MXPA06008765A

MXPA06008765A - New pyridin-2-one compounds useful as inhibitors of thrombin

Info

Publication number: MXPA06008765A
Application number: MXPA/A/2006/008765A
Authority: MX
Inventors: Nagard Mats; Berggren Kristina; Davidsson Ojvind; Fjellstrom Ola; Gustafsson David; Nilsson Ingemar; Therrien Eric; Hanessian Stephen; Inghardt Tord; Bayrakdarian Malken; Simard Daniel
Original assignee: Astrazeneca Ab; Bayrakdarian Malken; Berggren Kristina; Davidsson Oejvind; Fjellstroem Ola; Gustafsson David; Hanessian Stephen; Inghardt Tord; Naagaard Mats; Nilsson Ingemar; Simard Daniel; Therrien Eric
Priority date: 2004-02-06
Filing date: 2006-08-02
Publication date: 2006-12-13

Abstract

There is provided a compound of formula I, wherein the dashed line, R1, R2, R3a, R3b, A, D, E, G and L have meanings given in the description, which compounds are useful as, or are useful as prodrugs of, competitive inhibitors of trypsin-like proteases, such as thrombin, and thus, in particular, in the treatment of conditions where inhibition of thrombin is beneficial (e.g. conditions, such as thrombo-embolisms, where inhibition of thrombin is required or desired, and/or conditions where anticoagulant therapy is indicated).

Description

NEW PIRID1N-2-ONA COMPOUNDS USEFUL AS THROMBIN INHIBITORS FIELD OF THE INVENTION This invention relates to novel compounds useful for pharmaceutical use and / or to compounds that are metabolized into compounds that are competitive inhibitors of trypsin-like serine proteases, especially thrombin, to their use as medicaments, pharmaceutical compositions containing them and synthetic routes. for its production.

BACKGROUND OF THE INVENTION Blood coagulation is the key process involved in both hemostasis (ie, preventing blood loss from a damaged vessel), and in thrombosis (ie, the formation of a blood clot in a blood vessel, which some sometimes leads to obstruction of the vessel). Coagulation is the result of a series of complex enzymatic reactions. One of the last steps in this series of reactions is the conversion of proenzyme prothrombin into the active enzyme thrombin. It is known that thrombin plays a central role in coagulation. It activates the platelets, which leads to platelet aggregation, converts fibrinogen to fibrin monomers, which polymerize spontaneously in fibrin polymers, and activates factor XI I I, which in turn lattices the polymers to form insoluble fibrin. Additionally, thrombin activates factor V, factor VI I I and factor XI, which leads to the generation of a "positive feedback" of thrombin from prothrombin. By inhibiting platelet aggregation and fibrin formation and cross-linking, one would expect effective thrombin inhibitors to exhibit anti-thrombotic activity. In addition, it would be expected that the anti-thrombotic activity would be improved by the effective inhibition of the positive feedback mechanism. Undoubtedly, the convincing anti-thrombotic effects of a thrombin inhibitor in man have been described by S. Schulman and co-authors in N. Engl. J: Med. 349, 1713-1721 (2003).

PREVIOUS TECHNIQUE The initial development of low molecular weight thrombin inhibitors has been described by Ciaesson in Blood Coagul. Fibrinol. 5.41 1 (1994). Blombáck and co-authors (in J Clin. Lab. Invest. 24, suppl. 107.59 (1969)) reported thrombin inhibitors based on the amino acid sequence located around the cleavage site for the fibrinogen chain Aa. From the sequences of described amino acids, these authors suggested that the tripeptide sequence Phe-Val-Arg (P9-P2-P1, which will be referred to hereinafter as P3-P2-P1 sequence) could be the most effective inhibitor. Thrombin inhibitors based on peptidyl derivatives, which have cyclic or acyclic basic groups in the P1 position (for example, groups containing amino, amidino or guanidino functions), are described, for example, in international patent applications numbers WO 93 / 11152, WO 93/18060, WO 94/29336, WO 95/23609, WO 95/35309, WO 96/03374, WO 96/25426, WO 96/31504, WO 96/32110, WO 97/02284, WO 97 / 23499, WO 97/46577, WO 97/49404, WO 98/06740, WO 98/57932, WO 99/29664, WO00 / 35869, WO 00/42059, WO 01/87879, WO 02/14270, WO 02 / 44145 and WO 03/018551, in European Patent Applications Nos. 185 390, 468 231, 526 877, 542 525, 559 046 and 641 779, 648780, 669317 and in U.S. Patent No. 4,346,078. Serine protease inhibitors (e.g., thrombin) based on electrophilic ketones at the P1 position are also known, such as the compounds described in European Patent Applications Nos. 195212, 362 002, 364344 and 530 167. Protease Inhibitors Serine-like trypsin based on arginine derivatives with C terminal boronic acid (and its isothiouronium analogs) are known from European Patent Application No. 293881.

The achiral thrombin inhibitors have a phenyl group in the P2 position of the molecule, and a cyclic or acyclic basic group in the P3 position, are described in the international patent applications numbers WO 94/20467, WO 96/06832, WO 96/06849, WO 97/1 1693, WO 97/24135, WO 98/01422 and WO01 / 68605, as well as in Bioorg Med. Chem. Lett. 7, 1283 (1997). The international patent applications numbers WO 99/26920 and WO01 / 79155 describe thrombin inhibitors having groups in the P2 position based, respectively, on 2-aminophenols and 1,4-benzoquinones. Similarly, phenol-based compounds are also described in international patent applications numbers WO01 / 68605 and WO 02/28825. Other known inhibitors of thrombin and other trypsin-like serine proteases are based (at the P2 position of the molecule) on the 3-amine-2-pyridone structural unit. For example, the compounds based on 3-amino-2-pyridone, 3-amino-2-pyrazinone, 5-amino-6-pyrimidone, 5-amino-2,6-pyrimidione and 5-amino-1, 3 , 4-triazin-6-one are described in the international patent applications numbers WO 96/18644, WO 97/01 338, WO 97/30708, WO 98/16547, WO 99/26926, WO 00/73302, WO 00 / 75134, WO01 / 38323, WO01 / 041 17, WO 01/70229, WO 01/79262, WO 02/057225, WO 02/064140 and WO 03/29224, in U.S. Patent Nos. 5,668,289 and 5,792,779, as well as in Bioorg. Med. Chem. Lett. 8, 817 (1998) and J. Med. Chem. 41, 4466 (1998). Thrombin inhibitors based on saturated 2-oxo-3-amino-substituted aza-heterocycles are described in International Patent Application No. WO 95/35313. More recently, thrombin inhibitors have been described which are based on 4-amino-3-morpholinone (see J. Med. Chem. 46, 1 165 (2003)). None of the aforementioned documents describes or suggests compounds based (at the 2P position) on the structural unit 1 -amino-2-pyridone or 1-amino-2-piperidone. Moreover, a need remains for effective inhibitors of trypsin-like serine proteases, such as thrombin. There is also a need for compounds that have a favorable pharmacokinetic profile. One would expect these compounds to be useful as anticoagulants and therefore for the therapeutic treatment of thrombosis and related disorders.

DESCRIPTION OF THE INVENTION According to the invention, a compound of the formula I is provided I where the dotted line is absent or represents a link; A represents C (O), S (O) 2, C (O) O (in the latter group the portion O is linked to R), C (O) NH, S (O) 2N H (in these latter groups the NH portion is attached to R1) or alkylene of 1 to 6 carbon atoms; R1 represents (a) alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms (these last three groups are optionally substituted by one or more substituents selected from halo, CN , cycloalkyl of 3 to 10 carbon atoms (optionally substituted by one or more substituents selected from halo, OH, = O, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms and aryl), OR4a, S (O) nR b, S (O) 2N (R4c) (R4d), N (R4e) S (O) 2R f, N (R4g) (R4h), B1-C (O) -B2-R4i, aryl and Het1), (b) cycloalkyl of 3 to 10 carbon atoms or cycloalkenyl of 4 to 10 carbon atoms, in which the last two groups are optionally substituted by one or more substituents selected from halo, = O, CN, alkyl from 1 to 10 carbon atoms, cycloalkyl of 3 to 10 carbon atoms (optionally substituted by one or more substituents selected from halo, OH, = O, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 atoms of carbon and aryl), OR a, S (O) nR4b, S (O) 2N (R c) (R4d), N (R4e) S (O) 2R4f, N (R4g) (R4h), B3-C (O) -B-R4i, aryl and Het2, (c) aryl, or (d) Het3; R4a to R4 'independently represent, in each case, (a) H, (b) Alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms (the last three of which groups are optionally substituted by one or more substituents selected from halo, OH, alkoxy of 1 to 6 carbon atoms, aryl and Het4), (c) Cycloalkyl of 3 to 10 carbon atoms, cycloalkenyl of 4 to 10 carbon atoms (whose last two groups are optionally substituted by one or more substituents selected from halo, OH, = O, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, aryl and Het5), (d) aryl or (e) Het6, provided that R4b does not represent H when n is 1 or 2; the group -DE- (a) when the dotted line represents a bond, represents -C (R5a) = C (R5b) -, or (b) when the dotted line is absent, represents - C (R6a) (R6b) -C (R7a) (R7b) -; R5a and R5b independently represent H, halo, OH, alkyl of 1 to 4 carbon atoms, (CH2) 0.4O (alkyl of 1 to 3 carbon atoms) (the last two groups of which are optionally substituted by an OH group or one or more F atoms); R6a, R6b, R7a and R7b independently represent H, F or methyl; or R5a and R5b together represent n-aikylene of 2 to 4 carbon atoms; or one of R6a and R6b, together with one of R7a and R7b represents 7-alkylene of 1 to 4 carbon atoms; R2 represents (a) H, (b) halo; (c) alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms (whose last four groups are optionally substituted by one or more substituents selected from halo, OH, CN, alkoxy of 1 to 4 carbon atoms, C (O) OH, C (O) O-alkyl of 1 to 4 carbon atoms and OC (O) -alkyl of 1 to 4 atoms carbon) or (d) together with R3a, R2 represents n-alkylene of 2 to 3 carbon atoms, T - (/ 7-alkylene of 1 to 2 carbon atoms) or (n-alkylene of 1 to 2 carbon atoms) -T1, whose last three groups are optionally substituted by halo, or (e) together with R3a and R3b, R2 represents T2- [C (H) =], wherein T2 is attached to the carbon atom to which the R2 group is attached; R3a and R3b independently represent H, F or methyl (whose last group is optionally substituted by one or more F atoms), or (a) together with R2, R3a represents n-alkylene of 2 to 3 carbon atoms, (n -alkylene of 1 to 2 carbon atoms) - or (N-alkylene of 1 to 2 carbon atoms) -T1, whose last three groups are optionally substituted by halo, or (b) together with R2, R3a and R3b represent T2 - [C (H) =], where T2 is attached to the carbon atom to which the R2 group is attached; T1 and T2 independently represent O, S, N (H) or N (alkyl of 14 carbon atoms); G represents (a) -C (O) N (R8a) - [CH (C (O) R9)] 0 -? - alkylene of 0 to 3 carbon atoms- (Q1) a-, (b) -C ( O) N (R8b) -alkenylene of 2 to 3 carbon atoms- (Q1) a-, (c) R9 represents H or an aromatic heterocyclic group of 5 to members containing one or two rings and containing, as the hetero atom (s), a sulfur atom or an oxygen atom, and / or one or more nitrogen atoms, the heterocyclic group of which is optionally substituted by one or more selected substituents halo and alkyl of 1 to 6 carbon atoms; Q1 represents O, NR10a, [N (H)] 0-? C (O) -alkylene of 0 to 2 carbon atoms, C (O) NHNHC (O), or -N = C (R10b) -; a represents 0 or 1; Q2a represents Q.2b represents L represents (a) alkylene of 0 to 6 carbon atoms-Ra, (b) alkylene of 0 to 2 carbon atoms-CH = CH-alkylene of 0 to 2 carbon atoms-Ra, (c) alkylene of 0 to 2 carbon atoms-C = C-alkylene of 0 to 2 carbon atoms-Ra, • - < - '* •? ° and- ~ ysí \ where the dotted line represents an optional double bond, or Ar represents phenyl or naphthyl; Het represents a 5- to 10-membered heterocyclic group which includes one or two rings, and which contains, as the hetero atom (s), a sulfur or oxygen atom and / or one or more nitrogen atoms; R 1 1 a represents H or one or more substituents selected from halo, OH, CN, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms (the latter two groups of which are optionally substituted by one or more substituents selected from halo, OH, alkoxy of 1 to 4 carbon atoms, C (O) OR12a and C (O) N (R12b) R12c) and S (O) 0-2R12d; Rn by Rn c independently represent H or one or more substituents selected from halo, OH, CN, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms (the latter two groups of which are optionally substituted by one or more substituents selected from halo, OH, alkoxy of 1 to 4 atoms carbon, C (O) OR12a and C (O) N (R12b) R12c), S (O) 0-2R12d, = O, = NH, = NOH y = N-CN; R12a to R12c independently represent H, alkyl of 1 to 6 carbon atoms or cycloalkyl of 3 to 7 carbon atoms (the latter two groups of which are optionally substituted by an OH or N (R12e) R12f group or by one or more halogen atoms ); R12d represents, independently in each case, alkyl of 1 to 6 carbon atoms optionally substituted by an OH or N (R12e) R12f group or by one or more halogen atoms; R12e and R12f represent, independently in each case, H or alkyl of 1 to 4 carbon atoms optionally substituted by one or more halogen atoms; Ra up Rd independently represent (d) (and) (F) (g) Hetx or Rb to Rd can also represent H; Q3 represents O, N (R10c), S (O) 2, S (O) 2NH, C (O) or -CH = N-; Q4 represents O, S or CH2; a represents 0 or 1; Hetx represents a 5-6 membered heterocyclic group containing one to four heteroatoms selected from oxygen, nitrogen and / or sulfur, said heterocyclic group may be substituted by one or more substituents selected from halo, = O, alkyl from 1 to 6 carbon atoms and alkoxy of 1 to 6 atoms carbon (whose last two groups are optionally substituted by one or more halogen atoms); R13a to R13c independently represent (a) H, (b) CN, (c) NH2, (d) OR15 or (e) C (O) OR16; R15 represents (a) H, (b) alkyl of 1 to 10 carbon atoms, alkenyl of 3 to 10 carbon atoms, alkynyl of 3 to 10 carbon atoms, (c) cycloalkyl of 3 to 10 carbon atoms, cycloalkenyl from 4 to 10 carbon atoms, whose last two groups are optionally substituted by one or more substituents selected from halo and alkyl of 1 to 6 carbon atoms, or (d) alkyl of 1 to 3 carbon atoms, whose last group is optionally interrupted by oxygen, and is substituted by aryl or by -O-aryl; R16 represents (a) alkyl of 1 to 10 carbon atoms, alkenyl of 3 to 10 carbon atoms, alkynyl of 3 to 10 carbon atoms, the last three groups of which are optionally interrupted by one or more oxygen atoms, or (b) ) cycloalkyl of 3 to 10 carbon atoms, cycloalkenyl of 4 to 10 carbon atoms, the latter two groups of which are optionally substituted by one or more substituents selected from halo and alkyl of 1 to 6 carbon atoms, or (c) alkyl of 1 to 3 carbon atoms, whose last group is optionally interrupted by oxygen, and is substituted by aryl or -O-aryl; R8a to R8c, R10a to R10c and R14a to R14g independently represent (a) H or (b) alkyl of 1 to 4 carbon atoms (the latter group of which is optionally substituted by one or more substituents selected from halo and OH), or R14a and R14b independently represent C (O) O-alkyl of 1 to 6 carbon atoms (the alkyl part of which the latter group is optionally substituted by aryl and / or one or more halogen atoms), or R14c represents (a) alkyl of 1 to 4 carbon atoms substituted by cycloalkyl of 3 to 7 carbon atoms or aryl, (b) cycloalkityl of 3 to 7 carbon atoms, (c) C (O) O-alkyl of 1 to 6 carbon atoms (the alkyl part of which the latter group is optionally substituted by aryl and / or one or more halogen atoms), (d) C (O) alkyi of 1 to 6 carbon atoms, (e) C (O) N (H) -alkyl of 1 to 6 carbon atoms (the part alkyl of which the latter group is optionally substituted by aryl and / or one or more halogen atoms) or (f) S (O) 2-Alkyl of 1 to 6 carbon atoms (the alkyl part of which the last group is optionally substituted by aryl and / or one or more halogen atoms), or R14c and R14d together represent n-alkylene of 3 to 6 carbon atoms optionally interrupted by O, S, N (H) or N (alkyl of 1 to 4 carbon atoms) and / or substituted by one or more alkyl groups of 1 to 4 carbon atoms; each aryl independently represents a carbocyclic aromatic group of 6 to 10 carbon atoms, said group may contain either one or two rings, and may be substituted by one or more substituents selected from (a) halo, (b) CN, (c ) alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms (whose last three groups are optionally substituted by one or more substituents selected from halo, OH, alkoxy of 1 to 6 carbon atoms, C (O) OH, C (O) O-alkyl of 1 to 6 carbon atoms, phenyl (whose last group is optionally substituted by halo) and Het7), (d) cycloalkyl of 3 to 10 atoms carbon, cycloalkenyl of 4 to 10 carbon atoms (the latter two groups of which are optionally substituted by one or more substituents selected from halo, OH, = O, alkyl of 1 to 6 carbon atoms, C 1-6 alkoxy, phenyl (the latter group of which is optionally substituted by halo) and Het 8), (e) OR17a, (f) S (O) pR 7b, (g) S (O) 2N (R17c) (R17d), (h) N (R17e) S (O) 2R17f, (i) N (R179) (R17h), (j) B5-C (O) -B6-R17i, (k) phenyl (whose last group is optionally substituted by halo), (I) Het9 and (m) Si (R18a) (R18b) (R18c); R1 to R? 17i independently represent, in each case, (a) H, (b) alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms (the last three groups of which are optionally substituted by one or more substituents selected from halo, OH, alkoxy of 1 to 6 carbon atoms, phenyl (whose last group is optionally substituted by halo) and Het10), (c) cycloalkyl of 3 to 10 carbon atoms, cycloalkenyl of 4 to 10 atoms carbon (the latter two groups of which are optionally substituted by one or more substituents selected from halo, OH, = O, alkyl of 1 to 6 carbon atoms, C 1 -C 6 -alkoxy, phenyl (the latter group of which is optionally substituted by halo) and Het 1 1), (d) phenyl (the latter group of which is optionally substituted by halo) or (e) Het 12, provided that R 1 7b do not represent H when p is 1 or 2; Het1 to Het12 independently represent 4 to 14 membered heterocyclic groups containing one or more heteroatoms selected from oxygen, nitrogen and / or sulfur, whose heterocyclic groups may contain one, two or three rings, and may be substituted by one or more selected substituents of (a) halo, (b) CN, (c) alkyl of 1 to 10 carbon atoms, alkenyl of 2 to carbon atoms, alkynyl of 2 to 10 carbon atoms (the last four groups of which are optionally substituted by one or more substituents selected from halo, OH, alkoxy of 1 to 6 carbon atoms, C (O) OH, C ( O) O-alkyl of 1 to 6 carbon atoms, phenyl (the latter group of which is optionally substituted by halo) and Heta), (d) cycloalkyl of 3 to 10 carbon atoms, cycloalkenyl of 4 to 10 carbon atoms (whose The last two groups are optionally substituted by one or more substituents selected from halo, OH, = O, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, phenyl (the last group of which is optionally substituted by halo) and Hetb), (e) = O, (f) OR19a (g) S (O) qR19b (h) S (O) 2N (R19c) (R19d), (i) N (R19e) S (O) 2R19f, (j) N (R199) (R19h), (k) B7-C (O) -B8-R19i, (I) phenyl (whose last group is optionally substituted by halo), (m) Hetc and (n) Si (R20a) (R20b) (R20c); R19a to R19 'independently represent, in each case, (a) H, (b) alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms (the last three groups of which are optionally substituted by one or more substituents selected from halo, OH, alkoxy of 1 to 6 carbon atoms, phenyl (the latter group of which is optionally substituted by halo) and Hetd), (c) cycloalkyl of 3 to 10 carbon atoms, cycloalkenyl of 4 to 10 carbon atoms (the latter two groups of which are optionally substituted by one or more substituents selected from halo, OH, = O, alkyl of 1 to 6 carbon atoms, C 1-6 alkoxy, phenyl (the latter group of which is optionally substituted by halo) and Hete), (d) phenyl (the latter group of which is optionally substituted by halo) or (e) Hetf, provided that R 19b does not represent H when q is 1 or 2; Heta to Hetf independently represent 5- or 6-membered heterocyclic groups containing from one to four heteroatoms selected from oxygen, nitrogen and / or sulfur, the heterocyclic groups of which may be substituted by one or more substituents selected from halo, = O and alkyl of 1. to 6 carbon atoms; B1 to B8 independently represent a direct link, O, S or NH; n, p and q independently represent 0, 1 or 2; R18a, R18b, R18c, R20a, R20b and R20c independently represent alkyl of 1 to 6 carbon atoms or phenyl (the latter group of which is optionally substituted by halo or alkyl of 1 to 4 carbon atoms); unless otherwise specified: (i) the alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, alkylene and alkenylene groups as well as the alkyl part of the alkoxy groups may be substituted by one or more halogen atoms, and ( ii) Cycloalkyl and cycloalkenyl groups can containing one or two rings, and additionally they may be fused to the ring in one or two phenyl groups; or a derivative thereof acceptable for pharmaceutical use. Hereinafter, these compounds will be referred to as "the compounds of the invention". The term "acceptable derivatives for pharmaceutical use" includes salts acceptable for pharmaceutical use (e.g., acid addition salts). For the avoidance of doubt, the definitions of the terms aryl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, alkylene groups, alkenylene and alkoxy provided above, apply, unless otherwise stated, in each use of such terms herein. The term "halo", when used herein, includes fluoro, chloro, bromo and iodo. The heterocyclic groups (Het, Het1 to Het12, Heta to Hetf and Het) can be fully saturated, partially unsaturated, of a fully aromatic or partially aromatic character. The values of the heterocyclic groups (Het, Het1 to Het12, Heta to Hetf and Hetx) which may be mentioned include 1-azabicyclo [2.2.2joctaniio, benzimidazolyl, benzo [c] isoxazolidinyl, benzisoxazolyl, benzodioxanil, benzodioxepanyl, benzodioxolyl, benzofuranyl, benzofurazanyl, benzomorpholinyl, 2, 1, 3-benzoxadiazolyl, benzoxazolidyl, benzoxazolyl, benzopyrazolyl, benzo [e] pyrimidine, 2,3-benzothiadiazolyl, benzothiazolyl, benzothienyl, benzotriazolyl, chromanyl, chromenyl, cinolinyl, 2,3-dihydrobenzimidazolyl, 2,3-dihydrobenzo [d] furanyl, 1,3-dihydrobenzo- [cjfuranyl, 1,3-dihydro-2, 1-benzisoxazolyl, 2, 3-dihydropyrrolo [2,3-b] -pyridinyl, dioxanyl, furanyl, hexahydropyrimidinyl, hydantoinyl, imidazole, imidazo [1,2-a] pyridinyl, imidazo [2,3-o] thiazole, indolyl, isoquinolinyl, isoxazolid inyl, isoxazolyl, maleimido, morpholinyl, naphtho [1,2-b] furanyl, oxadiazolyl, 1,2- or 1,3-oxazinanyl, oxazolyl, phthalazinyl, piperazinyl, piperidinyl, purinyl, pyranium, pyrazinyl, pyrazolyl, pyridinyl, pyridonyl, pyrimidinyl, pyrrolidinonyl, pyrrolidinyl, pyrrolinyl, pyrrolo [2,3-fc] pyridinyl, pyrrolo [5, - < f)] pyridinium. pyrrolo [2,3-c] pyridyl inyl, pyrrolyl, quinazolinyl, quinolinyl, sulfolanyl, 3-sulfolenyl, 4,5,6,7-tetrahydrobenzimidazolyl, 4,5,6,7-tetrahydrobenzopyrazolyl, 5, 6, 7, 8 -tetra h id robe nzo [e] pyrimidine, tetrahydrofuranyl, tetrahydropyranyl, 3,4,5,6-tetrahydropyridinyl, 1, 2,3,4-tetrahydropyrimidinyl, 3,4,5,6-tetrahydropyrimidinyl, thiadiazolyl, thiazolidinyl, thiazolyl, thienyl, thieno [5, 1-c] pyridinyl, thiochromanyl, triazolyl, 1,4-triazolo [2,3-? b] pyrimidinyl, xanthenyl and the like. The Het values that may be mentioned include 1-azabicyclo [2.2.2] octam, benzimidazolyl, benzo [c] isoxazolidinyl, benzisoxazolyl, benzo [bjfuranyl, benzopyrazolyl, benzodioxanyl, benzodioxepany, benzodioxolyl, benzofuranyl, benzofurazanyl, benzomorpholinyl, 2, 1, 3-benzoxadiazolyl, benzoxazolidinyl, benzoxazolyl, benzopyrazolyl, benzo [e] pyrimidine, 2, 1, 3-benzothiadiazbenzo [e] pyrimidine, benzothiazolyl, benzo [b] thienyl, benotriazolyl, 2-oxo-2,3-dihydrobenzimidazolyl, 1,3-dihydro-2,1-benzisoxazolyl, 2,3-dih idropyrole [2,3-b] pyridinyl, furanyl , 2-iminohexahydropyrimidinyl, imidazolyl, imidazo [1,2-a] pyridinyl, indolyl, isoquinolinyl, isoxazolidinyl, isoxazolyl, 1,4-oxadiazolyl, 1,4-oxadiazoliol, 1,2-oxazinanyl, 2-imino -1, 3-oxazinanyl, piperazinyl, piperidinyl, 2-oxo-piperidinyl, pyrazinyl, pyridinyl, pyrimidinyl, 2-iminopyrrolidinyl, 3-pyrrolinyl, pyrrolo [2,3-b] pyridinyl, pi rrolo [5, 1-b] pyridinyl, pyrrolo [2,3-c] pyridinyl, pyrrolyl, quinolinyl, 4,5,6,7-tetrahydrobenzimidazolyl, 4,5,6,7-tetrahydrobenzopyrazolyl, 5,6,7,8-tetra h id robe nzo [e] pyrimidine, 3,4,5,6-tetrahydropyrimidinyl, 2-imino-thiadiazolyl, thiazolyl, thienyl and thieno [5,1-c] pyridinyl. The values of Het1 that may be mentioned include benzodioxolyl, benzo [6] furanyl, 2,3-dihydrobenzo [o] furanyl, pyridinyl, pyrimidinyl and thienyl. The values of Het3 which may be mentioned include benzodioxanil, benzo [6] dioxepanil, benzodioxolyl, benzomorpholinyl, 2,1, 3-benzoxadiazolyl, 2-oxo-benzoxazolidinyl, benzopyrazolyl, 2,1, 3-benzothiadiazolyl, benzo [i > ] thienyl, 2-oxo-chromenyl, 2,3-dihydrobenzo [/ j] furanyl, 1-oxo-1,3-dihydrobenzo [c] furanyl, furanyl, imidazolyl, imidazo [2,3- /)] thiazolyl, isoquinolinyl , isoxazolyl, naphtho [1,2- b] furanyl, pyrazinyl, pyrazolyl, pyridinyl, pyridonyl, pyrrolyl, quinolinyl, sulfolanyl, 3-sulfolenyl, 2,4-dioxo-1, 2,3,4-tetrahydropyrimidinyl, thiazolyl, thienyl, 1,3,4-triazolo [2,3-β] pyrimidinyl and xanentyl.

