxamide; ? - (3-3- [Amino (imine) methyl] phenyl-1 -5 - [(2R; 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2 -dihydro-7-quinolinyl) -2-phenylacetamide; 3-1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-7- [(methylsulfonyl) amino] -2-oxo-1, 2 -dihydro-3-quinolinylbenzenecarboximidamide; 3- (7 - [(Cyclohexylsulfonyl) amino] -1-5 - [(2R; 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3- quinolinyl) benzenecarboximidamide; 3- (7 - [(Cyclohexylmethyl) sulfonyl] amino-1-5 - [(2R, 6S) -2,6-d.methyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2 -dihydro-3-quinolinyl) benzenecarboximidamide; 3-1-5 - [(2R / 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-7 - [(phenylsulfonyl) amino] -1,2-dihydro-3 -quinolinylbenzenecarboximidamide; 3- (7 - [(Benzylsulfonyl) amino] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 2- / J-pyridinyl] pentyl-2-oxo-1, 2 -dihydro-3-quinolinyl) benzenecarboximidamide; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboxylamide; 1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -? Iridinyl] pentyl-3- (3-hydroxyphenyl) -3,4-dihydro-2 (1 / - /) - quinolinone; 3- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -N-hydroxybenzenecarboximidamide; 3- (1 -5 - [(2R; 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidohydrazide; 3- [3- (Aminomethyl) phenyl] -1 -5 - [(2R; 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3,4-dihydro-2 (1 -) -quinolinone; 3- (3-Aminophenyl) -1-5 - [(2R, 6S) -2,6-d.methyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-3,4-dihydro-2 (1 H) -quinolinone; 1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-3- [3- (methylamino) phenyl] -3,4-dihydro-2 (1 / - /) - quinolinone; 3- [3- (Dimethylamino) phenyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3,4-dihydro-2 (1 / - /) - quinolinone; 3- (1-5 - [(2R / 6S) -2,6-D-methyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl ) -4-hydroxybenzenecarboximidamide; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 - /) - pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) tetrahydro -1 (2 / - /) - pyridinecarboximidamide; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) - 1-pyrrolidinecarboxamidamide; 5- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentiol-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl ) -2-thiophenecarboximidamide; 5- (1-5 - [(2R 6S) -2,6-D-methyltetrahydro-1 (2H) -pyridinyl] pentiol-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -2-furancarboximidamide; 2- (1-5 - [(2R; 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) - 1,3-oxazole-5-carboximidamide; 5- (1-5 - [(2R; 6S) -2,6-D-methyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl ) -1, 3-oxazole-2-carboximidamide; 1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3- (1H-pyrazol-3-yl) -3,4-dihydro-2 (1 -) - quinolinone; 1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3-tetrahydro-1 H -pyrazol-3-yl-3,4-dihydro-2 (1H) - quinolinone; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -1- pyrazolidinecarboximidamide; 5- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -1 H -imidazole-2-carboximidamide; 3- (2-Amino-1 - / - imidazol-5-yl) -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3,4-dihydro- 2 (1 H) -quinolinone; 2- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -1H-imidazole-5-carboxymedanda; 3- (5-Amino-1H-imidazol-2-yl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 - /) - pyridinyl] pentyl-3,4- dihydro-2 (1fy) -quinolinone; 1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3- (3-pyridinyl) -3,4-dihydro-2 (1 H) -quinolinone; 3- (6-Amino-3-pyridinyl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 2H; -pyridinyl] pentyl-3,4-dihydro-2 (1 / - /) - quinolinone; 3- [6- (Dimethylamino) -3-pyridinyl] -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3,4-dihydro-2 ( 1 / - /) - quinolinone; 3- (6-Amino-2-pyridinyl) -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3,4-dihydro-2 (1 H) - quinolinone; 6- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) - 2-pyridinecarboximidamide; 3- (2-Amino-4-pyridinyl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 ('2HA pyridinyl] pentyl-3,4-dihydro-2 (1 -) -quinolinone; 4- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 - /) - pyridinyl] pentyl-2-oxo-1, 2,3,4- tetrahydro-3-quinolinyl) -2-pyridinecarboximidamide; 4- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -2-pyrimidinecarboximidamide; 3- (2-Amino-4-pyrimidinyl) -1-5 - [(2R; 6S) -2,6-dimethyltetrahydro-1 2H-pyridinyl ] penti-3,4-dihydro-2 (1 / - /) - quinolinone; 2- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl- 2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -4-pyrimidinecarboximidamide; 3- (4-Amino-2-pyrimidinyl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 - /) - pyridinyl] pentyl-3,4-dihydro- 2 (1 / - /) - quinolinone; 6- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -2- pyrazinecarboximidamide; 3- (6-Amino-2-pyrazinyl) -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) pyridinyl] pentyl-3,4-dihydro-2 (1 / -) - quinolinone; 4- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -1, 3,5-triazine-2-carboximidamide; 3- (4-Amino-1, 3,5-triazin-2-yl) -1-5 - [(2R, 6S) -2,6-d.methyltetrahydro-1 (2H) -pyridinyl] pentyl- 3,4-dihydro-2 (1 H) -quinolinone; 5- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -1, 2,4-triazine-3-carboximidamide; 3- (3-Amino-1, 2,4-triazin-5-yl) -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3, 4-dihydro-2 (1 / - /) - quinolinone; 3 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) methyl] benzenecarboximidamide; 3- (3-Aminobenzyl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 f2H) -pyridinyl] pentyl-3,4-dihydro-2 (1 / - /) - quinolinone; 3- [3- (Aminomethyl!) Benzyl] -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3,4-dihydro-2 (1 / -) -quinolinone; 3 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) methyl] tetrahydro-1 ('2 / - / -pyridinecarboxamidamide; 3 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) methyl] -1-pyrrolidinecarboxyramide; 5 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2R) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) methyl] -2-thiophenecarboximidamide; 5 - [(1-5 - [(2R; 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) methyl] -2-furancarboxyramide; 2 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3 -quinolinyl) methyl] -1,3-oxazole-5-carboximidamide; 5 - [(1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) methyl] -1 H-imidazole-2-carboximidamide; 2-1 (1-5 - [(2R, 6S) -2,6-D-methyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) methyl] -1H-imidazole-5-carboximidamide; 6 - [(1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) methyl] -2-pyridinecarboximidamide; 3 - [(6-Amino-2-pyridinyl) methyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3,4-dihydro -2 (1H) -quinolinone; 4 - [(1 -5 - [(2R; 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) methyl] -2-pyrimidinecarboximidamide; 3 - [(2-Amino-4-pyrimidinyl) methyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3,4-dihydro-2 (1 / - /) - quinolinone; 2 - [(1-5 - [(2R 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) methyl] - 4-pyrimidinecarboximidamide; 3 - [(4-Amino-2-pyrimidinyl) methyl] -1-5 - [(2R; 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-3,4-dihydro- 2 (1 -) -quinolinone; 6 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) methyl] -2-pyrazinecarboximidamide; 3 - [(6-Amino-2-pyrazinyl) methyl] -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3,4-dihydro-2 (1 / - /) - quinolinone; 3- (3-Aminocyclohexyl) -1 -5 - [(2R; 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3,4-dihydro-2 (1 / - /) -quinolinone; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) cyclohexanecarboxylamide; 3 - [(3-Aminocyclohexyl) methyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3,4-dihydro-2 (1 / -) -quinolinone; 3 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3 quinolinyl) methyl] cyclohexanecarboximidamide; 3- (3-aminocyclopentyl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3,4-dihydro-2 (1 - /) -quinolinone; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) cyclopentanecarboximidamide; 3 - [(3-Aminocyclopentyl) methyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2r7) -pyridinyl] pentyl-3,4-dihydro-2 (1 - /) - quinolinone; 3 - [(1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) methyl] cyclopentanecarboxyramide; 3- (1-4 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] butyl-2-oxo-1, 2,3,4-tetrahydro-3 -quinolinyl) benzenecarboximidamide; 3- (1-6 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] hexyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidamide; 2- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2H) -quinolyl] -N-2 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H ) -pyridinyl] ethylacetamide; 3- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2H) -quinolinyl] -N - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] methylpropanamide; 3-1- [2- (2 - [(2R) 6S) -2,6-D-methyltetrahydro-1 (2H) -pyridinyl] ethylammonyl) ethyl] -2-oxo- 1, 2,3 , 4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3- [1 - (2-2 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] ethoxyethyl) -2-oxo-1, 2,3,4-tetrahydro- 3-quinolinyl] benzenecarboximidamide; 3- (1-4 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] phenyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidamide; 3- (1-4 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] benzyl-2-oxo-1, 2,3,4-tetrahydro-3- quinolinyl) benzenecarboximidamide; 3- [1 - (4 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] methylphenyl) -2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl] benzenecarboximidamide; 3- (1-4 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] cyclohexyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidamide; 3- [1- (4 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] cyclohexylmethyl] -2-oxo-1, 2,3,4-tetrahydro -3-quinolinyl] benzenecarboximidamide; 3- [1- (4 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] methylcyclohexyl) -2-oxo-1, 2,3,4-tetrahydro-3 -quinolinyl] benzenecarboximidamide; 3- (1-3 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] cyclopentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidamide; 3- [1- (3 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] cyclopentylmethyl) -2-oxo-1, 2,3,4-tetrahydro- 3-quinolinyl] benzenecarboximidamide; 3- [1 - (3 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] methylcyclopentyl) -2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl] benzenecarboximidamide; 3- (1- (E) -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] -2-pentenyl-2-oxo- 1, 2,3,4-tetrahydro- 3-quinolinyl) benzenecarboxyramide; 3- [2-Oxo-1 - (5-piperidinapentyl) -1, 2,3,4-tetrahydro-3-quinolinyl] benzenecarboximidamide; 3-2-Oxo-l - [5- (2,2,6,6-tetramethylpiperidine) pentyl] -1,2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; acid-1-5- [3-3- [Amino (imine) methyl] pheny1-2-oxo-1 (2 / - /) -quinolinyl] pentyl-2-piperidinecarboxylic acid; acid-1-5- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2H) -quinolinyl] pentyl-3-piperidinecarboxylic acid; 1 -5- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2H) -quinolinyl] pentyl-4-piperidinecarboxylic acid; 3-1- [5- (3,5-D ymethyl) iperidine) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3-1- [5- (4-Hydroxypiperidine) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3-1 - [5- (2-lminapiperidine) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3-2-Oxo-1 - [5- (4-oxopiperidine) pentyl] -1,2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3- [1- (5-2 - [(Dimethylamino) methyl] piperidinapentyl) -2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl] benzenecarboximidamide; 3- (1 -5- [4- (Dimethylamino) piperidine] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidamide; <RTI ID = 0.0> amino-1 </ RTI> -3- [3-3- [amino (imine) methyl] phenyl-2-oxo-1 (2 - /) -quinolinyl] pentyl-4-piperidinesulfonic acid; 3-2-Oxo-l - [5- (2-phenylpiperidine) pentyl] -1,2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3-1 - [5- (2,5-Dimethyl-1-? -rolidolidinyl) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3-2-Oxo-l - [5- (1-pyrrolidinyl) - entyl] -1,2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 1 -5- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2H) -quinolinyl] pentyl-2-pyrrolidinecarboxylic acid; N- (1-5- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2 H) -quinolinyl] pentyltetrahydro-1 H -pyrrol-3-yl) -N-methylacetamide; 3-1- [5- (3-Amino-1-pyrrolidinyl) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3- (1 -5- [2,5-bis (Methoxymethyl) -1-pyrrolidinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidamide; 3- (1 -5- [2- (Hydroxymethyl) -1-pyrrolidinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidamide; 3- (1 -5- [2- (Hydroxymethyl) -5-methyl-1-pyrrolidinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidamide; 3-1 - [5- (Diisopropylamino) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3-1 - [5- (Diethylamino) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3-1 - [5- (Methylamino) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3-1 - [5- (1-methyl-1 / - / - imidazol-2-yl) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3-1- [5- (2,5-Dimethyl-1H-imidazol-1-yl) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3- [1 - (5-Morpholinopentyl) -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylj-benzenecarboximidamide; 3-f-15- (3,5-Dimethylmorpholino) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3- [2-Oxo-1- (5-piperazinylpentyl) -1,2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3-1- [5- (2,6-Dimethyl-piperazine) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl-benzenecarboximidamide; 3-2-Oxo-1 - [5- (1 H -pyrazol-1 -yl) pentyl] -, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3- [2-Oxo-1 - (5-tetrahydro-1 H -pyrazol-1-ylpentyl) -1, 2,3,4-tetrahydro-3-quinolinyl] benzenecarboximidamide; 3-1 - [5- (2,5-Dimethyltetrahydro-1 H -pyrazol-1-yl) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3- (7-Chloro-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl ) benzenecarboximidamide; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-7-fluoro-2-oxo-1, 2,3,4-tetrahydro- 3-quinolinyl) benzenecarboximidamide; 3- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-7-sulfanyl-1, 2,3,4-tetrahydro-3-quinolinyl ) benzenecarboximidamide; 3- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-7- (methylsulfanyl) -2-oxo-1, 2,3,4-tetrahydro-3 -quinolinyl) benzenecarboximidamide; 3- [1-5 - [(2R; 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-7- (trifluoromethyl) -1, 2,3,4-tetrahydro-3 -quinolinyl] benzenecarboximidamide; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-7-methyl] -2-oxo-1, 2,3,4-tetrahydro-3- quinolinyl) benzenecarboximidamide; acid-3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo- 1, 2,3,4-tetrahydro-7-quinolinecarboxylic acid; methyl3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4 -tetrahydro-7-quinolinecarboxylate; 3- (7-Cyano-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1,2,3,4- tetrahydro-3-quinolinyl) benzenecarboximidamide; 3-3- [Amino (imine) methyl] phenyl-1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4 -tetrahydro-7-quinolinecarboxyramide; 3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-N-hydroxy-2-oxo-1, 2,3,4-tetrahydro-7-quinolinecarboximidamida; 3-1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-7- [hydrazine (imine) methyl] -2-oxo-1, 2,3,4- tetrahydro-3-quinolinylbenzenecarboximidamide; 3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3 , 4-tetrahydro-7-quinolylcarboxamide; 3- [1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-7- (hydroxymethyl) -2-oxo-1, 2,3,4-tetrahydro-3 -quinolinyl] benzenecarboximidamide; 3- (7- (Aminomethyl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3 -quinolinyl) benzenecarboximidamide; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-7-nitro-2-oxo-1, 2,3,4-tetrahydro-3-quinolin L) benzenecarboxymoxydamda; 3- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-7-hydroxy-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl ) benzenecarboximidedamide; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2R) -pyridinyl] pentyl-7-methoxy-2-oxo-1, 2,3,4-tetrahydro -3-quinolinyl) benzenecarboxyramide; 3- (7- (Benzyloxy) -1-5 - [(2R 6S) -2,6-dimethyltetrahydro-1 2 HJ-pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidamide; acid-2 - [(3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 -) -pyridinyl] pentyl-2- oxo-1, 2-dihydro-7-quinolinyl) -oxi] acetic acid; acid-3 - [(3-3- [Amino (imine) methylphenyl-1-5 - [(2R; 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2- oxo-1, 2-dihydro-7-quinolinyl) oxy] propanoic; acid-4 - [(3-3- [Amino (imine) methyl] phenyl-1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl- 2-oxo-1,2-dihydro-7-quinolinyl) oxy] -butane; acid-2 - [(3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2- oxo-1, 2-dihydro-7-quinolinyl) amino] acetic; Acid-3 - [(3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl- 2-oxo-1,2-dihydro-7-quinolinyl) amino] propanoic acid; acid-4 - [(3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo -1, 2-dihydro-7-quinolyl) amino] butanoic; 3- [1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 - /) - pyridinyl] pentyl-7- (2-hydroxyethoxy) -2-oxo-l, 2, 3,4 -tetrahydro-3-quinolinyl] benzenecarboximidamide; 3- [1-5 - [(2R; 65) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-7- (1 / - / - 1, 2,3,4 -tetraazol-5-ylmethoxy) -1, 2,3,4-tetrahydro-3-quinolinyl] benzenecarboximidamide; 3- (7-Amino-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl ) benzenecarboximidamide; 3- (7- (Butylamino) -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / -fJ-pyridinyl] pentyl-2-oxo-1, 2,3 4-tetrahydro-3-quinolinyl) benzenecarboximidamide; 3- (7- (Dimethylamino) -1 -5 - [(2R; 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo- 1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidamide; 3- (7-Aniline-1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl ) benzenecarboxamidamide; 3- (7- (Benzylamino) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 ('2H-pyridinyl] pentiol-2-oxo-1, 2,3,4 -tetrahydro-3-quinolinyl) benzenecarboxyramide; N- (3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R; 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl) ] pentyl-2-oxo-1,2-dihydro-7-quinolinyl) acetamide; N- (3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2.6- dimethyltetrahydro-1- (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-7-quinolyl] cyclohexanecarboxamide; N- (3-3- [Amino (imine) methyl] phenyl-1- 5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-7-quinoline] -2-cyclohexylacetamide; N- (3- 3- [Amino (imine) methyl] phenyl-1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-7 -quinolinyl) benzenecarboxamide; N- (3-3- [Amino (imine) methyl] phenyl-1 - 5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) ~ pyridinyl] pentyl-2-oxo -1,2-dihydro-7-quinolinyl) -2- phenylacetamide; 3-1 -5 - [(2R; 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-7- [(methylsulfonyl) amino] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl benzenecarboximidedamda; 3- (7 - [(Cyclohexylsulfonyl) amino] -1-5 - [(2R; 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3, 4-tetrahydro-3-quinolinyl) benzenecarboxyramide; 3- (7 - [(Cyclohexylmethyl) sulfonyl] amino-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4 -tetrahydro-3-quinolinyl) benzenecarboxamidamide; 3-1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / -y) -pyridinyl] pentyl-2-oxo-7 - [(phenylsulfonyl) amino] -1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboxyramide; 3-. { 1 - [5- (2,6-Dimethyl-piperidin-1-yl) -pentyl] -2-oxo-1,2-dihydro-quinolin-3-yl} -4-hydroxy-benzamidine; acid-4-. { 1 - [5- (2,6-Dimethyl-piperidin-1-yl) -pentyl] -2-oxo-1, 2,3,4-tetrahydro-quinolin-3-yl} methyl benzoic ester; 4-. { 1 - [5- (2,6-Dimethyl-piperidin-1-yl) -pentyl] -2-oxo-1, 2,3,4-tetrahydro-quinolin-3-yl} -benzamidine; 3-Phenyl-1 - (5-piperidin-1-yl-pentyl) -1 H -quinolin-2-one; 3-. { 1 - [5- (2,6-Dimethyl-piperidin-1-yl) -pentyl] -2-oxo-1, 2,3,4-tetrahydro-quinolin-3-yl} -benzamide; 3-Phenyl-1 - (5-piperidin-1-yl-pentyl) -3,4-dihydro-1 H -quinolin-2-one; 2 (1 H) -Quinolinone, 1, 1 '- (1,5-pentylidene) bis [3,4-dihydro-3-phenyl-, ± -; 3- (7 - [(Benzylsulfonyl) amino] -1- 5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2-) pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidamide; and 1 - [5- (2,6-Dimethyl-piperidin-1-yl) -pentyl] -3- (4-methoxy-phenyl) -3,4-dihydro-1 H -quinolin-2-one.