The values of Het9 which may be mentioned include morpholinyl, 1,3,4-oxadiazoliol, oxazolyl and pyrazolyl. The values of Het10 that may be mentioned include isoxazolyl, oxazolyl and thiazolyl. The Hetc values that may be mentioned include isoxazolyl, morpholinyl, oxazolyl, pyridinyl, thienyl and triazolyl (for example 1, 3,4-triazolyl). The Hetx values that may be mentioned include dihydrooxadiazolyl (for example 4,5-dihydro-1,2,4-oxadiazol-3-yl), oxadiazolyl (for example 1,2,4-oxadiazol-3-yl), tetrazolyl (for example triazol-1-yl) and triazolyl (for example 1,2,4-triazol-1-yl). Substituents in the heterocyclic groups (Het, Het1 up to Het12, Heta up to Hetf and Hetx), where appropriate, can be placed in any atom in the ring system including a heteroatom. The point of attachment of the heterocyclic groups (Het, Het1 to Het12, Heta to Hetf and Hetx) can be by means of any atom in the ring system, including (where appropriate) a heteroatom, or an atom of any carbocyclic ring merged that may be present as part of the ring system. For the avoidance of doubt, the cycloalkyl and cycloalkenyl groups may be monocyclic, or, when the amount of carbon atoms permits, be bi- or tri-cyclic (although monocyclic cycloalkyl and cycloalkenyl are preferred). In addition, when a cycloalkyl or cycloalkenyl group is fused with two phenyl groups, the Phenyl groups can also be fused together (to form a fused tricyclic ring system). The compounds of the formula I may show tautomerism. All tautomeric forms and their mixtures are included within the scope of the invention. The compounds of the formula I may also contain one or more asymmetric carbon atoms and therefore may exhibit optical and / or diastereoisomerism. The diastereoisomers can be separated using conventional techniques, for example chromatography or fractional crystallization. The various stereoisomers can be isolated by separation of a racemic mixture or other mixture of the compounds using for example fractional crystallization techniques or H PLC. Alternatively, the desired optical isomers can be made by reacting the appropriate optically active starting materials under conditions that will not cause racemization or epimerization, or by derivatization, for example with a homochiral acid followed by separation of the diastereomeric esters by conventional means (e.g. , H PLC, chromatography on silica). All stereoisomers are included within the scope of the invention. The abbreviations are listed at the end of this specification. The wavy lines in the links in the structural fragments mean the joined positions of these fragments.

Compounds of formula I which may be mentioned include those in which: (1) R5a represents H, halo, OH, alkyl of 1 to 4 carbon atoms (the latter group of which is optionally substituted by alkoxy of 1 to 3 carbon atoms) ) or alkoxy of 1 to 4 carbon atoms; (2) R5b, R6a, R6b, R7a and R7b independently represent H, F or methyl; (3) R2 represents (a) H, (b) halo; (c) alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms (the latter four groups of which are optionally substituted by one or more substituents selected from halo, OH, CN, alkoxy of 1 to 4 carbon atoms, C (O) OH, C (O) O-alkyl of 1 to 4 carbon atoms and OC (O) -alkyl of 1 to 4 atoms carbon) or (d) together with R3a, R2 represents / V-alkylene of 2 to 3 carbon atoms or O- (V-alkylene of 1 to 2 carbon atoms), the latter two groups of which are optionally substituted by halo and wherein the O atom of the last group is attached to the C atom to which it is attached in the R2 group; (4) R3a and R3b independently represent H, F or methyl, or R3a, together with R2, represents / V-alkylene of 2 to 3 carbon atoms or O - (? / - alkylene of 1 to 2 carbon atoms), whose last two groups are optionally substituted by halo and wherein the O atom of the last group is attached to the C atom to which the group R2 is attached: (5) R 1 a represents H or one or more substituents selected from halo, OH , CN, alkyl of 1 to 6 carbon atoms and alkoxy of 1 to 6 carbon atoms (the latter two groups of which are optionally substituted by one or more substituents selected from halo, OH, alkoxy of 1 to 4 carbon atoms, C ( O) OR12a and C (O) N (R12b) R12c); (6) R 1b and R 11c independently represent H or one or more substituents selected from halo, OH, CN, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms (the latter two groups of which are optionally substituted by one or more substituents selected from halo, OH, alkoxy of 1 to 4 carbon atoms, C (O) OR12a and C (O) N (R12b) R12c), = O, = NH, = NOH and =? - CN; (7) R12a to R12c independently represent H, alkyl of 1 to 6 carbon atoms or cycloalkyl of 3 to 7 carbon atoms (the latter two groups of which are optionally substituted by one or more halogen atoms); (8) Ra up to Rd independently represent (a) (g) (h) or Rb to Rd can also represent H. Other compounds of formula I that may be mentioned include those in which: R8a through R8c, R10a to R10c and R14a to R14g independently represent (a) H or (b) alkyl of 1 to 6 carbon atoms (whose last group is optionally substituted by one or more substituents selected from halo and OH), or R14c represents (a) ) alkyl of 1 to 4 carbon atoms substituted by cycloalkyl of 3 to 7 carbon atoms or aryl, (b) cycloalkyl of 3 to 7 carbon atoms, (c) C (O) O-alkyl of 1 to 6 carbon atoms carbon (the alkyl part of which the latter group is optionally substituted by aryl and / or one or more halogen atoms), (d) C (O) alkyl of 1 to 6 carbon atoms, (e) C (O) N (H) -alkyl of 1 to 6 carbon atoms (the alkyl part of which the latter group is optionally substituted by aryl and / or one or more halogen atoms) or (f) S (O) 2-alkyl of 1 to 6 carbon atoms (the alkyl part of which the latter group is optionally substituted by aryl and / or one or more halogen atoms), or R14c and R14d together represent n- alkylene of 3 to 6 carbon atoms optionally interrupted by O, S, N (H) or N (alkyl of 1 to 4 carbon atoms) and / or substituted by one or more alkyl groups of 1 to 4 carbon atoms. The compounds of the formula I can alternatively be represented as compounds of the formulas la and Ib, the Ib wherein R1, R2, R3a, R3b, R5a, R5b, R6a, R6b, R7a, R7b, A, G and L are as defined above. In this regard, the person skilled in the art will understand that the preferences given below with respect to the compounds of formula I apply equally (where appropriate) to the compounds of formulas 1 a and 1 B (either together or separately). Preferred values of G include: (a) -C (O) N (R8a) -alkylene of 0 to 3 carbon atoms; (b) -C (O) N (R8a) -CH (C (O) R9) -alkylene of 0 to 3 carbon atoms; (c) -C (O) N (R8a) -alkylene of 1 to 3 carbon atoms-Q1-; (d) -C (O) N (R8) -alkenylene of 2 to 3 carbon atoms; (and) When G represents -C (O) N (R8a) -alkylene of 0 to 3 carbon atoms-Q1-, preferred values of L include: (to) (b) (c) When G represents -C (O) N (R8b) -alkenylene of 2 to 3 carbon atoms-, Preferred values of L include: Preferred compounds of the formula I include those in which: (1) A represents C (O), S (O) 2, C (O) NH (in which latter group the NH portion is attached to R1) or alkylene of 1 to 4 carbon atoms; (2) R1 represents (a) alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms (the last three groups of which are optionally substituted by one or more substituents selected from halo, CN, cycloalkyl of 3 to 8 carbon atoms (optionally substituted by one or more substituents selected from halo, OH, = O, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms and aryl), OR4a, SR b, S (O) 2R4b, S (O) 2N (H) R4c, N (H) S (O) 2R f, N (R4g) (R4h), C (O) R4i, OC (O) R4i, C (O) OR4i, N (H) C (O) R i, C ( O) N (H) R, aryl and Het1), (b) cycloalkyl of 3 to 8 carbon atoms or cycloalkenyl of 4 to 8 carbon atoms, whose last two groups are optionally fused with one or two phenyl groups and are substituted optionally by one or more substituents selected from halo, = O, alkyl of 1 to 6 carbon atoms, cycloalkyl of 4 to 6 carbon atoms (optionally substituted by one or more substituents selected from halo, alkyl of 1 to 4 carbon atoms , alkoxy of 1 to 4 atoms, carbon and phenyl), OR4a, SR4b, S (O) 2R4b, S (O) 2N (H) R4c, N (H) S (O) 2R4f, N (R4g) (R4h ), OC (O) R4i, C (O) OR4i, N (H) C (O) R4, C (O) N (H) R4i, aryl and Het2, (c) aryl, or (d) Het3; (3) R4a to R4 'independently represent, in each case, (a) H, (b) alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms (whose last three groups are optionally substituted by one or more substituents selected from halo, OH, alkoxy 1 to 4 carbon atoms, aryl and Het4), (c) cycloalkyl of 4 to 6 carbon atoms, cycloalkenyl of 4 to 6 carbon atoms (the latter two groups of which are optionally substituted by one or more substituents selected from halo, = O and alkyl of 1 to 4 carbon atoms), (d) aryl or (e) Het6, provided that R4b does not represent H when n is 1 or 2; (4) R5a represents H, F, methyl or methoxy; (5) R5b represents H; (6) R6a and R6b both represent H, represent both methyl, or both represent F; (7) R7a and R7b represent both H; (8) R 2 represents H, halo, alkoxy of 1 to 4 carbon atoms or alkyl of 1 to 4 carbon atoms (the latter group of which is optionally substituted by one or more substituents selected from halo (for example F), OH or methoxy ); (9) R3a and R3b independently represent H or F; (10) Group G-L takes any of the following definitions (a) C (O) N (R8a) -alkylene of 0 to 6 carbon atoms-Ra, (b) C (O) N (R8a) -CH (C (O) R9) C5 O-Alkylene-Ra (c) C (O) N (R8a) -alkylene of 0 to 3 carbon atoms -CH = CH-alkylene of 0 to 2 carbon atoms-Ra (d) C (O) N (R8a) -alkylene of 0 to 3 carbon atoms-CH = C-alkylene of 0 to 2 carbon atoms-Ra (g) (h) (i) (j) (k) (l) (m) (n) Alkylene-f- Het - ~ Rd (or) R11c wherein Q1a represents O, NR10a or [N (H)] 0-1C (O) -alkylene of 0 to 2 carbon atoms; (11) R9 represents a 5- to 10-membered aromatic heterocyclic group containing one or two rings and containing, as the heteroatom (s), a sulfur or oxygen atom and / or one to three nitrogen atoms, the group of which heterocyclic is optionally substituted by one or more substituents selected from halo and alkyl of 1 to 4 carbon atoms; (12) Het represents a monocyclic group of 5 or 6 members, or an 8, 9 or 10 membered bicyclic heterocyclic group containing, as the hetero atom (s), a sulfur or oxygen atom and / or one to four nitrogen atoms; (13) R11a represents H or one to three substituents selected from halo, OH, CN, alkyl of 1 to 4 carbon atoms and alkoxy of 1 to 4 carbon atoms (the latter two groups of which are optionally substituted by one or more substituents selected from OH, halo, C (O) OR12a and C (O) N ( R12b) R12c (for example one or more substituents selected from the last three groups)); (14) R11 represents H or one to three substituents selected from halo, OH, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms and = O; (15) R11c represents H or one to three substituents selected from halo, OH, CN, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms (the latter two groups of which are optionally substituted by one or more substituents selected from halo, OH and alkoxy of 12 carbon atoms), = 0, = NH, = NOH y = N-CN; (16) R 2a to R 12c independently represent H, alkyl of 1 to 4 carbon atoms (optionally substituted by a group N (R 12e) R 12f) or cycloalkyl of 3 to 6 carbon atoms (for example H, alkyl of 1 to 4 carbon atoms (optionally substituted by a group N (R12e) R12f) or cycloalkyl of 3 to 6 carbon atoms (for example, H, alkyl of 1 to 4 carbon atoms) carbon or cycloalkyl of 3 to 6 carbon atoms); (17) Ra represents (d) (and) (18) Rb represents (a) H (b) (c) (19) Rc and R independently represent (a) (d) R can also represent H; (20) Q3 represents O, S (O) 2, S (O) 2 NH, C (O) or -CH = N-; (21) Q4 represents O or S; (22) R15 represents H, alkyl of 1 to 6 carbon atoms, alkenyl of 3 to 6 carbon atoms (the latter two groups of which are optionally interrupted by an oxygen atom), cycloalkyl of 3 to 6 carbon atoms or alkyl of 1 to 2 carbon atoms (whose last group is substituted by aryl); (23) R16 represents alkyl of 1 to 6 carbon atoms, alkenyl of 3 to 6 carbon atoms, cycloaicyl of 3 to 6 carbon atoms or alkyl of 1 to 2 carbon atoms substituted by aryl; (24) R8a to R8c represent H or methyl; (25) R10a to R10c independently represent H or alkyl of 1 to 3 carbon atoms (the latter group of which is optionally substituted by OH or one or more halogen atoms); (26) R14a represents alkyl of 1 to 2 carbon atoms, C (O) O-alkyl of 1 to 5 carbon atoms (the alkyl part of which the latter group is optionally substituted by phenyl) or H (for example H or alkyl of 1 to 2 carbon atoms); (27) R14b to R14g independently represent H or alkyl of 1 to 2 carbon atoms (whose last group is optionally substituted by one or more halogen atoms, but preferably is unsubstituted), or R14c represents cycloalkyl of 4 to 6 carbon atoms carbon or C (O) O-alkyl of 1 to 5 carbon atoms (the alkyl part of which the latter group is optionally substituted by phenyl) or R14c and R14 together represent n-alkylene of 4 to 5 carbon atoms optionally interrupted by O; (28) each aryl independently represents phenyl or naphthyl, each of which groups may be substituted by one or more substituents selected from (a) halo, (b) CN, (c) alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 4 carbon atoms, alkynyl of 2 to 4 carbon atoms (the last three groups of which are optionally substituted by one or more substituents selected from halo, OH, alkoxy of 1 to 2 carbon atoms, C (O) OH, C (O) O-alkyl of 1 to 2 carbon atoms and phenyl), (d) cycloalkyl of 3 to 6 carbon atoms carbon optionally substituted by one or more substituents selected from halo, = O and alkyl of 1 to 4 carbon atoms, (e) OR17a, (f) SR17b, S (O) 2R17b, (g) S (O) 2N (H) ) R17c, (h) N (H) S (O) 2R17f, (i) N (H) R17g, (j) C (O) R7i, C (O) OR17i, OC (O) R17i, C (O) ) N (H) R17i, N (H) C (O) R17, N (H) C (O) OR17i, (k) phenyl (the latter group of which is optionally substituted by one or more halogen atoms), (1) ) Het9 and (m) Si (CH3) 3; (29) R17a to R17 'independently represent, in each case, (a) H, (b) alkyl of 1 to 8 carbon atoms optionally substituted by one or more substituents selected from halo, OH, alkoxy of 1 to 2 carbon atoms, phenyl (the latter group of which is optionally substituted by one or more halogen atoms) and Het10 (for example one or more substituents selected from halo, OH, alkoxy of 1 to 2 carbon atoms and phenyl (the latter group of which is optionally substituted by one or more halogen atoms)), (c) cycloalkyl of 3 to 6 carbon atoms optionally substituted by one or more substituents selected from halo , = O and alkyl of 1 to 4 carbon atoms, (d) phenol optionally substituted by one or more halogen atoms or (e) Het12, provided that R17b does not represent H; (30) Het1 to Het12 independently represent 5- to 13-membered heterocyclic groups containing from one to four heteroatoms selected from oxygen, nitrogen and / or sulfur, the heterocyclic groups of which may contain one, two or three rings and may be substituted by one or more substituents selected from (a) halo, (b) CN, (c) alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 4 carbon atoms, alkynyl of 2 to 4 carbon atoms (the last three groups of which are substituted optionally by one or more substituents selected from halo, OH and alkoxy of 1 to 2 carbon atoms), (d) cycloaikyl of 3 to 6 carbon atoms optionally substituted by one or more substituents selected from halo, = O and alkyl of 1 to 4 carbon atoms, (e) = 0, (f) OR19a, (g) s (0) 2R19b, (h) S (O) 2N (H) R19c, (i) N (H) S (O) 2R1 f, (j) N (H) R19g (k) C (O) R19i, C (O) OR19i, C (O) N (H) R19i, N (H) C (O) R19i, N (H) C (O) OR 9i , (I) phenyl (whose last group is optionally substituted by halo) and (m) Hetc; (31) R19a to R19i independently represent, in each case, (a) H, (b) alkyl of 1 to 6 carbon atoms optionally substituted by one or more substituents selected from halo, OH, alkoxy of 1 to 2 carbon atoms and phenyl, (c) cycloalkyl of 3 to 6 carbon atoms optionally substituted by one or more substituents selected from halo, = O and alkyl of 1 to 4 carbon atoms, (d) phenyl optionally substituted by halo or (e) Hetf , provided that R19b does not represent H; (32) Heta up to Hetf independently represent 5- or 6-membered heterocyclic groups, which contain, as heteroatoms, an oxygen or sulfur atom and / or one to three nitrogen atoms, whose heterocyclic groups may be substituted by one or more substituents selected from halo and alkyl of 1 to 4 carbon atoms; (33) the alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, alkylene and alkenylene groups, as well as the alkyl part of the alkoxy groups, may be substituted by one or more Cl atoms or, particularly, F atoms. prefer the compounds of the formula I in which R3a and R3b both take the same definition (ie, compounds in which R5 and R6 both represent H, represent both F or represent both methyl, CH2F, CHF2 or CF3). When A represents C (O) or C (O) NH (in which latter group the NH portion is linked to R1), preferred compounds of formula I also include those in which R1 represents: (a) alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, the last three groups of which are (i) substituted by a substituent selected from cycloalkyl of 3 to 8 carbon atoms (optionally substituted by one or more substituents selected from halo, OH, = O, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms and aryl), aryl and Het1, and (ii) optionally substituted by one or more additional substituents selected of halo, CN, cycloalkyl of 4 to 6 atoms carbon (optionally substituted by one or more substituents selected from halo and alkyl of 1 to 4 carbon atoms), OR4a, SR4b, S (O) 2R4b, S (O) 2N (H) R4c, N (H) S ( O) 2R f, N (R4g) (R4h), OC (O) R4i, C (O) OR4i, N (H) C (O) R4i, C (O) N (H) R4i, aryl and Het1; (b) cycloalkyl of 3 to 8 carbon atoms or cycloalkenyl of 4 to 8 carbon atoms, whose last two groups are (i) fused with one or two fepyl groups and optionally substituted by one or more substituents selected from halo, alkyl 1 to 4 carbon atoms and C (O) OR 4i, or (ii) substituted by aryl and optionally further substituted by one or more substituents selected from halo and alkyl of 1 to 4 carbon atoms; (c) aryl; or (d) Het3, wherein R4a to R4c, R4f to R4i, aryl and Het1 are as defined above or as defined below. When A represents S (O) 2, the preferred compounds of formula I also include those in which R 1 represents: (a) alkyl of 1 to 3 carbon atoms or alkenyl of 2 to 3 carbon atoms, the latter of which groups they are substituted by aryl and are optionally further substituted by one or more halogen atoms; (b) alkyl of 1 to 6 carbon atoms optionally substituted by one or more substituents selected from halo, OR4a and S (O) 2R4b; (c) monocyclic cycloalkyl of 3 to 6 carbon atoms, optionally substituted by one or more substituents selected from halo and alkyl of 1 to 4 carbon atoms; (d) Bicyclic cycloalkyl of 6 to 8 carbon atoms optionally substituted by one or more substituents selected from halo, = O and alkyl of 1 to 4 carbon atoms; (e) aryl; or (f) Het3, wherein R a and R 4b are as defined above or as defined below. When A represents alkylene of 1 to 6 carbon atoms, preferred compounds of formula I also include those in which R 1 represents: (a) alkyl of 1 to 6 carbon atoms or alkenyl of 2 to 6 carbon atoms, whose the last two groups are optionally substituted by one or more substituents selected from halo and OH; (b) cycloalkyl of 3 to 8 carbon atoms or cycloalkenyl of 4 to 8 carbon atoms (for example of 4 to 6 carbon atoms), the latter two groups of which are optionally substituted by one to four substituents selected from halo, = O , OH, alkyl of 1 to 4 carbon atoms, O-Alkyne of 14 atoms carbon (the latter two groups of which are optionally substituted by one or more halogen atoms (for example F)) and aryl, or, particularly, (c) aryl (for example naphthyl or, particularly, phenyl), or (d) Het3 , (for example, any of the groups listed in (b) through (d) above). The compounds of formula I that are most preferred include those in which the GL group takes any of the preferred definitions provided in (10) (a), (c), (d), (e), (g), (h), (i), (k), (I), (m), (o) and (p) above. The most preferred compounds of formula I include in particular compounds in which: (1) A represents C (O), S (O) 2, C (O) NH (in the latter group the NH portion is attached to R1) or alkenylene of 1 to 3 carbon atoms; (2) R1 represents (a) alkyl of 1 to 5 carbon atoms, alkenyl of 2 to 4 carbon atoms (the latter two groups of which are optionally substituted by one or more substituents selected from halo, bicyclic cycloalkyl of 6 to 8 carbon atoms. carbon, monocyclic cycloalkyl of 3 to 6 carbon atoms (the latter two groups of which are optionally substituted by one or more substituents selected from halo, = O, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms and phenyl (whose last group is optionally substituted by one or more substituents selected from halo, alkyl of 1 to 4 carbon atoms and C 1-4 alkoxy)), OR 4a, SR 4b, S (O) 2R 4b, C (O) R 4i, OC (O) R, C (O) OR 4i, aryl and Het 1), (b) 3-cycloalkyl to 6 carbon atoms or cycloalkenyl of 4 to 8 carbon atoms (for example 4 to 6 carbon atoms), whose last two groups are optionally fused with one or two phenyl groups and are optionally substituted by one or more substituents selected from halo, = O, alkyl of 1 to 4 carbon atoms, OR4a, C (O) OR4i and phenyl (whose the latter group is optionally substituted by one or more substituents selected from halo, alkyl of 1 to 4 carbon atoms and alkoxy of 1 to 4 carbon atoms), (c) aryl, or (d) Het3; (3) R4a to R4 'independently represent, in each case, (a) H, (b) alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 4 carbon atoms (the latter two groups of which are optionally substituted by one or more substituents selected from halo, OH, alkoxy of 1 to 4 carbon atoms and phenyl), (c) cycloalkyl of 4 to 6 carbon atoms (whose last group is optionally substituted by one or more substituents selected from halo and alkyl of 1 to 2 carbon atoms) or (d) phenyl (the latter group of which is optionally substituted by one or more substituents selected from halo, alkyl of 1 to 4 carbon atoms and alkoxy of 1 to 4 carbon atoms) provided that R4b does not represent H; (4) R 2 represents H, halo (such as Ci) or alkyl of 1 to 3 carbon atoms (whose last group is optionally substituted by F); (5) R3a and R3b both represent H or both represent F; (6) R5a represents H; (7) R6a and R6b represent both H; (8) The GL group takes any of the following definitions: (i) C (O) N (H) -alkylene of 0 to 5 carbon atoms-Ra1, (ii) C (O) N (H) -alkylene of 0 to 3 carbon atoms-CH = CH-Ra2, (ii) C (O) N (H) -alkylene of 1 to 3 carbon atoms-C = C-CH2-Ra3, (v) (saw) (vii) (ix) (x) (xi) (xii) (xiii) where Q1 a is as defined above; (9) Het represents a monocyclic group of 5 to 6 members, a bicyclic group of 8 members, or a bicyclic heterocyclic group with 9 to 10 members fused in the ring containing, as heteroatom (s), a sulfur or oxygen atom and / or from one to three nitrogen atoms, whose heterocyclic group (i) when it is 5 or 6 members, is fully aromatic, fully saturated or mono-unsaturated, (ii) when it is 8 members, is fully aromatic, or preferably, fully saturated, or (iii) when it is 9 or 10 members, it is totally aromatic or partially aromatic; (10) R11a represents H or one to three substituents selected from halo, OH, CN, alkyl of 13 carbon atoms and alkoxy of 13 carbon atoms (the latter two groups of which are optionally substituted by one or more substituents selected from OH, halo , C (O) OR 2a and C (O) N (R12b) R12c (for example one or more substituents selected from the last three groups)); (11) R11b represents one or two substituents selected from halo and alkyl of 1 to 3 carbon atoms or, preferably, R11b represents H; (12) R11c represents H or one to three substituents selected from halo, OH, CN, alkyl of 1 to 3 carbon atoms (whose last group is optionally substituted by one or more substituents selected from halo and OH), = O, = NH y = N-CN; (13) R12a to R12c independently represent H, alkyl of 1 to 3 carbon atoms (optionally substituted by a group N (R12e) R12f) or cycloalkyl of 3 to 5 carbon atoms (for example H, alkyl of 13 carbon atoms or cycloalkyl of 3 to 5 carbon atoms); (14) R12e and R12f independently represent H or alkyl of 1 to 2 carbon atoms; (15) Ra1, Ra2 and Ra3 represent Ra as defined above, but preferably independently represent wherein Q31 represents, O, C (O) or -CH = N- and a represents 0 or, preferably, 1; (16) Rb represents (a) H, (b) (F) (17) R ° represents (18) Rd represents H, (19) R13a represents H, CN, NH2 or OR15; (20) R13b represents H, NH2, OR15 or C (O) OR16; (21) R13c represents H or OH; (22) R15 represents H or alkyl of 1 to 5 carbon atoms; (23) R16 represents alkyl of 1 to 2 carbon atoms substituted by aryl; (24) R10a represents H or alkyl of 1 to 2 carbon atoms (whose last group is optionally substituted by OH); (25) R14a represents H, methyl, C (O) O-alkyl of 3 to 4 carbon atoms or C (O) OCH2-phenyl (for example methyl, or preferably, H); (26) R14b to R14d and R14f to R14g independently represent methyl, or preferably, H, or R1 G represents alkyl of 1 to 2 carbon atoms substituted by one to three halogen atoms (for example F), cycloalkyl of 4 to 5 carbon atoms (for example cyclopentyl), C (O) O-alkyl of 3 to 4 carbon atoms or C (O) OCH2-phenyl (for example one of the last three groups), or R14c and R14d together represent n- alkylene of 4 carbon atoms; (27) R e represents H or, preferably, methyl; (28) each aryl independently represents phenyl or naphthyl, each of which groups may be substituted by one or more substituents selected from (a) F, Cl, Br, (b) CN, (c) alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 3 carbon atoms (the latter two groups of which are optionally substituted by one or more substituents selected from F, Cl, C (O) OH, C (O) OCH3 and phenyl), (d) cycloalkyl of 3 to 5 carbon atoms, (e) OR17a, (f) S-alkyl of 1 to 2 atoms of carbon, S (O) 2-alkyl of 1 to 2 carbon atoms (the alkyl portions of which the last two groups are optionally substituted by one or more F atoms), (g) S (O) 2 NH2, S (O) 2N (H) CH 3, (h ) N (H) S (O) 2-alkyl of 1 to 2 carbon atoms, alkyl part of which the latter group is optionally substituted by one or more F atoms), (i) NH 2, N (H) alkyl of 1 to 2 carbon atoms, (j) CHO, C (O) -alkyl of 1 to 4 carbon atoms (the alkyl part of which the latter group is optionally substituted by one or more atoms of F or Cl), C (O) OH, C (O) O-alkyl of 1 to 4 carbon atoms C (O) NH2, C (O) N (H) -alkyl of 1 to 4 carbon atoms, N (H) C (O ) -alkyl of 1 to 4 carbon atoms, N (H) C (O) O-alkyl of 1 to 4 carbon atoms, (k) phenyl (the last group of which is substituted) optionally by one or more substituents selected from F, Cl and Br), (I) Het9 and (m) Si (CH3) 3; (29) R17a represents (a) H, (b) alkyl optionally substituted by phenyl or one or more substituents selected from F, Cl, and Het10 (for example, one or more substituents selected from F and Cl), (c) cycloalkyl from 3 to 5 carbon atoms or (d) phenyl optionally substituted by one to four substituents selected from F, Cl and Br; (30) Het1 represents a heterocyclic group of 5 to 10 members, containing one to three heteroatoms selected from oxygen, nitrogen and / or sulfur, whose heterocyclic groups may contain one or two rings and may be substituted by one to three selected substituents of F, Cl, Br, alkyl of 1 to 4 carbon atoms, = O and OH; (31) Het3 represents a 5- to 13-membered heterocyclic group containing one to four heteroatoms selected from oxygen, nitrogen and / or sulfur, whose heterocyclic groups may contain one, two or three rings, and may be substituted by one to four substituents selected from (a) F, Cl, Br, (b) alkyl of 1 to 4 carbon atoms (whose last group is optionally substituted by one or more substituents selected from F, Cl and OH), (c) cycloalkyl of 3 to 5 carbon atoms, (d) = O, (e) OH, O-alkyl of 1 to 2 carbon atoms (whose last group is optionally substituted by one or more substituents selected from F and Cl), (g) S (O) 2-alkyl of 1 to 2 carbon atoms (the latter group of which is optionally substituted by one or more carbon atoms) ), S (O) 2-phenyl (the phenyl part of which the latter group is optionally substituted by one to four substituents selected from F, Cl, Br, methyl and methoxy. (h) S (O) 2 NH 2, S (O) 2 N (H) -alkyl of 1 to 2 carbon atoms, (i) N (H) S (O) 2-alkyl of 1 to 2 carbon atoms, ( j) NH2) N (H) -alkyl of 1 to 2 carbon atoms, (j) C (O) -alkyl of 1 to 4 carbon atoms, C (O) -phenyl (the phenyl part of which the latter group is optionally substituted by one to four substituents selected from F, Cl, Br, methyl and methoxy), C (O) O H, C (O) O-alkyl of 1 to 4 carbon atoms, C (O) NH 2, C (O) N (H) -alkyl of 1 to 4 carbon atoms, N (H) C (O) -alkyl of 14 carbon atoms, N (H) C (O) O-alkyl of 1 to 4 carbon atoms, (1) phenyl (the latter group of which is substituted optionally by one to four substituents selected from F, Cl and Br) and (m) Hetc; (32) Het9 represents a 5 to 6 membered monocyclic heterocyclic group containing, as the heteroatom (s), a sulfur or oxygen atom and / or one to three nitrogen atoms, the heterocyclic group of which may be substituted by one or more substituents selected from F, Cl, Br, alkyl of 1 to 4 carbon atoms, = O and OH; (33) Het1 0 represents a 5- or 6-membered monocyclic heterocyclic group containing, as the heteroatom (s), a sulfur or oxygen atom and / or one to three nitrogen atoms, the heterocyclic group of which may be substituted by one or more substituents selected from F, Cl, Br, alkyl of 1 to 4 carbon atoms and alkoxy of 1 to 4 carbon atoms; (34) Het ° represents a 5- or 6-membered heterocyclic group containing, as heteroatom (s), an oxygen or sulfur atom (for example an oxygen atom) and / or from one to three (for example one or two) nitrogen atoms, which heterocyclic group can be substituted by one or more substituents selected from F, Cl, Br, alkyl of 1 to 4 carbon atoms and alkoxy of 1 to 4 carbon atoms (for example one or more substituents selected from F, Cl, Br and methyl). The most preferred definitions of Ra1 include wherein R13a is as defined above, but preferably represents OH, CN or NH2 and Q31 and R14e are as defined above. The most preferred definitions of Ra2 and Ra3 include -N (H) R14c, wherein R14c represents alkyl of 1 to 2 carbon atoms, or preferably, H. The compounds of formula I that are still more preferred include those in which the GL group takes any of the following definitions. (D wherein a represents 0, 1 or 2 (such as 2 or, particularly, 1); Rb is as defined above, but particularly represents tetrazol-1-yl, H, (for example one of the last three groups), wherein R13b is as defined above, but particularly represents NH2 or, preferably, H; R14c is as defined above, but particularly represents alkyl of 1 to 2 carbon atoms optionally substituted by one to 3 F atoms (for example CH2CF3), H, cyclopentyl or C (O) O-alkyl of 3 to 4 atoms carbon (for example, one of the last three groups); R 1 1 a is as defined above, but, (i) when R b represents H, R 1 1 a particularly represents one to three substituents selected from F, Cl, OH, methyl (whose last group is optionally substituted by OH or, particularly, C (O) N (R12b) R 2c) and methoxy (whose last group is substituted by C (O) N (H) R12b), (i) when Rb represents -C (= NR1 3b) N H2, R 1 1 a particularly represents one or two substituents selected from F and OH or, preferably, R 1 1 a represents H, (iii) when R b represents - (CH 2) 0-3-N (H) R 14c, R 1 1 a particularly represents H or one or two substituents selected from F, Cl, Or H, methyl, methoxy and CF 3 (for example H or one or two substituents selected from Cl, OH and methyl or, preferably, a single Cl substituent). (2) wherein Rc represents -C (= NR13b) NH2 or, particularly, -N (H) R14c, whose groups are preferably linked at the 4-position relative to the point of attachment of the CH2 group; R i 3b and R? 4c s or n tg | co m o was previously defined, but preferably represent H. (3) wherein Z1 represents -CH2C = C-, -CH = CH-, C (O) CH2 or, preferably, C (O) or - (CH2) a-; when Z1 represents -CH2C = C-, - CH = CH-, Het represents a 5-membered aromatic heterocyclic group, containing one, or particularly, two nitrogen atoms; when Z1 represents C (O) CH2, Het represents a group fully saturated 6-membered heterocyclic containing one, or particularly, two nitrogen atoms; when Z1 represents C (O), Het represents a 6-membered aromatic heterocyclic group, which contains two nitrogen atoms or, particularly, one nitrogen atom; when Z1 represents - (CH2) ab- Het represents a 5- or 6-membered monocyclic or 9- or 10-membered bicyclic heterocyclic group containing, as heteroatom (s) (a) a sulfur atom, or (b) an atom of nitrogen and, optionally, one or two additional heteroatoms selected, of nitrogen, oxygen and sulfur, whose heterocyclic group (i) when it has 5 or 6 members, in fully aromatic or fully saturated, (ii) when it has 9 or 10 members, it is totally aromatic or partially aromatic; ab represents from 0 to 3, but preferably represents 1 or 2 or, when Het has 5 members, it also preferably represents 3; Rd represents H, -C (= NR13b) NH2 or -N (H) R14c, but Rd when Het has from 5 to 10 members, particularly represents -N (H) R14c; but Rd, when Het has 5 or 10 members, represents particularly -N (H) R14c; R11c is as defined above, but preferably represents H or (I) when Het has 6 members and is aromatic (by example a pyridinyl group), one or two substituents selected from F, Cl, methyl and CH 2 OH, (I I) when Het has 6 members and is fully saturated, a methyl or a substituent = NH; R13b is as defined above, but preferably represents H; R14c is as defined above, but preferably represents H or, when Het has 6 members, methyl. (4) where Q represents O or NR 1 0 a. R1 üa represents H, methyl or -CH2CH2OH; Het represents a 6-membered or 10-membered aromatic heterocyclic group containing two nitrogen atoms, or preferably, a nitrogen atom; Rd represents H or -N (H) R14c; R14c is as previously defined herein, but preferably represents H; R1 1 ° is as defined above here, but preferably represents H or, when Het contains two atoms of nitrogen, represents Cl. wherein Q1 a represents O or NR10a; R1 0a represents H, methyl or -CH2CH2OH; Het represents a 6-membered or 10-membered aromatic heterocyclic group, which contains two nitrogen atoms or, preferably, one nitrogen atom; Rd represents H or -N (H) R 4c; R14c is as defined above, but preferably represents H; R1 1 c is as defined above, but preferably represents H or, when Het contains two nitrogen atoms, represents Cl. (5) wherein Q2a represents N or CH; ac represents 0 or 1, but, when Q? 2aa represents CH, preferably represents 1; Het represents a 6-membered aromatic heterocyclic group containing two nitrogen atoms or, preferably, a nitrogen atom (for example a pyridinyl group, such as a pyridin-4-yl group); Rd and R1 1 c are as defined above, but preferably represent H; (6) wherein Z2 and Z3 independently represent H or F, but, preferably, Z2 and Z3 both represent H or both represent F; Z4 represents - (CH2) 2C (O) - or, preferably, -CH2C (O) -, -CH2O-, -CH2-C (H) = N- or -C (H) = N-; R13a is as defined above, but preferably represents H. Particularly preferred compounds of the invention are the compounds of the formula wherein X1 represents CH or N; when X1 represents CH (a) Rx it takes the same definitions as Rb before, (b) Ry takes the same definitions as R11a above; when X1 represents N (a) Rx it takes the same definitions as Rd previously, and (b) Ry takes the same definitions as R11c above; r represents 1 to 3; and R \ R2, R3a, R3b, R11a, R11c, Rb, Rd and A are as defined above, the compounds of which will also be referred to hereafter as "the compounds of the invention". Preferred compounds of the formula include those in which: when X 1 represents CH, R x represents tetrazol-1-yl, H, (CH 2) 1-2 N (H) R 14 c (for example CH 2 N (H) R 1 c) or (for example, any of the last three groups); when X1 represents N, Rx represents H or -N (H) R14c; when X1 represents CH, Ry represents H or one to three substituents selected from halo, alkyl of 1 to 2 carbon atoms, alkoxy of 1 to 2 carbon atoms (the latter two groups of which are optionally substituted by one or more F atoms) , OH, CH2OH and OCH2C (O) N (H) R12b (for example H or one to three halogen atoms); when X1 represents N, Ry represents H or one to three substituents selected from halo and alkyl of 1 to 2 carbon atoms; R represents H or, preferably, alkyl of 1 to 3 carbon atoms optionally substituted by N (CH 3) 2 (for example ethyl or (CH 2) 2-3 N (CH 3) 2, particularly (CH 2) 3 N (CH 3) 2); r represents 2 or, particularly, 1. Particularly preferred compounds of the formula include those in which: A represents C (O), S (O) 2, C (O) NH (in which last group the NH portion is linked to R1) or alkylene of 1 to 3 carbon atoms (for example 1 to 2 carbon atoms) (the latter group of which is optionally substituted by one or more F atoms (for example it is unsubstituted)); R1 represents (a) alkyl of 1 to 3 carbon atoms substituted by phenyl (the latter group of which is optionally substituted by one or more substituents selected from halo, alkyl of 1 to 4 carbon atoms and alkoxy of 1 to 4 carbon atoms ( whose last two groups are optionally substituted by one or more atoms of F)), (b) phenyl or naphthyl (the latter two groups of which are optionally substituted by one or more substituents selected from CN, halo, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms (the latter two groups of which are optionally substituted by one or more atoms of F), O-phenyl, O-CH 2 -Het 10 and Het 9 (for example one or more substituents selected from halo, alkyl of 1 to 4 carbon atoms and alkoxy of 1 to 4 carbon atoms (the last two groups are optionally substituted by one or more atoms of F)), (c) a 5- to 6-membered monocyclic heterocyclic group (preferably aromatic) containing, as heteroatom (s), an oxygen or sulfur atom and / or from one to three nitrogen atoms, the heterocyclic group of which is optionally substituted by one to four substituents selected from F, Cl, Br, = O, OH, alkyl of 1 to 4 carbon atoms (the latter group of which is optionally substituted by one or more halogen atoms or by OH), alkoxy of 1 to 4 carbon atoms, S (O) 2-phenyl, C (O) -phenyl, phenyl and Hetc (for example one to four substituents selected from F, Cl, Br, alkyl of 1 to 4 carbon atoms and alkoxy of 1 to 4 carbon atoms, such as one to four substituents selected from F, Cl, Br and alkyl of 1 to 4 carbon atoms), (d) a bicyclic heterocyclic group of 9 or 10 members (preferably partially aromatic), containing one to three heteroatoms selected from oxygen, nitrogen and / or sulfur (by example two oxygen atoms), which heterocyclic group is optionally substituted by one to four substituents selected from F, Cl, Br, alkyl of 1 to 4 carbon atoms and alkoxy of 1 to 4 carbon atoms, (e) alkyl of 1 to 5 carbon atoms, or (f) cycloalkyl of 4 to 7 carbon atoms or cycloalkenyl of 5 to 7 carbon atoms, whose last two groups are optionally substituted by one or more methyl groups (for example R 1 represents a group as which is defined in points (a) through (c) above); Het9 represents a 5- or 6-membered heterocyclic monocyclic group containing, as the heteroatom (s), a sulfur or oxygen atom and / or one or two nitrogen atoms, the heterocyclic group of which may be substituted by one to three substituents selected from F, Cl and methyl; Het10 represents a 5 to 6 membered monocyclic aromatic heterocyclic group, which contains, as the heteroatom (s), a sulfur or oxygen atom and / or one or two nitrogen atoms, the heterocyclic group of which may be substituted by one to three selected substituents of F, Cl, methyl and methoxy; Hetc represents a 5- or 6-membered monocyclic heterocyclic group containing, as the heteroatom (s), an oxygen or sulfur atom and / or one or two nitrogen atoms, the heterocyclic group of which is optionally substituted by one to four substituents selected from F, Cl, Br, alkyl of 1 to 4 atoms carbon and alkoxy of 1 to 4 carbon atoms; R 2 represents H, methyl or halo (such as Cl); Rsa and R3 represent both H; when X1 represents CH and Rx represents H, then Ry represents one to three substituents selected from OH, methyl, CH2OH, OCH2C (O) N (H) R12b and halo (particularly one to three halogen atoms (for example one to three Cl atoms, such as two Cl atoms attached at positions 2 and 5 relative to the point of attachment of the group (CH2) r)); when X1 represents CH and Rx represents (CH2) 1. 2N (H) R14c, then Ry represents H or, preferably, one or two substituents selected from halo, alkyl of 1 to 2 carbon atoms and alkoxy of 1 to 2 carbon atoms (the latter two groups of which are optionally substituted by one or more atoms of F) (and particularly Ry represents one or two halogen atoms (for example one or two Cl atoms, such as a Cl atom attached at position 3 relative to the point of attachment of the group (CH2) r) ); when X1 represents CH and Rx represents tetrazol-1-yl, then Ry represents one or two halo (for example Cl atoms) or, preferably, H; when X1 represents CH and Rx represents then Ry represents one or two atoms of F or, preferably, H; When X1 represents CH, the group if present, it is attached to position 3, or preferably, to position 4 relative to the point of attachment of the group (CH2) r; when X1 represents CH, the group (CH2) 1-2N (H) R14 °, if present, is attached at position 5, or preferably, position 6 relative to the point of attachment of the group (CH2) r; when X1 represents CH, the tetrazol-1-yl group, if present, is attached at the 5-position, or preferably at the 6-position relative to the point of attachment of the group (CH2) r; R 13b represents OH, OCH 3 or, preferably, C (O) OCH 2 -phenyl or H; when X1 represents N and Rx represents H, Ry represents H or, preferably, one or two substituents selected from halo (for example F) and methyl; when X1 represents N and Rx represents -N (H) R14c, Ry represents H or one or two methyl groups (for example H or methyl); R14c represents CH2CF3, H, cyclopentyl or C (O) O-alkyl of 4 carbon atoms (for example one of the last three groups, such as C (O) O-alkyl of 4 carbon atoms (for example C (O )OR- ferf-butyl) or, preferably, H). The compounds of the formula which are still more preferred include those in which: A represents C (O), C (O) NH (in which the last group of the NH portion is attached to R1) or, in particular, S (O) 2 or alkylene of 1 to 3 carbon atoms (for example 1 to 2 carbon atoms) (the latter group of which is optionally gem-disubstituted by two F atoms (for example it is unsubstituted)); R represents (a) alkyl of 1 to 2 carbon atoms substituted by phenyl (the latter group of which is optionally substituted by one or more substituents selected from F, Cl and Br), or (b) phenyl (the latter group of which is optionally substituted by one or more substituents selected from F, Cl, Br, CN, alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms (the latter two groups of which are optionally substituted by one or more F atoms (thus forming, for example, alkyl of 1 to 2 carbon atoms, CF3, alkoxy of 1 to 2 carbon atoms or OCF3)), O-phenyl, O-CH2-Het10 and Het9) (such as one or more substituents selected from F, Cl, Br, alkyl of 1 to 3 carbon atoms (the latter group of which is optionally substituted by one or more F atoms (thus forming, for example, alkyl of 1 to 2 carbon atoms or CF3)) and alkoxy of 1 to 3 carbon atoms (for example, alkoxy of 1 to 2 carbon atoms)), or (c) naphthyl (for example, 1 -naphthyl), or (d) pyridinyl (e.g., pyridin-2-yl or pyridin-3-yl) optionally substituted by one or two substituents selected from F, Cl, (N-) oxo, OH, alkyl of 1 to 4 carbon atoms ( such as methyl, whose alkyl group is optionally substituted by one or more halogen atoms or by OH), or in particular, alkoxy of 1 to 4 carbon atoms (for example, re-butoxy or methoxy) or Hetc, (such as pyridinyl (e.g., pyridin-3-yl), optionally substituted by one or two substituents selected from F, Cl, alkyl of 1 to 2 carbon atoms or particularly, alkoxy of 1 to 2 carbon atoms), (e) pyridonyl ( for example 2-pyridon-3-yl) optionally substituted by one or two substituents selected from F, CI, and alkyl of 1 to 4 carbon atoms (for example methyl); (f) pyrazinyl (for example pyrazin-2-yl) optionally substituted by one or two substituents selected from F, Cl and methyl; (g) a 5-membered aromatic heterocyclic group containing, as the hetero atom (s), an oxygen or sulfur atom and / or one to three nitrogen atoms (for example imidazolyl, isoxazolyl, pyrazolyl, pyrrolyl, thiazolyl, or thienyl) , the heterocyclic group of which is optionally substituted by one to four (for example one to three) substituents selected from F, Cl, alkyl of 1 to 4 carbon atoms (for example methyl or ethyl), alkoxy of 1 to 4 carbon atoms (for example methoxy), S (O) 2-phenyl, C (O) -phenyl, phenyl, morpholinyl (for example morpholino-4-yl), 1,4-triazolyl (for example 1, 3,4-triazol-1-yl), thienyl (for example 2-thienyl) and pyridinyl (for example pyridin-2-yl), (h) 2,3-dihydrobenzofuranyl, benzomorpholinyl, benzodioxanyl, 2, 1, 3-benzoxadiazolyl, or, in particular, benzodioxolyl or quinolinyl, all groups are optionally substituted by one or more (for example one to three) substituents selected from F, Cl, alkyl of 1 to 2 carbon atoms and alkoxy of 1 to 2 carbon atoms, (i) alkyl (for example isopropyl or re-butyl), or (j) cyclopentyl, cyclohexyl or bicyclic cycloalkenyl of 7 carbon atoms (for example bicyclo [2.2.1] heptene, the last three groups of which are optionally substituted by one to four methyl groups (for example R1 represents a group as defined in (a) to (d) or, particularly, (a) to (c) above); Het9 represents a monocyclic heterocyclic group saturated with 6 members, which contains, as hetero atom (s), an oxygen atom and / or one or two atoms of nitrogen, the heterocyclic group of which can be substituted by one or two methyl substituents; Het10 represents a 5-membered monocyclic aromatic heterocyclic group containing, as the hetero atom (s), a sulfur atom or an oxygen atom and / or one or two nitrogen atoms, the heterocyclic group of which may be substituted by one three substituents selected from Cl and methyl; Hetc represents a 6-membered, monocyclic, aromatic heterocyclic group which contains, as the heteroatom (s), an oxygen atom and / or one or two nitrogen atoms, the heterocyclic group of which may be substituted by one or two methyl substituents; R2 represents methyl; X1 represents CH or N (for example CH); when X1 represents CH, Rx represents joined at position 4 relative to the point of attachment of the group (CH2) or Rx may also represent tetrazol-1-yl, or, particularly, CH2N (H) R14c (the latter of which are bound, for example, in the 6 in relation to the point of attachment of the group (CH2) r); Rx may alternatively represent H when X1 represents CH and Ry represents one to three substituents selected from OH, methyl, CH2OH, OCH2C (O) N (H) R12b and halo; R 3b represents C (O) OCH 2 -phenyl or, preferably, H; R14c represents C (O) O-fer-butyl or, particularly, H, ethyl, CH2CF3 or cyclopentyl (for example H or cyclopentyl).

Other preferred compounds of the formula include those in which: A represents CH (CH 3) CH 2 (in the latter group the unit CH (CH 3) is linked to R 1) or, particularly, CH 2, (CH 2) 2 or CF 2 CH 2 (in whose last group the unit CF2 is linked to R1); R1 represents (a) isopropyl or urea-butyl, (b) cyclopentyl, cyclohexyl or bicyclo [2. 2.1] hept-5-ene, (c) phenyl optionally substituted by one or two substituents selected from halo (for example F or Cl), CN, methyl, CF3, methoxy, OCF3, phenoxy, morpholino-4-yl or O-CH2- (2-chlorothiazol-5-yl), (d) imidazolyl optionally substituted by one to three substituents selected from Cl, methyl and phenyl, (e) isoxazolyl (for example isoxazol-3-yl or isoxazol-4-yl) optionally substituted by one or two substituents selected from methyl, phenyl and 2-thienyl, (f) thiazolyl (for example thiazol-5-yl) optionally substituted by one or two methyl groups, (g) thienyl (for example thien-2-yl) optionally substituted by Cl or pyridinyl (for example pyridin-2-yl), (h) pyrazolyl (for example, pyrazol-4-yl) optionally substituted by one to three substituents selected from Cl, methyl, ethyl, phenyl and morpholino-4-yl, (i) pyrrolyl (for example pyrrol-2-yl or pyrrol-3-yl) optionally substituted by one to three substituents selected from methyl, S (O) 2-phenyl, C (O) phenyl and 1,4-triazol-1-yl, (j) pyridinyl (e.g. pyridin-2-yl or pyridin-3-yl) optionally substituted by OH, methoxy or morpholino-4-yl, and optionally in the form of an? / -oxide, (k) pyridonyl (e.g. 2-pyridon-3-yl), (I ) pyrazinyl (for example pyrazin-2-yl), (m) benzodioxolyl (for example 5-benzodioxolyl) optionally substituted by halo (for example Cl), (n) benzomorpholinyl (for example 7-benzomorpholinyl) optionally substituted by methyl; (o) 2, 1, 3-benzoxadiazolyl (for example 2, 1, 3-benzoxadiazol-5-yl), (p) 2,3-d ihydrobenzofuranyl (for example 2,3-dihydrobenzofuran-5-yl) or ( q) quinolinyl (for example 8-q uinoinyl); the group It represents R ° represents H, F, Cl, OH, methyl or, particularly, tetrazoI-1-yl, OCH2C (O) N (H) R12b or CH2N (H) R14c, Rm represents H, methyl, CF3, methoxy, F or , particularly, Cl (for example: (a) when R ° represents H or Cl, then Rm represents Cl; (b) when R ° represents OH or methyl, then Rm represents F o, particularly Cl; and (c) when R ° represents tetrazol-1-yl, OCH2C (O) N (H) R12 or CH2N (H) R14c then Rm represents H, methyl, CF3, methoxy, F or, much more preferably, Cl); Rya represents H or, particularly, methyl. In one embodiment of the compounds of the formula which are still more preferred, Rx represents joined in position 4 in relation to the point of attachment of the group (CH2) r. Particularly preferred compounds of the invention are also compounds of the formulas Id and where s represents 2 to 4; t represents 1 to 3; u and v independently represent 0 to 2, the sum of u and v is 1 or 2; and R1, R2, R3a, R3b, R13a, R13b, R14a and R14b are as defined above, the compounds of which will also be referred to hereafter as "the compounds of the invention". Preferred compounds of the formula Id include those in which: s represents 3 or, particularly, 2; R? Sa and R? 4a both represent H. Preferred compounds of the formula include those in which: t represents 2 or, particularly, 1; u and v represent both 1; Ri 3b and R 4b represent both H. For the avoidance of doubt, the preferred definitions of the groups given above in relation to the compounds of the formulas le, also, where relevant, are preferred definitions of the equivalent groups in the compounds of the formula I. Preferred compounds of the invention include the compounds of the examples described hereinafter.