DETAILED DESCRIPTION OF THE INVENTION The term "alkyl" means a long and branched unsaturated or saturated carbon chain having from 1 to 20 carbon atoms. Typical alkyl groups include methyl, isobutyl, pentyl, 2-methyl-pentyl, pent-1,4-dienyl, but-1-enyl, and the like.

The term "cycloalkyl" means an unsaturated or saturated carbon chain that forms a ring having from 3 to 20 carbon atoms. Typical examples include cyclopropyl, cyclohexyl and the like. The term "cycloalkylalkyl" means a cycloalkyl group linked to an alkyl group wherein "cycloalkyl" and "alkyl" are as defined above and include, for example, cyclopropylmethyl, cyclopentylethyl and the like. The term "heteroalkyl" means a long and branched unsaturated or saturated carbon chain having from 1 to 20 carbon atoms wherein one or more carbon atoms is replaced by a heteroatom selected from oxygen, nitrogen, sulfur, sulfoxide or sulfone. Typical "heteroalkyl" groups include methoxymethyl, 3-thiomethylpropyl and 2-thiomethoxyethoxymethyl and the like. The term "aryl" represents an unsaturated carbocyclic ring (s) of 6 to 16 carbon atoms which is optionally substituted by OH, O (alkyl), SH, S (alkyl), amine , halogen, acid, ester, amide, alkyl ketone, aldehyde, nitrile, fluoroalkyl, nitro, sulfone, sulfoxide or alkyl (Ci-e). Typical rings include phenyl, naphthyl, phenatryl and anthracenyl. Preferred aryl rings are phenyl, substituted phenyl and naphthyl. The term "arylalkyl" means an aromatic radical linked to an alkyl radical wherein "aryl" and "alkyl" are as defined above and include, for example, benzyl and naphthylmethyl. The term "heterocycle" means a mono or polycyclic saturated or unsaturated ring (eg, bicyclic) incorporating one or more heteroatoms (e.g., 1-4) selected from N, O and S. A heterocycle is understood to be optionally substituted with OH, O (alkyl), SH, S (alkyl), amine, halogen, acid, ester, amide, alkyl ketone, aldehyde, nitrile, fluoroalkyl, nitro, sulfone, sulfoxide or Ci-β alkyl. Examples of suitable monocyclic heterocycles include, but are not limited to, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, triazolyl, tetrazolyl, tetrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, piperidinyl, pyrrolidinyl, piperazinyl, acetidinyl, aziridinyl. , morpholinyl, thietanyl, oyetanil saturated or unsaturated. Preferred monodiheterocycles include, but are not limited to, 2- or 3-furanyl; 1-, 2- or 3-pyrrolyl; 1-, 2-, 4- or 5-imidazolyl; 1-, 3-, 4- or 5-pyrazolyl; 2-, 4- or 5-thiazolyl; 3-, 4- or 5-isothiazole; 2-, 4- or 5-oxazolyl; 3-, 4- or 5-isoxazolyl; 1-, 3- or 5-triazolyl; 1-, 2- or 3-tetrazolyl; 2-, 3-, 4-pyridinyl; 2-pyrazinyl; 2-, 4- or 5-pyrimidinyl; 1-, 2-, 3- or 4-piperidinyl; 1 -, 2- or 3-pyrrolidinyl; 1 -, 2- or 3-pyrrolidinyl; 1- or 2-piperazinyl; 1 -, 2- or 3-acetydin; 1- or 2-aziridinyl; 2-, 3- or 4-morpholinyl; 2- or 3-tietanil; 2- or 3-oxetanyl. Examples of suitable bicyclic heterocycles include but are not limited to indolizinyl, isoindolyl, benzothienyl, benzothienyl, benzoxazolyl, benzimidazolyl, quinolinyl, isoquinolinyl and preferably 1-, 2-, 3-, 4-, 5-, 6- or 7 -indolyl; 1-, 2-, 3-, 5-, 6-, 7- or 8-indolizinil; 1-, 2-, 3-, 4-, 5-, 6- or 7-isoindolyl; 2-, 3-, 4-, 5-, 6- or 7-benzothienyl; 2-, 4-, 5-, 6- or 7-benzoxazolyl; 1-, 2-, 4-, 5-, 6- or 7-benzimidazolyl; 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolinyl; 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolinyl. The term "heteroatom" as used herein represents oxygen, nitrogen or sulfur (O, N or S) as well as sulfoxyl or sulfonyl (SO or SO2) unless otherwise indicated. It is understood that the alkyl chains interrupted by one or more heteroatoms mean that a carbon atom of the chain is replaced with a heteroatom having the appropriate valence. Preferably, an alkyl chain is interrupted by 1 to 4 heteroatoms and that two adjacent carbon atoms are not replaced. Examples of such groups include methoxymethyl, 3-thiomethylpropyl and 2-thiomethoxyethoxymethyl. The term "amine" refers to a group such as NH2, NHalkyl, NH (cycloalkyl), NH (cycloalkylalkyl), NH (aryl), NH (arylalkyl), NH (heteroaryl), NH (heteroarylalkyl), N (alkyl) (alkyl), N (alkyl) (cycloalkyl), N (alkyl) (cycloalkylalkyl), N (alkyl) (aryl), N (alkyl) (arylalkyl), N (alkyl) (heteroaryl), N (alkyl) (heteroarylalkyl ), N (cycloalkyl) (cycloalkyl), N (cycloalkyl) (cycloalkyl) alkyl, N (cycloalkyl) (aryl), N (cycloalkyl) (arylalkyl), N (cycloalkyl) (heteroaryl), N (cycloalkyl) (heteroarylalkyl ), N (cycloalkylalkyl) (cycloalkylalkyl), N (cycloalkylalkyl) (aryl), N (cycloalkylalkyl) (arylalkyl), N (cycloalkylalkyl) (heteroaryl), N (cycloalkylalkyl) (heteroarylalkyl), N (aryl) (cycloalkylalkyl) ), N (aryl) (aryl), N (aryl) (arylalkyl), N (aryl) (heteroaryl), N (aryl) (heteroarylalkyl), N (arylalkyl) (arylalkyl), N (arylalkyl) (heteroaryl) ), N (arylalkyl) (heteroarylalkyl), N (heteroaryl) (heteroaryl), N (heteroaryl) (hetero) arylalkyl), N (heteroarylalkyl) (heteroarylalkyl). The term "acid" refers to C (= O) OH. The term "ketone" refers to C (= O) alkyl, C (= O) cycloalkyl, C (= O) cycloalkylalkyl, C (= O) aryl, C (= O) arylalkyl, C (= O) heteroaryl, C (= O) heteroarylalkyl.

The term "ester" refers to a group such as C (= O) Oalkyl, C (= O) Occloalkyl, C (= O) Ocloalkylalkyl, C (= O) aryl, C (= O) Oarylalkyl, C (= O) Otero-heteroaryl, C (= O) -heteroarylalkyl. The term "amide" refers to a group such as C (= 0) NH2, C (= O) NHalkyl, C (= O) NH (cycloalkyl), C (= O) NH (cycloalkylalkyl), C (= O) ) NH (aryl), C (= O) NH (arylalkyl), C (= O) NH (heteroaryl), C (= O) NH (heteroarylalkyl), C (= O) N (alkyl) (alkyl), C (= O) N (alkyl) (cycloalkyl), C (= O) N (alkyl) (cycloalkylalkyl), C (= O) N (alkyl) (aryl), C (= O) N (alkyl) (arylalkyl) , C (= O) N (alkyl) (heteroaryl), C (= O) N (alkyl) (heteroarylalkyl), C (= O) N (cycloalkyl) (cycloalkyl), C (= 0) N (cycloalkyl) ) (cycloalkylalkyl), C (= 0) N (cycloalkyl) (aryl), C (= O) N (cycloalkyl) (arylalkyl), C (= O) N (cycloalkyl) (heteroaryl), C (= O N (cycloalkyl) (heteroarylalkyl), C (= O) N (cycloalkylalkyl) (cycloalkyl), C (= O) N (cycloalkylalkyl) (aryl), C (= O) N (cycloalkylalkyl) (arylalkyl) ), C (= O) N (cycloalkylalkyl) (heteroaryl), C (= O) N (cycloalkylalkyl) (heteroarylalkyl), C (= O) N (aryl) (cycloalkylalkyl), C (= O) N (aryl) (aryl), C (= O) N (aryl) (arylalkyl), C (= O) N (aryl) (heteroaryl), C (= O) N (aryl) (hetero) oarylalkyl), C (= O) N (arylalkyl) (arylalkyl), C (= O) N (arylalkyl) (heteroaryl), C (= O) N (arylalkyl) (heteroarylalkyl), C (= O) N (heteroaryl) (heteroaryl), C (= O) N (heteroaryl) (heteroarylalkyl), C (= O) N (heteroarylalkyl) (heteroarylalkyl). The term "urea" refers to a group such as NHC (= O) N (alkyl) (alkyl), NHC (= O) N (alkyl) (cycloalkyl), NHC (= O) N (alkyl) (cycloalkylalkyl) , NHC (= O) N (alkyl) (aryl), NHC (= O) N (alkyl) (arylalkyl), NHC (= 0) N (alkyl) (heteroaryl), NHC (= 0) N (alkyl) ) (heteroarylalkyl), NHC (= O) N (cycloalkyl) (cycloalkyl), NHC (= 0) N (cycloalkyl) (cycloalkylalkyl), NHC (= O) N (cycloalkyl) (aryl), NHC (= O) ) N (cycloalkyl) (arylalkyl), NHC (= O) N (cycloalkyl) (heteroaryl), NHC (= O) N (cycloalkyl) (heteroarylalkyl), NHC (= O) N (cycloalkylalkyl) (cycloalkylalkyl), NHC ( = O) N (cycloalkylalkyl) (aryl), NHC (= O) N (cycloalkylalkyl) (arylalkyl), NHC (= O) N (cycloalkylalkyl) (heteroaryl), NHC (= 0) N (cycloalkylalkyl) (heteroarylalkyl) ), NHC (= 0) N (aryl) (cycloalkylalkyl), NHC (= O) N (aryl) (aryl), NHC (= O) N (aryl) (arylalkyl), NHC (= O) N (aryl) (heteroaryl), NHC (= O) N (aryl) (heteroarylalkyl), NHC (= O) N (arylalkyl) (arylalkyl), NHC (= O) N (arylalkyl) (heteroaryl), NHC (= 0) N (arylalkyl) (heteroarylal) chyl), NHC (= 0) N (heteroaryl) (heteroaryl), NHC (= 0) N (heteroaryl) (heteroarylalkyl), NHC (= O) N (heteroarylalkyl) (heteroarylalkyl). The term "halogen" refers to chlorine, fluorine, bromine and iodine. The highlighted or triangular arrows are only a representation of a stereochemical descriptor. All stereoisomers including the enantiomers and diastomers are included in Formulas I to IV and are provided in this invention. When specific isomers are drawn, they are the preferred isomers. In some situations, the compounds may exist as tautomers. All tautomers are included in Formulas I to IV and are provided in this invention.

When the compounds are administered, some metabolic change may occur. All metabolites are included in Formulas I to IV and are provided in this invention. When a link to a substitute is shown to cross the link by connecting 2 atoms in a ring, then said substitute can be linked to any atom in the ring, provided that the atom will accept the substitute without violating its valence. When several atoms of the substitute are bound to the ring atom, then it is the first atom of the listed substitutes that are attached to the ring. When a bond is represented by a line such as "-", it means that the link may be absent or present on condition that the resulting compound is stable and of satisfactory valence. The compounds of the present invention are capable of forming acid addition salts (see, for example, Berge S. M et al., "Pharmaceutical Salts", Journal of Pharmaceutical Science, 1977: 1-10) with inorganic acids such as, for example, hydrochloric acid, sulfuric acid and the like as well as salts derived from organic acids such as, for example, dicarboxylic and monoaliphatic acids or aliphatics and aromatic sulfonic acids. The acid addition salts are prepared by contacting the free base form with a sufficient amount of the desired acid to produce the salt. The free base form can be regenerated by contacting the salt form with a base. While the free base may differ more from the salt form in terms of physical properties, such as solubility, the salts are equivalent to their respective free bases for the purposes of the present invention.

Certain compounds of the present invention can exist in unsolvated form as well as in solvated form including the hydrated form. In general, the solvated form including the hydrated form are equivalent to the unsolvated form and are included within the scope of the present invention. The "prodrugs" include any covalently linked carrier that releases the active drug origin in accordance with Formulas I to IV in vivo. Examples of prodrugs include acetates, formates, benzoate derived from alcohols and amines present in the compounds of Formulas I to IV. They also include derivatives of the functionality of amidine or guanine and would include C (= NR3) NH2 wherein R3 is select from OH, NH2, C1-4 alkoxy, aryloxy Ce-io, C1-10 alkoxycarbonyl, aryloxycarbonyl Ce-io. Preferred derivatives include examples wherein R3 is OH, NH2, methoxy and ethoxycarbonyl. The following table provides a list of the abbreviations and definitions thereof, used in the present invention.

Abbreviation Description AMC Aminomethylcoumarin APTT Activated partial thromboplastin time BOC Butyloxycarbonyl-tertiary BOP-reagent Benzotriazole-1-yloxy-tris (dimethylamino) phosphonium hexafluorophosphate Bz Benzoate CDCI3 Deuterochloroform DMF Dimethyl formamide DMSO Dimethylsulfoxide 1H-NMR Proton nuclear magnetic resonance HCl Hydrogen chloride HF Hydrogen fluoride HMPA Hexamethylphosphoramide HPLC High pressure liquid chromatography MOT Average occlusion time MS (APCI) Mass spectrometry (atmospheric pressure Cl) MS (Cl) Mass spectrometry (chemical ionization) MS (ES) Mass spectrometry (electro spray) NaOH Sodium hydroxide nBuLi n-butyl lithium NH4CI Ammonium chloride Pd / C Palladium on carbon Pt02 Platinum oxide r.t. or RT Ambient temperature TFA Trifluoroacetic acid THF Tetrahydrofuran Thrombin time VAZO-52 2,2'-Azobis-2-methylenedronitrile Also provided in this invention is a method for preventing and treating chronic, subacute and acute thrombotic disorders in a mammal comprising the administration to said mammal of an effective amount of a compound of Formulas I to IV. The compounds are useful as anticoagulants for the treatment and prophylaxis of disorders such as arterial and venous thrombosis, pulmonary embolism and ischemic events such as myocardial infarction or cerebral infarction. These compounds also have therapeutic utility for the prevention and treatment of complications of resident vascular access ports and arteriovenous shunts and coagulopathies associated with cardiopulmonary bypass or other extracorporeal systems. These compounds are useful for the prevention or treatment of unstable angina, refractory angina, intermittent claudication, disseminated intravascular coagulation and ocular accumulation of fibrin. Since thrombin and serine proteases have also been shown to activate a number of different cell types, these compounds are useful for the treatment or prophylaxis of septic shock and other inflammatory responses such as chronic or acute atherosclerosis. The compounds also have utility in the treatment of neoplasia / metastasis and neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. In a preferred method, the thrombotic disorder is selected from venous thrombosis, arterial thrombosis, pulmonary embolism, myocardial infarction, cerebral infarction, angina, cancer and diabetes. A further embodiment of this invention is a pharmaceutical formulation comprising a compound of Formulas I to IV administered with a diluent, excipient or carrier thereof.

Preparation of the Compounds of the Invention The compounds of Formulas I to IV can be prepared by any of the methods known to those skilled in the art of organic chemistry. The following general schemes represent the preferred routes to provide the compounds of this disclosure. Reactions are typically carried out in solvents appropriate to the reagents and substrates used. It is understood that the functionality present in the molecule must be compatible with the reactants and the proposed reaction conditions. Not all compounds of Formulas I to IV fall within a given class, can be compatible with some of the reaction conditions described. Such restrictions are readily apparent to those skilled in the art of organic synthesis and subsequently alternative methods should be used. The quinolinones of Formula I are prepared in accordance with Scheme 1.

Scheme 1 Step a: Treatment of an ortho-nitro benzaldehyde appropriately substituted with a phenyl acetic acid, such as 3-cyano-phenylacetic acid in an acetic anhydride in the presence of the base, such as triethylamine at elevated temperatures such as at reflux, producing the (E) -2- (3-cyanophenyl) -3- (2-nitrophenyl) prop-2-anoic acid.

Step b: The reduction of nitro and the alkene function is affected by the hydrogenation of the material in the presence of palladium on carbon under a hydrogen atmosphere. Allowing this reaction to proceed for a period of 24 hours, results in the formation of 3- (3-cyanophenyl) -1,2,3,4-tetrahydro-2-quinolinone. This is, of course, done so that the cyano substitute can undergo palladium reduction on carbon and hydrogen. In some situations, it is necessary to use an alternate substitute that is subsequently converted to the cyano group. Such substitutes may include an ester, acid, amide or hydroxymethyl group. Alternatively in situations where the concomitant reduction of the substitutes in the 3-phenyl ring, as with the bromo or cyano substitute, then the reduction to produce the quinolinone is affected by milder procedures such as the use of Raney nickel as a catalyst of hydrogenation. It is also apparent that the NO2 group can be selectively reduced, for example, Sn / HCl, H2S / NH3 or by careful hydrogenation. These anilines can subsequently be cyclized with sulfuric acid in acetic anhydride at elevated temperature to produce the dihydroquinolinones according to the procedure of Hiño et al., Chem. Pharm. Bull., 1987: 2819 and He et al., J. Chem. Soc, 1949: 3164.