PREPARATION The compounds of the formula I (including the compounds of the formula le, Id and le) can be made according to techniques familiar to those skilled in the art, for example as those described below. According to a further aspect of the invention, there is provided a process for the preparation of a compound of the formula I, which comprises: (a) for the compounds of the formula I in which the group G represents (i) C (O) N (R8a) - [CH (C (O) R9)] 0 -? - Alkylene of 0 to 3 carbon atoms- (Q1) a-, (ii) C (O) N (R8) -alkenylene of 2 to 3 carbon atoms- (Q1) a-, (iii) C (O) N (R8b) -alkynylene of 2 to 3 carbon atoms- (Q1) ) a-, (iv) Alkylene-? x (v) wherein Q2a represents N or NHCH, coupling a compound of formula II, wherein the dotted line, R \ R2, R3a, R3b, A, D and E are as defined above, with a compound of the formula l l l, H-Ga-L wherein L is as defined above and Ga represents (i) -N (R8a) - [CH (C (O) R9)] 0 -? - alkylene of 0 to 3 carbon atoms- (Q1) a- , (ii) -N (R8b) -alkenylene of 2 to 3 carbon atoms- (Q1) a- (iii) -N (R8b) -alkynylene of 2 to 3 carbon atoms- (Q1) a- (iv ) * ~ ~ N (R ^ CQ ^ Alkylene- "Q Q '- and ~ (v) wherein Q2a represents N or NHCH and Rsa, R8D, R8C, R Q1, Q are already as defined here above, for example in the presence of a coupling agent (for example, oxalyl chloride in D MF, EDC, DCC, HBTU, HATU, PyBOP or TBTU), an appropriate base (eg, pyridine, DMAP, TEA, 2,6,4-coidine or DIPEA) and an appropriate organic solvent (per example, dichloromethane, acetonitrile, EtOAc or D MF); (b) for the compounds of formula I in which G represents and L represents La, whose last group represents L as defined hereinabove, except that it does not represent alkylene of 0 carbon atoms-Ra, cyclization of a compound of formula IV, where the dashed line, R \ R2, R3a, R3b, A, D, E and La are as defined here above, for example at elevated temperature (for example 60 ° C for reflux) in the presence of an appropriate solvent (for example, pyridine, toluene, 1,4-dioxane or TH F) and optionally in the presence of an appropriate catalyst (for example, (n-Bu) 4N F, which can be used particularly when the solvent of the reaction is THF); (c) for compounds of formula I in which Ra, Rb, RG or Rd represents -C (= N H) NH2, -C (= NN H2) NH2 or -C (= NOH) NH2, reaction of a compound of formula V, wherein Lb represents L as defined above, except that Ra, Rb, Rc or Rd (as appropriate) is replaced by a cyano group or -C (= NH) O-alkyl of 1 to 4 carbon atoms, and the dotted line, R1, R2, R3a, R3b, A, D, E and G are as defined above, with an appropriate source of ammonia, hydrazine or hydroxylamine (for example ammonia gas, ammonium acetate, hydrazine, mono- Hydrazine hydrochloride, hydroxylamine or hydroxylamine hydrochloride) under conditions known to those skilled in the art (for example, conditions such as those described in Tetrahedron Lett 40, 7067 (1999)), for example from room temperature (for example 15 to 25). ° C) to high temperature (for example 60 ° C for reflux) in the presence of an appropriate solvent (for example ethanol); (d) for the compounds of the formula I in which R13a, R13b or R13c represents H, deprotection of a corresponding compound of the formula I in which R13a, R13b or R13c, (as appropriate) represents C (O) O -CH2aryl (for example C (O) O-benzyl), for example under conditions known to those skilled in the art (such as hydrogenation in the presence of an appropriate catalyst (for example Pt / C or, particularly, Pd / C), a suitable solvent (for example an alcohol such as ethanol or, particularly, methanol) and, optionally, an acid (for example HCl)); (e) for the compounds of the formula I in which R14c represents H, deprotection of a corresponding compound of the formula I in which R14c represents C (O) O-alkyl of 1 to 6 carbon atoms (for example C (O) O-fer? -butyl), for example under conditions known to those skilled in the art (for example hydrolysis with acid or base, such as, by deprotection of compounds in which R14a represents C (O) O-yerf -butyl, reaction with HCl gas in the presence of an appropriate solvent (for example an alcohol such as ethanol or, particularly, methanol), or reaction with trifluoroacetic acid below room temperature (for example from 0 to 4 ° C) , optionally in the presence of an appropriate solvent such as DCM); (f) reaction of a compound of formula VI, where the dotted line, Ry R? a, R, A, D, E, G and L are as defined above, with a compound of the formula VII, R1-A-Lg1 Vil wherein Lg1 represents an appropriate suppressible group (eg halo, trifluoromethanesulfonate or OH) and R1 and A are as defined above, for example under conditions known to those skilled in the art (such as below room temperature (eg, example 0 ° C) in the presence of an appropriate base (for example K2CO3 or pyridine) and an appropriate solvent (for example DCM)); (g) for the compounds of the formula I in which A represents C (O) NH, the reaction of a compound of the formula VI, as defined above, with a compound of the formula VIII, R1-N = C = O Vil wherein R1 is as defined above, for example under conditions known to those skilled in the art (such as at room temperature (for example 15 to 25 ° C) in the presence of an appropriate solvent (for example DCM)); (h) for the compounds of the formula I in which A represents alkylene of 1 to 6 carbon atoms, the reaction of a compound of formula VI, as defined above, with a compound of formula IX, R1-alkylene of 0 to 5 carbon atoms-CHO IX wherein R1 is as defined above, for example under conditions known to those skilled in the art (such as at reflux in the presence of an appropriate solvent (e.g. ethanol), followed by reduction in the presence of a reducing agent. (for example NaBH3CN), for example under conditions known to those skilled in the art (for example at room temperature (such as 15 to 25 ° C) in the presence of a suitable solvent (such as ethanol), or (i) for the compounds of the formula I in which Ra, Rb, Rc or Rd represents -C (= NCN) NH2, reaction of a corresponding compound of the formula I in which Ra, Rb, Rc or Rd, respectively, represents -C (= NH) NH2 with cyanogen bromide, for example under conditions known to those skilled in the art (e.g. in the presence of an appropriate base (such as an alkali metal alkoxide such as sodium ethoxide) and an appropriate solvent (such as a lower alkyl alcohol such as ethanol). compounds of formula II can be prepared by hydrolysis of a compound of formula X, wherein the dotted line, R1, R2, R3a, R3b, A, D and E are as defined herein above, for example under conditions known to those skilled in the art (e.g. by basic hydrolysis in the presence of a hydroxide of alkali metal (for example LiOH or, particularly, NaOH) and an appropriate solvent (for example water, THF, methanol or a mixture thereof)). The compounds of the formula IV can be prepared by coupling a compound of the formula II, as defined above, with a compound of the formula XI, wherein La is as defined above, for example under familiar conditions for those skilled in the art (for example those described in WO 01/79262, such as room temperature (for example 15 to 25 ° C) in the presence of a coupling agent (for example EDC) and an appropriate solvent (for example DMF)).

As will be appreciated by a person skilled in the art, in some cases, the compounds of the formula V are identical to certain compounds of the formula I (for example compounds in which Rb, Rc or Rd represents H and R 1 1 a , R1 1 bo R1 1 c, respectively, represent CN). In this respect, the compounds of the formula V can be prepared by analogy with the processes described herein for the preparation of the compounds of the formula I. Compounds of formula VI can be prepared by reduction of a compound of formula XII, wherein the dotted line, R, R3a, R3b, D, E, G and L are as defined above, for example under conditions that are familiar to those skilled in the art (such as by reaction with zinc metal (e.g. zinc powder or iron metal powder) in the presence of an appropriate acid (for example acetic acid or hydrochloric acid) and optionally in the presence of an appropriate solvent (for example methanol)). The compounds of the formula VI can be prepared alternatively by reaction of a compound of the formula XI wherein the dotted line, R2, R3a, R3b, D, E, G and L are as defined above, with O- (diphenylphosphinyl) hydroxylamine, for example under conditions known to those skilled in the art (e.g. environment (such as 15 to 25 ° C) in the presence of an appropriate base (such as Cs 2 CO 3) and an appropriate solvent (such as DMF)). Compounds of formula IX can be prepared by oxidation of an alcohol of formula XIV, R1-alkylene of 0 to 5 carbon atoms-CH2OH XIV wherein R1 is as defined above, for example under conditions known to those skilled in the art, such as reaction with PCC, oxalyl chloride and DMSO (Swern oxidation) or, particularly, Dess-Martin periodinnan in the presence of an appropriate solvent (such as DCM). The compounds of the formula X can be prepared by reaction of a compound of the formula XV, wherein the dotted line, R2, R3a, R3b, D and E are tai as defined above, with a compound of the formula VI I, VI II or IX as defined above, for example under conditions known to those skilled in the art. the material (for example, conditions described in steps (f), (g) and (h) of the process above, with respect to the compounds of the formula I). The compounds of formula XI can be prepared by methods familiar to those skilled in the art. For example, compounds of formula XI can be prepared by reaction of a compound of formula XVI or XVI I, NC-ÍCH? G-L 'XVI wherein La is as defined above, with hydroxylamine or an acid addition salt thereof, for example under conditions described in step (c) of the process above with respect to the compounds of formula I.

The compounds of formula XI I can be prepared by analogy with the compounds of formulas I and XIX. The compounds of the formula XI I I can be prepared by analogy with the compounds of the formulas I and XX. The compounds of the formula XIV can be prepared by reduction of a carboxylic acid of the formula XVII I, R 1 -alkylene of 0 to 5 carbon atoms-C (O) OH XVII I wherein R1 is as defined above, for example under conditions known to those skilled in the art, such as reaction with LiAIH4 or, particularly, borane in the presence of an appropriate solvent (such as THF). The compounds of formula XV can be prepared by reduction of a compound of formula XIX, wherein the dotted line, R2, R3a, R3b, D and E are as defined above, for example under conditions described herein above with respect to the preparation of the compounds of the formula Vi.

The compounds of the formula XV can be prepared alternatively by the reaction of a compound of the formula XX, wherein the dotted line, R2, R3a, R3b, D and E are as defined above, with O- (d-ifenylphosphinyl) hydroxylamine, for example under conditions described herein above with respect to the preparation of the compounds of formula VI . The compounds of the formula XIX can be prepared by nitrosation of a corresponding compound of the formula XX, as defined above, for example under conditions familiar to those skilled in the art, for example reaction with a nitrosating agent (such as nitrous acid). , NOC, N2O3, N2O or, particularly, an alkyl nitrite of 1 to 6 carbon atoms (for example tert-butyl nitrite)) in the presence of an appropriate solvent (for example diethyl ether) and optionally in the presence of an appropriate base (for example pyridine). The compounds of the formula XX can be prepared by esterification of a compound of the formula XXI, wherein R2, R3a, R3b, D and E are as defined above, in the presence of an alkyl alcohol of 14 carbon atoms, for example under conditions known to those skilled in the art (for example by esterification in the presence of a suitable acid (for example HCl) and an appropriate solvent (for example an alcohol of 14 carbon atoms (such as methanol), water, or a mixture thereof)). Compounds of formula XX in which the dotted line is absent can alternatively be prepared by reaction of a compound of formula XXII, or a protected derivative thereof, wherein R2, R6a, R6b, R7a and R7b are as defined above, with a compound of formula XXI I I, wherein Lg2 represents an appropriate suppressible group (eg halo or OS (O) 2R ', where R' represents, for example, alkyl of 14 carbon atoms, perfluoroalkyl of 1 to 4 carbon atoms, phenyl, toluyl or benzyl ) and R3a and R3b are as defined above, in the presence of an appropriate base (for example a metal hydride or, particularly, a metal amide (such as lithium bis (trimethylsilyl)), for example under known conditions by those skilled in the art (for example at low temperature (such as from -78 to -10 ° C)) in the presence of an appropriate solvent (such as THF)). Compounds of formula XXI in which the dotted line represents a bond, can be prepared by hydrolysis of a compound of formula XXIV, wherein R2, R3a, R3b, R5a and R5b are as defined above, for example under conditions known to those skilled in the art (for example by reflux in concentrated HBr). Compounds of formula XXI in which the dotted line is absent can be prepared by hydrolysis of a compound of formula XXV where R2, R3a, R3b, R6a, R6b, R7a and R7b are as defined above, for example under conditions known to those skilled in the art (for example those mentioned above in relation to the compounds of formula XXI in which the dotted line represents a link). The compounds of the formula XXI I can be prepared by oxidation of a compound of the formula XXVI, or a protected derivative thereof, wherein R2, R6a, R6b, R7a and R7b are as defined above, with an appropriate oxidizing agent (for example H2O2, (Ph10) n, Hg (OAc) 2 or, particularly, RuO4, whose last reagent can be formed in situ by oxidation of RuO2 (for example by an excess of NalO4)), for example under conditions known to those skilled in the art (for example at room temperature (such as 15 to 25 ° C) in the presence of an appropriate solvent (such as ethyl acetate, water or a mixture of them)). As will be understood by one skilled in the art, the conversion of the compounds of the formula XXVI into the corresponding compounds of the formula XX may require, in any of the steps of the reaction, protection of the N-H group of the piperidone ring system. Suitable protecting groups for this purpose include benzyloxycarbonyl and, particularly, tert-butyloxycarbonyl. The protecting group can be introduced before the compound of formula XVI is converted to the compound of XII (for example, by reaction, under conditions which are familiar to those skilled in the art, of a compound of XXVI with di-carbonate dicarbonate). tert-butyl). In addition, the protecting group can conveniently be removed again under conditions that are familiar to those skilled in the art (e.g., by reaction with trifluoroacetic acid), once the compound of formula XX has been formed. The compounds of the formula XXIV can be prepared by reaction of a compound of the formula XXVI I, wherein R2, R3a, R3b, R5a, R5b and Lg2 are as defined above, with an appropriate source of the cyanide ion (per KCN example), for example under conditions that are familiar to those skilled in the art (for example at room temperature (such as 15 to 25 ° C) in the presence of an appropriate solvent (such as methanol)). The compounds of the formula XXV can be prepared by reaction of a compound of the formula XXI I, as defined above, with a compound of the formula XXVIII, wherein R3a, R3b and Lg2 are as defined above, for example under conditions familiar to those skilled in the art (e.g., the conditions described above with respect to the preparation of the compounds of formula XX). The compounds of the formula XXVI I in which Lg2 represents halo can be prepared by halogenation of a compound of the formula XXIX, wherein R2, R3a, R3b, R5a and R5b are as defined above, for example under conditions that are familiar to those skilled in the art (for example by reaction with triphenylphosphine and a / V-halosuccinimide (such as N BS) in the presence of an appropriate solvent (such as DCM)). The compounds of the formula XXIX in which R3a and R3b represent both H, can be prepared by reduction of a corresponding compound of the formula XXX, wherein R2, R5a and R5b are as defined above, for example under conditions which are familiar to those skilled in the art (for example by reaction with sodium borohydride in the presence of an appropriate solvent (such as methanol, THF) or a mixture of them)). The compounds of the formula XXX can be prepared by formylation of a corresponding compound of the formula XXXI, wherein R, R5a and R5b are as defined above, for example under conditions that are familiar to those skilled in the art (e.g. by reaction with an appropriate source of the formyl group (such as DM F) in the presence of a appropriate base (such as re-butyl-lithium or mesityl-lithium (the last reactant of which can be formed in situ by reaction between ferr-butyl-lithium and bromomesitylene)) Compounds of formulas III, VI, VI, XVI , XVI I, XVI II, XXI II, XXVI, XXVI II and XXX are commercially available, are known in the literature, or can be obtained by analogy with the processes described herein, or by conventional synthetic procedures, according to standard techniques, from readily available starting materials using the appropriate reagents and reaction conditions. In this regard, the compounds described herein can also be obtained by analogy with synthetic procedures described in the prior art documents mentioned above (and WO 94/20467, WO 94/29336, WO 95/23609, WO 96/06832 , WO 96/06849, WO 97/1 1693, WO 97/24135, WO 98/01422, WO 01/68605, WO 99/26920, WO 01/79155, WO 01/68605, WO 96/1 8644, WO 97 / 01338, WO 97/30708, WO 98/16547, WO 99/26926, WO 00/73302, WO 01/041 17, WO 01/79262, WO 02/064140, WO 02/057225, WO 03/29224, US 5,668,289, US 5,792,779 and WO 95/35313 in particular). Substituents in alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl and heterocyclic groups in compounds of the Formulas I, II, IV, V, VI, X, XI I, XI II, XV, XIX, XX, XXI, XXI I, XXIV, XXV, XXVI, XXVI I, XXIX, XXX and XXXI can be entered and / or intercrt using techniques familiar to those skilled in the art by way of intercrsions of standard functional groups, according to standard techniques, from readily available starting materials, using appropriate reagents and reaction conditions. For example, hydroxy can be crted to alkoxy, phenyl can be halogenated to give halophenyl, halogen can be displaced by cyano, etc. The person skilled in the art will realize that various standard substituents or intercrsions and transformations of functional groups within certain compounds of the formula I will provide other compounds of the formula I. For example, hydroxyamidino can be reduced to amidino. The compounds of the formula I can be isolated from their reaction mixtures using cntional techniques. In accordance with the present invention, pharmaceutically acceptable derivatives of the compounds of formula I also include "protected" derivatives and / or prodrug-acting compounds of the compounds of formula I. Compounds that can act as Prodrugs of the compounds of formula I which may be mentioned, include compounds of formula I in which R13a, R13b or R13c is other than H or R represents C (O) O-alkyl of 1 to 6 carbon atoms, Alkyl part of this group is optionally substituted by aryl and / or one or more halogen atoms (for example compounds in which R represents C (O) O-yer-butyl). The compounds of the invention may exhibit tautomerism. All tautomeric forms and their mixtures are included within the scope of the invention. Particular tautomeric forms that may be mentioned include those that are connected to the double bond position in the amidine or guanidine functionalities that the Ra to Rd groups may represent. The compounds of the invention may also contain one or more asymmetric carbon atoms and thus may exhibit optical and / or diastereoisimerism. The diastereoisomers can be separated using cntional techniques, for example, chromatography. The various stereoisomers can be isolated by separation of a racemic mixture or other of the compounds, using cntional techniques, for example HPLC. Alternatively, the desired optical isomers can be made by reacting the appropriate optically active starting materials under conditions that will not cause racemization or epimerization, or by derivatization, for example with a homochiral acid followed by separation of the diastereoisomeric derivatives by cntional means (e.g. HPLC, chromatography on silica). All stereoisomers are included within the scope of the invention.

Those skilled in the art will realize that in the processes described above and hereinafter, it may be necessary to protect the functional groups of the intermediates by protecting groups. The functional groups that it is desirable to protect include hydroxy, amino and carboxylic acid. Suitable protecting groups for hydroxy include optionally substituted and / or unsaturated alkyl groups (for example methyl, allyl, benzyl or tert-butyl), triaJq or iisifyl groups or diarylalkysilyl (for example t-butyldimethylsilyl, f-butyldiphenylsilyl or trimethylsilyl) and tetrahydropyranyl. Suitable protecting groups for the carboxylic acid include alkyl of 1 to 6 carbon atoms or benzyl esters. Suitable protecting groups for amino and amidino include butyloxycarbonyl, benzyloxycarbonyl or 2-trimethylsilylethoxycarbonyl (Teoc). The amidino nitrogens can also be protected by hydroxy or alkoxy groups, and can be mono- or di-protected. The protection and deprotection of the functional groups can take place before or after the coupling, or before or after any other reaction in the aforementioned schemes. The protecting groups can be removed according to techniques that are familiar to those skilled in the art and as described hereinafter. Connoisseurs of the subject will realize that, In order to obtain compounds of the invention in an alternative, and sometimes more convenient, form, the individual steps of the process mentioned hereinabove may be performed in a different order, and / or the individual reactions may be performed in a separate order. different stage in the general route (ie, substituents can be added to chemical transformations, or these can be performed with intermediates other than those mentioned hereinbefore, in conjunction with a particular reaction). This can eliminate the need for protective groups, or make it necessary. The type of chemistry involved will dictate the need and type of protective groups, as well as the sequence to perform the synthesis. The use of protecting groups is fully described in "Protective Groups in Organic Chemistry", edited by JW F McOmie, Plenum Press (1973), and in "Protective Groups in Organic Synthesis", 3a. edition, T. W. Greene and P. G. M. Wutz, Wiley-Interscience (1999). The protected derivatives of the compounds of the invention can be chemically converted to compounds of the invention using standard deprotection techniques (eg, hydrogenation). The person skilled in the art will also realize that certain compounds of the formula I (for example, compounds in which R13a, R13b or R13c is other than H) can also be referred to as "protected derivatives" of other compounds of the formula I (for example, those in which R13a, R13b or R13c represents H). Those skilled in the art will also realize that certain compounds of the formula I will be useful as intermediates in the synthesis of certain other compounds of the formula I. Some of the intermediates referred to herein above are novel: (a) a compound of formula I I, or a derivative thereof protected; (b) a compound of the formula IV, or a derivative thereof protected; (c) a compound of V, or a protected derivative thereof; (d) a compound of formula VI, or a derivative thereof protected; (e) a compound of formula X, or a derivative thereof protected; (f) a compound of the formula XI I, or a protected derivative thereof; (g) a compound of formula XV, or a derivative thereof protected; and (h) a compound of formula XIX, or a protected derivative thereof.

MÉDICO AND PHARMACEUTICAL USE The compounds of the invention may have pharmaceutical activity as such. However, other compounds of the invention (including compounds of the formula I in which R 3a, R? Sb 0 R? Sc is d isti nt0 of H or R14c represents C (O) O-feri-butyl) may not possess such activity, but can be administered parenterally or orally, and therefore can be metabolized in the body to form compounds that are active pharmacologically (including, without limitation to the, the corresponding compounds of the formula I in which R13a, R1 3b, R13c or R14c represents H). These compounds (which also include compounds that may possess some pharmacological activity, but that activity is appreciably lower than that of the "active" compounds for which they are metabolized), can therefore be described as "prodrugs" of the active compounds. Thus, the compounds of the invention are useful because they possess pharmacological activity, and / or are metabolized in the body after oral or parenteral administration to form compounds possessing pharmacological activity. The compounds of the invention, therefore, are indicated for pharmaceutical use. According to a further aspect of the invention, the compounds of the invention are provided for their pharmaceutical use. In particular, the compounds of the invention are potent inhibitors of thrombin, either as such and / or (in the case of prodrugs), metabolized after their administration to form potent thrombin inhibitors, for example as can be demonstrated in the tests described later. By "prodrug of a thrombin inhibitor", we include compounds that form a thrombin inhibitor, in an amount that is detectable experimentally, and within a predetermined time (for example, approximately 1 hour), after its oral or parenteral administration (see, for example, Test E below), or, alternatively, after incubation in the presence of microsomes in the liver (see, for example, Test F below). Thus, it is expected that the compounds of the invention will be useful in those conditions where thrombin inhibition is beneficial (as determined by reference to a clinically relevant endpoint, e.g., conditions, such as thrombo-embolisms, wherein the thrombin inhibition is required or desired, and / or under conditions where anticoagulant therapy is indicated), including the following: The treatment and / or prophylaxis of thrombosis and hypercoagulability in the blood and / or tissues of animals , including man. It is known that hypercoagulability can lead to thromboembolic diseases. The conditions associated with hypercoagulability and thrombo-embolic diseases are usually referred to as thrombophilic conditions. These conditions include, without limitation, resistance to the inherent or acquired activated protein C, such as the factor V Leiden mutation, deficiencies in antithrombin II, protein C, protein S, heparin cofactor II, inherited or acquired, and conditions with increased plasma levels of coagulation factors such as those caused by prothrombin measurement G20210A. Other conditions known to be associated with hypercoagulability and thrombo-embolic disease include antiphospholipid antibodies in circulation (anticoagulant lupus), homocysteinemia, heparin-induced thrombocytopenia, and defects in fibrinolysis, as well as coagulation syndromes (eg, disseminated intravascular coagulation (DIC)) and vascular damage in general (eg, due to trauma) or surgery). In addition, it is known that low physical activity, low cardiac output or advanced age, increase the risk of thrombosis and hypercoagulability, and may be only one of several factors that increase the risk. These conditions include, but are not limited to, prolonged bed rest, prolonged air travel, hospitalization to treat an acute medical disorder, such as heart failure or respiratory failure. Additional conditions with increased risk of thrombosis with a component of hypercoagulability are pregnancy and hormonal treatment (for example, with estrogen). The treatment of conditions where there is an undesirable excess of thrombin without signs of hypercoagulability, for example in neurodegenerative diseases, such as Alzheimer's disease. Particular disease states that may be mentioned include the therapeutic and / or prophylactic treatment of venous thrombosis (e.g., deep vein thrombosis, DVT) and pulmonary embolism, arterial thrombosis (e.g., in myocardial infarction, unstable angina, accident) vascular brain due to thrombosis and peripheral arterial thrombosis), and systemic embolism usually from the atrium during atrial fibrillation (for example, non-valvular or valvular atrial fibrillation) or from the left ventricle after transmural myocardial infarction, or caused by congestive cardiac deficiency; prophylaxis or re-occlusion (ie, thrombosis) after thrombolysis, percutaneous trans-luminal angioplasty (PTA), and coronary bypass operations; the prevention of thrombosis after microsurgery and vascular surgery in general. Additional indications include the therapeutic and / or prophylactic treatment of disseminated intravascular coagulation caused by bacteria, multiple trauma, intoxication or other mechanism; anticoagulant treatment when the blood is in contact with surfaces foreign to the body, such as vascular grafts, vascular stents, vascular catheters, mechanical and biological prosthetic valves or other medical device; and anticoagulant treatment when the blood is in contact with medical devices outside the body, such as during cardiovascular surgery using a heart-lung machine or in hemodialysis; the therapeutic and / or prophylactic treatment of idiopathic and adult respiratory distention syndrome, pulmonary fibrosis after treatment with radiation or chemotherapy, chronic obstructive pulmonary disease, septic shock, septicemia, inflammatory responses, which include, without limitation, edema, acute or chronic atherosclerosis, such as coronary artery disease and the formation of atherosclerotic plaques, insufficiency cardiac disease, cerebral arterial disease, cerebral infarction, cerebral thrombosis, cerebral embolism, peripheral arterial disease, ischemia, angina (including unstable angina), reperfusion injury, restenosis after percutaneous trans-luminal angioplasty (PTA) and coronary artery bypass surgery . The compounds of the invention which inhibit trypsin and / or thrombin may also be useful in the treatment of pancreatitis. The compounds of the invention are therefore indicated both in the therapeutic treatment and in the prophylactic treatment of these conditions. According to a further aspect of the present invention, there is provided a method of treating a condition wherein thrombin inhibition is required, which method comprises administering a therapeutically effective amount of a compound of the invention to a suffering person. of such a condition or that is susceptible to it. The compounds of the invention will normally be administered orally, intravenously, subcutaneously, buccally, rectally, dermally, nasally, tracheally, bronchially, by any other parenteral route or by means of inhalation, in the form of pharmaceutical preparations containing the compound of the invention, either as a free base or as a non-toxic, organic or inorganic acid addition salt, acceptable for pharmaceutical use, in a dosage form acceptable for pharmaceutical use.

The preferred route of administration of the compounds of the invention is oral. Depending on the disorder and the patient to be treated, and the route of administration, the compositions may be administered in varying doses. The compounds of the invention can also be combined and / or co-administered with any antithrombotic agent or agents with a different mechanism of action, such as one or more of the following: the unfractionated heparin anticoagulants, low molecular weight heparin, other heparin derivatives, synthetic derivatives of heparin (for example fondaparinux), vitamin K antagonists, synthetic or biotechnological inhibitors of other coagulation factors other than thrombin (for example synthetic FXa inhibitors, FVI Ia and FlXa and RNAPc2), agents antiplatelets acetylsalicylic acid, ticlopdine and clopidogrel; thromboxane receptor and / or synthetase inhibitors; fibrinogen receptor antagonists; imitators of prostacyclin; phosphodiesterase inhibitors; ADP receptor antagonists; (P2X!, P2Y!, P2Y12 [P2T]); and inhibitors of carboxypeptidase U (CPU or TAFIa) and inhibitors of plasminogen activator inhibitor 1 (PAI-1). The compounds of the invention can also be combined and / or co-administered with thrombolytics such as one or more tissue plasminogen activators (natural, recombinant or modified), streptokinase, urokinase, prourokinase, complex anisolated plasminogen-streptokinase activator (APSAC), plasminogen activators of g salivary animal gland, and the like, in the treatment of thrombotic diseases, in particular myocardial infarction. According to a further aspect, there is thus provided a pharmaceutical formulation comprising a compound of the invention, in admixture with an adjuvant, diluent or carrier acceptable for pharmaceutical use. The accepted daily doses of the compounds of the invention in the therapeutic treatment of humans are from about 0.001 to 100 mg / kg of body weight in peroral administration and 0.001 -50 mg / kg of body weight in parenteral administration. For the avoidance of doubt, as used herein, the term "treatment" includes therapeutic and / or prophylactic treatment. The compounds of the invention have the advantage that they can be more effective, are less toxic, have a longer action, have a broader range of activity, are more selective (for example, to inhibit thrombin on other serine proteases, in particular trypsin and those that are involved in hemostasis), are more potent, produce fewer side effects, are more easily absorbed, and / or have a better pharmacokinetic profile (eg, greater oral bioavailability and / or lower elimination), than the compounds known in the prior art, and / or have other useful pharmacological, physical or What are the components of the previous technique.

BIOLOGICAL TESTS The following test procedures can be used.

PROOF OF DETERMINATION OF THE TIME OF COAGU LATION OF TROM BINA Lili The inhibitor solution (25uL) is incubated with plasma (25uL) for three minutes. Then human thrombin (T 6769; Sigma Chem. Co or Hematologic Technologies) is added in pH buffer solution for pH 7.4 (25 μL, 4.0 NIH units / mL), and coagulation is measured in an automatic device (KC). 10; Amelung). The thrombin coagulation time (TT) is expressed as absolute values (seconds), as well as the proportion of TT without inhibitor (TTO) with respect to the TT with inhibitor (TTi). These last proportions (scale 1 -0) are plotted against the inhibitor concentration (logarithmically transformed) and are adjusted to the sigmoidal dose response curves, according to the equation: y = a / [1 + (x / I C50) s] where: a = maximum scale, ie 1; s = slope of the dose response curve; and I C50 = the inhibitor concentration that doubles the coagulation time. The calculations are processed on a computer using the GraFit version 3 program, setting the equation equal to: Start at 0, defined end = 1 (Erithacus Software, Robin Leatherbarrow, Imperial College of Science, London, England).

PROOF B DETERMINATION OF THROMBIN INHIBITION WITH A CHROMOGENIC ROBOTIC ESSAY The potency of the thrombin inhibitor is measured with a chromogenic substrate method, in a robotic Plato 3300 microplate processor (Rosys AG, CH-8634 Hombrechtikon, Switzerland), using microtitre plates with 96 receptacles at half volume (Costar, Cambridge , MA, USA; Cat No. 3690). The stock solutions of the test substance in DMSO (72 μL), 0.1 -1 mmol / L, are serially diluted 1: 3 (24 +48 μL) with DMSO to obtain ten different concentrations, which are analyzed as samples in essay. 2 μL of test sample is diluted with 124 μL of assay buffer, 12 μL of solution with chromogenic substrate (S-2366, Cromogenix, Molndal, Sweden) in pH buffer of the assay, and finally 12 μL of a solution of a- thrombin, (human α-thrombin, Sigma Chemical Co. or Hematologic Technologies) in the pH buffer of the assay, and the samples are mixed. The final concentrations of the test are: test substance 0.00068-133 μmol / L, S-2366 0.30 mmol / L, a-thrombin 0.020 NIH units / mL. The increase in linear absorbance during 40 minutes of incubation at 37 ° C is used to calculate the percentage of inhibition for the test samples, compared with the targets without inhibitor. The robotic IC50 value, corresponding to the concentration of the inhibitor that causes 50% of the inhibition of thrombin activity, is calculated from a logarithmic concentration against the inhibition curve in percentage.

TEST C DETERMINATION OF THE CONSTANT OF INHIBITION K¡ FOR THE HUMAN THROMBIN Ki determinations are made using a chromogenic substrate method, performed at 37 ° C in a Cobas Bio centrifugal analyzer (Roche, Basel, Switzerland). The residual enzymatic activity after incubation of human a-thrombin with various concentrations of the test compound is determined at three different substrate concentrations, and is measured as the change in optical absorbance at 405 nm. The solutions of the test compound (100 μL, normally in pH or salt buffer with 10 g / L of BSA) are mixed with 200 μL of human a-thrombin (Sigma Chemical Co) in the assay pH regulator (0.05 mol / L of Tris-HCl with pH of 7.4, ionic strength of 0.15 adjusted with NaCl) containing BSA (10 g / L), and analyzed as samples in the Cobas Bio. A sample of 60 μL, together with 20 μL of water, is added to 320 μL of substrate S-2238 (Cromogenix AB, Molndal, Sweden) in the assay regulator, and the absorbance change is monitored (? A / min) The final concentrations of S-2238 are 16.24 and 50 μmol / L and of thrombin 0.125 NIH / mL units. The steady-state reaction rate is used to construct Dixon points, that is, diagrams of inhibitor concentration against 1 / (? A / min). For reversible, competitive inhibitors, the damage points for the different substrate concentrations typically form straight lines that intersect at x = -Ki.

TEST DETERMINATION OF PARTIAL TIME OF TROMBOPLASTIN ACTIVATED (APTT) The APTT is determined in grouped normal human cipher plasma, with the PTT Automated 5 reagent manufactured by Stago. The inhibitors are added to the plasma (10 μL of inhibitor solution for 90 μL of plasma) and incubated with the APTT reagent for 3 days. minutes followed by the addition of 100 μL of calcium chloride solution (0.025 M) and the APTT was determined by using the KC10 coagulation analyzer (Amelung), according to the instructions of the reagent producer. The coagulation time is expressed as absolute values (seconds), as well as the proportion of APTT without inhibitor (APTT0) with respect to APTT with inhibitor (APTT1). These last proportions (range of 1 to 0), are plotted against the inhibitor concentration (logarithmic transform) and adjusted to the sigmoidal dose response curves according to the equation y = a / [1+ (x / IC50) s] where: a = maximum range, that is, 1; s = slope of the response curve; and IC50 = the inhibitor concentration that doubles the clotting time. The calculations are processed on a computer using the GraFit Version 3 program, setting the equation to: Start at 0, defined end = 1 (Erithacus Software, Robin Leatherbarrow, Imperial College of Science, London, England). 1C50 is defined as the concentration of inhibitor in human plasma that doubles the partial time of activated thromboplastin.

PROOF E DETERMINATION OF ELI MY NATION IN PLASMA AND BIODISPE N I BI LI DAD ORAL IN RATS The determination of plasma elimination and oral bioavailability are estimated in Sprague Dawley rats. The compound is dissolved in water or in another suitable vehicle. For determination of plasma elimination, the compound is administered as a subcutaneous (se) or intravenous (iv) bolus injection, at a dose of 1-4 μmol / kg. Blood samples are collected at frequent intervals up to 24 hours after administration of the drug. For bioavailability estimates, the compound is orally administered at 10 μmol / kg by forced feeding and blood samples are collected frequently up to 24 hours after dosing. The blood samples are collected in heparinized tubes and centrifuged within 30 minutes, in order to separate the plasma from the blood cells. The plasma is transferred to plastic bottles with screw caps and stored at -20 ° C until analysis Before the analysis, the plasma is thawed and precipitated with 50 μL of acetrile.The samples are centrifuged for 20 minutes at 4000 rpm. 75 μL of the supernatant is diluted with 75 μL of 0.2% formic acid, 10 μL volumes of the resulting solutions are analyzed by LC-MS / MS and the concentrations of the thrombin inhibitor are determined using standard curves. perform with the computer program WinNonlin TM Professional (Pharsight Corporation, California, USA), or an equivalent program. The area under the curve (AUC) of plasma concentration-time profiles is estimated using the trapezoidal log / linear rule and extrapolated to infinite time. The plasma elimination (CL) of the compound is determined as CL = Dose (iv / sc) / AUC (iv / sc).

The oral bioavailability is calculated as F = CL x AUC (po) / Dosage (po).

The elimination in plasma is reported as mL / min / kg and the oral bioavailability as a percentage (%).

TEST F DETERMINATION OF IN VITRO STABILITY Sprague-Dawley rat liver microsomes and human liver samples are prepared according to the internal SOPs. The compounds are incubated at 37 ° C at a total microsomal protein concentration of 0.5 mg / mL in 0.1 mol / L potassium phosphate buffer with a pH of 7.4, in the presence of the NADPH cofactor (1.0 mmol / L). The initial concentration of the compound is 1. 0 μmol / L. Samples are taken for analysis at 5 time points, 0, 7, 15, 20 and 30 minutes after the start of incubation. The enzymatic activity in the collected sample is stopped immediately by adding an equal volume of acetonitrile containing 0.8% formic acid. The concentration of the remaining compound in each of the collected samples is determined by means of LC-MS / MS. The constant (k) of the elimination rate of the thrombin inhibitor is calculated as the slope of the ln [thrombin inhibitor] point against the incubation time (minutes). The rate of elimination constant is then used to calculate the half-life (T1 / 2) of the thrombin inhibitor, which is then used to calculate the intrinsic elimination (CLint) of the thrombin inhibitor in liver microsomes such as: CLint ( in μL / min / mg) = (In2 x incubation volume) (T1 / 2 x protein concentration) TEST G MODEL OF VENOUS THROMBOSIS Thrombogenic stimuli are vessel damage and stasis of blood flow. The rats are anesthetized and the abdomen is opened. A partial occlusion in the vena cava, caudal to the vein of the left kidney, is obtained with an incision around the vein and a cannula, which is then removed. A filter paper soaked with FeCI3 is placed on the outer surface of the distal part of the the vena cava The abdomen is filled with saline and closed. At the end of the experiment the rat is sacrificed, the vena cava is removed, the thrombus is collected and its wet weight is determined.

GENERAL EXPERIMENTAL DETAILS Where Prep-HPLC is mentioned, a Waters Fraction Lynx Purification System with an ACE C8 column of 5 μm 21 x 100 mm or a Gilson HPLC system with a 10 μm 21.2 x 250 mm kromasil C8 column was used. The mobile phase used with the Waters system was a gradient that started at 5% acetonitrile up to 100% in 100 mM of ammonium acetate buffer. The mobile phase used with the Gilson system was a 0% gradient of acetonitrile up to 95% in 100 mM of ammonium acetate buffer. The flow rate was 25 mL / minute. With the Waters system, the fraction collection activated by MS was used. With the Gilson HPLC system, the UV-activated fraction collection was used. The mass spectra were recorded in either a Micromass ZQ of a single quadrupole or in a Micromass Quattro Micro, both equipped with a pneumatically assisted electro dew interface (LC-MS).

REAGENTS The following list of reagents was used in the Preparations and examples shown below. Unless otherwise stated, each of these reagents is commercially available.

LIST 1 (a) Phenylmethanesulfonyl chloride (b) Benzenesulfonyl chloride (c) 4-methoxybenzenesulfonyl chloride (d) 2-methoxy-4-methylbenzenesulfonyl chloride (e) 3,4-d-Chlorobenzenesulfonyl chloride (f) 3- Chloride methoxybenzenesulfonyl (g) 2,5-dimethylbenzenesulfonium chloride (h) Naphthalene-1-sulfonyl chloride (i) 2,4-dimethoxybenzenesulfonyl chloride (j) (4-chlorophenyl) methanesulfonyl chloride (k) 4-ethylbenzenesulfonyl chloride (I) 2, 5-d imethylthiophene-3-sulphonyl chloride (m) 2, 5-dichlorobenzenesulfonyl chloride (n) 2-Chloro-6-methylbenzenesulfonyl chloride (o) 4-Chloro-2-fluorobenzenesulfonyl chloride LIST 2 (a) Phenylacetic acid (b) O-tolylacetic acid (c) Acid (2,5-dimethylphenyl) acetic acid (d) (5-Fluoro-2-methylphenyl) acetic acid (e) (3-trifluoromethylphenyl) acetic acid (f) Acid (5-) cORO-2-fluorophenyl) acetic LIST 3 (a) Benzaldehyde (b) 3-Methoxybenzaldehyde (c) 3-Pyridinecarboxaldehyde (d) 2-Methoxynicotinaldehyde (obtainable as described in J. Org Chem. 55.69 (1990)) LIST 4 (a) Isobutyraldehyde (b) 1-phenyl-1 H-pyrazole-5-carbaldehyde (c) 2,5-dimethyl-1- (4H-1, 2,4-triazol-4-yl) -1 H-pyrrole -3-carbaldehyde (d) 4-benzoyl 1-1 -methyl-1 H -pyrryl-2-carbaldehyde (e) 2,3-dihydrobenzo [b] furan-5-carboxaldehyde (f) 2,4-Dimethyl-1 , 3-thiazole-5-carbaldehyde (g) 1,5-dimethyl-1 H -pyrazole-4-carbaldehyde (h) 1 - (phenylsulfonyl) -1H-pyrrole-2-carbaldehyde (¡) 3,5-dimethyl-4-isoxazolecarbaldehyde (j) 5-chloro-2-phenyl-3H-imidazole-4-carbaldehyde (k) 1,3-dihydro-2,1,3-benzoxadiazole-5-carbaldehyde (I) 2-pyrazinecarboxaldehyde (m) cyclopentanecarboxaldehyde (n) 5-pyridin-2-ylthiophene-2-carbaldehyde (o) 5-chloro-1,3-dimethyl-1H-pyrazole-4-carbaldehyde (p) 6-Chloropiperonal (q) 1-methyl-1 - / - imidazole-2-carbaldehyde (r) cyclohexanecarboxaldehyde (s) 4-methyl-3,4-di idro-2H-1,4-benzoxazine-7-carbaldehyde (t) 4-cyanobenzaldehyde (u) 2-phenoxybenzaldehyde (v) 1-ethyl-3-methyl-1H-pyrazole-4-carbaldehyde (w) 5-methylimidazole-4-carboxaldehyde (x) 5-chloro-1-methyl -3-phenyl-1H-pyrazole-4-carbaldehyde (and) 2-morpholino-4-yl-pyridine-3-carbaldehyde (z) 3,3-Dimethylbutyraldehyde (aa) 5-chloro-2-thiophenecarboxaldehyde (ab) 2-fluoro-5-formylbenzonitrile (ac) 5-methyl -3-phenyl-4-isoxazolecarbaldehyde (ad) 3- (trifluoromethoxy) benzaldehyde (ae) 5-chloro-2-fluorobenzaldehyde (af) 2-methyl-1H-im i dazol-5-carb aldehyde (ag) 2-fluoro -5-methoxybenzaldehyde (ah) 2-morpholinbenzaldehyde (ai) 1,3-Dimethyl-5-morpholino-1 H-pyrazole-4-carbaldehyde (aj) 8-quinolinecarbaldehyde (ak) 5- (2-thienyl) -3-isoxazolecarbaldehyde (al) 2-phenylpropionaldehyde (am) bicyclo [2.2.1] hept-5-ene-2-carb aldehyde (an) 3 - [(2-chloro-1,3-thiazol-5-yl) methoxy] benzenecarbaldehyde (ao) 3-Methyl-5-phenyl-4-isoxazolecarbaldehyde 10 (ap) 1, 3-dimethyl-5-morpholino-4-yl-1 H-pyrazole-4-carbaldehyde LIST 5 (a) [(4-aminomethyl-phenyl) -minomethyl] -carbamic acid benzyl ester (obtainable as described in WO 94/29336) (b) (5-Aminomethyl-6-methylpyridinyl) -ery-butyl ester 2-yl) carbamic (obtainable as described in WO 97/01338) 20 (c) (4-aminomethylpyridin-2-yl) carbamic acid ferritilic acid ester (obtainable as described in the preparation 3 below) (d) (4-bromomethylpyridin-2-yl) carbamic acid ε-butyl ester (obtainable as described in WO 00/66557) . (e) C- (3-fluoro-4-methylpyridin-2-yl) methylamine (which is may be obtained as described in WO 00/075134) (f) (5-aminomethylpyridin-2-yl) carbamic acid ε-butyl ester (obtainable as described in WO 97/01338) (g) (2-aminomethyl-4-chlorobenzyl) carbamic acid ferf-butyl ester (obtainable as described in US Pat.

WO 02/050056) (h) [/ V,? / '- Di (éri-butoxycarbonyl)] 2-aminoethoxyguanidine (which can be obtained as described in WO99 / 55355) (i) (5-aminomethyl-6-methylpyridin-2-yl) carbamic acid ferritilic acid ester (obtainable as described in WO 97/01338) (j) [5- (aminomethyl) -4,6-dimethylpyridin-2-yl] -eryi-butyl carbamate (obtainable as described in WO 97/01338) (k) [2- (1 H-tetrazol-1-yl) benzyl] amine (obtainable as described in WO 02/064211) (I) 5- (aminomethyl) -3,6-dimethylpyridin-2- amine (obtainable as described in WO 99/11267) (m) [2- (aminomethyl) benzyl] carbamic acid-butyl ester (obtainable as described in WO 02/057225) (n) [5] -Cloro-2- (1H-tetrazol-1-yl) benzyl] amine (obtainable as described in WO 02/064559) (o) 2- [2- (aminomethyl) -4-chlorophenoxy] -? -ethylacetamide (obtainable as described in WO97 / 30708) (p). { 2- [2- (aminomethyl) -4-chlorophenyl] ethyl} urea-butyl carbamate (obtainable as described in Bioorg, Med.

Chem. Lett., 13.34773 (2003)) (q) urea-butyl (2-aminomethyl) -4-fluorobenzyl] carbamate (obtainable as described in preparation 6 below) (r) [2- (aminomethyl) -4-methoxybenzyl] carbamic acid-butyl ester (which can be obtained as described in Preparation 7 below) (s) [2- (aminomethyl) -4-methylbenzyl] -ery-butyl carbamate (obtainable as described in Preparation 8 below) ( t) [2- (Aminomethyl) -4- (trifluoromethyl) benzyl] carbamic acid-butyl ester (obtainable as described in Preparation 9 below) PREPARATIONS PREPARATION 1 METHYL ESTER OF ACID (1-AMINO-4-METHYL-2-OXO-1.2- DIHYDROPYRIDIN-3-IL) ACETIC (A) 2-METOXY-4-METHYL-PYRIDINE-3-CARBALDEHYDE The compound indicated in the subtitle was prepared from 2-methoxypyridine according to the procedures described in J Org. Chem. 55.69 (1990) and Tetrahedron Lett. 29,773 (1988).

(BH2-METOXI-4-MET1L-PIR1D1N-3-IDMETANOL Sodium borohydride (540 mg, 14.2 mmol) was added to a solution of 2-methoxy-4-methylpyridine-3-carbaldehyde (1.8 g, 12.9 mmol, see step (a) above) in a mixture of THF and methanol (30 mL, 1: 1) at 0 ° C. The reaction mixture was stirred at room temperature for 2 hours. Water (10 mL) was added and the aqueous layer was extracted with ethyl acetate (3 x 25 mL). The combined organic layers were dried (Na2SO), filtered and the solvent was evaporated under reduced pressure. The residue was purified by flash chromatography (SiO2, 40% ethyl acetate in hexane) to give the compound indicated in the subtitle. (1.68 g, 85%) as a colorless oil. 1 H NMR (400 MHz, CDCl 3) d 2.17 (s, 3 H), 3.68 (br s, 1 H), 3.72 (s, 3 H), 4.49 (s, 2 H), 6.53 (d, 1 H), 7.72 (d, 1 HOUR)(O 3-BROMOMETIL-2-METOXY-4-METHYL PYRIDINE Triphenylphosphine (2.35 g, 13.2 mmol) and N-bromosuccinimide (3.46 g, 13.2 mmol) were added to a solution of (2-methoxy-4-methylpyridin-3-yl) -methanol (1.35 g, 8.81 mmol, see step (b) above) in DCM (40 mL) at 0 ° C. The reaction mixture was stirred at room temperature for 5 hours. Water (20 mL) was added, the layers were separated and the aqueous layer was extracted with DCM (3 x 20 mL). The combined organic layers were dried (Na2SO), filtered, and the solvent was evaporated under reduced pressure. Purification by flash chromatography (SiO2, 10% ethyl acetate in hexane) gave the compound indicated in the subtitle (1.43 g, 75%) as a colorless oil. 1 H NMR (400 MHz, CDCl 3) d 2.38 (s, 3 H), 4.00 (s, 3H), 4.58 (s, 2H), 6.74 (d, 1H), 7.98 (d, 1H) (D) (2-METOXY-4-METHYL PYRIDINE-3-IDACETONITRILE Potassium cyanide (633 mg, 9.70 mmol) was added to a solution of 3-bromomethyl-2-methoxy-4-methylpyridine (1.40 g, 6.48 mmol, see step (c) above) in methanol (40 mL). ) and the solution was stirred for 12 hours at room temperature. The solvent was evaporated under reduced pressure and the residue was partitioned between a solution of NaHCO3 (sat., 10 mL) and ethyl acetate. The aqueous layer was extracted with ethyl acetate (3 x 25 mL). The combined organic layers were dried (Na2SO), filtered and the solvent was evaporated under reduced pressure. Purification by flash chromatography (SiO2, 25% ethyl acetate in hexane) gave the compound indicated in the subtitle (0.95 g, 90%) as a colorless oil. NMR with 1H (400 MHz, CDCl 3) d 2.35 (s, 3H), 3.65 (s, 2H), 3.96 (s, 3H), 6.73 (d, 1H), 7.99 (d, 1H).

(E) METHYL ESTER OF ACID (4-METHYL-2-OXO-1, 2- DIHIDROPIR1D1 -3-IDACÉTICO (2-Methoxy-4-methylpyridin-3-yl) acetonitrile (825 mg, 5.09 mmol, see step (d) above) was dissolved in HBr (37%, 10 mL) and the solution was heated to 100 ° C. for 5 hours and further stirred at room temperature for 24 hours. The solvent was evaporated under reduced pressure and the resulting carboxylic acid was used directly in the next step. HCl (conc., 3 mL) was added to a solution of the pure acid (9.13 g, 50 mmol) in methanol (120 mL) and the reaction mixture was stirred for 10 hours at room temperature. The reaction mixture was then concentrated by evaporation under reduced pressure and the residue was dissolved in DCM and washed with NaHCO3. The organic layer was dried (Na2SO4), filtered and the solvent was evaporated to give the compound indicated in the subtitle (8.9 g, 97%). NMR with H (400 MHz, CD3OD) d 2.12 (s, 3H), 3.56 (s, 2H), 3.60 (s, 3H), 6.07 (d, 1H), 7.15 (d, 1H).

(F) METHYL ESTER OF ACID (1-AMINO-4-METHYL-2-OXO-1.2- DIHLDROPIRIDIN-3-IL) ACETIC Cesium carbonate (1.6 g, 11.6 mmol) and O- (diphenylphosphinyl) -hydroxylamine (1.54 g, 6.62 mmol, see Synthesis 592 (1988) and Tetrahedron Lett. 23, 3835 (1982)) were added to a solution of methyl ester of (4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetic acid (0.60 g, 3.31 mmol, see step (e) above) in DMF (10 mL). The suspension was stirred at room temperature for 18 hours, filtered and the solvent was evaporated under reduced pressure. Purification by flash chromatography (3% methanol in ethyl acetate) gave the base compound (380 mg, 60%) as a yellow oil. NMR with H (400 MHz, CD3OD) d 2.09 (s, 3H), 3.57 (s, 2H), 3.61 (s, 3H), 5.05 (br d, 2H), 5.96 (d, 1H), 7.37 (d, 1 HOUR).

PREPARATION 2 The compounds (i) to (viii) listed below were prepared from the base compound of Preparation 1 by the following General Method A. The compounds (ix) to (xiv) listed below were prepared from the base compound of Preparation 1 by the following General Method B. Unless otherwise specified, the compounds (xv) through (xviii) listed below were prepared from the base compound of Preparation 1 by the following General Method C.

GENERAL METHOD A The specific sulfonyl chloride (0.61 mmol, 1.2 mol equiv .; see List 1 above) and pyridine (125 μL, 120 mg, 1.53 mmol) was added to a solution of (1-amino-4-methyl-2-oxo-1,2-dihydropyridin-3-methyl) methyl ester. il) acetic (100 mg, 0.51 mmol, see Preparation 1 above) in DCM (4 mL) at 0 ° C. The reaction mixture was stirred at room temperature for 12 hours. The pyridine and the solvent were evaporated under reduced pressure. Purification by flash chromatography (SiO2, 50-70% ethyl acetate in hexane) gave the sulfonamides listed in (i) to (viii) below (62-92%).

GENERAL METHOD B STEP (i) Borane tetrahydrofuran complex (solution 1) was added M, 1.5 eq.) To a stirred solution of the specific acid (1.0 eq, see, List 2 above) in THF (0.2 M) at 0 ° C. The mixture was allowed to warm to room temperature for 1 hour and stirring was continued for another hour. Water was carefully added at 0 ° C and the mixture was extracted with ethyl acetate. The organic phases were combined, dried and the solvent removed under reduced pressure to give the reduced product. The crude alcohol was used without further purification. The alcohol was dissolved in DCM (0.2 M) and added to the Dess-Martin periodinan solution (1.5 eq). The suspension The resulting mixture was stirred until the reaction was complete (from 0.5 hour to overnight). Hexane was added to the mixture and the resulting suspension was filtered through a pad of Celite® / silica gel. The pad was washed with a solution of 30% ethyl acetate in hexane. The solvents were removed under reduced pressure to give the corresponding aldehyde, which was used in step (ii) without further purification.

STEP (ii) The specific aldehyde (0.50 mmol, see step (i) above) was added to (1-amino-4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetic acid methyl ester (76 mg, 0.39 mmol, see Preparation 1 above) in anhydrous ethanol (1.5 mL) and the reaction mixture was heated for reflux for 12 hours. The mixture was allowed to return to room temperature and NaBH 3 CN (49 mg, 0.77 mmol) was added and stirring was continued for 4 hours. HCl (10%) was added and after stirring for 10 minutes the pH was neutralized with NaHCO3 (sat.). The mixture was extracted with ethyl acetate (3 x.10 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and the solvent was evaporated under reduced pressure. Purification directly after this by flash chromatography (SiO2, 45% ethyl acetate in hexane) gave the reductive amination products listed in (ix) to (xiv) below (45-69%).