Step c: Alkylation is typically achieved by treatment with an appropriate electrophile and by the addition of a base in a dipolar aprotic solvent. Typical conditions include, for example, the use of a bis-electrophilic substrate such as 1,5-dibromopentane in a dipolar aprotic solvent such as DMF or DMSO and the addition of a base, such as sodium hydride. Alternatively, alkylation can be achieved by the addition of a transfer reagent phase such as an alkylammonium salt such as benzyltriethylammonium chloride and using a base such as sodium ethoxide. The reaction rates are typically improved by the application of heat and therefore, reactions run from 0 ° to 70 ° C.

Step d Treatment with an amine, such as cis-2,6-dimethylpiperidine at an elevated temperature such as 50 ° C produces the expected N-alkylated piperidine. The amine may be used as a solvent or alternatively the amine may be added in stoichiometric proportions and the reaction mixture refluxed in a solvent such as ethanol, acetonitrile or toluene. The product, such as the appropriate acid addition salt, is subsequently neutralized by the addition of the base such as aqueous potassium hydroxide. In situations where the amine is volatile, then the reaction mixture is heated, typically from 50 ° C to 150 ° C in a sealed tube.

Step e: The conversion of nitrile to hydroxyamidine is achieved by the reaction of nitrile with hydroxylamine in methanol at room temperature. Typically the hydroxylamine hydrochloride is added to the nitrile containing the substrate at room temperature and the reaction is initiated by the addition of the base such as potassium carbonate or diisopropylethylamine. The reaction is usually monitored by HPLC to determine the absence of the starting material, the nitrile and is typically completed in a 24-hour period.

Step f: The amidoxime is activated by the addition of acetic anhydride of the trifluoroacetic anhydride intermediate in a solvent such as acetic acid or trifluoroacetic acid to produce the O-acylated, which can be isolated or alternatively used directly in the subsequent reduction step. This stage and the subsequent reduction can be combined, for example, the reduction with Pd / C is carried out in acetic acid / anhydride acid or trifluoroacetic acid / trifluoroacetic anhydride. Alternatively, the treatment of the nitrile with hydrogen chloride in an alcohol solvent produces the corresponding iminoether hydrochloride. These intermediates are subsequently treated with a source of ammonium, for example, ammonium in methanol or ammonium chloride or ammonium acetate and the mixture is stirred and heated, if necessary to produce the amidine. A process for the preparation of the compounds of Formula I, when the optional bond is present, is shown in Scheme 2.

Scheme 2 Step a: The treatment of 3,4-dihydro-quinolin-2-one with a strong base, such as BuLi and tetramethylpiperidine, occurs after exchange with mercury (II) chloride and subsequently the addition of the 3-bromo derivative ( see Fernández et al., Syntesis, 1995: 1362). Alternatively, the required 3-bromohydroquinolin-2-one is available from 3-bromoquinoline via its N-oxide according to the procedure of Leclerc et al., J. Med. Chem., 1986: 2427.

Step b: A cross-coupling reaction of palladium using an aryl boronic acid, such as 3- (methoxycarbonyl) phenyl boronic acid or aryl stannane, effects the transformation of the vinyl bromide to the corresponding arylalkene. Typically, the triphenylphosphine tetrakis of palladium (0) is added to a mixture of the halide and aryl boronic acid in a solvent such as a mixture of toluene and DMF and the mixture is subsequently heated to 100 ° C under a nitrogen atmosphere. The procedure is analogous to that described by Timari et al., Syn. Lett., 1997: 1067. An alternative process employing zinc aryl halide organometals has been described by Leclerc et al., J. Med. Chem., 1986: 2427. Alternatively, in accordance with the procedure of Meng et al., J. Het. Chem., 1991: 1481, the vinyl halide can be irradiated with a mercury lamp in a quartz beaker in the presence of, for example, thiophene to produce 3- (2-thienyl). The use of benzene as a solvent would produce the 3-phenyl adductor.

Step c: Alkylation is typically achieved by treatment with an appropriate electrophile and by the addition of a base in a dipolar aprotic solvent. Typical conditions include, for example, the use of a bis-electrophilic substrate such as 1,5-dibromopentane in a dipolar aprotic solvent such as DMF or DMSO and the addition of a base, such as sodium hydride. Alternatively, alkylation can be achieved by the addition of a transfer reagent phase such as an alkylammonium salt, such as benzyltriethylammonium chloride and using a base such as sodium ethoxide. Typically the reaction rates are improved by the application of heat and therefore the reactions run from 0 ° C to 70 ° C.

Step d: Treatment with amine, such as cis-2,6-dimethylpiperidine at an elevated temperature such as 50 ° C produces the expected N-alkylated piperidine. The amine can be used as a solvent or alternatively, the amine can be added in stoichiometric proportions and the reaction mixture refluxed in a solvent such as ethanol, acetonitrile or toluene. In situations where the amine is volatile, the reaction mixture is subsequently heated, typically from 50 ° C to 150 ° C in a sealed tube.

Step e: The conversion of the methyl ester to the amide is achieved by the addition of ammonium hydroxide to a solution of the ester in a solvent such as THF. The reaction mixture is stirred at room temperature for several hours or alternatively, it is heated in a sealed tube. An alternate process for transformation involves converting the ester to the corresponding carboxylic acid with aqueous sodium hydroxide and subsequently converting the acid to the corresponding acid chloride with for example oxalyl chloride, catalytic DMF in a solvent such as methylene chloride. Finally, the acid chloride is subsequently treated with aqueous ammonium, which easily produces the amide.

Step f: The addition of trichloroacetyl chloride and triethylamine to a solution of the amide in methylene chloride at 0 ° C and subsequently stirring with heating at room temperature for 1 hour easily produces the nitrile.

Steps g and h: The conversion of the nitrile to the corresponding amidine is achieved in accordance with the procedure of Scheme 1. An alternate procedure for producing the required quinolinones proceeds in accordance with the procedure of Chupp et al., J. Het. Chem., 1979: 65-71 and described in Scheme 3.

Scheme 3 Step a: The aniline is converted to the anilide by treatment with the appropriate arylacetyl chloride in a solvent such as methylene chloride.

Step b: The treatment of the anilide with the Vilsmier reagent, prepared from DMF and phosphoryl chloride in methylene chloride, produces after reflux the appropriate quinolinone.

Step c: Treatment with an amine, such as cis-2,6-dimethylpiperidine at an elevated temperature such as 50 ° C produces the expected N-alkylated piperidine. The amine can be used as a solvent or alternatively, the amine can be added in stoichiometric proportions and the reaction mixture refluxed in a solvent such as ethanol, acetonitrile or toluene. In situations where the amine is volatile, the reaction mixture is subsequently heated, typically from 50 ° C to 150 ° C in a sealed tube.

Step d: The aryl bromide is converted to the corresponding nitrile by, for example, treatment with copper cyanide in a solvent such as DMF. Typically, the reaction mixture is heated to 160 ° C and maintained at this temperature for several hours, typically 12, to produce the required product. Alternatively, the bromine or iodine or triflate is converted to the nitrile by treatment with a transition metal, such as triphenylphosphine tetrakis palladium and zinc cyanide. The mixture is then heated in a solvent such as DMF, typically at a temperature of 80 ° C for several hours or until the reaction is judged to be complete by, for example, TLC.

Stage e: Nitrile can be converted to amidine by several procedures. Two useful methods include: conversion of nitrile to hydroxyamidine which is achieved by allowing the nitrile to react with hydroxylamine in methanol at room temperature. Typically, the hydroxylamine hydrochloride is added to the nitrile containing the substrate at room temperature and the reaction is initiated by the addition of the base such as potassium carbonate or diisopropylethylamine. Amidoxime can be reduced directly to amidine, but is typically activated by the addition of acetic anhydride or trifluoroacetic anhydride to produce the O-acylated or O-trifluoroacetyl, intermediate, which can be isolated or alternatively used directly in the subsequent reduction step. The reduction with Pd / C is carried out in acetic acid / acetic anhydride or trifluoroacetic acid / trifluoroacetic anhydride. Alternatively, the nitrile can be treated with anhydrous HCl in an alcohol solvent such as methanol to produce the ether imine hydrochloride. This intermediate is subsequently heated with an ammonium source to produce the expected amidine. Typical sources of ammonium include ammonium in methanol or ammonium acetate and ammonium chloride. Scheme 4 represents an alternate procedure for preparing the indispensable compounds of Formula I. It is particularly useful for introducing heterocyclic functionality into C-3.

Scheme 4 Step a: The treatment of hydroquinolin-2-one with strong base, such as butyl lithium and subsequently tributylstannyl chloride or hexabutyldistannan, easily produces the corresponding 3-stanyl quinolin-2-one.

Step b: The addition of the stannane to a solution of 3-bromobenzonitrile in a solvent such as THF, DMF, toluene or dioxane and in the presence of palladium such as Pd (PPh3) 2Cl2 or Pd (PPh3) 4 with the application of heat such as reflux produces the 3-aryl (or the 3-heteroaryl adduct in the case of a substituted halo heterocycle).

Stages c-f: Typical procedures for these transformations are available in the above schemes. The substituted acetic acid derivatives used in these reactions are prepared by various standard procedures. For example, substituted benzoic acids or benzochlorides can be made in accordance with Scheme 5.

Step a: The substituted benzoic acid is converted to the corresponding acid chloride with, for example, oxalyl chloride and the catalytic DMF in a solvent such as methylene chloride at 0 ° C at room temperature over a period of several hours, such as 1 to 4 hours.

Step b: The addition of ethereal diazomethane to the acid chloride in, for example, ether at about 5 ° C. The mixture is subsequently stirred for 1 hour at room temperature at which, in situations of advantage, the acid chloride typically goes into solution and precipitates the intermediary diazo species from the solution. Rearrangement with silver oxide, freshly prepared from silver nitrate and aqueous sodium hydroxide in an alcohol solvent such as methanol at reflux, yields the methyl acetic acid ester. During the reaction, nitrogen loss is observed as effervescence and forms a silver mirror. The replacement of methanol with water produces the corresponding acid.

Step c: The conversion of the methyl ester is carried out by the addition of aqueous base, such as lithium hydroxide in a solvent such as THF / methanol / water and stirring the reaction mixture at room temperature for several hours.

The compounds of the present invention are further characterized by their ability to inhibit the catalytic activity of factor Xa, which is demonstrated in the following tests. The compounds of the present invention can be prepared by tests by dissolving them in a stabilizer to give solutions whose concentrations vary from 1 to 100 μM. In a test for determining the inhibitory dissociation constant, Ki, for a given compound, a fluorogenic or chromogenic substrate of factor Xa will be added to a solution containing a test compound and factor Xa; the catalytic activity resulting from the enzyme was determined spectrophotometrically. This test is well known to those skilled in the art and is commonly used to determine antithrombotic activity. The compounds of the present invention can be used as anticoagulants in vitro or ex vivo as in the case of activation by contact with foreign thrombogenic surfaces as found in the channel used in extracorporeal deviations. The compounds of the invention can also be used to cover the surface of said thrombogenic ducts. For this purpose, the compounds of the invention can be prepared as lyophilized powders, redissolved in an isotonic saline solution or a similar diluent and added in an amount sufficient to maintain the blood in an anticoagulated state. The therapeutic agents of the present invention can be administered alone or in combination with pharmaceutically acceptable carriers. The proportion of each carrier is determined by the solubility and chemical nature of the compound, the route of administration and standard pharmaceutical practice. For example, the compounds can be injected parenterally; either intramuscularly, intravenously or subcutaneously. For parenteral administration, the compound can be used in the form of sterile solutions containing other solutes, for example, enough saline or glucose solution to render the solution isotonic. The compounds can be administered orally in the form of tablets capsules or granules containing suitable excipients such as starch, lactose, white sugar and the like. The compounds may also be administered sublingually in the form of troches or lozenges in which each active ingredient is mixed with sugar or corn syrup, flavoring and coloring agents and subsequently dehydrated sufficiently to make the appropriate mixture to compress it into a solid form. The compounds may be administered orally in the form of solutions which may contain flavoring and / or coloring agents. Typical formulations will contain from about 5 to 95 weight percent of a compound of the invention. The amount of the compound of the invention to be used to prevent and treat thrombotic disorders is that amount which is effective to prevent or treat the condition without causing unacceptable side effects. Such effective amounts will be from about 0.01 mg / kg to about 500 mg / kg, preferably from about 1 mg / kg to about 100 mg / kg. The doctors will determine the precise doses of the therapeutic agents present that are the most appropriate. The doses may vary according to the route of administration and the particular compound selected. In addition, the doses may vary with the particular patient being treated. When the composition is administered orally, typically a greater amount of the active agent will be required to produce the same effect as that caused with a minor amount provided parenterally. To further assist the understanding of the present invention, the following non-limiting examples of said factor Xa inhibitor compounds are provided. The following examples, of course, should not be construed as specifically limiting the present invention, variations currently known or further developed, are within the scope of one skilled in the art and considered to fall within the scope of the present invention as described. in this document. The preferred compounds of the present invention are synthesized using conventional preparation steps and recovery methods known to those skilled in the art of organic and bio-organic synthesis, because they provide a new and unique combination for the complete synthesis of each compound. The preferred synthetic routes for intermediates involved in the synthesis, as well as the resulting anti-thrombotic compounds of the present invention are the following.

EXAMPLES In general, the evaporation of the reaction mixtures is carried out by rotary evaporation under vacuum at room temperature of 18 ° C to 25 ° C or at elevated temperatures above 50 ° C. Chromatography, preferably by liquid chromatography at medium pressure, generally performed in Merck Kieselgel. The reverse phase purification via high pressure liquid chromatography (HPLC), for particular polar compounds was performed on C-18 reverse phase silica gel using an elution gradient of water and acetonitrile containing 0.1% trifluoroacetic acid. The final products displayed mass spectrum and nuclear magnetic resonance (NMR) spectrum consistent with their assigned structure. Intermediates were not typically characterized and their purity was routinely determined by HPLC or thin layer chromatography.

EXAMPLE 1 1- [5- (2,6-Dimethylpiperidine) pentyl] -3- (4-methoxyphenyl) -1,2,3,4-tetrahydro-2-quinolinone Step (a) Preparation of: ac Do- (E) -2- (4-Methoxyphenyl) -3- (2-nitrophenyl) -2-propanoic In a mixture of o-nitrobenzaldehyde (6.19 g, 41.0 mmol) and 4-methoxyphenyl acetic acid (1) (10.02 g, 60.3 mmol) in acetic anhydride (20 mL) was added triethylamine (5.66 mL, 41.0 mmol) and the mixture of reaction was stirred and heated to reflux (150 ° C) for 15 minutes. The solution was cooled, diluted with water and extracted with ethyl acetate (3x200 mL). The combined organic extracts were washed with brine (2x100 ml), dried with magnesium sulfate, filtered and evaporated in vacuo and dried under high vacuum to give 16.20 g as an orange solid. The product (2) was crystallized from ethyl acetate in hexane to give 10.21 g (87%) as a solid. 1 H NMR (DMSO, 300 M): d 8.06 (1 H, m), 7.91 (1 H, s), 7.47 (3 H, m), 6.97 (2 H, d, J = 8.78 Hz), 6.76 (2 H, d , J = 8.97 Hz), 3.68 (3H, s).

Step (b) Preparation of: 3 - (- 4-Methoxyphenyl) -1,2,3,4-tetrahydro-2-quinolinone To (2) (8.22 g, 28.6 mmol) in methanol (100 ml) was added 20% palladium on carbon (1.0 g) and hydrogen at 23 ° C for 3 hours. The mixture was filtered through celite and the filter pad was washed with THF and DMF. The combined filtrate and washings were concentrated in vacuo. The product (3) was crystallized from methanol in water to give 6.4 g (88%) as a solid. 1 H NMR (DMSO, 300 M): d 10.26 (1 H, s), 7.14 (4 H, m), 6.84 (4 H, m), 3.69 (3 H, s), 3.32 (1 H, s), 3.11 (2 H , d, J = 7.69 Hz).

Step (c) Preparation of: 1- (5-Bromopentyl) -3- (4-methoxyphenyl) -1,2,3,4-tetrahydro-2-quinolinone To quinolinone (3) (2.02 g, 7.98 mmol) in DMF (10 mL) was added sodium hydride (0.35 g, 8.75 mmol), and the solution was stirred at 70 ° C for 15 minutes until bubbling stopped . To this solution was added 1,5-dibromopentane (4.37 ml, 31.9 mmol), and the solution was stirred at 70 ° C for an additional 12 hours. The solution was cooled, diluted with water and extracted with ethyl acetate (4x200 ml). The combined organic extracts were washed with brine (2x100 mL), dried with magnesium sulfate, filtered and evaporated in vacuo. The residue was purified on a silica gel column eluted with 20 to 40% ethyl acetate in hexane. The product (4) was isolated 2.43 g (76%) as a yellow oil. 1 H NMR (DMSO, 300 M): d 7.26-6.94 (6H, m), 6.80 (2H, d, J = 7.69 Hz), 3.91-3.78 (2H, m), 3.67 (3H, s), 3.50 (2H , m), 3.33 (1 H, s), 3.12 (2 H, d, J = 6.78 Hz), 1.81 (2 H, m), 1.57 (2 H, m), 1.41 (2 H, m).

Step (d) Preparation of: 1- [5- (2,6-Dimethylpiperidine) pentyl] -3- (4-methoxyphenyl) -1,2,3,4-tetrahydro-2-quinolinone To (4) (0.32 g, 0.795 mmol) was added cis-2,6-dimethylpiperidine (6.2 mL, 46.0 mmol), and the solution was stirred at 70 ° C for 48 hours. The solution was cooled, diluted with water and extracted with ethyl acetate (3x100 ml). The combined organic extracts were washed with saturated sodium bicarbonate (2 x 100 mL), washed with brine (2 x 100 mL), dried with magnesium sulfate, filtered and evaporated in vacuo. The residue was purified by preparative HPLC (Vydac 218TP1022 C18, was eluted with a mixture of solvents consisting of (i) 0.1% trifluoroacetic acid in water and (i) 0.1% trifluoroacetic acid in acetonitrile, gradient profile 95: 5 (!) :( i) to 60: 40 (i) :( ii) for 90 minutes, flow rate 20 ml / minute,? = 214 nM) and lyophilized to give 276 mg (78%) of the product (5) as an oil. 1 H NMR (DMSO, 400 MHz): d 7.28-6.98 (6H, m), 6.82 (2H, d, J = 8.68 Hz), 3.99-3.81 (4H, m), 3.70 (3H, s), 3.24-3.15 (3H, m), 1.86-1.29 (14H, m), 1.24 (6H, m). Cl MS M + 1 = 437. HPLC: RT = 14.4 min. (Beckman 235328 C-18 5 μm 4.6 mm x 25 cm, eluting with a mixture of solvents consisting of (i) 0.1% trifluoroacetic acid in water and (i) 0.1% trifluoroacetic acid in acetonitrile, gradient profile 80: 20 (i) :( ii) at 10:90 (i) :( i¡) for 23 minutes, flow rate 1.5 ml / minute,? = 214 nM).