GENERAL METHOD C The specific aldehyde (0.52 mmol, see List 3 above) dissolved in methanol (1.5 mL) was added to methyl ester of acid (1-amino-4-methyl-2-oxo-1,2-dihydropyridin-3-yl). ) -acetic (100 mg, 0.48 mmol, see Preparation 1 above) in methanol (1.5 mL). Sodium cyanoborohydride (63 mg, 2.85 mmol) and zinc chloride (195 mg, 1.43 mmol) were added and the reaction mixture was stirred at room temperature overnight. Another portion of sodium cyanoborohydride (90 mg, 1.43 mmol) and acetic acid (10 droplets) was added and stirring was continued for another 3 hours. Sodium hydroxide (2 M) was added and the mixture was extracted with DCM (3 x 10 mL). The combined organic layers were dried by a phase separator and the solvent was evaporated under reduced pressure. Purification by flash chromatography (SiO2, ethyl acetate: hexane, 1: 2) gave the products listed under (xv) to (xviii) below. (i) methyl ester of (4-metii-2-oxo-1-phenylmethanesulfonylamino-1,2-dihydro-pyridin-3-yl) acetic acid NMR with 1H (400 MHz, CDCl 3) d 2.22 (3H, s), 3.67 (5H, s), 4.35 (2H, s), 6.15 (1H, d), 7.28-7.44 (6H, m), 9.26 (1H, br) (ii) methyl ester of (1-benzenesulfonylamino-4) acid methyl-2-oxo-1,2-dihydro pyridin-3-yl) -acetic NMR with 1H (400 MHz, CDCl 3) d 2.17 (3H, s), 3.37 (2H, s), 3.60 (3H, s), 6.16 (1H, d), 7.41-7. 63 (6H, m), 9.07 (1H, b) (iii) methyl ester of [1- (4-methoxyphene, I-methanesulfonyl) -4-methyl-2-oxo-1, 2- d i h pyridin-3? I] acetic NMR with 1H (400 MHz, CDCl 3) d 2. 16 (3H, s), 3.38 (2H,, 5 s), 3.59 (3H, s), 3.87 (3H, s), 6.14 (1H, d) ), 6.85 (2H, d), 7.53 (2H, d), 7.61 (2H, d), 9.26 (1H, br) (iv) methyl ester of [1- (2-methoxy-4-methylbenzenesulfonylamino) -4 -methyl-2-oxo-1, 2-dihydropyridin-3-yl-acetic acid 10 NMR with 1H (400 MHz, CDCl 3) d 2.09 (s, 2H), 2.36 (s, 3H), 3.36 (s, 2H), 3.53 (s, 3H), 4.01 (s, 3H), 6. 03 (d, 1H), 6.69 (d, 1H), 6.79 (s, 1H), 7.48 (d , 1H), 7.58 (d, 1H), 9.30 (s, 1H) (v) [1- (3,4-dichlorobenzenesulfonylamino) -4-methyl-2-oxo-1,2-dihydro-pyridic acid methyl ester in-3-i I] 5-acetic NMR with 1H (400 MHz, CDCl 3) d 2.20 (s, 3H), 3.44 (s, 2H), 3.63 (s, 3H), 6.20 (d, 1H), 7.38 (dd , 1H), 7.43 (d, 1H), 7.58 (d, 1H), 7.63 (d, 1H), 9.41 (s, 1H) (vi) [1- (3-methoxy benzenesulfonyl) methyl ester] lam i no) -4-met i l-2-oxo-1,2-dihydro-pyridin-3-yl] acetic NMR with 1H (400 MHz, CDCl 3) d 2.16 (s, 3H), 3. 37 (s, 2H), 3.59 (s, 3H), 3.75 (s, 3H), 6.15 (d, 1H), 7.07-7. 09 (m, 2H), 7.21 (d, 1H), 7.31 (t, 1H), 7.63 (d, 1H) 5 (vii) methyl ester of acid [1- (2,5- dimethylbenzenesulfonylamino) -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl] acetic NMR with 1H (400 MHz, CDCl 3) d 2.14 (s, 3H), 2.22 (s, 3H), 2.59 ( s, 3H), 3.36 (s, 2H), 3.57 (s, 3H), 6.08 (d, 1H), 7.14 (d, 1H), 7.22 (d, 1H), 7.45 (s, 1H), 7.52 (d , 1H) (viii) [4-ethyl-1- (naphthalene-1-sulfonylamino) -2-oxo-1,2-dihydro-pyridin-3-yl] -acetic acid methyl ester. NMR with 1H (400 MHz, CDCl 3) d 2.12 (s, 3H), 3.16 (s, 2H), 3.53 (s, 3H), 6.11 (d, 1H), 7.37-7.49 (m, 3H), 7.54 (t , 1H), 7.88 (d, 1H), 7.98 (d, 1H), 8.05 (d, 1H), 8.50 (d, 1H), 9.31 (br s, 1H) (ix) methyl ester of acid (4-methyl) -2-oxo-1-phenethylamino-1,2-dihydro-pyridin-3-yl) acetic NMR with 1H (400 MHz, CDCl 3) d 2.18 (s, 3H), 2.85 (t, 2H), 3.28 (q, 2H), 3.67 (s, 2H), 3.70 (s, 3H), 6.03 (d, 1H), 6.12 (t, 1H), 7.19-7.36 (m, 5H) (x) [4-methyl] methyl ester -2-oxo-1- (2-o-tolyl-ethylamino) -1,2-dihydropyridin-3-yl] acetic NMR with 1H (400 MHz, CDCl 3) d 2.18 (s, 3H), 2.29 (s, 3H ), 2.85 (t, 2H), 3.22 (t, 2H), 3.67 (s, 2H), 3.69 (s, 3H), 6.05 (d, 1H), 7.12-7.18 (m, 4H), 7.37 (d, 1H) (xi) methyl ester of acid. { 1- [2- (2,5-dimethylphenyl) ethylamino] -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl} NMR with 1H (400 MHz, CDCl 3) d 2.19 (s, 3H), 2.26 (s, 3H), 2.28 (s, 3H), 2.82 (t, 2H), 3.22 (t, 2H), 3.67 (s, 2H), 3.70 (s, 3H), 6.06 (d, 1H), 6.92 (d, 1H) ), 6.97 (s, 1H), 7.02 (d, 1H), 7.39 (d, 1H) (xii) methyl ester of acid. { 1- [2- (5-fluoro-2-methylphenyl) ethylamino or] -4-met i l-2-oxo-l, 2-dihydro pyridin-3-yl} NMR with 1H (400 MHz, CDCl 3) d 2.17 (s, 3 H), 2.24 (s, 3 H), 2. 81 (t, 2 H), 3.22 (t, 2 H), 3.66 (s, 2 H), 3.69 ( s, 3H), 6.05 (d, 1H), 6.50 (t, 1H), 6.50 (dd, 1H), 6.88 (dd, 1H), 7.06 (dd, 1H), 7.35 (d, 1H) (xiii) ester acid methyl. { 4-Methyl-2-oxo-1- [2- (34-trifluoromethylphenyl) ethylamino] -1,2-dihydro-pyridin-3-yl} acetic NMR with 1H (400 MHz, CDCl 3) d 2.18 (s, 3H), 2.92 (t, 2H), 3.30 (t, 2H), 3.66 (s, 2H), 3.69 (s, 3H), 6.04 (d, 1H), 7.33 (d, 1H), 7.40-7.43 (m, 2H), 7.46-7.48 (m, 2H) (xiv) methyl ester of acid. { 1- [2- (5-chloro-2-fluorophen i l) ethylamino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} NMR acetic acid with 1H (400 MHz, CDCl 3) d 2.18 (s, 3H), 2.84 (t, 2H), 3.25 (t, 2H), 3.66 (s, 2H), 3.70 (s, 2H), 6.04 (d, 1H), 6.95 (t, 1H), 7.15 (dq, 1H), 7.21 (dd, 1H) ), 7.32 (d, 1H) (xv) [1 - (benzylamino) -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl] -methyl acetate yield = 42%. 1 H NMR (400 MHz, CDCl 3) d 2.19 (s, 3 H), 3.71 (s, 2 H), 3.74 (s, 3 H), 4.14 (s, 2 H), 5.94 (d, 1 H), 7.18 (d, 1 H) ), 7.30-7.41 (m, 5H) (xvi). { 1 - [(3-methoxy benz I) am i no] -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl} methyl acetate 1 H NMR (400 MHz, CDCl 3) d 2.16 (s, 3 H), 3.69 (s, 2 H), 3.71 (s, 3 H), 3.79 (s, 3 H), 4.08 (d, 2 H), 5.92 (d, 1 H) ), 6.29 (t, 1H), 6.84 (dd, 1H), 6.91 (s, 1H), 6.94 (d, 1H), 7.20 (d, 1H), 7.24 (t, 1H) MS m / z 317 (M + H) + (xvi i). { 4-methy1-2-oxo-1 - [(pyridin-3-ylmethyl) am i no] -1,2-dihydro-pyridin-3-yl} methyl acetate 3-Pyridinecarboxaldehyde (10.6 mmol) was added to a solution of methyl (1-amino-4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetate (2.2 mmol); see Preparation 1 above) in methanol (40 mL) and acetic acid (10 mL) and the resulting solution was stirred at room temperature. After 22 hours, the solution was concentrated and the acetic acid was removed by co-concentrating the residue from toluene, hexane and methanol. Sodium cyanoborohydride (6 mmol) was added to the residue in methanol (40 mL) and acetic acid (10 mL), and the resulting solution was stirred at room temperature overnight before being concentrated.The residue was diluted with ethyl acetate and washed with NaHCO3 (aqueous sat) and brine, dried, filtered, and the solvent was evaporated under reduced pressure Purification by flash chromatography (SiO2, 0-10% methanol in DCM with 0.2% acetic acid. and 0.1% TEA) gave the desired product. (xvi) { 1 - [(3- me toxi benz I) am i no] -4-methyl-2-oxo-1,2-dihydropyridin-3 -yl.} methyl acetate NMR with 1H (400 MHz, CDCl 3) d 2.16 (s, 3H), 3.69 (s, 2H), 3.71 (s, 3H), 3.79 (s, 3H), 4.08 (d, 2H), 5.92 (d, 1H), 6.29 (t, 1H), 6.84 (dd, 1H), 6.91 (s, 1H) ), 6.94 (d, 1H), 7.20 (d, 1H), 7.24 (t, 1H) MS m / z 317 (M + H) + (xvii). { 4-methyl-2-oxo-1 - [(pyridin-3-ylmethyl) amino] -1,2-dihydropyridin-3-yl} methyl acetate 3-Pyridinecarboxaldehyde (10.6 mmol) was added to a solution of methyl (1-amino-4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetate (2.2 mmol, see Preparation 1 above) in methanol (40 mL) and acetic acid (10 mL) and the resulting solution was stirred at room temperature. After 22 hours, the solution was concentrated and the acetic acid was removed by co-concentrating the residue from toluene, hexane and methanol. Sodium cyanoborohydride (6 mmol) was added to the residue in methanol (40 mL) and acetic acid (10 mL) and the resulting solution was stirred at room temperature overnight before being concentrated. The residue was diluted with ethyl acetate and washed with NaHCO3 (aqueous sat) and brine. It was dried, filtered, and the solvent was evaporated under reduced pressure. Purification by flash chromatography (SiO2, 0-10% methanol in DCM with 0.2% acetic acid and 0.1% TEA) gave the desired product. 1 H NMR (400 MHz, CDCl 3) d 8.52-8.58 (m, 2 H), 7.70 (d, 1 H), 7.24-7.30 (m, 1 H), 7.12 (d, 1 H), 6.25 (t, 1 H), 5.93 (d, 1H), 4.14 (d, 2H), 3.70 (s, 3R), 3.67 (s, 2R), 2.16 (s, 3H). (xvi i i) (1- { [(2-methoxy pyridin-3-yl) methyl] to mino.} -4-meti-2-oxo- 1,2-dihydropyridin-3-yl) methyl acetate. 2-Methoxynicotinaldehyde (3.6 mmol) was added to a solution of methyl (1-amino-4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetate (2.4 mmol, see Preparation 1 above) in methanol (40 mL) and acetic acid (10 mL) and the resulting solution was stirred at room temperature. After 4.5 hours, sodium cyanoborohydride (7.4 mmol) was added and the resulting solution was stirred at room temperature for 3 hours before being concentrated. The residue was diluted with ethyl acetate and washed with NaHCO3 (aqueous sat) and brine, dried, filtered and concentrated. Purification by flash chromatography (SiO2, DCM: methane, 900: 25) gave the desired product. NMR with 1H (500 MHz, CDCl 3) d 8.13 (d, 1H), 7.50 (d, 1H), 7.23 (d, 1H), 6.85 (dd, 1H), 6.50 (t, 1H), 5.99 (d, 1H) ), 4.14 (d, 2H), 3.98 (s, 3H), 3.72 (s, 3H), 3.68 (s, 2H), 2.19 (s, 3H).

PREPARATION 3 TEK7-BUTYL ESTER OF ACID (4-AMINOMETILPIRIDIN-2-IDCARBAMIC (A) ESTER TERT-BUTYLLIC OF ACID 4-AZIDOMETILPIRIDIN-2- IDCARBÁMICO A mixture of (4-bromomethylpyridin-2-yl) carbamic acid tert-butyl ester (3.0 g, 0.010) was stirred overnight. mol; which can be obtained as described in WO 00/66557) and sodium azide (1.36 g, 0.0209 mol) in water (20 mL) and DMF (40 mL) was stirred overnight. The reaction mixture was poured into water (300 mL) and extracted with ethyl acetate (3x). The combined organic layers were washed with water, dried (Na 2 SO 4), filtered and the solvent was evaporated under reduced pressure. The crude crystallized product (2.6 g, 100%) was used and used without further purification. NMR with 1H (500 MHz, CDCl 3) d 10.14 (bs, 1H), 8.36 (d, 1H), 7.99 (bs, 1H), 6.91 (m, 1H), 4.37 (bs, 2H), 1.54 (s, 9H) ).

(B) ATS-BUTYL ESTER TERT (4-AMINOMET1LPIRID1N-2-IDCARBAMIC) A solution of sodium borohydride 0.92 g, 24 mmol in water (25 mL) was added to a mixture of Pd / C (10%, 50 mg ) in water (25 mL) under stirring, then (4-azidomethylpyridin-2-yl) carbamic acid tert-butyl ester (0.40 g, 6.1 mmol, see step (a) above) in THF ( 75 mL) rather quickly under cooling with ice The reaction was stirred at room temperature for 4 hours.An aqueous solution of sodium hydrogen sulfate was slowly added to give an acid pH.The reaction mixture was filtered by suction to Through a Celite® pad, which was further washed with water, the combined aqueous layer was washed with ethyl acetate, made alkaline by the addition of NaOH (aqueous), and extracted with ethyl acetate (3x). The combined organic phases were washed with water, dried (Na2SO4), filtered and the solvent was evaporated under reduced pressure. The crude product was crystallized (1.1 g, 85%) and used without further purification. NMR with 1H (300 MHz, CDCl 3) d 10.06 (m, 1H), 8.25 (m, 1H), 7.94 (m, 1H), 6.88 (m, 1H), 3.83 (bs, 2H), 1.50 (s, 9H) ).

PREPARATION 4 The compounds (i) to (xlii) listed below were prepared from the base compound of Preparation 1 by the following general method. The specific aldehyde (2.0 mmol, 2 mol equiv, see list 4 above) was dissolved in methanol / THF (5 mL, 2: 1). To the resulting solution was added, with stirring, a solution of (1-amino-4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetic acid methyl ester (196 mg, 1.0 mmol; Preparation 1 above) in methanol / THF (5 mL, 2: 1). Acetic acid (1 mL) was added and imine formation was allowed to stir at room temperature for 5 to 20 hours. Sodium cyanoborohydride (377 to 628 mg, 3 to 5 mmol, 3 to 5 mol equiv.) Was added and the reaction mixture was stirred at room temperature for 18 hours (or until total imine conversion was observed). ). The solvent was evaporated under reduced pressure and the crude product mixtures were dissolved in DCM and extracted with NaHCO3 (sat.) Using phase separators. They were extracted polar products especially below, with ethyl acetate (4 to 10 mL), if necessary. The organic phase was eluted through a plug of silica (1 g), eluting with a gradient of DCM / MeOH mixtures (1: 0 to 3: 1). Alternatively, the product was purified with Biotage Horizon Flash, eluting with MeOH / DCM / Et3N (2: 98: 0.1). Evaporation of the relevant fractions gave crude products (alkylated esters) that were used without further purification. (i) [1 - (isobuty lam i no) -4-methyl-2-oxo-1,2-dihydropyridin-3-yl] -methyl acetate (ii) (4-metii-2-oxo-1- {[[(1-phenyl-1H-pyrazol-5-yl) methyl] -amino} -1,2-dihydropyridin-3-yl) methyl acetate (iii) [1- ( { [2 , 5-dimethyl-1- (4H-1,2,4-triazol-4-yl) -1H-pyrrol-3-yl] methyl.} Amino) -4-methyl-2-oxo-1, 2- Methyl dihydropyridin-3-yl] acetate (iv) (1- {[[4-benzoyl-1-methyl-1 H-pyrrol-2-yl) methyl] amino} -4-methyl-2- methyl oxo-1, 2-dihydropyridin-3-yl) acetate (v) (1 - [(2,3-dihydro-1-benzofuran-5-ylmethyl) amino] -4-methyl-2-oxo-l, Methyl 2-dihydropyridin-3-yl) acetate (vi) (1 -. {[[(2,4-dimethyl-1,3-thiazol-5-yl) methyl] amino.} -4-methyl-2 methyl-1, 2-dihydropyridin-3-yl) methyl acetate (vii) (1- {[[(1,5-dimethyl-1H-pyrazol-4-yl) methyl] amino} -4- Methyl-2-oxo-l, 2-dihydropyridin-3-yl) methyl acetate (viii) [4-methyl-2-oxo-1- ( { [1- (phenylsulfonyl) -1H-pyrrole-2-- il] -methyl] amino) -1,2-dihydropyridin-3-yl] acetate methyl (ix) (1 - [(3,5-dimethylisoxazol-4-yl) methyl] amino.}. Methyl-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetate (x) (1 - [(4-chloro-2-phenyl-1H-imidazol-5-yl) methyl] amino.} -4- methyl-2-oxo-1,2-dihydropyridin-3-yl) acetate of methyl (xi). { 1 - [(2,1,3-benzoxadiazol-5-ylmethyl) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} methyl acetate (xii). { 4-Methyl-2-oxo-1 - [(pyrazin-2-ylmethyl) amino] -1,2-dihydro-pyridin-3-yl} acetate (xii i). { 1 - [(Cyclopentylmethyl) amino] -4-methy1-2-oxo-l, 2-dihydro-pyridin-3-yl} methyl acetate (xiv) (4-methyl-2-oxo-1- { [(5-pyridin-2-yl-2-thienyl) methyl] -amino.} -1, 2-dihydropyridin-3- il) methyl acetate (xv) (1- {[[5-chloro-1,3-dimethyl-1 H -pyrazol-4-yl) methyl] amino.} -4-methyl-2-oxo Methyl, -1,2-dihydropyridin-3-yl) acetate (xvi) (1- {[[6-chloro-1,3-benzodolox-5-yl) methyl] amino} -4- methyl-2-oxo-1,2-dihydropyridin-3-yl) methyl acetate (xvii) (4-methyl-1- { [(1-methyl-1 H -imidazole-2-yl) methyl] amino.} -2-oxo-1,2-dihydropyridin-3-yl) methyl acetate (xvi ii). { 1 - [(Cyclohexylhexyl) amino] -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl} methyl acetate (xix) (4-methyl-1- { [(4-methyl-3,4-dihydro-2H-1,4-benzoxazin-7-yl) methyl] amino.} -2-oxo Methyl -1, 2-dihydropyridin-3-yl) acetate (xx). { 1 - [(4-Cyanobenzyl) amino] -4-meth l-2-oxo-1,2-dihydro-pyridin-3-yl} methyl acetate (xxi). { 4-methyl-2-oxo-1 - [(2-phenoxybenzyl) amino] -1,2-dihydro-pyridin-3-yl} methyl acetate (xxii) (1 - [(1-ethyl-3-methyl-1H-pyrazol-4-yl) methyl] amino.} -4- methyl-2-oxo-1,2-dihydropyridin-3-yl) methyl acetate (xxiii) (4-methyl-1- { [(4-methyl-1H-imidazol-5-yl) methyl] amino} - methyl 2-oxo-l, 2-dihydropyridin-3-yl) acetate (xxiv) (1 - [(5-chloro-1-methyl-3-phenyl-1H-pyrazol-4-yl) methyl] - amino.} -4-Methyl-2-oxo-1,2-dihydropyridin-3-yl) methyl acetate (xxv) (4-methyl-1 - [(2-morpholino-4-ylpyridin-3-yl) methyl) amino.} -2-oxo-1,2-dihydropyridin-3-yl) methyl acetate (xxvi). { 1 - [(3,3-dimethylbutyl) amino] -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl} methyl acetate (xxvii) (1- ({[[(5-chloro-2-thienyl) methyl] amino} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) methyl acetate (xxviii). { 1 - [(3-cyano-4-fluorobenzyl) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} methyl acetate (xxix) (4-methyl-1 - [(5-methyl-3-p-enyl-isoxazol-4-yl) methyl] -amino.} -2-oxo-1,2-dihydropyridin-3-yl ) methyl acetate (xxx) (4-met i l-2-oxo-1- { [3- (t rif luoromethoxy) benz I] ami no.} -1, 2-dihydropyridin-3-ii) methyl acetate (xxxi). { 1 - [(5-Chloro-2-fluorobenzyl) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} methyl acetate (xxxi i) (4-methyl-1- { [(2-methyl-1 H-imidazol-5-yl) methyI] amino.} - 2-oxo-1,2-dihydropyridin-3 -il) methyl acetate (xxxiii). { 1 - [(2-Fluoro-5-methoxybenzyl) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} methyl acetate (xxxiv). { 4-methyl-1 - [(2-morpholino-4-ylbenzyl) amino] -2-oxo-1,2-dihydropyridin-3-yl} methyl acetate (xxxv) (1- {[[1, 3-dimethyl-5-morf or lino-4-y1-1 H-pyrazol-4-yl) -methyl] amino} -4-methyl-2 methyl-1, 2-dihydropyridin-3-yl) methyl acetate (xxxvi). { 4-methyl-2-oxo-1 - [(quinolin-8-ylmethyl) amino] -1,2-dihydropyridin-3-yl} methyl acetate (xxxvi i) [4-methyl-2-oxo-1- ( { [5- (2-thienyl) isoxazol-3-yl] methyl] .amino) -1,2-dihydropyridin- 3-yl] methyl acetate (xxxvi ii). { 4-methyl-2-oxo-1 - [(2-phenylpropyl) amino] -1,2-dihydro-pyridin-3-yl} methyl acetate (xxxix). { 1 - [(bicyclo [2.2.1] hept-5-eV-2-ylmethyl) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} methyl acetate (xl) [1- ( { 3 - [(2-chloro-1,3-ti azo l-5-i I) methoxy] benz I.} to me no) -4-metiI- Methyl 2-oxo-1,2-dihydropyridin-3-yl] acetate (xli) (4-methyl-1-. {[[(3-methyl-5-phenylisoxazol-4-yl) methyl]] -amino.) -2-oxo-1, 2-dihydro-pyridin-3-yl) acetate (xlii) (1- { [(1,3-dimethyl-5-morpholino-4-yl-1H- pyrazol-4-yl) -methi to me no.} -4-methyl-I-2-oxo-1,2-dihydropyridin-3-yl) methyl acetate PREPARATION 5 p-r (2,2-PIFLUORO-2-PIRIDtN-2-ILETIL) AMINO1-4-METHYL-2-OXO- 1.2-DIHYDROPYRIDIN-3-METHYL ILIACETATE (A) TRIFLUOROMETANOSULFONATO DE 2.2-DIFLUORO-2-PIRIDIN- 2-ILLETILO The compound indicated in the subtitle was prepared from according to the method described in J Med. Chem. 46,461 (2003)) (B) { 1-r (2,2-DIFLUORO-2-PIRIDlN-2-ILETIL) AMINOT-4-METHYL-2-OXO-1,2-DIHYDROPYRIDIN-3-IL} ACETATE A solution of 2,2-difluoro-2-pyridin-2-ylethyl trifluoromethanesulfonate (2.0 mmol, see step (a) above) and methyl ester of (1-amino-4-methyl-2-oxo-) acid is stirred. 1,2-dihydropyridin-3-yl) acetic acid (2.09 mmol, see Preparation 1 above) in 1,2-dichloroethane (40mL) at 50 ° C for 3 days before being concentrated. Purification by flash chromatography (SiO2, ethyl acetate) gave the base compound. NMR with 1H (500 MHz, CDCl 3) d 8.63 (d, 1H), 7.82 (dt, 1H), 7.69 (d, 1H), 7.37 (dd, 1H), 7.29 (d, 1H), 6.27 (t, 1H) ), 5.98 (d, 1H), 3.85-3.93 (m, 2H), 3.68 (s, 3H), 3.63 (s, 2H), 2.15 (s, 3H). PREPARATION 6 r2- (AMIOMETHYL) -4-FLUOROBENCIL1CARBAMATO OF TERT-BUTYL (A) 2-BROMINE-5-METHYL FLUOROBENZOATE To a solution of 2-bromo-5-fluorobenzoic acid (3.0 g, 13. 7 mmol) in methanol (4 mL) was added methanol saturated in HCl (70 mL). The reaction mixture was stirred for 24 hours and then concentrated. The excess HCl was removed by co-evaporation at Starting from methanol to give the compound indicated in the subtitle (97%), which was used in the next step without further purification. NMR with 1H (500 MHz, CDCl 3) d 3.96 (s, 3H), 7.09 (dt, 1H), 7.55 (dd, 1H), 7.65 (dd, 1H) (b) 2-CYANO-5-METHYL FLUOROBENZOATE Methyl 2-bromo-5-fluorobenzoate was dissolved (3.0 g, 12.87 mmol; see step (a) above) was dissolved in dry DMF (18 mL). The resulting solution was degassed by washing with N2 gas for 5 minutes. Copper (I) cyanide (2.3 g, 25.74 mmol) was added and the reaction mixture was degassed again before being refluxed for 90 minutes. NaCN (aqueous, 10% o) was added and the mixture was extracted with DCM. The DCM phase was dried through a phase separator, and the solvent was removed in vacuo. The crude product was dissolved in toluene and washed once with water. The organic layer was dried over MgSO4, and filtered. The solvent was removed in vacuo to give the compound indicated in the subtitle, crude (77%), which was used in the next step without further purification. NMR with H (500 MHz, CDCl 3) d 4.04 (s, 3 H), 7.38 (dt, 1 H), 7.82-7.87 (m, 2 H) (C) r2-AMINOMETLL) -5-FLUOROFENLL1METANOL Lithium aluminum hydride (1.12 g, 29.5 mmol) was dispersed in dry THF (10 mL) and the resulting mixture was cooled with an ice bath. Methyl 2-cyano-5-fluorobenzoate (1.76 g, 9.85 mmol, see step (b) above) was dissolved in THF (10 + 5 mL) and added to the reducing agent. The reaction mixture was stirred for 10 minutes and then the ice bath was removed. After 1 hour, the reaction was quenched with water (2 L), NaOH (2M, 4 mL) and then more water (2 mL), after which the resulting mixture was stirred for 10 minutes. The mixture was diluted with diethyl ether (50 mL) and filtered. The organic layer was dried over MgSO 4 and filtered. The solvent was removed in vacuo to give the compound indicated in the subtitle (81% >), which was used without further purification. 1 H NMR (500 MHz, CDCl 3) d 4.01 (s, 2H), 4.63 (s, 2H), 6. 95 (dt, 1H), 7.11 (dd, 1H), 7.23 (dd, 1H) (D) r4-FLUORO-2- (HYDROXYMETHYL) TERT-BUTYL BENZYLARBAMATE [2- (Aminomethyl) -5-fluorophenyl] methanol (1.24 g, 7.99 mmol, see step (c) above) was dissolved in DCM (20 mL) and di-ε-butyl dicarbonate (1.74 g, 7.99 mmol) was added. ), dissolved in DCM (5 mL). The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with DCM and washed once with water. The DCM phase was dried by a phase separator and the solvent was removed in vacuo. The co-evaporated butanol from toluene to give the compound indicated in the subtitle (96%), which was used without further purification. 1 H NMR (500 MHz, CDCl 3) d 1.45 (s, 9H), 2.83 (br s, 1H), 4.35 (d, 2H), 4.74 (s, 2H), 5.06 (br s, 1H), 6.99 (dt) , 1H), 7.11 (dd, 1H), 7.29-7.31 (m, 1H) (E) r2- (AZIDOMETHYL) -4-FLUOROBENCIL1 TERT-BUTYL CARBAMATE [4-Fluoro-2- (hydroxymethyl) benzyl] carbamate-buty-butyl (1.96 g, 7.70 mmol, see step (d) above) was dissolved in dry THF (25 mL) and the resulting mixture was cooled in a cold water bath. Diphenylphosphoryl azide (2.75 g, 10.0 mmo!) And DBU (1.52 g, 10.0 mmol) were added. The mixture was stirred under an inert atmosphere and the ice bath was allowed to warm to room temperature overnight. The reaction mixture was diluted with water and extracted twice with ethyl acetate. The organic phase was washed with brine and dried over MgSO 4 and filtered before removing the solvent in vacuo. Purification by flash chromatography (SiO2, heptane: ethyl acetate 10: 1) gave the compound indicated in the subtitle (76%). NMR with 1H (500 MHz, CDCl 3) d 1.48 (s, 9H), 4.34 (d, 2H), 4.45 (s, 2H), 4.83 (br s, 1H), 7.04 (dt, 1H), 7. 08 ( dd, 1H), 7.32-7.39 (m, 1H) (F) r2- (AMINOMETIL-4-FLUOROBENCIL1 TERT-BUTYL CARBAMATE TEA (1.76 g, 17. 55 mmol) in methanol (15 mL) was added to urea-butyl [2- (azidomethyl) -4-fluorobenzyl] carbamate (1.64 g, 5.85 mmol, see step (e) above) and the mixture was washed with N2 gas. 1,3-Propanedithiol (1.90 g, 17.55 mmol) dissolved in methanol (15 mL) was added. The reaction mixture was stirred at room temperature for 2 days. The white precipitate that formed was filtered and washed with methanol. The filtrate was collected and the solvent removed in vacuo. Purification by flash chromatography (SiO2, 2.5% methanol in DCM + 1% TEA) gave the base compound (82%). NMR with 1H (500 MHz, CDCl 3) d 1.48 (s, 9H), 3.94 (s, 2H), 4.33 (d, 2H), 5.80 (br s, 1H), 6. 94 (dt, 1H), 7.06 ( dd, 1H), 7.32 (dd, 1H).