EXAMPLE 2 3- (1 -5 - [(2r?, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3 quinolinyl) -4-hydroxybenzenecarboximidamide Step (a) Preparation of: 3 - [(E) - (2-nitrophenyl) methylidene] -1-benzofuran-2-one Ortho-hydroxyphenyl acetic acid (1.835 g, 0.012 mmol) was added to a mixture of ortho-nitrobenzaldehyde (1.835 g, 0.012 mmol), acetic anhydride (10 mL) and triethylamine (1.7 mL, 0.12 mol) and subsequently the mixture was heated at 140 ° C for 15 minutes. The mixture was cooled to 80 ° C, at which point water (10 ml) was added carefully. The aforesaid material was washed with methanol and dried to produce the required product (7) (0.905 g, 28%). An additional amount of product (1523 g) was coated from the filtrate. 1 H NMR (DMSO, 400 MHz): d 8.36 (1 H, d, J = 8.3 Hz), 8.15 (1 H, s), 8.0-7.8 (3 H, m), 7.42 (1 H, t, J = 7.0 Hz), 7.31 (1 H, d, J = 7.5 Hz), 7.04 (2H, m). APCI MS 267.

Step (b) Preparation of: 3- (2-hydroxyphenyl) -3,4-dihydro-2 (1W) -quinolinone 8 To 3 - [(E) - (2-nitrophenyl) methylidene] -1-benzofuran-2-one (7) (2.18 g, 7.65 mmol) in methanol (70 mL) and THF (30 mL) was added Pd / C to 20% (0.050 g) and the hydrogenated mixture for 5 hours. Filter and chromatograph, eluting 30% EtOAc to 50% EtOAc in hexane to provide the required product (8) (0.913 g, 49%). 1 H NMR (DMSO, 300 MHz): d 9.52 (1 H, s), 7.15 (2 H, m), 7.05 (1 H, m), 6.97 (1 H, m), 6.89 (2 H, d, J = 7.3 Hz), 6.83 (1 H, d, J = 7.9 Hz), 6.67 (1 H, t, J = 7.3 Hz), 3.96 (1 H, dd, J = 10.4 Hz, 6.4 Hz), 3.19 (1 H, dd, J = 15.8 Hz, 10.6 Hz), 2.99 (1 H, dd, J = . 8 Hz, 10.6 Hz). APC I MS 240. Analysis Ci5H? 3N ?? 2: Required: C, 75.30; H, 5.48; N, 5.85. Found: C, 74.95; H, 5.51; N, 5.61.

Step (c) Preparation of: 3- (5-bromo-2-hydroxyphenyl) -3,4-dihydro-2 (1W) -quinolinone 8 A 3- (2-hydroxyphenyl) -3,4-dihydro-2 (1 H) -quinolinone (8) (0.650 g, 2.72 mmol) in disulphide on carbon (10 mL) and methylene chloride (10 mL) was added. slowly added (10 minutes) a solution of bromine (0.17 ml, 3.30 mmol) in disulphide on carbon (5 ml). After 2 hours a precipitate had been completely formed which was collected and washed with ether (2 x 10 ml). This produced the required product (9) (0.738 g, 85%). 1 H NMR (DMSO, 400 MHz): d 10.29 (1 H, s), 7.21 (2 H, m), 7.16 (2 H, m), 6.91 (2 H, m), 6.78 (1 H, d, J = 8.5 Hz ), 3.93 (1 H, dd, J = 12.0 Hz, 6.4 Hz), 3.19 (1 H, dd, J = 15.4 Hz, 12.1 Hz), 2.97 (1 H, dd, J = 15.4 Hz, 6.3 Hz). APCI MS 318/320.

Step (d) Preparation of: 3- [2- (benzyloxy) -5-bromophenyl] -3,4-dihydro-2 (1 y) -quinolinone 9 10 To 3- (5-bromo-2-hydroxyphenyl) -3,4-dihydro-2 (1H) -quinolinone (9) (3.16 g, 9.94 mmol) in DMF (15 mL) was added cesium carbonate (5.2 g, 31 mmol) and subsequently benzyl bromide (1.18 ml, 9.92 mmol). The mixture was stirred at room temperature for 16 hours, diluted with ethyl acetate (200 ml), washed with brine (100 ml) and then dried over MgSO 4. Chromatographed, silica gel, eluting 20% EtOAc in hexane, yielding the required product (10) (2.77 g, 68%). 1 H NMR (CDCl 3, 300 MHz): d 8.40 (1 H, brs), 7.30 (7H, m), 7.17 (1 H, d), J = 7.5 Hz), 6.98 (1 H, t, J = 6.3 Hz ), 6.84 (1 H, d, J = 8.3 Hz), 6.78 (1 H, d, J = 7.9 Hz), 5.07 (2 H, s), 4.09 (1 H, dd, J = 13.2 Hz, 6.6 Hz) , 3.38 (1 H, dd, J = 15.2 Hz, 13.2 Hz), 2.99 (1 H, dd, J = 15.8 Hz, 6.6 Hz). APCI MS 408/410.

Step (e) Preparation of: 4- (benzyloxy) -3- (2-oxo-1,2,3,4-tetrahydro-3-quinolinyl) benzenecarbonitrile 11 A 3- [2- (Benzyloxy) -5-bromophenyl] -3,4-dihydro-2 (1 / - /) -quinolinone (10) (2.77 g, 6. 79 mmol) in DMF (8 ml) was added copper (I) cyanide (2.7 g, 30 mmol) and subsequently the mixture was heated to an oil bath temperature of 160 ° C for 16 hours. The mixture was cooled, diluted with ethyl acetate (200 mL) and washed with aqueous NH OH (2 x 100 mL). After washing with brine (2 x 100 mL) and drying over MgSO 4, the product was isolated by chromatography, silica gel, eluting 30% to 50% ethyl acetate in hexane, to yield (11) (1.077 g, 45%). %). 1 H NMR (DMSO, 300 MHz): d 10.40 (1 H, s), 7.77 (1 H, dd, J = 8.4 Hz, 2.0 Hz), 7.69 (1 H, d, J = 2.2 Hz), 7.40-7.1 (8 H , m), 6.89 (2H, m), 5.22 (2H, m), 4.04 (1 H, dd, J = 13.5 Hz, 6.6 Hz), 3.31 (1 H, dd, J = 15.7 Hz, 13.2 Hz), 2.93 (1 H, dd, J = 15.7 Hz, 6.6 Hz). APCI MS 355 Step (f) Preparation of: 4- (benzyloxy) -3- [1- (5-bromopentyl) -2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl] benzenecarbonitrile 12 To 4- (benzyloxy) -3- (2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -benzenecarbonitrile (11) (0.270 g, 0.76 mmol) in DMF (3 mL) was added hydride sodium (60% in oil) (0.035 g, 0.9 mmol) and 1, 5-dibromopentane (0.5 ml, 3.67 mmol) and subsequently the solution was stirred for 1 hour. The solution was diluted with 1 N HCl (10 mL) and extracted with ethyl acetate (2 x 100 mL). The combined organic extracts were washed with brine (2 x 100 mL), dried with magnesium sulfate, filtered and evaporated in vacuo. The residue was purified on a silica gel column eluted with 20% ethyl acetate in hexane. The product (12) was isolated 0.230 g (60%) as an oil. 1 H NMR (CDCIA, 300 MHz): d 7.57 (1 H, dd, J = 8.6 Hz, 2.0 Hz), 7.42 (1 H, d, J = 2.0 Hz), 7.40-7.2 (6H, m), 7.13 ( 1 H, d, J = 6.4 Hz), 7.02 (3H, m), 5.15 (2H, m), 4.04 (1 H, dd, J = 12.9 Hz, 5.9 Hz), 3.98 (2H, m), 3.39 ( 2H, t, J = 6.6 Hz), 3.30 (1 H, dd, J = 15.4 Hz, 12.9 Hz), 2.96 (1 H, dd, J = 15.4 Hz, 5.9 Hz), 1.88 (2H, m), 1.75 -1.45 (4H, m). APC I MS 503/505.

Step (g) Preparation of: 3- (1 -5 - [(2?, 6S) -2,6-dimethyltetrahydro-1 (2A7) -pyridinyl] pentyl-2-oxo-1,2,3,4-tetrahydro -3-quinolinyl) -4-hydroxybenzenecarboximidamide 12 13 A (12) 4- (benzyloxy) -3- [1- (5-bromopentyl) -2-oxo-1, 2,3,4-tetrahydro-3-quinolonyl-benzenecarbonitrile (0.23 g, 0.457 mmol) was added c / s-2,6-dimethylpiperidine (5 mL, 37.0 mmol) and the solution was stirred at 70 ° C for 48 hours. The mixture was evaporated in vacuo. HPLC: RT = 18.06 min. (Beckman 235328 C18 5 μm 4.6 mm x 25 cm, eluted with a mixture of solvents consisting of (i) 0.1% trifluoroacetic acid in water and (ii) 0.1% trifluoroacetic acid in acetonitrile, gradient profile 80:20 ( i) :( ii) at 10:90 (i) :( ii) for 23 minutes, flow rate 1.5 ml / minute,? = 214 nM). This mixture was dissolved in ethanol (10 ml) and treated with hydrochloride, hydroxylamine (0.70 g, 10 mmol) and diisopropylethylamine (1.8 ml, 10 mmol). After stirring for 24 hours, the reaction mixture was evaporated and HPLC indicated that the reaction was complete to produce 4- (benzyloxy) -3- (1-5 - [(2R, 6S) -2,6-dimethyltetrahydro- 1 (2 - /) - pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -? -hydroxybenzenecarboximidamide RT = 12.37 min. (Beckman 235328 C18 5 μm 4.6 mm x 25 cm, eluted with a mixture of solvents consisting of (i) 0.1% trifluoroacetic acid in water and (ii) 0.1% trifluoroacetic acid in acetonitrile, gradient profile 80:20 ( i) :() at 10:90 (i) :( ii) for 23 minutes, flow rate 1.5 ml / minute,? = 214 nM). To this mixture was added trifluoroacetic acid (5 ml) and trifluoroacetic anhydride (1 ml). After 2 hours the reaction mixture was evaporated and the HLPC indicated that the reaction was complete RT = 21.5 min. (Beckman 235328 C18 5 μm 4.6 mm x 25 cm, eluted with a mixture of solvents consisting of (i) 0.1% trifluoroacetic acid in water and (ii) 0.1% trifluoroacetic acid in acetonitrile, gradient profile 80:20 ( i) :( ii) at 10:90 (i) :( ii) for 23 minutes, flow rate 15 ml / minute,? = 214 nM).

The residue was redissolved in trifluoroacetic acid (10 ml) and treated with 20% Pd / C (0.05 g) and hydrogenated for 16 hours. The mixture was filtered through celite, treated with water 1 ml and then evaporated. The residue was purified by preparative HPLC (Vydac 218TP1022 C18, eluted with a mixture of solvents consisting of (i) 0.1% trifluoroacetic acid in water and (ii) 0.1% trifluoroacetic acid in acetonitrile, gradient profile 95: 5 ( i) :( ii) at 60:40 (i) :( ii) for 90 minutes, flow rate 20 ml / minute,? = 214 nM), was converted to the HCl salt by ion exchange chromatography and subsequently was lyophilized to give dihydrocioride 3- (1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro- 3-quinolinyl) -4-hydroxybenzenecarboximidamide (0.123 g, 50%) of the product (13) as a powder. Cl MS M + 1 = 463. HPLC: RT = 10.1 min. (Beckman 235328 C18 5 μm 4.6 mm x 25 cm, eluted with a mixture of solvents consisting of (i) 0.1% trifluoroacetic acid in water and 0.1% trifluoroacetic acid in acetonitrile, gradient profile 80:20 (i): (ii) at 10:90 (¡) :( ¡) for 23 minutes, flow rate 1.5 ml / minute,? = 214 nm). 1 H NMR (DMSO, 400 MHz): d 10.89 (1 H, s), 10.2 (1 H, s9brs), 9.09 (2 H, s), 8.8 (1 H, s), 7.62 (2 H, m), 7.20 ( 3H, m), 7.0 (2H, m), 3.90 (3H, m), 3.40 (1H, m), 3.20 (2H, m), 3.00 (1H, m), 2.85 (2H, m), 1.80 -1.2 (18H, m). APCI MS 463 EXAMPLE 3 3- (1 -5 - [(2?, 6S) -2,6-dimethyl-tetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinoline l) benzenecarboximidamide Step (a) Preparation of: acid- (E) -2- (3-hydroxyphenyl) -3- (2-nitrophenyl) -2-propanoic 14 Within a mixture of o-nitrobenzyl aldehyde (19.22 g, 127 mmol) and 3-hydroxyphenyl acetic acid (19.30 g, 127 mmol) in acetic anhydride (87 mL) was added triethylamine (17.5 mL, 126 mmol) and the reaction mixture it was stirred and heated to reflux (150 ° C) for 45 minutes. The solution was diluted with water (200 ml), cooled, diluted with 2N NaOH (200 ml) and washed with ether. The aqueous solution was subsequently acidified with 6N HCl in a pH of 3 and stirred for 3 hours. The solid was collected and dried under high vacuum at 45 ° C to give 23.15 g (64%) of the required product (14). 1 H NMR (DMSO, 300 MHz): d 8.09 (1 H, m), 7.93 (1 H, s), 7.48 (2 H, m), 7.00 (2 H, m), 6.59 (1 H, m), 6.48 ( 2H, m). Cl MS M + 1 = 285.

Step (b) Preparation of: 3- (3-hydroxyphenyl) -3,4-dihydro-2 (1H) -quinolinone To (E) -2- (3-hydroxyphenyl) -3- (2-nitrophenyl) -2-propanoic acid (14) (26.29 g, 92.0 mmol) in methanol (600 mL) was added palladium on carbon at 20 ° C. % (1.5 g) and the mixture is hydrogen at 45 PSI of H2 at 30 ° C for 3.5 hours. The mixture was filtered through celite and the filter pad was washed with MeOH. The combined filtrate and washings were concentrated in vacuo. The product (15) was crystallized from methanol in water to give 17.95 G (82%) as a solid. 1 H NMR (DMSO, 400 MHz): d 10.30 (1 H, s), 9.31 (1 H, s), 7.14 (2 H, m), 7.05 (1 H, m), 6.90 (2 H, m), 6.61 ( 3H, m), 3.70 (1 H, m), 3.20-3.06 (2H, m) Step (c) Preparation of: 3- (2-oxo-1,2,3,4-tetrahydro-3-quinolinyl) phenyl trifluoromethanesulfonate 16 To 3- (3-hydroxyphenyl) -3,4-dihydro-2 (1H) -quinolinone (15) (3.01 g, 12.6 mmol) in THF (40 mL) was added sodium hydride (0.55 g, 13.8 mmol) and the solution was stirred at room temperature for 5 minutes. To this solution was added N-phenyltrifluoromethanesulfonimide (4.92 g, 13.8 mmol) and the solution was stirred at room temperature for 1 hour. The solution was cooled, diluted with water and extracted with ethyl acetate (3 x 200 mL). The combined organic extracts were washed with brine (2 x 200 mL), dried with magnesium sulfate, filtered and evaporated in vacuo. The residue was purified on a silica gel column and eluted with 20 to 40% ethyl acetate in hexane. The product (16) was isolated 4.29 g (92%) as a yellow solid. 1 H NMR (CDCl 3, 400 MHz): d 8.06 (1 H, s), 7.40-7.15 (6 H, bm), 7.00 (1 H, m), 6.76 (1 H, m), 3.87 (1 H, m) , 3.22 (2H, m). Cl MS M + 1 = 372.

Step (d) Preparation of: 3- (2-oxo-1,2,3,4-tetrahydro-3-quinolini-Benzenecarbonitrile 16 17 To 3- (2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) phenyl trifluoromethanesulfonate (16) (0.410 g, 1.11 mmol) in DMF (5 mL) was added zinc cyanide (0.078 g, 0.690 mmol) and tetrakis (triphenylphosphine) palladium (0) (0.128 g, 0.11 mmol). The reaction mixture was stirred and heated to 100 ° C for 1 hour. The solution was cooled, diluted with water (200 ml) and 2 M sulfuric acid and extracted with ethyl acetate (3 x 200 ml). The combined organic extracts were washed with brine (2 x 100 mL), dried with magnesium sulfate and evaporated in vacuo. The product (17) was crystallized from hexane and ethyl acetate to give (0.222 g, 81%) as a solid. 1 H NMR (CDCb, 300 MHz): d 8.23 (1 H, s), 7.70-7.18 (6H, bm), 7.04 (1 H, m), 6.81 (1 H, m), 3.89 (1 H, m) , 3.24 (2H, m). Cl MS M + 1 = 249.

Step (e) Preparation of: 3- [1- (5-bromopentyl) -2-oxo-1,2,3,4-tetrahydro-3-quinolinyl] benzenecarbonitrile To 3- (2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarbonitrile (17) (2.76 g, 1.1 mmol) in DMF (15 mL) at 0 ° C was added 1.5 dibromopentane (10.22 g, 44.4 mmol) and sodium hydride (0.48 g, 12.0 mmol) and the solution was stirred at this temperature for 3 hours. The solution was diluted with water and extracted with ethyl acetate (3 x 200 mL). The combined organic extracts were washed with brine (2 x 100 mL), dried with magnesium sulfate, filtered and evaporated in vacuo. The residue was purified on a silica gel column eluted with 20% ethyl acetate in hexane. The product (18) was isolated 1.59 g (36%) as a yellow oil. 1 H NMR (300 MHz, CDCl 3): d 7.58-7.28 (5H, bm), 7.20 (1 H, m), 7.05 (2H, m), 3.99 (2H, m), 3.85 (1 H, m), 3.41 ( 2H, m), 3.19 (2H, m), 1.91 (2H, m), 1.70 (2H, m), 1.54 (2H, m). Cl MS M + 1 = 397/399, M-1 = 395/396.

Step (f) Preparation of: 3- (1-5 - [(2 /? 6S) -2,6-dimethyltetrahydro-1 (2W) -pyridinyl] pentyl-2-oxo-1,2,3,4- tetrahydro-3-quinolinyl) benzenecarbonitrile 18 Í9 A 3- [1- (5-bromopentyl) -2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl] -benzenecarbonitrile (18) (1.59 g, 4.00 mmol) in DHF (3 mL) is added cis-2,6-dimethylpiperidine (10 mL, 74.mmol). The solution was stirred at 70 ° C for 24 hours.

The solution was cooled, diluted with water and extracted with ethyl acetate (3 x 200 mL). The combined organic extracts were washed with saturated sodium bicarbonate (2 x 100 mL), washed with brine (2 x 100 mL), dried with magnesium sulfate, filtered and evaporated in vacuo, co-evaporated with toluene and dried. dried under high vacuum to give (19) in a quantitative production as a yellow oil. 1 H NMR (CDCl 3l 300 MHz): d 7.50-6.96 (8H, bm), 3.91 (2H, m), 3.80 (1H, m), 3.13 (2H, m), 2.67 (2H, bs), 2.36 (2H , bs), 1.66-1.15 (12H, bm), 1.01 (6H, m). HPLC: RT = 14.25 min. (Beckman 235328 C18 5 μm 4.6 mm x 25 cm, eluted with a mixture of solvents consisting of (i) 0.1% trifluoroacetic acid in water and (i) 0.1% trifluoroacetic acid in acetonitrile, gradient profile 80:20 ( i) :( ii) at 10:90 (i) :( ii) for 23 minutes, flow rate 1.5 ml / minute,? = 214 nM).

Step (g) Preparation of: 3 (1-5 - [(2?, 6S) -2,6-dimethyltetrahydro-1 (2W) -pyridinyl] pentyl-2-oxo-1,2,3,4-tetrahydro- 3-quinolinyl) -N-hydroxybenzenecarboximidamide 9 20 A 3- (1-5 - [(2R; 6S) -2,6-dimethyltetrahydro-1 (2H) -piperidinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarbonitrile ( 19) (1.00 g, 2.33 mmol) in methanol (20 mL) was added hydroxylamine hydrochloride (0.40 g, 5.76 mmol) and diisopropylethylamine (0.40 mL, 2.30 mmol). The solution was stirred at room temperature for 16 hours. The solvent was evaporated in vacuo and the oil was dried under high vacuum to give (20) in quantitative production. HPLC: RT = 9.22 min. (Beckman 235328 C18 5 μm 4.6 mm x 25 cm, eluted with a mixture of solvents consisting of (i) 0.1% trifluoroacetic acid in water and (ii) 0.1% trifluoroacetic acid in acetonitrile, gradient profile 80:20 ( i) :( ii) at 10:90 (i) :( ii) for 23 minutes, flow rate 1.5 ml / minute,? = 214 nM).

Step (h) Preparation of: 3- (1-5 [(2 /? 6S) -2,6-dimethyltetrahydro-1 (2A7) -pyridinyl] pentyl-2-oxo-1,2,3 , 4-tetrahydro-3-quinolinyl) -? / - [(2,2,2-trifluoroacetyl) oxy] benzenecarboximidamide twenty-one A 3- (1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl [pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -N -hydroxybenzenecarboximidamide (20) (1.07 g, 23.1 mmol) was added trifluoroacetic anhydride (10 mL) and the solution was stirred at room temperature for 3 hours. The solvent was removed in vacuo to give (21) as a yellow oil in quantitative production. HPLC: RT = 18.37 min. (Beckman 235328 C18 5 μm 4.6 mm x 25 cm, eluted with a mixture of solvents consisting of (i) 0.1% trifluoroacetic acid in water and (ii) 0.1% trifluoroacetic acid in acetonitrile, gradient profile 80:20 ( i) :( ii) at 10:90 (i) :( ii) for 23 minutes, flow rate 1.5 ml / minute,? = 214 nM).

Step (i) Preparation of: 3- (1-5 [(2?, 6S) -2,6-dimethyltetrahydro-1 (2) -pyridinyl] pentyl-2-oxo-1,2,3,4-tetrahydro- 3-quinolinyl) benzenecarboximidamide 2! to A 3- (1-5 - [(2R.6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) - / V - [(2,2,2-trifluoroacetyl) oxy] -benzenecarboximidamide (21) (1.27 g, 23.1 mmol) in trifluoroacetic acid (16 ml) was added 20% palladium on carbon (0.2 g) and the Mix hydrogen 33 PSI H2 at 33 ° C for 3 hours. The mixture was filtered and the filter pad was washed with trifluoroacetic acid. The combined filtrate and washings were evaporated in vacuo and the residue was purified by preparative HPLC (Vydac 218TP54 C18, eluting with a mixture of solvents consisting of (i) 0.1% trifluoroacetic acid in acetonitrile, gradient profile 95: 5 (i) :( ii) to 60:40 (i) :( ii) for 90 minutes, speed of flow 20 ml / minute,? = 214 nm) and lyophilized to give the TFA salt of (22) as a grayish solid. To the solid in acetonitrile (2 ml) and water (2 ml) were added ion exchange resin Amberlite® IRA-400 (Cl). The mixture was filtered through additional resin and the filtrate was lyophilized to give 619 mg (52%) of (22) as a grayish solid. 1 H NMR (DMSO, 400 MHz): d 9.35 (1 H, s), 9.07 (2 H, s), 7.66 (2 H, m), 7.49 (2 H, m), 7.21 (3 H, m), 6.97 (1 H , m), 3.95 (3H, m), 3.42 (4H, bs), 3.35-2.86 (6H, bm), 1.75-1.26 (8H, bm), 1.20 (6H, m). Cl MS M + 1 = 447. HPLC: RT = 9.65 min. (Beckman 235328 C18 5 μm 4.6 mm x 25 cm, eluted with a mixture of solvents consisting of (i) 0.1% trifluoroacetic acid in water and (i) 0.1% trifluoroacetic acid in acetonitrile, gradient profile 80:20 ( i) :( ii) at 10:90 (i) :( ii) for 23 minutes, flow rate 1.5 ml / minute,? = 214 nM).

EXAMPLE 4 3- [3- (aminomethyl) phenyl] -1-5 [(2?, 6S) -2,6-d.methyltetrahydro-1 (2H) -? Iridinyl] pentyl-3,4-dihydro-2 ( 1 / -r) -quinolinone 19 23 3- (1-5 [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarbonitrile (19) (0.71 g, 16.5 mmol) was hydrogen on Raney nickel (0.5 g) in methanol (45 ml) and triethylamine (5 ml) for 4 hours at room temperature. The mixture was filtered and the filter pad was washed with methanol. The combined filtrate and washings were evaporated in vacuo and the residue was purified by preparative HPLC (Vydac 218TP54 C18, eluted with a mixture of solvents consisting of (i) 0.1% trifluoroacetic acid in water and (ii) 0.1 trifluoroacetic acid. % in acetonitrile, gradient profile 95: 5 (i) :() to 60:40 (i) :( ii) for 90 minutes, flow rate 20 ml / minute,? = 214 nm) and lyophilized to give the TFA salt of (23) as a grayish solid. Oily exchange solid in acetonitrile (2 ml) and water (2 ml) was added ion exchange resin Amberlite® IRA-400 (Cl). The mixture was filtered through additional resin and the filtrate was lyophilized to give 380 mg (45%) of (23) as a grayish solid. 1 H NMR (DMSO, 400 MHz): d 8.38 (2H, s), 7.35-7.10 (7H, m), 6.95 (1 H, m), 3.92 (4H, m), 3.83 (1H, m), 3.36 (4H, s), 3.23-2.86 (6H, bm), 1.75-1.30 (8H, bm), 1.21 (6H, m). Cl MS M + 1 = 434. HPLC: RT = 9.56. (Beckman 235328 C18 5 μm 4.6 mm x 25 cm, eluted with a mixture of solvents consisting of (i) 0.1% trifluoroacetic acid in water and (ii) 0.1% trifluoroacetic acid in acetonitrile, gradient profile 80:20 (i) :( ii) a :90 (i) :( ii) for 23 minutes, flow rate 1.5 ml / minute,? = 214 nM).

The compounds of the invention have demonstrated the inhibitory activity of factor Xa in the standard tests commonly employed by those skilled in the art.

Determination of Factor Xa IC50 and Constants K1 The ability of compounds to act as inhibitors of the catalytic activity of human factor Xa is indicated by determining the concentration of the test substance which inhibits by 50% (IC50) the ability of the human factor Xa to penetrate the chromogenic substrate S2765 (N-CBz-D-Arg-L-Gly-L-Arg-p-nitrianiline, 2HCl, DiaPharma). Typically, 145 μL human factor Xa (1 nM final, Enzyme Research Laboratories) in 10 mM HEPES, 150 mM NaCl, 0.1% BSA, pH 7.4 (HBSA stabilizer) and 5 μL of the test substrate in DMSO (2% final) they were incubated for 60 minutes at room temperature. Following preheating at 37 ° C for 5 minutes, 100 μL of S2765 in HBSA stabilizer was added to this mixture. The hydrolysis rate S2765 was determined at 37 ° C by measuring the initial rate of change of optical density at OD405 nM every 10 seconds for 5 minutes using a Kinetic Microplate Reader ThermoMax®. For the determinations of K, the conditions of the test were essentially the same as the previous ones except for the following. The concentration of factor Xa was 50 pM and that the substrate, in this case a fluorogenic S2765 (for example, S2765 labeled AMC instead of pNA, California Peptide Research), was in the range of 10 to 500 μM. The test compound and substrate in HBSA stabilizer were incubated as indicated above and the reaction was started with enzyme stabilizer. The information (constant velocity state at various substrate concentrations and inhibitors) of the competitive inhibition was analyzed using the methods described by Segel (Enzyme Kinetics, Wiley Interscience Publications, 1993). A non-linear regression program, Kaleidograph and / or Microsoft Excel, was used to estimate the kinetic parameters (Km Vma and K¡) by using Michaelis-Menten and the reciprocal adjustments of the Dixon diagram.

Determination of the Thrombin IC50 and the K2 Constants The ability of the compounds to act as inhibitors of the catalytic activity of human thrombin is indicated by the determination that the concentration of the substrate proves that it inhibits by 50% (IC50) the ability of human thrombin to penetrate the chromogenic substrate Chromozyme TH (Tosyl-Gly-Pro-Arg-pNA * Ac, Boehringer Mannheim). Typically, 145 μL of human thrombin (0.75 nM, Enzyme Research Laboratories) in an HPB stabilizer (10 mM HEPES, 100 mM NaCl, 0.05% BSA, 0.1% PEG-800, pH 7.4) and 5 μL of test substance in DMSO (final 2%) were incubated for 60 minutes at room temperature. Following with preheating at 37 ° C for 5 minutes, 100 μL of Chromozyme TH in HPB stabilizer was added to this mixture. The hydrolysis rate of Chromozyme THF was determined at 37 ° C by the initial rate of change of optical density at OD405 nM every 10 seconds for 5 minutes using a Kinetic Microplate Reader ThermoMax®. For determinations K, the test conditions were essentially the same as those already mentioned except for the following. The concentration of thrombin used was 50 pM and that a fluorogenic TH-Chromozyme (for example, Chromozyme TH with AMC instead of the pNA label, Novabiochem) was in the range of 1 to 40 μM. The test compound and the substrate in HPB stabilizer solution were incubated as above and the reaction was started with the stabilizer-enzyme and ran at 24 ° C. The kinetic analysis was performed as for the determinations of factor Xa K-- Determination of Trypsin IC5o and K.substances. The ability of the compounds to act as inhibitors of the human trypsin catalytic activity is indicated by the determination that the concentration of the substrate proves that it inhibits by 50% (IC 50) the ability of human trypsin to penetrate the substrate. chromogenic S2222 (N-Bz-L-lle-L-Glu-L-Gly-L-Arg-p-nitroaniline HCl, DiaPharma). Typically, 145 μL of human trypsin (0.5 nM final) in 10 mM HEPES, 150 nM NaCl, 0.1% BSA and 5 μL of the test substrate in DMSO (final 2%) were incubated for 60 minutes at room temperature. Following preheating at 37 ° C for 5 minutes, 100 μL of S2222 in HBSA stabilizer (100 μM final) was added to this mixture and the S2222 hydrolysis rate was determined at 37 ° C by measuring the optical density at OD ^ nM every 10 seconds for 5 minutes using a Kinetic Microplate Reader ThermoMax®. For K i determinations, the conditions of the test were essentially the same as those already mentioned except that the reaction was started with enzyme stabilizer and ran at 24 ° C using a substrate range of 10 to 500 μM. The kinetic analysis was carried out as for the determinations of factor Xa K- Determination of the tissue factor / factor Vlla IC50 The ability of the compounds to act as inhibitors of the catalytic activity of the human tissue factor / factor Vlla complex is indicated by the determination of the concentration of the test substrate that inhibits 50% (IC50 the ability of a human recombinant tissue factor / Vlla factor complex to penetrate the Vlla Spectrozyme of the chromogenic substrate (CH3SO2-D-CHA-Arg-pNA * AcOH, American Diagnostica) Typically, 50 μL of the human factor Vlla (Enzyme Research Laboratories) were incubated for 10 minutes as a 1: 1 mixture (of each final 5 nM) with 95 μL of human recombinant tissue factor (American Diagnostica) in a Modified HBSA stabilizer (10 mM Hepes, 5mM CaC, 0.1% BSA, pH 8.0) Subsequently, 5 μL of the test substance in DMSO (2% final) were added and incubated for 60 minutes at room temperature. Following with preheating at 37 ° C for 5 minutes, 100 μL of Vlla Spectrozyme (500 μM final) was added to this mixture in modified HBSA and the speed of hydrolysis Spectrozyme Vlla was determined at 37 ° C by measuring the optical density in an OD405 nM every 10 seconds for 5 minutes using a Kinetic Microplate Reader ThermoMax®.

In Vitro Test for Human Prothrombinase This test demonstrated the ability of the compounds of the invention to inhibit the human prothrombinase complex (PTase) (typically comprising human factor Va, human factor Xa, Ca2 + and phospholipid moiety) and thereby penetration Subsequent prothrombin to the thrombin field. For determination of IC50 (PTase) of the compounds of the invention, PTase activity was expressed by thrombin activity. The PTase reaction was performed in 100 μL of the mixture containing PTase (20 μM) PCPS (Avanti Polar Lipids following a modified procedure from Barenholz et al., Biochemistry, 1977; 16: 2806-2810) within 30 : 70, 2.5 nM human factor Va (Enzyme Research Laboratories) and 2.5 pM human factor Xa (Enzyme Research Laboratories) in modified HEPES stabilizer (10 mM Hepes, 150 mM NaCl, 0.1% PEG-8000, 0.05% BSA , 2.5 mM CaCl2, pH 7.4), 3 μM human prothrombin (Enzyma Research Laboratories) and various concentrations of the test compounds (1 nM to 100 μM in DMSO, 2% final). The reaction was initiated by co-incubation PTase with a test compound for 60 minutes at room temperature, followed by the addition of prothrombin for 6 minutes at room temperature. Then, the reaction was tempered by the addition of 100 μL of 20 mM EDTA. The activity of thrombin (product) is subsequently measured in the presence of 50 μL S2238 (final 250 μM, HD-Phe-Pip-Arg-pNA * Ac, DiaPharma) as substrate by measuring the change at 37 ° C in OD405 nM for 5 minutes at 10-second intervals using a Kinetic Microplate Reader ThermoMax®.

Prothrombin Time Determination (PT) Blood, rat, rabbit, dog and human (typically 1.8 ml) was collected and added to a sodium citrate solution (3.8%) to produce a 1: 10 dilution. After centrifugation (2000 g for 10 minutes), the blood plasma was stored at -70 ° C to 0 ° C. Conventional prothrombin time tests were carried out in the presence of various concentrations of the test compound and the concentration of the test compound required to double the determined coagulation time. Typically, the test compound (50 μL volume of variation concentrations 0.1 μM to 1000 μM) and blood plasma (100 μL volume) were incubated at 37 ° C for 10 minutes and subsequently the tissue thromboplastin, typically Neoplastin, was added. of American Bioproducts with calcium. The fibrin formation and the time required to form a clot was determined using a ST4 Clots Detection System in duplicate. In an ex vivo modification of this test, the drug was administered intravenously or orally to a group of rats or rabbits. Blood samples were collected at various times and the PT coagulation test was performed as described above.

Antithrombotic Model of Arterio-Venous Deviation Stasis In vivo measurements of antithrombotic activity were performed according to the procedure of Vogel et al., Thromb. Res., 1989; 54: 399-410. Briefly, the vena cava was exposed, the collateral veins were ligated and the sutures were located freely around the inferior vena cava. These sutures were tightened after administration of the drug to induce stasis in the ligated portion of the vena cava. After an appropriate time, the thrombus was isolated and weighed. The effect of variation of drug concentrations administered intravenously or orally on thrombus mass reflected thrombotic activity. Alternatively and according to the procedure of Smith et al., Br. J. Pharmacol., 1982; 77: 29-38, the right carotid artery and the left jugular artery were exposed and cannulated. A division that contains silk or compressed cotton threads, is then inserted, which connects the two cannulated veins. Once the drug has been administered, the division is closed and the thrombus that forms on the foreign surface in the division is removed after a period of time. The weight of the clot then reflects the thrombotic activity.

Arterial Thrombosis Model Carotid Arterial Lesion Model Induced with FeCI3 The injury induced with FeCb to the carotid artery in rats was induced according to the method described by Kurz KD, Main RW, Sandusky GE, Thrombosis Research, 1990; 60: 269- 280 and Schumacher WA et al., J. Pharmacology and Experimental Therapeutics, 1993; 267: 1237-1242. Male Sprangue-Dawley rats (375-410 g) were anesthetized with urethane (1500 mg / kg ip). The animals were placed on a heating pad at 37 ° C. The carotid artery was exposed through a mid cervical incision. Saturation dissection was carefully used to isolate the carotid vessel vein. Using forceps, the artery was lifted to provide enough clearance to insert two small pieces of polyethylene tubing (PE-205) underneath it. A temperature probe (Physitemp MT23 / 3) was placed between one piece of tubing and the artery. The lesion was induced by topical application in the carotid artery above the temperature probe of a small disc (3 mm diameter) of Whatman No. 1 filter paper previously immersed in a 35% FeCb solution. The incision area was covered with aluminum foil to protect the FeCb from degradation by light. The temperature of the vein is monitored for 60 minutes after the application of FeCl3 as an indication of blood flow. Changes in vein temperature were recorded in a thermistor (Cole-Palmer Model 08533-41). The time between FeCb application and the time in which the vein temperature decreased abruptly (> 2.4 ° C) was recorded as the time for vein occlusion. The mean occlusion time (MOT), therefore, refers to the occlusion time in animals treated with drugs divided by the control time of occlusion. Inhibitory compounds were given as an intravenous bolus (0.75 mg / kg) followed immediately by an intravenous infusion (50 μg / kg / min via femoral vein). Typically, the compounds of the invention show 50% inhibition of the proteolytic activity of factor Xa on a synthetic substrate in concentrations between 50 μM to 1 nM.