PREPARATION 7 r2- (AMINOMETHYL) -4-METHODOXIBENClL1 TERT-BUTYL CARBAMATE The base compound was prepared by a method analogous to that described in Preparation 6, steps (b) through (f) above, using methyl 2-bromo-5-methoxybenzoate in place of methyl 2-bromo-5-fluorobenzoate in the step (b), and reaction times of 2 hours, 2 hours and 1 hour for steps (b), (c) and (d), respectively. 1 H NMR (500 MHz, CDCl 3) d 1.44 (s, 9 H), 3.83 (s, 3 H), 4.04 (d, 2 H), 4.27 (d, 2 H) 5.76 (br s, 1 H), 6.83 (dd, 1 H) ), 7.03 (d, 1H), 7.24 (d, 1H).

PREPARATION 8 r2- (AMINOMETHYL) -4-METHYLBENCIL1CARBAMATE OF 7? R7-BUTYL The base compound was prepared by a method analogous to that described in the above preparation 6, using 2-doro-5-methylbenzoic acid in place of 2-bromo-5-fluorobenzoic acid in step (a), and the following variations to the procedures: (I) in step (b), the mixture was initially refluxed for 18 hours, then an additional portion of CuCN (1 equiv.) was added and the reaction mixture was further refluxed for 16 hours. hours; (II) in step (e), toluene: ethyl acetate (15: 1) was used for chromatography; and (III) in step (f), no precipitate was formed and the purification was directly performed directly after the concentration of the reaction mixture. NMR with 1H (500 MHz, CDCl 3) d 1.46 (s, 9H), 2.36 (s, -3H), 3.92 (s, 2H), 4 35 (d, 2H), 5.98 (br s, 1H), 7.08 ( d, 1H), 7. 13 (s, 1H), 7.24 (d, 1H).

PREPARATION 9 r2- (AMINOMETIL) -4- (TRIFLUOROMETHYL) BENZYLLCARBAMATE OF TER7-BUTYL The base compound was prepared by an analogous method to that described in Preparation 6 above, using 2-chloro-5- (trifluoromethyl) benzoic acid in place of 2-bromo-5-fluorobenzoic acid in step (a), and the following variations in the procedure: (I) in step (b), the reaction mixture was refluxed for 3 days and the purification with chromatography was with heptane: ethyl acetate (15: 1); (II) In step (e), the crude product was not purified before using it in step (f); and (III) in step (f), the reaction mixture was stirred for 24 hours. 1 H NMR (500 MHz, CDCl 3) d 1.48 (s, 9 H), 3.98 (s, 2 H), 4.36 (s, 2 H), 7.50 (d, 1 H), 7. 56 (d, 1 H), 7.72 (s) , 1 HOUR) EXAMPLES EXAMPLE 1 Unless otherwise indicated, compounds (i) through (xxxvi) listed below, were prepared from the corresponding compounds of Preparation 2 by the Next General Method. Sodium hydroxide (29 mg, 0.71 mmol) was added to a solution of the specific ester (0.24 mmol, see Preparation 2 above) in THF: water: methanol (3 mL, 2: 2: 1) and the mixture was stirred of the reaction at room temperature for 3 hours. The mixture was acidified (HCl, 1 M) to a pH-2 and extracted with ethyl acetate (3 x 5 mL). The combined organic layers were dried (Na2SO), filtered and the solvent was evaporated under reduced pressure. The residue (the carboxylic acid) was used without further purification. DIPEA (125 mL, 0.71 mmol) and the specific amine (0.31 mmol, see List 5 above) were added to the crude carboxylic acid (see above) in DMF (4 mL) at 0 ° C. After 30 minutes, EDC (69 mg, 0.36 mmol) and HOBt (49 mg, 0.36 mmol) were added and the reaction mixture was stirred at 0 ° C for 1 hour and then at room temperature for 2 days. The DMF was removed under reduced pressure. NaHCO3 (sat., 2mL) was added and the aqueous layer was extracted with ethyl acetate (3 x 5 mL). The combined organic layers were dried (Na2SO), filtered and the solvent was evaporated under reduced pressure. Purification by flash chromatography (SiO2, 5% methanol in ethyl acetate) gave the amides listed in (i) to (xv) below as oils. Yields after two steps for these amides were 68-84%. (i) benzylic acid ester [amino- (4- {[2- (4-methyl-2-oxo-1-fe nylmethanesulfo nylamino-1,2-d-hydro pyridin-3-yl) to cethylamino ] methyl.}. - phenyl) methylene or] carbamic NMR with 1H (400 MHz, CD3OD) d 2.21 (3H, s), 3.35 (2H, s), 4.39 (2H, s), 4.43 (2H, s), 5.18 (2H, s) , 6.17 (1H, d), 7.26-7-55 (13H, m), 7.69 (2H, d) (ii) benzylic ester of [amino- (4- ({[2- (1- benzenes ulphonylamino-4-methyl-l-2-oxo-1,2- dihydropyridin-3-yl) acetylamino] methyl.} phenyl) methylene] carbamic NMR with 1H (400 MHz, CDCl 3) d 2.11 (s, 3H ), 3.29 (s, 2H), 4.25 (s, 2H), 5.21 (s, 2H), 6.11 (d, 1H), 6.91-7.70 (m, 18H), 10.05 (br s, 1H). (iii) benzyl ester of acid. { amino- [4- ( { 2- [1- (4-methoxybenzenesulfonylamino) -4-methyl-2-oxo-1,2-dihydropyridin-3-yl] acetylamino} methyl]) pheni I] methylene} carbamic NMR with 1H (400 MHz, CD3OD) d 2.18 (3H, s), 3.36 (2H, s), 3.72 (3H, s), 4.32 (2H, s), 5.18 (2H, s), 6.17 (1H, d), 6.91 (2H, d), 7.26-7. 54 (9H, m), 7.61 (2H, d), 7.69 (2H, d) (iv) benzyl ester of acid. { Amino- [4- ( { 2- [1- (2-methoxy-4-methyl-benzenesulfonylamino) -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl-acetylamino}. methyl) phenyl] methylene} -carbamic NMR with 1H (400 MHz, CDCI3) d 2.19 (s, 3H), 2.33 (s, 3H), 3.38 (s, 2H), 3.92 (s, 3H), 4.32 (s, 2H), 5.19 (s, 2H), 6.20 (d, 1H), 6.73 (d, 1H), 6.97 (s, 1H) ), 7.30-7.38 (m, 5H), 7.41 (d, 2H), 7.48 (d, 1H), 7.54 (d, 1H), 7.80 (d, 2H) (v) benzyl ester of acid. { amino- [4- ( { 2- [1- (3,4-dichlorobenzenesulfonylamino) -4-methyl-2-oxo-1,2-dihydropyridin-3-yl] to cethylamine} methyl) phenyl] methylene or} carbon. NMR with 1H (400 MHz, CDCl 3) d 2.22 (s, 3 H), 3.38 (s, 2 H), 4.34 (s, 2 H), 5.19 (s, 2 H), 6.21 (d, 1 H), 7.29-7. 36 (m, 5H), 7.41-7.66 (m, 3H), 7.55 (s, 2H), 7.78 (d, 1H), 7.83 (s, 1H) (vi) benzyl acid ester. { Amino- [4- ( { 2- [1- (3-methoxybenzenesulfonylamino) -4-methyl-2-oxo-1,2-dihydropyridin-3-yl] acetylamine.} Methyl) phenyl] methylen } carbamic NMR with 1H (400 MHz, CD3OD) d 2.30 (s, 3H), 3.30 (s, 2H), 3.70 (s, 3H), 4.25 (d, 1H), 5.20 (s, 2H), 6.17 (d , 1H), 6.89 (br s, 1H), 7.04 (d, 1H), 7.13-7, 37 (m, 7H), 7.43 (d, 2H), 7.48 (d, 1H), 7.71 (d, 2H) (vii) benzylic acid ester { amino- [4- (. {2- 2- (2,5-dimethyl-benzenesulfon-lamino) -4-methyl-2-oxo-1,2-dlhydropyridin-3 -iI] acetylamino.} methyl) phenyl] methylene.). -carbamic NMR with 1H (400 MHz, CDCl 3) d 2.23 (s, 3H), 2.30 (s, 3H), 2.60 (s, 3H), 3.35 (s, 2H), 4.27 (d, 2H), 5.20 (s, 2H), 6.12 (d, 1H), 6.91 (br s, 1H), 7.11-7.49 ( m, 11H), 7.77 (d, 2H). (viii) benzyl ester of amino- [4- (2- [4-methyl-1- (naphthalene-1-sulfonylamino) -2-oxo-1,2-dihydropyridin-3-yl] acetylamino} methyl) phenyl] methylene} carbamic NMR with 1H (400 MHz, CDCl 3) d 2.19 (s, 3H), 3.15 (s, 2H), 4.11 (s, 2H), 5.17 (s, 2H), 5.99 (d, 1H), 7.00 (d, 4H), 7.26-7.51 (m, 8H), 7.60 (d, 2H), 7.83 (d, 1H), 7.99 (d, 2H), 8.56 (br d, 1H) (ix) acidic-butyl ester [ 4-chloro-2- (. {2- [4-metll-1- (naphtha-1-yl-l-ynylamino) -2-oxo-1,2-dihydro-pyridyl-3-yl] acetylamino .}. methyl) benzyl] carbamic The specific ester (0.47 mmol) was hydrolysed as described in General Method C above, except that the volume of the solvent was 5 mL and the reaction time was 5.5 hours. The resulting crude carboxylic acid (0.06 mmol) was dissolved in DCM (1 mL) and TEA (2 eq.) And the specific amine (1 eq., See List 5 above) were added. The mixture was cooled to 0 ° C and PyBOP (1 equiv.) Was added. The reaction mixture was stirred at 0 ° C for 30 minutes and then allowed to warm to room temperature and further stirred overnight. Additional portions of TEA (2 equiv.), Amine (0.4 equiv.) And PyBOP (0.3 equiv.) Were added and the reaction was stirred for 4 hours. The solvent was removed under reduced pressure and the residue was purified by chromatography (SiO2, 5% methanol in DCM) to give the product (89%). 1 H NMR (500 MHz, CDCl 3) d 1.49 (s, 9 H), 2.29 (s, 3 H), 3.12 (s, 2 H), 4.14 (br s, 2 H), 4.21 (br s, 2 H), 6.14 (d , 1H), 6.74 (t, 1H), 7.21 (bs, 2H), 7.45 (t, 1H), 7.56-7.64 (m, 2H), 7.88-7.93 (m, 1H), 8.08 (d, 1H), 8.11 (d, 1H), 8.62 (br s, 1H) (x) benzylic acid ester [amino- (4 { [2- (4-methyl-2-oxo-1-phenethylamino-1, 2- dihydropyridin-3-yl) acetyl amino] methyl] phenyl) methylene] carbamic NMR with 1H (400 MHz, CD3OD) d 2.32 (s, 3H), 2.81 (t, 2H, J = 7.4 Hz), 3.20 (q, 2H, J = 7.5 Hz), 3.58 (s, 2H), 4.37 (d, 2H, J = 6.0 Hz), 5.20 (s, 2H), 6.09- 6.13 (m, 2H), 7.03-7.78, (m, 15H), 9.50 (br s, 1H). (xi) benzyl ester of acid. { amino- [4- (2- [4-methyl-2-oxo-1- (2-o-tolylethyl-amino) -1, 2-di-idro-pyridin-3-yl] -acetylamino} methyl) phenyl] methyleneocarbamic NMR with 1H (400 MHz, CDCI3) d 2.24 (s, 3H), 2.32 (s, 3H), 2.79 (t, 2H), 3.14 (q, 2H), 3.58 (s, 2H), 4.35 (d, 2H), 5.20 (s, 2H), 6.12 (d, 1H), 7.06-7.13 (m, 4H), 7.15 (d, 2H), 7.28-7.37 (m, 4H), 7. 43 (d, 2H), 7.66 (d, 3H). (xii) benzylic acid ester (amino-. {4 - [(2- {1- [2- (2,5-dimethylphen I) etiimethyl] -4-methyl-2-oxo- 1,2-dihydro-pyridin-3-yl.}. Α-cedylamino) methyl] phenyl}. M ethylene) carbamic NMR with 1H (400 MHz, CDCl 3) d 2.20 (s, 3H), 2.25 (s, 3H), 2.31 (s, 3H), 2.76 (t, 2H), 3.14 (q, 2H), 3.58 (s, 2H), 4.35 (d, 2H), 5.19 (s, 2H), 6.11 (d, 1H), 6.18 (s, 1H), 6.91 (d, 2H), 7.00 (d, 1H), 7.14 (d, 2H), 7.26-7.36 (m, 5H), 7.43 (d, 2H), 7.67 (d, 3H), 9.27 (br s, 1H) (xiii) ε-butyl acid ester. { 5 - [(2- { 1- [2- (5-fluoro-2-methylphen i I) and the meth] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl .}. α-Cetylamino) methyl] pyridin-2-yl} Carbamoyl NMR with 1H (400 MHz, CDCl 3) d 1.52 (s, 9H), 2.19 (s, 3H), 2.34 (s, 3H), 2.75 (t, 2H), 3.12-3.14 (m, 2H), 3.56 (s, 2H), 4.28 (d, 1H), 6.12 (d, 2H), 6.79 (s, 1H), 6.83 (d, 1H), 7.05 (d, 1H), 7.33 (d, 1H), 7.46-7.48 (m, 1H), 7.55 (s, 1H), 7.83 (d, 1H), 8.1 (d, 1H), 8.76 (s, 1H) (xiv) urea-butyl acid ester. { 5 - [(2- { 4-methyl-2-oxo-1 - [2- (2-trifluoromethylphenyl) ethylamino] -1,2-dihydropyridin-3-yl} acetylamino) methyl] pyridin-2-yl} carbamic NMR with 1H (400 MHz, CDCl 3) d 1.52 (s, 9H), 2.35 (s, 3H), 2.86-2.89 (m, 2H), 3.22-3.26 (m, 2H), 3.56 (s, 2H), 4.31 (d, 2H), 6.12 (d, 2H), 7.31 (d, 2H), 7.39-7.42 (m, 2H), 7.48-7.50 (m, 2H), 7.52-7.54 (m, 2H), 7.88 ( d, 1H), 8.09 (s, 1H), 8.26 (s, 1H). (xv) 2-1- [2- (5-Chloro-2-fluorophenyl) ethylamino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} -? / - (3-fluoro-4-methylpyridin-2-ylmethyl) acetamide NMR with 1H (400 MHz, CDCI3) d 2.21 (s, 3H), 2.32 (s, 3H), 2.81 (t, 2H), 3.25 (t, 2H), 3.65 (s, 2H), 4.55 (s, 2H), 6.08 (d, 1H), 6.17 (br s, 1H), 6.93, 6.99 (m, 2H), 7.14-7. 18 (m, 2H), 7.31 (d, 1H), 7.82 (br s, 1H), 8.1 (br s, 1H) (xvi). { 2 - [( { [1- (benzylamino) -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl] acetyl} amino) methyl] -4-chlorobenzyl} urea-butyl carbamate The corresponding ester of Preparation 2 was hydrolyzed with sodium hydroxide as described in the above General Method. The amide coupling was then performed as described with respect to Example 1 (ix) above, except without the extra addition of reagents. The crude residue was purified by flash chromatography and preparative HPLC to give the desired product. NMR with 1H (500 MHz, CDCl 3) d 1.46 (s, 9H), 2.36 (s, 3H), 3.61 (s, 2H), 4.08 (d, 2H), 4.27-4.32 (m, 2H), 4.39 (d , 2H), 5.34 (br s, 1H), 6.03 (d, 1H), 6.38 (br s, 1H), 7.13-7.20 (m, 3H), 7.24-7.37 (m, 6H), 7.61 (br s, 1 HOUR).

MS m / z 525.2 (M + H) + (xvi i) ((E) - { [2- ( { [1- (benzylamino) -4-methyl-2-oxo-1,2-di idropyridin-3-yl] acetyl} amino) ethoxy] amino.}. methyltridene) -bis-di-butyl-biscarbamate The compound was prepared according to the method described with respect to Example (xvi) above, except that no preparative HPLC was needed to provide the desired product in a sufficiently pure form. NMR with 1H (500 MHz, CDCl 3) d 1.50 (s, 18H), 2.32 (s, 3H), 3.53 (q, 2H), 3.61 (s, 2H) 4.10 (t, 2H), 4.12 (d, 2H) , 5.99 (d, 1H), 6.43 (t, 1H), 7.15 (d, 1H), 7.29-7.38 (m, 5H), 7.67-7.72 (m, 1H), 8.02 (s, 1H), 9.09 (s) , 1 HOUR). MS m / z 573.6 (M + H) + (xviii). { 5- [([1 - (benzylamine) -4- methyl I-2-OXO-1, 2-dihydro-pyridin-3-yl] acetyl] amino) methyl] -6-methylpyridin-2 -il} urea-butyl carbamate. The corresponding ester of Preparation 2 was hydrolyzed as described in the General Method above, except that the reaction mixture was stirred overnight. The amide coupling was performed as described with respect to Example 1 (ix) above, but without the extra addition of reagents and with the use of TBME: methanol (97: 3) as eluent for chromatography. NMR with 1H (500 MHz, CDCl 3) d 1.49 (s, 9H), 2.33 (s, 3H), 2.35 (s, 3H), 3.59 (s, 2H), 4.01 (d, 2H), 4.31 (d, 2H), 6.01 (d, 1H), 6.27 (t, 1H), 7.07 (br s, 1H), 7.16 (d, 1H), 7.27-7. 35 (m, 4H), 7. 40 (d, 1H), 7.44 (t, 1H), 7.63 (d, 1H). (xix) (4-chloro-2-. {[[(. {4-methyl-2-oxo-1 - [(2-phenylethyl) amino] -1,2-dihydro-pyridin-3-yl}. acetic) amin or] methyl butyl} benzyl) carbamate The corresponding ester of Preparation 2 was hydrolysed as described in the General Method above, except that the reaction mixture was stirred overnight. Then the amide coupling reaction was performed as described with respect to Example 1 (ix) above, except that the amine (0.1 equiv.) Was the only reagent added in the extra addition step, and the mixture of the reaction for 4 hours. The crude product was purified by preparative HPLC. NMR with 1H (500 MHz, CDCI3) d 1.46 (s, 9H), 2.36 (s, 3H), 2.85 (t, 2H), 3.24 (q, 2H), 3.59 (s, 2H), 4.20-4. 30 (m, 2H), 4.37 (d, 2H), 5.28 (br s, 1H), 6.12-6.20 (m, 2H), 7.10 (s, 1H), 7.14 (d, 1H), 7.19-7 . 26 (m, 4H), 7.28-7. 33 (m, 2H), 7.36 (d, 1H), 7.60 (br s, 1H). MS m / z 539 (M + H) + (xx) (6-methyl-5. {[[(. {4-methyl-2-oxo-1 - [(2-phenylethyl) amino] -1, 2-dihydropyridin-3-yl.}. Acetyl) amino] methyl.}. Pyridin-2-yl) carbamate tert-butyl ester. The corresponding ester of Preparation 2 was hydrolyzed as described in the General Method above, except that the reaction mixture was stirred overnight. The amide uptake reaction was then performed as described with respect to Example 1 (ix) above, except that the amine (0.1 equiv) was the only reagent added in the extra addition step, and stirred the reaction mixture for 3 hours. The crude product was purified by preparative HPLC. NMR with 1H (500 MHz, CDCl 3) d 1.52 (s, 9H), 2.34 (s, 3H), 2.36 (s, 3H), 2.84 (t, 2H), 3.21 (q, 2H), 3.58 (s, 2H) ), 4.30 (d, 2H), 6.10 (t, 1H), 6.13 (d, 1H), 7.14 (s, 1H), 7.19-7. 26 (m, 3H), 7.29-7. 40 (m, 4H), 7.44 (t, 1H), 7.63 (d, 1H). MS m / z 507 (M + H) + (xxi) (4-chloro-2-. {[[( { 1 - [(3-methoxy benzyl) amino] -4-methyl 1-2- oxo-1, 2-dihydropyridin-3-yl.}. acetyl) amino] methyl} benzyl) carbamic acid-butyl ester The corresponding compound of Preparation 2 was hydrolyzed as described in the General Method above. Then the amide coupling reaction was performed as described with respect to Example 1 (ix) above, except that 1.3 equivalents of the specific amine were used, and no extra reagents were added. NMR with 1H (500 MHz, CDCl 3) d 1.44 (s, 9H), 2.33 (s, 3H), 3.60 (s, 2H), 3.80 (s, 3H), 4.05 (d, 2H), 4.28 (d, 2H), 4.38 (d, 2H), 5.40 (br s, 1H), 6.03 (d, 1H), 6.39 (br s, 1H), 6.84-6.88 (m, 3H), 7.26-7.24 (m, 5H) 7.61 (br s, 1H). MS m / z 557 (M + H) + (xxi i) (5 - [( { 1 - [(3-methoxy benzyl) am i no] -4-methyl-2-oxo-1, 2 < RTI ID = 0.0 > dihydropyridin-3-yl} < / RTI > acetyl) amino] methyl, butyl, butyl, -6-methylpyridin-2-yl) carbamic acid. The corresponding ester of Preparation 2 was hydrolyzed as described in the General Method. Then the amide coupling reaction as described in the General Method, except that TEA was used instead of DIPEA and HOAt instead of HOBt. NMR with 1H (500 MHz, CDCl 3) d 1.50 (s, 9H), 2.33, (s, 3H), 2.34 (s, 3H), 3.40 (s, 2H), 3.80 (s, 3H), 4.00 (d, 2H), 4.30 (d, 2H), 6.02 (d, 1H), 6.36 (t, 1H), 6.83-6.87 (m, 3H), 7.20 (d, 1H), 7.23 (t, 1H), 7.38 (d , 1H), 7.40 (s, 1H), 7.48 (t, 1H), 7.63 (d, 1H) MS m / z 522 (M + H) + (xxiii) (4-chloro-2- { [( {4-met l-2-oxo-1 - [(pyrid-n-3-ylmethyl) -amino] -1,2-dihydropyridin-3-yl} acetyl) amino] methyl. benzyl) -ery-butyl carbamate. The corresponding ester from Preparation 2 was hydrolyzed with lithium hydroxide (1 M aqueous, 1.5 equiv.) In THF: MeOH (1: 1) and the crude carboxylate was coupled with the specific amine (see List 5 above) in accordance with the procedure described in the previous General Method, except that TEA was used instead of DIPEA and HOAt instead of HOBt. NMR with H (500 MHz, CDCl 3) d 8.56 (d, 1H), 8.53 (s, 1H), 7.64 (d, 1H), 7.52 (s, 1H), 7.24-7.31 (m, 2H), 7.12-7.21 (m, 3H), 6.35 (br s, 1H), 6.04 (d, 1H), 5.35 (br s, 1H), 4.40 (d, 2H), 4.29 (d, 2H), 4.12 (d, 2H), 3.59 (d, 2H), 2.34 (s, 3H), 1.44 (s, 9H). . MS m / z 528 (M + H) + (xxiv) (6-methyl-5. {[[(. {4-methyl-2-oxo-1 - [(pyridin-3-methyl) amino] ] -1, 2-dihydropyridin-3-yl.} -acetyl) amine] methyl]. Pyridin-2-yl) -ery-butyl carbamate It was prepared according to the procedure described with respect to Example 1 (xxi ii) above. 1 H NMR (400 MHz, CDCl 3) d 8.52-8. 60 (m, 2H), 7.58- 7.68 (m, 2H), 7.34-7.44 (m, 2H), 7.25-7.30 (m, 1H), 7.16 (d, 1H), 6.26-6.34 (m, 1H), 6.04 (d, 1H), 4.32 (d, 2H), 4.05 (d, 2H), 3.59 (s, 2H), 2.36 (s, 6H), 1.50 (s, 9H). MS m / z 493 (M + H) + (xxv) [5- ( { [(1-. {[[(2-methoxypyridin-3-yl) methyI] amino.} -4-methyl-2-oxo 1,2-Dihydropyridin-3-yl) acetyl] amino.}. Methyl) -6-methyl-pyridin-2-yl-butylcarbamate was prepared according to the procedure described with respect to Example 1 (xxiii) above . NMR with 1H (400 MHz, CDCl 3) d 8. 11 (dd, 1H), 7.63 (d, 1H), 7.36-7. 45 (m, 3H), 7.24 (d, 1H), 7.19 (bs, 1H), 6.81 (dd, 1H), 6.57 (t, 1H), 6. 08 (d, 1H), 4.29 (d, 2H) , 4.06 (d, 2H), 3.94 (s, 3H), 3.57 (s, 2H), 2.34-2. 37 (m, 6H), 1.50 (s, 9H) MS m / z 523 (M + H) + (xxvi) [4-chloro-2- ( { [(1- { [(2-methoxypyridin -3-yl) methyl] amine.} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetyl] amino.} Methyl) benzyl] carbamate was prepared in accordance with the procedure described in Example 1 (xxiii) above. NMR with 1H (500 MHz, CDCl 3) d 8.10 (dd, 1H), 7.57 (bs, 1H), 7.38 (d, 1H), 7.10-7.26 (m, 4H), 6.80 (dd, 1H), 6.63 (bs, 1H), 6.08 (d, 1H), 5.38 (bs, 1H), 4.36 (d , 2H), 4.28 (bd, 2H), 4.10 d, 2H), 3. 93 (s, 3H), 3.57 (s, 2H), 2.34 (s, 3H), 1.44 (s, 9H). (xxvii) 2- (1-. {[[(2-methoxypyridin-3-yl) methyl] amino.} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) - - [2 - (1H-tetrazol-1-yl) benzyl] acetamide It was prepared according to the procedure described in Example 1 (xx? Ii) above. The crude compound was then purified by preparative HPLC. NMR with 1H (500 MHz, CD3OD) d 9.54 (s, 1H), 8.04 (dd, 1H), 7.60-7.67 (m, 2H), 7.51-7.57 (m, 2H), 7.47 (d, 1H), 7.41 (d, 1H), 6.87 (dd, 1H), 6.19 (d, 1H), 4.23 (s, 2H), 4.16 (s, 2H), 3.90 (s, 3H), 3.49 (s, 2H), 2.21 ( s, 3H) MS m / z 461 (M + H) + (xxvii i). { 5 - [([1- (benzylamino) -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl] acetyl} amino) methylene] -4,6-d meti I pirid in-2-M} urea-butyl carbamate. It was prepared according to the procedure described in Example 1 (xxii) above. NMR with 1H (500 MHz, CDCl 3) d 1.48 (s, 9H), 2.29 (s, 3H), 2.33 (s, 3H), 2.40 (s, 3H), 3.54 (s, 2H), 3.94 (d, 2H) ), 4.34 (d, 2H), 5.99 (d, 1H), 6.19 (t, 1H), 7.04 (br s, 1H), 7.14 (d, 1H), 7.23-7.28 (m, 3H), 7.29-7.35 (m, 3H), 7.56 (s, 1H) MS m / z 506 (M + H) + (xxix) 2- [1 - (benzylamino) -4-methyl-2-oxo-1,2-dihydropyridine -3-yl] - / - [2- (1H-tetrazol-1-yl) benzyl] acetamide It was prepared according to the procedure described in Example 1 (xxii) above. 1 H NMR (500 MHz, CDCl 3) d 2.27 (s, 3 H), 3.53 (s, 2 H), 4.10 (d, 2 H), 4.20 (d, 2 H), 6.01 (d, 1 H), 6.36 (t, 1 H) ), 7.19 (d, 1H), 7.27-7.35 (m, 6H), 7.43 (m, 1H), 7.50-7.63 (m, 3H), 8.96 (s, 1H) MS m / z 430 (M + H) + (xxx)? / - [(6-amino-2,5-dimethylpyridin-3-yl) metii] -2-. { 1 - [(3-methoxy-benzyl) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} Acetamide The corresponding ester of Preparation 2 was hydrolyzed as described in the General Method above. Then the amide coupling reaction was performed as described in the above General Method, except that 1.5 equivalents of the specific amine was used (see List 5 above) and that TEA was used in place of DIPEA and HOAt was used instead. of HOBt. NMR with 1H (400 MHz, CDCl 3) d 2.07 (s, 3H), 2.24 (s, 3H), 2.31 (s, 3H), 3.60 (s, 2H), 3.78 (s, 3H), 4.07 (s, 2H) ), 4.24 (d, 2H), 6.15 (d, 1H), 6.83-6.91 (m, 3H), 7.22 (t, 2H), 7.34 (d, 1H) MS m / z 436 (M + H) + ( xxxi) (4-methoxy-2-. {[[({4-methy1-2-oxo-1 - [(pyridin-3-yl-methyl) amino] -1,2-dihydropyridin-3 ethyl) amino] methyl] benzyl) carbamate was prepared according to the procedure described in Example 1 (xxi ii) above. NMR with 'H (400 MHz, CDCl 3) d 1.45 (s, 9H), 2.34 (s, 3H), 3.59 (s, 2H), 3.71 (s, 3H), 4.02 (d, 2H), 4.24-4. 29 (m, 2H), 4.40 (d, 2H), 5.29 (br s, 1H), 6.01 (d, 1H), 6.32 (br s, 1H), 6.73 (d, 1H), 6.77 (br s, 1H), 7.12 (d, 1H) , 7.23 (d, 1H), 7.45 (br s, 1H), 7.63 (d, 1H), 8.52 (s, 1H), 8.56 (d, 1H) MS m / z 523 (M + H) + (xxxi i) [2-. { [(. {4-methyl-2-oxo-1 - [(pyridin-3-ylmethyl) amino] -1,2-dihydropyridin-3-yl} acetyl) amino] methyl} -4- (Trifluoromethyl) benzyl] -carbamic acid-butyl ester. It was prepared according to the procedure described in Example (xxiii) above. NMR with 1H (500 MHz, CDCl 3) d 1.45 (s, 9H), 2.34 (s, 3H), 3.60 (s, 2H), 4 * .11 (d, 2H), 4.23-4.40 (m, 2H), 4.46 (d, 2H), 5.41 (t, 1H), 6.04 (d, 1H), 6.34 (br s, 1H), 7.17 (d, 1H), 7.24-7.30 (m, 1H), 7. 38 (br s, 1H), 7.42-7.50 (m, 2H), 7.59 (br s, 1H), 7.64 (d, 1H), 8.52 (s, 1H), 8.56 (d, 1H) MS m / z 560 (M + H) + (xxxi i i) 2-. { 4-met l-2-oxo-1 - [(pyridin-3-i I methyl) amino] -1,2-dihydro-iridin-3-yl} -? / - [(1-trityl-1 H-ben cim id azol-6-i I) meti I] acetamide It was prepared according to the procedure described in Example 1 (xxiii) above. 1 H NMR (500 MHz, CDCl 3) d 2.31 (s, 3 H), 3.49 (s, 2H), 4.09 (d, 2H), 4.16 (d, 2H), 6.02 (d, 1H), 6.25 (t, 1H), 6.34 (s, 1H), 6.99 (t, 1H), 7.04 (d , 1H), 7.12-7. 20 (m, 7H), 7.26-7. 36 (m, 10H), 7.62 (d, 1H), 7.70 (d, 1H), 7.90 (s, 1H), 8.54 (s, 1H), 8.57 (d, 1H) MS m / z 645 (M + H) + (xxxi) (6-. {[[( { 4-methyl-2-oxo-1 - [(pyridin-3-ylmethyl) amino] -1, 2-dihydropyridin-3-ylacetyl) amino] methyl.}. Pyridin-3-yl) carbamate Butyl It was prepared according to the procedure described in Example 1 (xxi i i) above. NMR with 1H (400 MHz, CDCI3) d 8.53 (m, 2H), 8.34 (d, 1H), 7.85 (d, 1H), 7.58-7.68 (m, 2H), 7.25 (m, 1H), 7.07-7.15 (m, 2H), 6.82 (s, 1H), 6.29 (t, 1H), 5.98 (d, 1H), 4.45 (d, 2H), 4.11 (d, 2H), 3.63 (s, 2H), 2.30 (s, 3H), 1.48 (s, 9H) (xxxv) (4-chloro-2- { [( { 1 - [(2,2-difluoro-2-pyridin-2-ylethyl) -amino] -4-methyl-2 oxo-1, 2-dihydropyridin-3-yl.}. acetyl) amino] methyl.} - benzyl) -eryi-butyl carbamate was prepared according to the procedure described in Example 1 (xxiii) above. NMR with 1H (500 MHz, CDCl 3) d 8.64 (d, 1H), 7.84 (t, 1H), 7.70 (d, 1H), 7.52 (bs, 1H), 7.40 (t, 1H), 7.31 (d, 1H), 7.22 (d, 1H), 7.10-7. 17 (m, 2H), 6.37 (bs, 1H), 6. 08 (d, 1H), 5.36 (bs, 1H), 4. 36 (d, 2H), 4.25 (s, 2H), 3.87 (dt, 2H), 3.55 (s, 2H), 2.34 (s, 3H), 1. 44 (s, 9H) (xxxvi) [4-chloro-2- ( { [(1- { [2, 2-difluoro-2- (1-oxidopyridin-2-yl) -ethyl] amino} -4-Methyl-2-oxo-1,2-dihydropyridin-3-yl) acetyl] amino.} .methyl-benzyl] carbamic acid ester To a solution of (4-chloro-2-. { . ( { 1 - [(2,2-difluoro-2-pyridin-2-ylethyl) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl.} Acetyl) amino ] -methyl] -benzyl) -ery butyl carbamate (0.20 mmol, see Example 1 (xxxv) above) in DCE (1 mL) was added mCPBA (0.29 mmol) and the resulting solution was stirred at room temperature for 3 hours. days. Then mCPBA (0.29 mmol) and 4,4'-thiobis (2-éri-butyl-5-methylphenol) (0.03 mmol) were added, together with DCE (1mL) and the resulting mixture was heated to 55 ° C for 4 hours. hours. The reaction mixture was diluted with DCM and washed with NaHCO3 (aqueous) and Na2SO3 (aqueous). The aqueous layer was extracted with DCM and the combined organic layers were dried by a phase separator and concentrated. The base compound was then purified by preparative HPLC. 1 H NMR (400 MHz, CDCl 3) d 8.12 (br s, 1 H), 7.71 (m, 1 H), 7.45 (br s, 1 H), 7.37 (m, 1 H), 7.20-7.26 (m, 2 H), 7.13 -7.19 (m, 2H), 6.33 (bs, 1H), 6.02 (d, 1H), 5.36 (brs, 1H), 4.39 (d, 2H), 4.20-4.31 (m, 4H), 3.56 (s, 2H), 2.32 (s, 3H), 1.45 (s, 9H).