The preceding biological test has been used to establish that the compounds of this invention are useful for preventing and treating thrombotic disorders, for example, venous thrombosis, deep vein thrombosis, thrombophlebitis, arterial embolism, cerebral and coronary arterial thrombosis, cerebral embolism, kidney embolism, pulmonary embolism, recurrent or first myocardial infarction, unstable angina and cerebral infarction, attacks and arteriosclerosis. The compounds of the present invention can be administered alone or in combination with one or more therapeutic agents. These include, for example, other anticoagulants, antiplatelets or platelet inhibiting agents including non-steroidal anti-inflammatory agents such as aspirin, ibuprofen, naproxen sodium, indomethacin, piroxicam and ticlopidine, thrombin inhibitors such as argatroban, efegatran, inogatran, factor Vlla inhibitors, fibrinolytic or thrombolytic agents such as tissue plasminogen activator, urokinase or streptokinase and GP antagonists lllb-lla. The compounds are therefore well adapted to the formulation for convenient administration to mammals for the prevention and treatment of such disorders. The following additional examples illustrate the typical formulations provided by the invention.

Formulation 1 Ingredient Amount Compound of Formulas I-IV 200 mg Sodium Benzoate 5 mg Isotonic Saline 1000 ml The above ingredients are mixed and dissolved in the saline for IV administration to a human suffering, for example arterial thrombosis.

Formulation 2 Ingredient Amount Compound of Formulas l-IV 100 mg Cellulose, microcrystalline 400 mg Stearic acid 5 mg Silicon dioxide 10 mg Sugar, confectionery 50 mg The ingredients are liquefied to uniformity and compressed into a tablet that is well adapted for oral administration to a human to prevent, for example, cerebral infarction.

Formulation 3 Ingredient Amount Compound of Formulas l-IV 200 mg Starch, dry 250 mg Magnesium stearate 10 mg The ingredients are combined and ground to provide appropriate material for filling the hard gelatin capsules administered to humans suffering from, for example, venous thrombosis.

Formulation 4 Ingredient Quantity% weight / weight Compound of Formulas l-IV 1 Polyethylene glycol 1000 74.5 Polyethylene glycol 4000 24.5 The ingredients are combined via fusion and then poured into molds containing 2.5 g of total weight.

Formulation 5 Ingredient Quantity% weight / weight Compound of Formulas l-IV 0.1% Propellant 11/12 98.9% Oleic acid 1% The ingredients are dispersed in oleic acid with the propellant. The mixture is added to an aerosol container fitted with a regulating device.

Claims

1. A compound according to Formula I or stereoisomers or pharmaceutically acceptable salts, esters, amide or prodrugs thereof, wherein: A is selected from CH2, CH, C (alkyl); B is selected from H, alkyl, cycloalkyl, heteroalkyl, cycloalkylalkyl, heteroalkylalkyl, aryl, arylalkyl, heterocycle, heterocycloalkyl, each optionally substituted with Ri and R2; D is selected from H, alkyl, cycloalkyl, heteroalkyl, cycloalkylalkyl, heteroalkylalkyl, aryl, arylalkyl, heterocycle, heterocycloalkyl, each optionally substituted with R1 and R2; E is absent or selected from O, S, NH; F is selected from N, NCH2, CH2N; G is absent or selected from alkyl, alkyl interrupted by one or more heteroatoms, cycloalkyl, cycloalkyl interrupted by one or more heteroatoms; J is absent or selected from aryl or heterocycle each optionally substituted with Ri and R2; K is absent or selected from an aryl or aryl interrupted by one or more heteroatoms, cycloalkyl interrupted by one or more heteroatoms, cycloalkylalkyl interrupted by one or more heteroatoms, each optionally substituted with Ri and R2; L is selected from H, chloro, fluoro, bromo, iodo, OH, O (alkyl), amine, alkyl, fluoroalkyl, amide, NO2, SH, S (O) n (alkyl), SO3H, alkyl SO3, aldehyde, ketone , acid, ester, urea, O-alkylamide, O-alkyl ester, O-alkyl acid, N-alkyl acid, alkylamine, alkylamide, alkyl ketone, alkyl acid, alkyl ester, alkylurea, N-alkylamide, N-alkyl ester, NC (= 0) alkyl, NC (= 0) aryl, NC (= 0) cycloalkyl, NC (= 0) cycloalkylalkyl, NC (= 0) alkylaryl, R1 (R2, nitrile; R1 is selected from H, amine, alkylamine, amide, C (= NH) NHNH2, alkylC (= NH) NHNH2, C (= NH) NHOH, alkylC (= NH) NHOH, NHC (= NH) NH2, alkylNHC (= NH) NH2, C (= S) NH2, alkylC (= S) NH2, C (= NH) alkyl, alkylC (= NH) alkyl, C (= NR3) N (R4) (R5), alkylC (= NR3) N (R4) (R5); R2 is selected from H, chloro, fluoro, bromo, iodo, OH, O-alkyl, amine, alkylaldehyde, alkylamide, alkyl ester, alkyl ketone, alkyl acid, O-alkylamide, O-alkyl acid, alkali ester, aminoalkyl acid, aminoalkylamide, amimoalkyl ester, NC (= 0) alkyl, NC (= 0) aryl, N C (= 0) cycloalkyl, NC (= 0) alkylaryl, alkylamine, amide, aldehyde, ester, ketone, N02, SH, S (O) n (C?.? 0alkyl), S03H, S03alkyl, CHO , acid, alkyl, C (= NH) alkyl, C (= NH) NHNH2, alkylC (= NH) NHNH2, C (= NH) NHOH, alkylC (= NH) NHOH, NHC (= NH) NH2, alkylNHC (= NH) NH2, C (= S) NH2, alkylC (S) NH2, alkylC (= NH) alkyl, C ( = NR3) N (R4) (R5), alkylC (= NR3) N (R4) (R5); R3, R4 and R5 are hydrogen atoms, alkyl group having 1 to 4 carbon atoms optionally interrupted by a heteroatom or R4 and R5 are linked to form - (CH2) PW- (CH2) q-, where p and q are an integer of 2 or 3, a certain position in the methylene chain is substituted or unsubstituted by an alkyl group having 1 to 4 carbon atoms, W is a direct bond, -CH2-, -O-, - N (R6) - or -S (0) r wherein R6 is H or alkyl and r is O or 1 or 2; n is selected from 0, 1, 2; X2 is C or N; X4 is C or N and - represent an additional optional link.

2. A compound according to claim 1 according to Formula II or stereoisomers or pharmaceutically acceptable salts, esters, amides or prodrugs thereof, wherein B, G, J, K, L and - are as defined above.

3. A compound according to Formula III or stereoisomers or pharmaceutically acceptable salts, esters, amides or prodrugs thereof, wherein X, Y, R7, R8 and - are as follows: X is selected from (CH2) 5, (CH2) 4, (CH2) ßl CH2C (= 0) NHCH2CH2, CH2CH2NHC (= 0) CH2, (CH2) 2NH (CH2) 2, (CH2) 20 (CH2) 2, CH2C6H4, CßHio, CH2C6H? O, CsHs, CH2CH = CHCH2CH2; And it is selected from 2,6-dimethylpiperidinyl, piperidinyl, 2,2,6,6-tetramethyl-piperidinyl-4-one, (2-carboxy) piperidinyl, (3-carboxy) piperidinyl, (4-carboxy) piperidinyl, 3,5-dimethylpiperidinyl, (4-hydroxy) piperidinyl, (2-imine) piperidinyl, piperidin-4-one-il, ( 2-dimethylammonomethyl) -piperidinium, (4-dimethylamino) -piperidinyl, (4-sulfonyloxy) -piperidinyl, (2-phenyl) piperidinyl, 2,5-dimethylpyrrolidinyl, pyrrolidinyl, (2-carboxy) pyrrolidinyl, (3-N-acetyl-N-methyl) pyrrolidinyl , (3-amino) pyrrolidinyl, (2,5-bis-methoxymethyl) -pyrrolidinyl, 2-hydroxymethyl-pyrrolidinyl, 2-hydroxymethyl-5-methyl-pyrrolidinyl, diisopropylamino, diethylamino, methylamino, 1-methyl-4,5-dihydro-1 H-imidazol-2-yl, 2,5-dimethyl-1 H-1-imidazolyl, morpholinyl, 2,6-dimethylmorpholinyl, piperazinyl, 2,6-dimethylpiperazinyl, 1 H-pyrazolyl, tetrahydro-1 H-pyrazolyl, 2,5-dimethyltetrahydro-1 H- 1-pyrazolyl and 1, 2,3,4-tetrahydro-2-oxo-3-phenyl-1-quinolinyl; R is selected from (3-amidino) phenyl, phenyl, 4-methoxyphenyl, 4- (amidino) phenyl, 3- (aminocarbonyl) phenyl, 3- (methoxycarbon i) phen i I, (3-hydroxy) phenyl, [ 3-hydroxylamino (imino) methyl] -phenyl, [3-hydrazine (imino) methyl] -phenyl, (3-aminomethyl) phenyl, (3-amino) phenyl, (3-methylamino) phenyl, (3-dimethylamino) ) phenyl, (5-amidino-2-hydroxy) phenyl, (1-amidin) piperid-3-yl, (1-amidino) pyrrolid-3-yl, (5-amidino) thien-2-yl, ( 5-amidino) furan-2-yl, (5-amidino) -1, 3-oxazol-2-yl, (2-amidino) -1, 3-oxazol-5-yl, 1H-pyrazol-5-yl, tetrahydro-1 H -pyrazol-3-yl, (1 -amidino) tetrahydro-1 H -pyrazol-3-yl, (2-amidino) -1 H-imidazol-4-yl, (2-amino) -1 H -imidazol-4-yl, (5-amidino) -1 H -imidazol-2-yl, (5-amino) -1 H -imidazol-2-yl, pyridin-3-yl, (4-amino) pyridin-3-yl, (4-dimethylamino) pyridin-3-yl, (6-amino) pyridin- 2-yl, (6-amidino) pyridin-2-yl, (2-amino) pyridin-4-yl, (2-amidino) pyridin-4-yl, (2-amidino) pyrimid-4-yl (2 -amino) pyrimidin-4-yl (4-amidino) pyrimid-2-yl (4-amino) pyrimidin-2-yl (6-amidino) pyrazin-2-yl (6-amino) pyrazin-2-yl, ( 4-amidino) -1, 3,5-triazin-2-yl, (4-amino) -1, 3,5-triazin-2-yl, (3-amidino) -1, 2,4-triazin-5 -yl, (3-amino) -1, 2,4-triazin-5-yl, (3-amidino) benzyl, (3-amino) benzyl, (3-aminomethyl) benzyl, (1 -amidino) p-perid -3-ilmethyl, (1-amidino) pyrrolid-3-ylmethyl, (5-amidino) thien-2-ylmethyl, (5-amidino) furan-2-ylmethyl, (5-amidino) oxazol-2-ylmethyl, (2-amidino) imidazol-5-ylmethyl, (5-amidino) imidazol-2-ylmethyl, (6-amidino) pyrridn-2-ylmethyl, (6-amino) pyridin-2-ylmethyl, (2-amidino) pyrimidin-4-ylmethyl, (2-amino) pyrimidin-4-ylmethyl, (4-amidino) pyrimidin-2-ylmethyl, (4-amino) pyrimidin-2-ylmethyl, (6-amidino) pyrazin-2-ylmethyl, (6-amino) pyrazin-2-ylmethyl, 3-aminocyclohexyl, 3-amidinocyclohexyl, 3-aminocyclohexylmethyl, 3-amidinocyclohexylmethyl, 3-aminociclopentyl, 3-amidinocyclopentyl, 3-aminociclopentylmethyl and 3-amidinocyclopentylmethyl and Re is selected from H, Cl, F, SH, SMe, CF3, CH3, C02H, C02Me, CN, C (= NH) NH2, C (= NH) NHOH, C (= NH) NHNH2, C (= 0) NH2, CH2OH, CH2NH2, N02, OH, OMe, OCH2Ph, OCH2CO2H, 0 (CH2) 2C02H, 0 (CH2) 3C02H, NHCH2CO2H, NH (CH2) 2C02H, OCH2CH2OH, OCH2 (1 H-tetrazol-5-yl), NH2, NHButil, NMe2, NHPh, NHCH2Ph, NHC (= 0) Me, NHC (= 0) c-Hexyl, NHC ( = 0) CH2c-Hexyl, NHC (= 0) Ph, NHC (= 0) CH2Ph, NHS (= 0) 2Me, NHS (= 0) 2c-Hexyl, NHS (= 0) 2CH2c-Hexyl, NHS (= 0) ) 2Ph and NHS (= 0) CH2Ph;

A compound according to Formula IV or stereoisomers or pharmaceutically acceptable salts, esters, amides or prodrugs thereof, wherein X, Y, R7, Rs and - are as follows: X is selected from (CH) 5, CH2C (= 0) NHCH2CH2, CH2CH2NHC (= 0) CH2, (CH2) 2NH (CH2) 2, (CH2) 20 (CH2) 2, CH2C6H4, CeH4CH2, CdHio, CeH? OCH2, C5HßCH2 and CH2CH = CHCH2CH2; Y is selected from 2,6-dimethylpiperidinyl, piperidinyl, 2,2,6,6-tetramethyl-piperidinyl-4-one, (2-carboxy) piperidinyl, (3-carboxy) piperidinyl, (4-carboxy) piperidinyl, , 5-dimethylpiperidinyl, (4-hydroxy) piperidinyl, (2-imino) piperidinyl, piperidin-4-one-il, (2-dimethylaminomethyl) -piperidinyl, (4-dimethylamino) -piperidinyl, (4-sulfonyloxy) -piperid N, (2-phenyl) piperidinyl, 2,5-dimethylpyrrolidinyl, pyrrolidinyl, (2-carboxy) pyrrolidinyl, (3-N-acetyl-N-methyl) pyrrolidinyl, (3-amino) pyrrolidinyl, (2,5- bis-methoxymethyl) -pyrrolidinyl, 2-hydroxymethyl-pyrrolidinyl, 2-hydroxymethyl-5-methyl-pyrrolidinyl, diisopropylamino, diethylamino, methylamino, 1-methyl-4,5-dihydro-1H-imidazol-2-yl, 2,5-dimethyl-1 H-1-imidazolyl, morpholinyl, 2,6-dimethylmorpholinyl, piperazinyl, 2,6-dimethylpiperazinyl, 1H-pyrazolyl, tetrahydro-1 H-pyrazolyl and 2,5-dimethyltetrahydro-1 H-1 -pyrazolyl; R is selected from (3-amidino) phenyl, (3-hydroxy) phenyl, [3-hydroxylamino (imino) methyl] -phenyl, [3-hydrazine (imin) methyl] -phenyl, (3-aminomethyl) phenyl , (3-amino) phenyl, (3-methylamino) phenyl, (3-dimethylamino) phenyl, (5-amidino-2-hydroxy) phenyl, (1 -amidino) piperid-3-yl, (1 -amidino) pyrrolid -3-yl, (5-amidino) thien-2-yl, (5-amidino) furan-2-yl, (5-amidino) -1, 3-oxazol-2-yl, (2-amidino) -1 , 3-oxazol-5-yl, 1 H -pyrazol-5-yl, tetrahydro-1 H -pyrazol-3-yl, (1 -amidino) tetrahydro-1 H -pyrazol-3-yl, (2-amidino) -1 H-imidazol-4-yl, (2-amino) -1 H -imidazol-4-yl, (5-amidino) -1 H -imidazol-2-yl, (5-amino) -1 H -imidazol-2-yl, pyridin-3-yl, (4-amino) pyridin-3-yl, (4-dimethylamino) pyridin-3-yl, (6-amino) pyrid n-2-yl, (6-amidino) pyridin-2-yl, (2-amino) pyridin-4-yl, (2-amidino) pyridin-4-yl, (2-amidino) pyrimid-4-yl , (2-amino) pyrimidin-4-yl, (4-amidino) pyrimid-2-yl, (4-amino) pyrimidin-2-yl, (6-amidino) pyrazin-2-yl, (6-amino ) pyrazin-2-yl, (4-amidino) -1, 3,5-triazin-2-yl, (4-amino) -1, 3,5-triazin-2-yl, (3-amidino) -1 , 2,4-triazin-5-yl, (3-amino) -1, 2,4-triazin-5-yl, (3-amidino) benzyl, (3-amino) benzyl, (3-aminomethyl) benzyl, (1 -amidino) piperid-3-ylmethyl, (1-amidino) pyrrolid-3-ylmethyl, (5-amidino) thien-2-ylmethyl, (5-amidino) furan-2-methyl, (5-amidino) oxazol-2-ylmethyl, (2-amidino) imidazol-5-ylmethyl, (5-amidino) imidazol-2-ylmethyl, (6-aminino) pyridin-2-ylmethyl, (6-amino) pyridin-2-ylmethyl, (2-amidino) pyrimidin-4-ylmethyl, (2-amino) pyrimidin-4-ylmethyl, (4-amidino) pyrimidin-2-ylmethyl, (4-amino) pyrimidin-2-methyl, (6-amidino) pyrazin-2-ylmethyl, (6-amino) pyrazin-2-ylmethyl, 3-aminocyclohexyl, 3-amidinocyclohexyl, 3-aminocyclohexylmethyl, 3-amidinocyclohexylmethyl, 3-aminociclopentyl, 3-amidinocyclopentyl, 3-aminocyclopentylmethyl and 3-amidinocyclopentylmethyl and selected from H, Cl, F, SH, SMe, CF3, CH3, C02H, C02Me, CN, C (= NH) NH2, C (= NH) NHOH, C (= NH) NHNH2, C (= 0) NH2, CH2OH, N02, OH, OMe, OCH2Ph, OCH2C02H, 0 (CH2) 2C02H, 0 (CH2) 3C02H, NHCH2C02H, NH (CH2) 2C02H, NH (CH2) 3C02H, OCH2CH2OH, OCH2 (1 H-tetrazol-5-yl), NH2, NHButil, NMe2, NHPh, NHCH2Ph, NHC (= 0) Me, NHC (= 0) c-Hexl, NHC (= 0) CH2c-Hexyl, NHC (= 0) Ph, NHC (= 0) CH2Ph, NHS (= 0) 2Me, NHS (= 0) 2c-Hexyl, NHS (= 0) 2CH2c-Hexyl, NHS (= 0) 2Ph and NHS (= 0) 2CH2Ph,

5. A compound according to claim 4, wherein X is (CH 2) 5.

6. A compound according to claim 4, wherein Y is 2,6-dimethylpiperidinyl.

7. A compound according to claim 4, wherein R7 is 2-hydroxy, 5-amidino phenol.

8. A compound according to claim 4, wherein Rs is H.

9. A compound according to claim 4, wherein X is (CH2) 5, Y is 2,6-dimethylpiperidinyl and R8 is H

10. A compound according to claim 4, wherein X is (CH 2) 5, Y is 2,5-dimethylpyrrolidinyl and Rs is H.

11. A compound which is: 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3- (3-hydroxyphenyl) -2 (1 / - /) - quinolinone; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -N- hydroxybenzenecarboximidamide; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidohydrazide; 3- [3- (Aminomethyl) phenyl] -1-5 - [(2R; 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2 (1 / - /) - quinolinone; 3- (3-Aminophenyl) -1-5 [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (W) -quinolinone; 1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3- [3- (methylamino) phenyl] -2 (1 - /) - quinolinone; 3- [3- (Dimethylamino) phenyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1 / -) -quinolinone; 3- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -4-hydroxybenzenecarboximidamide; 3- (1-5 - [(2R, 6S) -2,6-D-Methoxy-tetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinoline L) tetrahydro-1 (2 - /) - pyridinecarboximidamide; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -1-pyrrolidinecarboximidamide; 5- (1-5 - [(2R, 6S) -2,6-D-methyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -2 -thiophenecarboximidamide; 5- (1-5 - [(2R, 6S) -2,6-D-methyltetrahydro-1 (2-) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -2-furancarboximidamide; 2- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -1, 3-oxazole-5-carboximidamide; 5- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 - /) - pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) - 1,3-oxazole-2-carboximidamide; 1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3- (1H-pyrazol-3-yl) -2 (1H) -quinolinone; 1-5 - [(2R, 6S) -2,6-D'metltetrahydro-1 (2 / - /) - pyridinyl] pentyl-3-tetrahydro-1H-pyrazol-3-yl-2 (1 / - /) - quinolinone; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentiol-2-oxo-1,2-dihydro-3-quinolinyl) -1 -pyrazolidinecarboximidamide; 5- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -1 H -imidazole-2 -carboximidamide; 3- (2-Amino-1 r7-imidazol-5-yl) -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1 -) -quinolinone; 2- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinoline] -1 / - / - imidazol-5-carboximidamide; 3- (5-Amino-1H-imidazol-2-yl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1 -) -quinolinone; 1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3- (3-pyridinyl) -2 (1 / - /) - quinolinone; 3- (6-Amino-3-pyridinyl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1 / - /) -quinolinone; 3- [6- (Dimethylamino) -3-pyridinyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1 / - /) -quinolinone; 3- (6-Amino-2-pyridyl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1 -) -quinol ninth; 6- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -2-pyridinecarboximidamide; 3- (2-Amino-4-pyridinyl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1 / -) -quinolinone; 4- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -2 pyridinecarboximidamide; 4- (1-5 - [(2R, 6S) -2,6-D-methyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -2-pyrimidinecarboximidamide; 3- (2-Amino-4-pyrimidinyl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H-pyridinyl] pentyl-2 (1H) -quinolinone; 2- (1-5 - [(2R / 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -4-pyrimidinecarboximidamide; 3- (4-Amino-2 -pyrimidinyl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1 / - /) - quinolinone; 6- (1-5 - [(2R , 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -2-pyrazinecarboximidamide; 3- (6-Amino-2-pyrazinyl) ) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1 H) -quinolinone; 4- (1-5 - [(2R, 6S) - 2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -1,5,5-triazine-2-carboximidamide; 3- ( 4-Amino) -1, 3,5-triazin-2-yl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2 (1 -) -quinolinone; 5- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -1, 2,4- triazine-3-carboximidamide; 3- (3-Amino-1, 2,4-triazin-5-yl) -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1 / - /) - quinolinone; 3 - [(1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) methyl] benzenecarboximidamide; 3- (3-Aminobenzyl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2 (1 / - /) - quinolinone; 3- [3- (Aminomethyl) benzyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 2HA pyridinyl] pentyl-2 (1 H) -quinolinone; 3 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) methyl] tetrahydro- 1 (2 / - /) - pyridinecarboximidamide; 3 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) methyl] -1-pyrrolidinecarboximidamide; 5 - [(1-5-1 (2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) methyl] - 2-thiophenecarboximidamide; 5 - [(1-5 - [(2R; 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) methyl] -2 -furancarboximidamide; 2 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) methyl] -1 , 3-oxazole-5-carboximidamide; 5 - [(1 -5 - [(2R; 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolyl) methyl ] -1 H-imidazole-2-carboximidamide; 2 - [(1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) methyl] - 1H-imidazole-5-carboximidamide; 6 - [(1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) methyl] -2-pyridinecarboximidamide; 3 - [(6-Amino-2-pyridinyl) methyl] -1-5 - [(2R; 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1 / - /) - quinolinone; 4 - [(1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) methyl] -2 -pyrimidinecarboximidamide; 3 - [(2-Amino-4-pyrimidinyl) methyl] -1 -5 - [(2R; 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1 -) -quinolinone; 2 - [(1-5 - [(2R 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) metl] -4- pyrimidinecarboximidamide; 3 - [(4-Amino-2-pyrimidinyl) methyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2r - /) - pyridinyl] pentyl-2 (1H) -quinolinone; 6 - [(1 -5 - [(2R, 6S) -2,6-D-methyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) methyl] -2 -pyrazinecarboximidamide; 3 - [(6-Amino-2-pyrazinyl) methyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2 ( 1 -) -quinolonone; 3- (3-Aminocyclohexyl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1 / - /) -quinolinone; 3- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) cyclohexanecarboximidamide; 3 - [(3-Aminocyclohexyl) methyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2 (1 / - /) - quinolinone; 3 - [(1-5 - [(2R, 6S) -2,6-Dirnetyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinoline] methyl) cyclohexanecarboximidamide; 3- (3-Aminocyclopentyl) -1-5 - [(2R; 6S) -2,6-dimethyltetrahydro-1 2HA pyridinyl] pentyl-2 (1 -) -quinolinone; 3- (1-5 - [(2R, 6S) -2,6-D-methyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) cyclopentanecarboximidamide; 3 - [(3-Aminocyclopentyl) methyl] -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1H) -quinolinone; 3 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentiol-2-oxo-1,2-dihydro-3-quinolinyl) methyl] Cyclopentanecarboximidamide; 3- (1 -4 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] butyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- (1-6 - [(2R, 6S) -2,6-D] methyltetrahydro-1 (2H) -pyridinyl] hexyl-2-oxo-1,2-dihydro-3-quinolyl) benzenecarboximidamide; 2- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2H) -quinolinyl] -N-2 - [(2R, 6S) -2,6- Dimethyltetrahydro-1 (2H) - pyridinyl] ethylacetamide; 3- [3-3- [Amino (imine) methy1] phenyl-2-oxo-1 (2H) -quinolinyl] -N - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H ) -pyridinyl] methylpropanamide; 3-1- [2- (2 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] ethylamino) ethyl] -2-oxo-1,2-dihydro- 3-quinolinylbenzenecarboximidamide; 3- [1 - (2-2 - [(2R, 6S) -2,6-D-methyltetrahydro-1 (2H) -pyridinyl] ethoxyethyl) -2-oxo-1,2-dihydro-3-quinolinyl ] benzenecarboximidamide; 3- (1-4 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] phenyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- (1-4 - [(2R; 6S) -2,6-Dimethyltetrahydro-1 (2r - /) - pyridinyl] benzyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- [1- (4 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] methylphenyl) -2-oxo-1,2-d-hydro-3-qu Nolyl] benzenecarboximidamide; 3- (1 -4 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] cyclohexyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- [1- (4 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] cyclohexylmethyl) -2-oxo-1,2-dihydro-3-quinolinyl] benzenecarboximidamide; 3- [1 - (4 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] methylcyclohexyl) -2-oxo-1,2-dihydro-3-quinolinyl] benzenecarboximidamide; 3- (1-3 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] cyclopentyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- [1- (3 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] cyclopentylmethyl) -2-oxo-1,2-dihydro-3-quinolinyl] benzenecarboxymeramide; 3- [1 - (3 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] methylcyclopentyl) -2-oxo-1,2-dihydro-3-quinolinyl] benzenecarboximidamide; 3- (1 - (E) -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] -2-pentenyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- [2-Oxo-1 - (5-piperidinapentyl) -1,2-dihydro-3-quinolinylj-benzenecarboximidamide; 3-2-Oxo-1- [5- (2,2,6,6-tetramethylpiperidine) pentyl] -1,2-dihydro-3-quinolinylbenzenecarboximidamide; acid-1-5- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2H) -quinolinyl] pentyl-2-piperidinecarboxylic acid; 1 -5- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2H) -quinolinyl] pentyl-3-piperidinecarboxylic acid; acid-1-5- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2 -) -quinolinyl] pentyl-4-piperidinecarboxylic acid; 3-1 - [5- (3,5-Dimethylpiperidine) pentyl) -2-oxo-1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3-1 - [5- (4-Hydroxypiperidine) pentyl] -2-oxo-1,2-dihydro-3-quinoline-benzenecarboximidamide; 3-1 - [5- (2-lymnoperidine) pentyl-2-oxo-1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3-2-Oxo-l - [5- (4-oxopiperidine) pentyl] -1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3- [1- (5-2 - [(Dimethylamino) methyl] piperidinapentyl) -2-oxo-1,2-dihydro-3-quinolinyl-benzenecarboximidamide; 3- (1-5- [4- (Dimethylamino) pperidine] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; acid-1-5- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2 / - /) -quinolinyl] pentyl-4-piperidinesulfonic acid; 3-2-Oxo-l - [5- (2-phenylpiperidine) pentyl] -1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3-1 - [5- (2,5-Dimethyl-1-pyrrolidinyl) pentyl] -2-oxo-1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3-2-Oxo-l - [5- (1-pyrrolidinyl) pentyl] -1,2-dihydro-3-quinolinylbenzenecarboximidamide; acid-1-5- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2 / - /) -quinolinyl] pentyl-2-pyrrolidinecarboxylic acid; N- (1-5- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2 / - /) - quinolinyl] pentyltetrahydro-1 - / - pyrrol-3-yl) - N-methylacetamide; 3-1 - [5- (3-Amino-1-pyrrolidinyl) pentyl] -2-oxo-1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3- (1 -5- [2,5-bis (Methoxymethyl) -1-pyrrolidinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- (1 -5- [2- (Hydroxymethyl) -1-pyrrolidinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- (1 -5- [2- (Hydroxymethyl) -5-methyl-1-pyrrolidinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3-1 - [5- (Diisopropylamino) pentyl] -2-oxo-1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3-1 - [5- (Diethylamino) pentyl] -2-oxo-1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3-1 - [5- (Methylamino) pentyl] -2-oxo-1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3-1- [5- (1-Methyl-1H-imidazol-2-yl) pentyl] -2-oxo-1,2-dihydro-3-quinolinyl-benzenecarboximidamide; 3-1 - [5- (2,5-Dimethyl-1 H-imidazol-1 -yl) pentyl-2-oxo-1,2-dihydro-3-quinolinyl-benzenecarboximidamide; 3- [1 - (5-Morpholinopentyl) -2-oxo-1,2-dihydro-3-quinolinyl-benzenecarboximidamide; 3-1 - [5- (3,5-Dimethylmorpholino) pentyl] -2-oxo-1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3- [2-oxo-1- (5-Piperazinylpentyl) -1,2-dihydro-3-quinolinyl-benzenecarboximidamide; 3-1 - [5- (2,6-Dimethyl-piperazine) pentyl] -2-oxo-1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3-2-Oxo-l - [5- (1 H -pyrazol-1 -yl) pentyl] -1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3- [2-Oxo-1 - (5-tetrahydro-1 H -pyrazol-1-ylpentyl) -1,2-dihydro-3-quinolinylj-benzenecarboximidamide; 3-1 - [5- (2,5-Dimethyltetrahydro-1 H -pyrazol -yl) pentyl] -2-oxo-1,2-dihydro-3-quinolinylbenzenecarboximidamide; 3- (7-Chloro-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-7-fluoro-2-oxo-1,2-dihydro-3- quinolinyl) benzenecarboximidamide; 3- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-7-sulfanyl-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- [1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2rV) -pyridinyl] pentyl-7- (methylsulfanyl) -2-oxo-1,2-dihydro-3-quinolinyl ] benzenecarboximidamide; 3- [1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-7- (trifluoromethyl) -1,2-dihydro-3-quinolinyl] benzenecarboximidamide; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-7-methyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; acid-3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dih Dro-7-quinolinecarboxylic; Methyl3-3- [amino (lmin) methyl] phenyl-1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro -7-quinolinecarboxylate; 3- (7-Cyano-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro -7-quinolinecarboxyximumdam; 3-3- [Amino (imine) methyl] phenyl-1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] phenylN-hydroxy-2-oxo-1 , 2-dihydro-7-quinolinecarboximidamide; 3-1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-7- [hydrazine (imine) methyl] -2-oxo-1, 2- dihydro-3-quinolinylbenzenecarboximidamide; 3-3- [Amino (imine) methyl] phenyl-1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-7 -quinolinecarboxamide; 3- [1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-7- (hydroxymethyl) -2-oxo-1,2-dihydro-3- quinolinyl] benzenecarboximidamide; 3- (7- (Aminomethyl) -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinoline ) benzenecarboximidedamide; 3- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 - /) - pyridinyl] pentyl-7-nitro-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl) pentyl-7-hydroxy-2-oxo-1,2-dihydro-3- quinolinyl) benzenecarboximidamide; 3- (1 -5 - [(2R 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-7-methoxy-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- (7- (Benzyloxy) -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; acid-2 - [(3-3- [Amino (imine) methyl] phenyl-1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo -1, 2-dihydro-7-quinolinyl) oxy] acetic; acid-3 - [(3-3- [Amino (im!) methyl] phenyl-1 -5 - [(2R, 6S) -2,6-d, methyltetrahydro-1 (2 - /) - pyridinyl] pentyl -2-oxo-1, 2-dihydro-7-quinolinyl) oxy] propanoic; acid-4 - [(3-3- [Amino (imine) methyl] phenyl-1 - 5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo -1, 2-dihydro-7-quinolyl) oxy] butanoic; acid-2 - [(3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 -) -pyridinyl] pentyl-2- oxo-1, 2-dihydro-7-quinolinyl) amino] acetic acid; acid-3 - [(3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1 , 2-dihydro-7-quinolinyl) amino] propane; acid-4 - [(3-3- [Amino (imine) methyl] phenyl-1-5- / '2R, 6SJ-2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2-hydroxy-7-quinolinyl) amino] butanoic; 3- [1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pehthyl-7- (2-hydroxyethoxy) -2-oxo-1,2-dihydro- 3-quinolinyl] benzenecarboximidamide; 3- [1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 - /) - pyridinyl] pentyl-2-oxo-7- (1H-1, 2,3, 4-tetraazol-5-ylmethoxy) -1,2-dihydro-3-quinolinyl] benzenecarboxamidamide; 3- (7-Amino-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- (7- (Butylamino) -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl ) benzenecarboximidamide; 3- (7- (Dimethylamino) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 - /) - pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl ) benzenecarboximidamide; 3- (7-Aniline-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- (7- (Benzylamino) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 - /) - pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl ) benzenecarboximidamide; ? - (3-3- [Amino (imine) methyl] phenyl-1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro -7-quinolinyl) acetamide; ? - (3-3- [Amino (imine) methyl] phenyl-1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro -7-quinolinyl) cyclohexanecarboxamide; / V- (3-3- [Amino (imine) methy1] phenyl-1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo -1, 2-dihydro-7-quinolinyl) -2-cyclohexyl acetamide; N- (3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo- 1,2-dihydro-7-quinolinyl) benzenecarboxamide; ? / - (3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2 -dihydro-7-quinolinyl) -2-phenylacetamide; 3-1-5 - [(2R; 6S) -2,6-D-methyl-tetrahydro-1 (2H) -pyridinyl] pentyl-7 - [(methylsulfonyl) amino] -2-oxo-1,2-dih Dro-3-quinolylbenzenecarboxamidamide; 3- (7 - [(Cyclohexylsulfonyl) amino] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2- dihydro-3-quinolinyl) benzenecarboxamidamide; 3- (7 - [(Cyclohexylmethyl) sulfonyl] amino-1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3 -quinolinyl) benzenecarboxyramide; 3-1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentiol-2-oxo-7 - [(phenylsulfonyl) amino] -1 , 2-dihydro-3-quinolylnilbenzenecarboximidamide; 3- (7 - [(Benzylsulfonyl) amino] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 ('2H; -pyridinyl] pentyl-2-oxo-1, 2 -dihydro-3-quinolinyl) benzenecarboxylamide; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo- 1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidamide; 1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3- (3 -hydroxyphenyl) -3,4-dihydro-2 (1 / - /) - quinolinone; 3- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 -oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -N-hydroxybenzenecarboximidamide; 3- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidohydrazide; 3- [3- (Aminomethyl) phenyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 C2H; -pyridinyl] pentyl-3,4-dihydro-2 (1 - ) -quinolonone; 3- (3-Aminophenyl) -1 -5 - [(2R; 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3,4-dihydro-2 (1 -) -quinolinone; 1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3- [3- (methylamino) pheny] -3,4-dihydro-2 (1H ) -quinolinone; 3- [3- (Dimethylamino) phenyl] -1 -5 - [(2R; 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridyl] pentyl-3,4-dihydro-2 (1H) -quinolinone; 3- (1-5 - [(2R; 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -4- hydroxybenzenecarboximidamide; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentiol-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) tetrahydro -1 (2 / - /) - pyridinecarboximidamide; 3- (1-5 - [(2R, 6S) -2,6-D-methyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl -1 -pyrrolidinecarboximidamide; 5- (1-5 - [(2R; 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3, 4-tetrahydro-3-quinoxy) -2-thiophenecarboxamide; 5- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -2-furanecarboximidamide; 2- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 ( 2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -1,3-oxazole-5-carboximidamide; 5- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -1, 3-oxazole-2-carboxymeramide; 1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 - /) - pyridinyl] pentyl-3- (1-r7-pyrazol-3-yl) -3,4-dihydro-2 ( 1 H) -quinolinone; 1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3-tetrahydro-1 H -pyrazol-3-yl-3,4-dihydro-2 (1 / - /) - quinolinone; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -1- pyrazolidinecarboximidamide; 5- (1-5 - [(2R; 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3 quinolinyl) -1 H-imidazole-2-carboximidamide; 3- (2-Amino-1 H-imidazol-5-yl) -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3,4-dihydro-2 (1H) -quinolonone; 2- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -1H- imidazole-5-carboximidamide; 3- (5-Amino-1H-imidazol-2-yl) -1-5 - [(2R, 6S) -2,6-d-rnetyltetrahydro-1 (2 / - /) - pyridinyl] pentl-3 , 4-dihydro-2 (1H) -quinolinone; 1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3- (3-pyridinyl) -3,4-dihydro-2 (1 H) -quinolinone; 3- (6-Amino-3-pyridinyl) -1-5 - [(2R; 6S) -2,6-dimethyltetrahydro-1 C2Hj-pyridinyl] pentyl-3,4-dihydro-2 (1 / - / ) -quinolinone; 3- [6- (Dimethylamino) -3-pyridinyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3,4-dihydro-2 (1H) -quinolinone; 3- (6-Amino-2-pyridinyl) -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 f2H-pyridinyl] pentyl-3,4-dihydro-2 (1 / - /) - quinolinone; 6- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentl-2-oxo-1, 2,3,4-tetrahydro -3-quinolinyl) -2-pyridinecarboximidamide; 3- (2-Amino-4-pyridinyl) -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3,4-dihydro-2 (1H ) -quinolonone; 4- (1-5 - [(2R / 6S) -2,6-Dimethyltetrahydro-1 (2 - /) - pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl ) -2-pyridinecarboximidamide; 4- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -2- pyrimidinecarboximidamide; 3- (2-Amino-4-pyrimidinyl) -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 C2H > ) -pyridinyl] pentyl-3,4-dihydro-2 (1 -) -quinolinone; 2- (1 -5 - [(2R / 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -4- pyrimidinecarboximidamide; 3- (4-Amino-2-pyrimidinyl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-3,4-dihydro-2 (1H ) -quinolinone; 6- (1 -5 - [(2RJ6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -2-pyrazinecarboximidamide; 3- (6-Amino-2-pyrazinyl) -1 -5 - [(2R / 6S) -2,6-dimethyltetrahydro-1 2HJ pyridinyl] pentyl-3,4-dihydro-2 (1 / - /) -quinolinone; 4- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) -1, 3,5-triazine-2-carboximidamide; 3- (4-Amino-1, 3,5-triazin-2-yl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 -) -pyridinyl ] pentyl-3,4-dihydro-2 (1 -) -quinolinone; 5- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-qui nolinyl) -1, 2,4-triazine-3-carboximidamide; 3- (3-Amino-1, 2,4-triazin-5-yl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3,4- dihydro-2 (1 -) -quinolinone; 3 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) methyl] benzenecarboximidamide; 3- (3-Aminobenzyl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2HApyridinyl] pentyl-3,4-dihydro-2 (1 H) -quinolinone; 3- [3- (Aminomethyl) benzyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 ('2H) -pyridinyl] pentyl-3,4-dihydro-2 (1 -) -quinolinone; (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-S-quinolini methylJtetrahydro-I ^ A J -pyridinecarboximidamide; 3 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3 -quinolinyl) methy1-1-pyrrolidinecarboximidamide; 5 - [(1-5 - [(2R; 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2 , 3,4-tetrahydro-3-quinolinyl) methyl] -2-thiophenecarboxamidamide; 5 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinium] pentyl- 2-oxo-1, 2,3,4-tetrahydro-3-quinoliniI) methyl] -2-furancarboximidamide; 2 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) methyl] -1,3-oxazole-5-carboximidamide; 5 - [(1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) methyl] - 1 / - / - imidazole-2-carboximidamide; 2-1 (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) methyl] -1 - / - imidazole-5-carboximidamide; 6 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinoline l) methyl] -2-pyridinecarboximidamide; 3 - [(6-Amino-2-pyridinyl) methyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3,4-dihydro-2 (1H ) -quinolonone; 4 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl ) methyl] -2-pyrimidinecarboxyramide; 3 - [(2-Amino-4-pyrimidinyl) methyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3,4-dihydro-2 (1H) -quinolinone; 2 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) met l] -4-pyrimidinecarboximidamide; 3 - [(4-Amino-2-pyrimidinyl) methyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3,4-dihydro -2 (1H) -quinolinone; 6 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro- 3-quinolinyl) methyl] -2-pyrazinecarboximidamide; 3 - [(6-Amino-2-pyrazinyl) methyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-3,4-dihydro- 2 (1 -) -quinolinone; 3- (3-Aminocyclohexyl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridyl] pentyl-3,4-dihydro-2 (1 / - /) - quinolinone; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) cyclohexanecarboximidamide; 3 - [(3-Aminocyclohexyl) methyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3,4-dihydro-2 (1H) -quinolonone; 3 - [(1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3 quinolinyl) methyl] cyclohexanecarboximidamide; 3- (3-Aminocyclopentyl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 - /) - pyridinyl] pentyl-3,4-dihydro-2 (1H) -quinolinone; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) cyclopentanecarboximidamide; 3 - [(3-Aminocyclopentyl) methyl] -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-3,4-dihydro-2 (1 / - /) -quinolinone; 3 - [(1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) methyl] cyclopentanecarboxyramide; 3- (1-4 - [(2R / 6S) -2,6-Dimethyltetrahydro-1 (2W) -pyridinyl] butyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl ) benzenecarboximidamide; 3- (1-6 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] hexyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidamide; 2- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2H) -quinolinyl] -N-2 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] ethylacetamide; 3- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2H) -quinolinyl] -N - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] methylpropanamide; 3-1 - [2- (2 - [(2R; 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] ethylammonyl) ethyl] -2-oxo-1, 2,3,4-tetrahydro -3-quinolinylbenzenecarboximidamide; 3- [1- (2-2 - [(2RJ6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] ethoxyethyl) -2-oxo-1, 2,3,4-tetrahydro-3 -quinolinyl] benzenecarboxyramide; 3- (1-4 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] phenyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidamide; 3- (1-4 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] benzyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidamide; 3- [1- (4 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] methylphenyl) -2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl] benzenecarboximidamide; 3- (1-4 - [(2R; 6S) -2,6-Dimethyltetrahydro-1 (2 / -) -pyridinyl] cyclohexyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidamide; 3- [1- (4 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] cyclohexylmethyl) -2-oxo-1, 2,3,4-tetrahydro- 3-quinolinyl] benzenecarboximidamide; 3- [1- (4 - [(2R; 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] methylcyclohexyl) -2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl ] benzenecarboximidamide; 3- (1 -3 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] cyclopentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidamide; 3- [1- (3 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] cyclopentylmethyl) -2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl] benzenecarboximidamide; 3- [1- (3 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] methylcyclopentyl) -2-oxo-1, 2,3,4-tetrahydro-3 -quinolinyl] benzenecarboximidamide; 3- (1- (E) -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] -2-pentenyl-2-oxo-1, 2,3,4-tetrahydro- 3-quinolinyl) benzenecarboximidamide; 3- [2-Oxo-1 - (5-piperidinapentyl) -1, 2,3,4-tetrahydro-3-quinolinylj-benzenecarboximidamide; 3-2-Oxo-l - [5- (2,2,6,6-tetramethylpiperidine) pentyl] -1,2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; acid-1 -5- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2 / - /) -quinolinyl] pentyl-2-piperidinecarboxylic acid; acid-1-5- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2H) -quinolinyl] pentyl-3-piperidinecarboxylic acid; acid-1-5- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2H) -quinolinyl] pentyl-4-piperidinecarboxylic acid; 3-1- [5- (3,5-Dimethylpiperidine) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3-1- [5- (4-Hydroxypiperidine) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3-1 - [5- (2-lminapiperidine) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3-2-Oxo-l - [5- (4-oxopiperidine) pentyl] -1, 2, 3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3- [1- (5-2 - [(Dimethylamino) methyl] piperidinapentyl) -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylj-benzenecarboximidamide; 3- (1-5- [4- (D-methylamino) piperidine] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidamide; 5- (3-amino- (im) methyl] phenyl-2-oxo-1 (2 / - /) -quinolinyl] pentyl-4-piperidine sulfonic acid; 3-2-Oxo-l - [5- (2-phenylpiperidine) pentyl] -1,2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3-1 - [5- (2,5-Dimethyl-1-pyrrolidinyl) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3-2-Oxo-l - [5- (1-pyrrolidinyl) pentyl] -1,2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; acid-1-5- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2H) -quinolinyl] pentyl-2-pyrrolidinecarboxylic acid; N- (1-5- [3-3- [Amino (imine) methyl] phenyl-2-oxo-1 (2 H) -quinolinyl] pentyltetrahydro-1 H -pyrrol-3-yl) -N-methylacetamide; 3-1 - [5- (3-Amino-1-pyrrolidinyl) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3- (1 -5- [2,5-bis (Methoxymethyl) -1-pyrrolidinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidamide; 3- (1 -5- [2- (Hydroxymethyl) -1-pyrrolidinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidamide; 3- (1 -5- [2- (Hydroxymethyl) -5-methyl-1-pyrrolidinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidamide; 3-1 - [5- (Diisopropylamino) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3-1 - [5- (Diethylamino) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3-1 - [5- (Methylamino) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3-1 - [5- (1-methyl-1 / - / - imidazol-2-yl) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl-benzenecarboximidamide; 3-1 - [5- (2,5-Dimethyl-1 H-imidazol-1 -yl) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3- [1 - (5-Morpholinopentyl) -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylj-benzenecarboximidamide; 3-1- [5- (3,5-Dimethylmorpholino) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3- [2-Oxo-1- (5-piperazinylpentyl) -1,2,3,4-tetrahydro-3-quinolinylj-benzenecarboximidamide; 3-1- [5- (2,6-Dimethyl-piperazine) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl-benzenecarboximidamide; 3-2-Oxo-l - [5- (1H-pyrazol-1-yl) pentyl] -1,2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3- [2-Oxo-1 - (5-tetrahydro-1 H -pyrazol-1-ylpentyl) -1, 2,3,4-tetrahydro-3-quinolinylj-benzenecarboximidamide; 3-1 - [5- (2,5-Dimethyltetrahydro-1 H -pyrazol-1-yl) pentyl] -2-oxo-1, 2,3,4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3- (7-Chloro-1-5 - [(2R / 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl ) benzenecarboximidamide; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-7-fluoro-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl ) benzenecarboximidamide; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-7-sulfanyl-1, 2,3,4-tetrahydro -3-quinolinyl) benzenecarboximidamide; 3- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-7- (methylsulfanyl) -2-oxo-1, 2,3,4-tetrahydro -3-quinolinyl) benzenecarboximidamide; 3- [1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / -) -pyridinyl] pentyl-2-oxo-7- (trifluoromethyl) -1, 2,3,4-tetrahydro -3-quinolinyl] benzenecarboximidamide; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-7-methyl] -2-oxo-1, 2,3,4-tetrahydro -3-quinolinyl) benzenecarboximidamide; acid-3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3 , 4-tetrahydro-7-quinoline carboxylic acid; methyl3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4 -tetrahydro-7-quinolinecarboxylate - 3- (7-Cyano-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo- 1, 2, 3,4-tetrahydro-3-quinolinyl) benzenecarboximidamide; 3-3- [Amino (imine) methyl] phenyl-1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2 , 3,4-tetrahydro-7-quinolinecarboxyramidedam; 3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl- / V-hydroxy-2-oxo- 1, 2,3,4-tetrahydro-7-quinol-nacarboximidamide; 3-1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-7- [hydrazine (imine) methyl] -2-oxo-1, 2,3,4- tetrahydro-3-quinolinylbenzenecarboximidamide; 3-3- [Amino (mine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1, 2 , 3,4-tetrahydro-7-quinolinecarboxamide; 3- [1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-7- (hydroxymethyl) -2-oxo-1, 2,3,4-tetrahydro-3 -quinolinyl] benzenecarboximidamide; 3- (7- (Aminomethyl) -1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3 -quinolinyl) benzenecarboximidamide; 3- (1-5 - [(2R, 6S) -2,6-D-methyltetrahydro-1 (2 / - /) - pyridinyl] penti-7-n-tro-2-oxo- 1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboximidamide; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-7-hydroxy-2-oxo-1, 2,3,4- tetrahydro-3-quinolinyl) benzenecarboximidamide; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2R) -pyridinyl] pentyl-7-methoxy-2-oxo-1, 2,3,4-tetrahydro-3- quinolinyl) benzenecarboximidamide; 3- (7- (Benzyloxy) -1-5 - [(2R, 6S) -2,6-dithymethhydro-1 2 - / J-pyridinyl] pentyl-2-oxo-1, 2,3,4- tetrahydro-3-quinolinyl) benzenecarboximidamide; acid-2 - [(3-3- [Amino (imine) methy1] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl- 2-oxo-1,2-dihydro-7-quinolinyl) oxy] acetic acid; acid-3 - [(3-3- [Amino (imine) methylphenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo- 1,2-dihydro-7-quinolinyl) oxy] propanoic acid; acid-4 - [(3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R; 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2- oxo-1, 2-dihydro-7-quinolinyl) oxy] butanoic; acid-2 - [(3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-d.methyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo -1,2-dihydro-7-quinolinyl) amino] acetic; acid-3 - [(3-3- [Amino (imine) methyl] phenyl-1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 -) -pyridinyl] pentyl-2-oxo- 1,2-dihydro-7-quinolinyl) amino] propanoic acid; acid-4 - [(3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridine l] pentyl-2-oxo-1,2-dihydro-7-quinolinyl) amino] butanoic; 3- [1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-7- (2-hydroxyethoxy) -2-0X0-1, 2, 3, 4-tetrahydro-3-quinolinyl] benzenecarboximidamide; 3- [1 -5 - [(2R; 65) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-7- (1 / -1-, 2,3,4-tetraazole- 5-ylmethoxy) -1, 2,3,4-tetrahydro-3-quinolinylj-benzenecarboximidamide; 3- (7-Amino-1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2f) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3-quinolinyl ) benzenecarboximidamide; 3- (7- (Butylamino) -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 2H; -pyridinyl] pentyl-2-oxo-1, 2,3,4- tetrahydro-3-quinolinyl) benzenecarboximidamide; 3- (7- (Dimethylamino) -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro-3 -quinolinyl) benzenecarboximidamide; 3- (7-Aniline-1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro- 3-quinolinyl) benzenecarboximidamide; 3- (7- (Benzylamino) -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 ('2 / - / -pyridinyl] pentyl-2-oxo-1, 2,3,4- tetrahydro-3-quinolinyl) benzenecarboximidamide; N- (3-3- [Amino (imine) methyl] phenyl-1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-7-quinolinyl) acetamide; N- (3-3- [Amino (imine) methyl] phenyl-1 -5 - [(2R; 6S) -2,6-dimethyltetrahydro; -1 - (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-7-quinolinyl) c -clohexanecarboxamide; N- (3-3- [Amino (imine) methyl] phenyl-1-5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2- dihydro-7-quinolinyl) -2-cyclohexylacetamide; N- (3-3- [Amino (imine) methyl] phenyl-1 -5 - [(2R; 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2-dihydro-7-quinolinyl) benzenecarboxamide; N- (3-3- [Amino (imine) methyl] phenyl-1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2-dihydro-7-quinolyl] -2-phenylacetamide; 3-1 -5 - [(2R, 6S) -2,6-Dimeti-tetrahydro-1 (2H) -pyridinyl] pentyl-7 - [(methylsulfonyl) amino] -2-oxo-1, 2,3 , 4-tetrahydro-3-quinolinylbenzenecarboximidamide; 3- (7 - [(Cyclohexylsulfonyl) amino] -1-5 - [(2RJ6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4- tetrahydro-3-quinolinyl) benzenecarboximidamide; 3- (7 - [(Cyclohexylmethyl) sulfonyl] amino-1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4 -tetrahydro-3-quinolinyl) benzenecarboximidamide; 1 - [5- (2,6-Dimethyl-piperidin-1-yl) -pentyl] -3- (4-methoxy-phenyl) -3,4-dihydro-1 H -quinolin-2-one; 3-1 - [5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-7 - [(phenylsulfonyl) amino] -1, 2,3,4- tetrahydro-3-quinolinylbenzenecarboximidamide or 3- (7 - [(Benzylsulfonyl) amino] -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2-) -pyridinyl] pentyl-2 -oxo-1, 2,3,4-tetrahydro-3-quinolinyl) benzenecarboxymethyldane.

12. A compound which is: 3- (1 -5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) benzenecarboximidamide; 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -N-hydroxybenzenecarboximidamide; 3- [3- (Aminomethyl) phenyl] -1 -5 - [(2R, 6S) -2,6-dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2 (1 -) -quinolinone or 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1,2-dihydro-3-quinolinyl) -4-hydroxybenzenecarboximidamide .

13. A compound that is: 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2H) -pyridinyl] pentyl-2-oxo-1, 2,3,4-tetrahydro- 3-quinolinyl) -4-hydroxybenzenecarboximidamide or 3- (1-5 - [(2R, 6S) -2,6-Dimethyltetrahydro-1 (2 / - /) - pyridinyl] pentyl-2-oxo-1 , 2-dihydro-3-quinolinyl) -4-hydroxybenzenecarboximidamide.

14. A method for the treatment or prophylaxis of thrombotic disorders in a mammal comprising the administration to said mammal of an effective amount of a compound according to claim 1.

15. A method according to claim 14, wherein said disorder is venous thrombosis.

16. A method according to claim 14, wherein said disorder is arterial thrombosis.

17. A method according to claim 14, wherein said disorder is pulmonary embolism.

18. A method according to claim 14, wherein said disorder is myocardial infarction.

19. A method according to claim 14, wherein said disorder is cerebral infarction.

20. A method according to claim 14, wherein said disorder is restenosis.

21. A method according to claim 14, wherein said disorder is a cancer.

22. A method according to claim 14, wherein said disorder is angina.

23. A method according to claim 14, wherein said disorder is diabetes.

24. A method according to claim 14, wherein said disorder is a cardiac failure.

25. A method according to claim 14, wherein said disorder is atrial fibrillation.

26. A pharmaceutical formulation comprising a compound according to claim 1, mixed with a carrier, diluent or excipient.

27. A pharmaceutical formulation comprising a compound according to claim 2, together with a carrier, diluent or excipient.

28. A pharmaceutical formulation comprising a compound according to claim 11, together with a carrier, diluent or excipient.

29. A method for the inhibition of serine proteases comprising administering to a mammal an effective amount of the serine protease inhibitor according to claim 1.

30. A method according to claim 29, wherein said serine protease is factor Xa.