EXAMPLE 2 Unless otherwise indicated, compounds (i) through (xi) listed below were prepared from the corresponding compounds of Example 1 by the General Method A described below.

GENERAL METHOD A Palladium on carbon (10%, 5 mg) and HCl were added (conc., 2-3 drops) to a solution of the specific compound protected with benzylcarbonyl (0.06-0.007 mmol, see Example 1 above) in methanol (2 mL). The suspension was hydrogenated under atmospheric pressure at room temperature for 30 minutes. The suspension was filtered through Celite®, washed with methanol (3 x 5 mL) and the solvent was removed under reduced pressure. The residue was dissolved in a minimum volume of methanol and the deprotected product was precipitated from ethyl acetate. The yields were almost quantitative.

GENERAL METHOD B HCl gas was bubbled through a solution of the specific compound protected with Boc (0.06 mmol, see Example 1 above) in methanol (2 mL) for 5 minutes. The solution was stirred at room temperature for 30 minutes and the solvent was removed under reduced pressure to give the products as solids. The yields were almost quantitative.

GENERAL METHOD C The specific compound protected with Boc (0.04 mmol, see Example 1 above) was dissolved in ethyl acetate saturated with HCl (2 mL) and stirred at room temperature for 30 minutes. The solvent and excess reagents were evaporated under reduced pressure to give the desired product. (i) - (4-ca rba mimidoylbenzyl) -2- (4-meth I-2-OXO-1-fe -nimethane-sulfonylamin or-1,2-dihydro-pyridin-3-yl) to ceta mide The compound was further purified by preparative HPLC to give the final product. NMR with 1H (400 MHz, CD3OD) d 2.26 (s, 3H), 3.66 (s, 2H), 4.46 (s, 4H), 6.23 (d, 1H), 7.26-7. 67 (m, 10H), 8.71 (br s, 1H), 9.13 (br s, 1H). MS m / z 468.1 (M + H) + (ii) 2- (1 -be nce nosulfon i mi non-4-methyl-2-oxo-1,2-dihydro pyridin-3-yl) -? - (4-carbamimidoylbenzyl) to ceta mide. NMR with H (400 MHz, CD3OD) d 2.18 (s, 3H), 3.39 (s, 2H), 4.35 (s, 2H), 6.17 (d, 1H), 7.26-7.66 (m, 9H), 8.70 (br s, 1H), 9.18 (br s, 1H) MS m / z 454.4 (M + H) + (iii)? / - (4-carbamimidoyl benzyl) -2- [1 - (4-m ethoxy be nce n o-sulfonylamino) -4-methyl-2-oxo-1,2-dihydropyridin-3-yl] acetamide NMR with 1H (400 MHz, CD3OD) d 2.21 (s, 3H), 3.31 (s, 2H), 3.72 (s, 3H), 4.32 (s, 2H), 6.17 (d, 1H), 6.85 (d, 2H), 7.26-7.51 (m, 3H), 7.61 (d, 2H), 7.81 (d, 2H), 8.69 (br s, 1H), 9.11 (br s, 1H). MS m / z 484.4 (M + H) + (v)? / - (4-carbamimidoylbenzyl) -2- [1- (2-methoxy-4-methyl-benzenesulfonylamino) -4-methyl-2-oxo-1 , 2-dihydropyridin-3-yl] acetamide NMR with 1H (400 MHz, CDCl 3) d 2.21 (s, 3H), 2.37 (s, 3H), 3.41 (s, 2H), 3.95 (s, 3H), 4.38 (s, 2H), 6.22 (d, 1H), 6.76 (d, 1H), 7.00 (s, 1H), 7.46-7.53 (m , 4H), 7.74 (d, 1H), 8.75 (br s, 2H), 9.25 (br s, 2H) MS n7 / z 498.4 (M + H) + (v)? / - (4-carbamimidoylbenzyl) -2 - [1- (3,4-dichlorobenzene- sulfonylamino) -4-methyl-2-oxo-1,2-dihydropyridin-3-yl] acetamide The compound was further purified by preparative HPLC to give the final product. NMR with 1H (400 MHz, CD3OD) d 2.26 (s, 3H), 3.41 (s, 2H), 4.43 (s, 2H), 6.23 (d, 1H), 7.37-7.93 (m, 9H), 8.73, ( s, 1H), 9.27 (s, 1H) MS m / z 522.0 (M + H) + (vi)? / - (4-carbamimidoylbenzyl) -2- [1- (3-methoxybenzenesulfonylamino) -4-methyl -2-oxo-1, 2-dihydropyridin-3-yl] acetamide NMR with 1H (400 MHz, CD3OD) d 2.22 (s, 3H), 3.39 (s, 2H), 3.78 (s, 2H), 4.39 (s, 2H), 6.26 (d, 1H), 7.15 (d, 1H), 7.23 (d, 2H), 7.36 (t, 1H), 7.47 (t, 3H), 7.74 (d, 2H), 8.11 ( br s, 1 H), 8. 76 (br s, 1 H) MS m / z 482.0 (M + H) + (vii)? / - (4-ca rba mi midoyl benz l) -2- [1 - (2 , 5-dimethylbenzenesulfonylmelamine) -4-methyl-2-oxo-1,2-dihydropyridin-3-yl] acetamide. NMR with 1H (400 MHz, CD3OD) d 2.20 (s, 3H), 2.24 (s, 3H), 2.61 (s, 3H), 3.38 (s, 2H), 4.39 (s, 2H), 6.18 (d, 1H) ), 7.22 (d, 1H), 7.32 (t, 2H), 7.47 (d, 3H), 7.74 (d, 1H), 8.72 (br s, 1H), 9.22 (br s, 1H). MS m / z 482.1 (M + H) + (viii)? / - (4-carbamimidoylbenzyl) -2- [4-methyl-1- (naphthalene-1-sulfonylamino) -2-oxo-1,2-dihydropyridin- 3-yl] acetamide NMR with 1H (400 MHz, CD3OD) d 2.17 (s, 3H), 3.18 (s, 2H), 4.32 (s, 2H), 6.16 (d, 1H), 7.25 (d, 1H), 7.40 (d, 2H), 7.50 (t, 1H), 7.59-7.61 (m, 2H), 7.70 (d, 2H), 7.97-8.01 (m, 1H), 8.07 (d, 1H), 8.17 (d, 1H), 8.57-8.61 (m, 1H) , 8.71 (br s, 1H), 9.18 (br s, 1H) MS m / z 504.1 (M + H) + (ix)? / - (4-carbamimidoylbenzyl) -2- (4-methyl-2-oxo-) 1-phenethylamino-1,2-dihydropyridin-3-yl) acetamide. NMR with 1H (400 MHz, CD3OD) d 2.28 (s, 3H), 2.87 (t, 2H, J = 6.9 Hz), 3.30-3.34 (m, 2H), 3.68 (s, 2H), 4. 48 (s) , 2H), 6. 38 (d, 1H), 7.19-7. 29 (m, 5H), 7.52 (d, 2H), 7.68 (d, 1H), 7.72 (d, 2H), 8.78 (br s, 1H), 9.24 (br s, 1H) MS m / z 418.4 (M + H) + (x)? / - (4-carbamimidoylbenzyl) -2- [4-methyl-2-oxo-1- (2-o-tolylethylamino) -1,2-dihydropyridin-3-yl] acetamide. NMR with 1H (400 MHz, CD3OD) d 1.30 (s, 2H), 2.27 (s, 2H), 2.81 (br s, 2H), 3.15 (br s, 2H), 3.63 (s, 3H), 4.46 (s) , 3H), 6.30 (br s, 1H), 6.97-7.16 (m, 5H), 7.46-7.56 (m, 3H), 7.61 (br s, 1H), 7.68 (d, 2H), 8.71 (br s, 1H), 9.21 (br s, 1H) MS n7 / z 432.4 (M + H) + (xi)? / - (4-carbamimidoylbenzyl) -2-. { 1- [2- (2,5-dimethylphenyl) eti the mino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} acetamide. NMR with 1H (400 MHz, CD3OD) d 2.20 (s, 3H), 2.23 (s, 3H), 2.25 (s, 3H), 2.78 (t, 2H), 3.18 (t, 2H), 3.64 (s, 2H), 4.44 (s, 2H), 6.27 (d, 1H), 6.89 (d , 1H), 6.94-6.99 (m, 1H), 7.44 (d, 2H), 7.58 (d, 2H), 7.66 (d, 2H) MS m / z 446.5 (M + H) + (xii)? / - (2-aminomethyl-5-chlorobenzyl) -2- [4-methyl-1- (naphthalene-1-sulfonylamino) -2-oxo-1,2-dih id ropyridin-3-i I] acetamide The specific amide protected with Boc (0.05 mmol, see Example 1 above) was dissolved in HCl / dioxane (2mL) , 4 M) and stirred at room temperature for 2 hours. The solvent was evaporated under reduced pressure and the residue was purified by chromatography (SiO2, 10% methanol in DCM + 1% TEA). The compound was dissolved in DCM and washed with water (2x), dried by a phase separator and the solvent was evaporated under reduced pressure to give the product. NMR with 1H (500 MHz, CD3OD) d 2.15 (s, 3H), 3.23 (s, 2H), 4.20 (s, 2H), 4.33 (s, 2H), 5.98 (d, 1H), 6.88 (d, 1H), 7.34-7.38 (m, 2H), 7.43 (d, 1H), 7. 48 (t, 1H), 7.59-7.65 (m, 2H), 8.00 (d, 2H), 8.13 (d, 1H), 8.73 (d, 1H) MS m / z 525.2 (M + H) + (xiii)? / - (6-aminopyridin-3-ylmethyl) -2-. { 1- [2- (5-fIuoro-2-methylphenyl) -ethylamino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} acetamide NMR with 1H (400 MHz, CD3OD) d 2.21 (s, 3H), 2.27 (s, 3H), 2.88 (s, 2H), 3.37 (s, 2H), 3.65 (s, 2H), 4.26 (s, 2H), 6.52 (d, 1H), 6.78 (s, 1H), 6.89 (d, 1H), 6.97 (d, 1H), 7.08 (dd, 1H), 7.78-7.88 (m, 4H) MS m / z 424.6 (M + H) + (xiv)? / - (6-a min opirid i n-3-i I meti I) -2-. { 4-methi 1-2-oxo-l - [2- (2-trifluoromethylphenyl) ethylamino] -1,2-dihydropyridin-3-yl} acetamide. NMR with 1H (400 MHz, CD3OD) d 2.23 (s, 3H), 2.81-3.01 (m, 2H), 3.31 (s, 3H), 3.59 (s, 2H), 4.27 (s, 2H), 6.16-6.33 (m, 1H), 6. 95-7.01 (m, 1H), 7.49-7.54 (m, 5H), 7.75-7.81 (m 1H), 7.86-7.93 (m, 1H) MS m / z 460.5 (M + H) + (xv) hydrochloride ? - [2- (aminomethyl) -5-chlorobenzyl] -2- [1- (benzylamine) -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl] to keta measure NMR with 1H (500 MHz, CD3OD) d 2.21 (s, 3H), 3.60 (s, 2H), 4.11 (s, 2H), 4.27 (s, 2H), 4.43 (s, 2H), 6.16 (d, 1H), 7.28-7.39 (m, 7H), 7.42 (d, 1H), 7.46-7.48 (m, 1H) MS m / z 425.2 (M + H) + (xvi) N- [2- ( { [ami no ( imino) methyl] amino.}. oxy) ethyl] -2- [1 - (benzylamino) -4-methyl-2-oxo-1,2-dihydropyridin-3-yl] acetamide. It was prepared according to the General Method C above, except that the reaction was stirred for 7 hours at room temperature. 1 H NMR (500 MHz, CD3OD) d 2.27 (s, 3 H), 3.52 (t, 2 H), 3.61 (s, 2 H), 3.98 (t, 2 H), 4.18 (s, 2 H), 5.51 (s, 1 H) ), 6.22 (d, 1H), 7.29-7. 37 (m, 5H), 7.39 (d, 1H) MS m / z 373. 1 (M + H) + (xvii)? / - [(6-amino-2-methylpyridin-3-yl) methyl] hydrochloride] 2- [1- (benzylamino) -4-methyl-2-oxo-1,2-dihydropyridin-3-yl] acetamide It was prepared according to General Method C above, except that the reaction was stirred for 20 hours at room temperature. NMR with 1H (500 MHz, CD3OD) d 2.22 (s, 3H), 2.51 (s, 3H), 3.58 (s, 2H), 4.13 (s, 2H), 4.26 (s, 2H), 6.15 (d, 1H), 6.82 (d, 1H), 7. 27-7. 36 (m, 6H) 7.7 (d, 1H) MS m / z 392 (M + H) + (xviii)? / - [2- (aminomethyl) -5-chlorobenzyl] -2- hydrochloride. { 4-methyl-2-oxo-1 - [(2-phenylethyl) amino] -1,2-dihydropyridin-3-yl} Acetamide was prepared according to General Method C above, except that the reaction was stirred for 90 minutes at room temperature. NMR with 1H (500 MHz, CD3OD) d 2.24 (s, 3H), 2.86 (t, 2H), 3.32-3.34 (m, 2H), 3.61 (s, 2H), 4.25 (s, 2H), 4.42 (s) , 2H), 6.34 (d, 1H), 7.17-7.25 (m, 3H), 7.26-7.30 (m, 2H), 7.34 (dd, 1H), 7.40-7.47 (m, 2H), 7.63 (d, 1H) ) MS m / z 439 (M + H) + (xix)? / - [(6-amino-2-methylpyridin-3-yl) methyl] -2- hydrochloride. { 4-methyI-2-oxo-1 - [(2-phenylethyl) amino] -1,2-dihydro pyridin-3-yl-acetamide It was prepared according to General Method C above, except that the reaction was stirred for 90 minutes at room temperature. NMR with 1H (500 MHz, CD3OD) d 2.26 (s, 3H), 2.51 (s, 3H), 2.86 (t, 2H), 3.31- 3.34 (m, 2H), 3.60 (s, 2H), 4.27 (s, 2H), 6.34 (d, 1H), 6.81 (d, 1H), 7.17-7 . 25 (m, 3H), 7.26-7. 31 (m, 2H), 7.63 (d, 1H), 7.86 (d, 1H) MS m / z 406 (M + H) + (xx)? / - [2- (aminomethyl) -5-chlorobenzyl hydrochloride] -2-. { 1- [(3-methoxybenzyl) -amin or] -4-methyl-2-oxo-1,2-dihydropyri din-3-yl} acetamide NMR with 1H (400 MHz, CDCl 3) d 2.12 (s, 3H), 3.51 (s, 2H), 3.68 (s, 3H), 4.00 (s, 2H), 4.17 (s, 2H), 4.33 (s, -2H), 6.07 (d, 1H), 6.74-6. 82 (m, 3H), 7.13 (t, -1H), 7.25-7. 29 (m, 2H), 7.34 (d, 1H), 7.37 (s, 1H) MS m / z 457 (M + H) + (xxi)? / - [(6-Amino-2-methylpyridin-3) hydrochloride -yl) methyl] -2-. { 1 - [(3-methoxybenzyl) -amin or] -4-met] 1-2-0X0-1, 2-d i hydro pyridin-3-yl} acetamide NMR with 1H (400 MHz, CDCl 3) d 2.23 (s, 3H), 2.52 (s, 3H), 3.60 (s, 2H), 3.77 (s, 3H), 4.11 (s, 2H), 4.27 (s, 2H), 6.17 (d, 1H), 6.80-6. 92 (m, 4H), 7.23 (t, 1H), 7.37 (d, 1H), 7.87 (s, 1H) MS m / z 422 (M + H) + (xxii)? / - [2- (aminomethyl) -5-chlorobenzyl] -2-. { 4-methyl-2-oxo-1- [(pyridin-3-methylmethyl) amino] -1,2-dihydropyridin-3-yl} Acetamide was prepared according to the General Method C above, except that the reaction was stirred for 3 days at room temperature. NMR with 1H (500 MHz, CD3OD) d 8.92 (s, 1H), 8.82 (d, 1H), 8.66 (d, 1H), 8.08 (dd, 1H), 7.54 (d, 1H), 7.48 (d, 1H), 7.44 (d, 1H), 7.38 (dd, 1H), 6.22 (d, 1H) ), 4.43 (s, 4H), 4.28 (s, 2H), 3.58 (s, 2H), 2.20 (s, 3H) MS m / z 428 (M + H) + (xxiii)? / - [(6- amino-2-methylpyridin-3-yl) methyI] -2-. { 4-methyl-2- oxo-1 - [(pyridin-3-ylmethyl) amino] -1,2-dihydropyridin-3-yl} Acetamide was prepared according to General Method C above, except that the reaction was stirred for 3 days at room temperature. NMR with 1H (500 MHz, CD3OD) d 8.92 (s, 1H), 8.83 (d, 1H), 8.66 (d, 1H), 8.07 (t, 1H), 7.87 (d, 1H), 7.55 (d, 1H), 6.85 (d, 1H), 6.23 (d, 1H), 4.90 (d, 2H) ), 4.44 (s, 2H), 4.26 (s, 2H), 3.56 (s, 2H), 2.53 (s, 3H), 2.19 (s, 3H) MS m / z 393 (M + H) + (xxiv)? - [2- ( aminomethyl) -5-chlorobenzyl] -2- (1- {[[(2-methoxypyridin-3-yl) methyl] amino} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl Acetamide was prepared according to General Method C above, except that the reaction was stirred for 3 days at room temperature. The crude product was purified by preparative HPLC. NMR with 1H (500 MHz, CD3OD) d 8.03 (dd, 1H), 7.52 (dd, 1H), 7.34-7.43 (m, 3H), 7.30 (dd, 1H), 6.85 (dd, 1H), 6.18 (d , 1H), 4.38 (s, 2H), 4.13 (s, 2H), 4.08 (s, 2H), 3.87 (s, 3H), 3.53 (s, 2H), 2.20 (s, 3H), 1.89 ( s, 3H) MS m / z 458 (M + H) + (xxv)? / - [(6-amino-2-methylpyridin-3-yl) methyl] -2- (1- { [( 2-methoxy-p i ridin-3-yl) methyl] amino.} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) -acetamide It was prepared according to the General Method C above , except that the reaction was stirred for 3 days at temperature ambient. The crude product was purified by preparative HPLC. NMR with 1H (500 MHz, CD3OD) d 8.06 (dd, 1H), 7.54 (dd, 1H), 7.37-7. 41 (m, 2H), 6.88 (dd, 1H), 6.41 (d, 1H), 6.20 (d, 1H), 4.23 (s, 2H), 4.15 (s, 2H), 3.90 (s, 3H), 3.54 (s, 2H), 2.34 (s, 3H), 2.23 (s, 3H), 1.97 (s, 3H) MS m / z 423 (M + H) + (xxvi) A / - [(6-amino) hydrochloride -2,4-dimethylpyridin-3-yl) methyl] -2- [5- (benzyamino) -2-methyl-6-oxo-cyclohexa-1,3-diene-1-yl-acetamide It was prepared according to General Method C above, except that the reaction was stirred overnight at room temperature. NMR with 1H (500 MHz, CD3OD) d 2.22 (s, 3H), 2.45 (s, 3H), 2.56 (s, 3H), 3.54 (br s, 2H), 4.11 (br s, 2H), 4.32 (s) , 2H), 6.14 (br s, 1H), 6.68 (s, 1H), 7.27-7.36 (m, 6H) (xxxvi i)? / - [2- (aminomethyl) -5-methoxybenzyl] -2-. { 4-methyl-2-oxo-1 - [(pyridin-3-ylmethyl) amino] -1,2-dihydropyridin-3-yl} Acetamide was prepared according to the procedure described in Example 2 (xxvi) above. NMR with 1H (500 MHz, CD3OD) d 2.24 (s, 3H), 3.61 (s, 2H), 3.75 (s, 3H), 3.80 (s, 2H), 4.18 (s, 2H), 4.42 (s, 2H), 6.15 (d, 1H), 6.80 (d, 1H), 6.89 (s, 1H) ), 7.25 (d, 1H), 7.36 (d, 1H), 7.41 (dd, 1H), 7.84 (d, 1H), 8. 52 (s, 1H), 8.47 (s, 2H) MS m / z 422 (M + H) + (xxxviii)? / - [2- (aminomethyl) -5- (trifiuoromethyl) benzyl] -2-. { 4- methyl-2-oxo-1 - [(pyridin-3-ylmethyl) amino] -1,2-dihydropyridin-3-yl} acetarmide It was prepared according to the procedure described with respect to Example 2 (xxvi) above. NMR with 1H (500 MHz, CD3OD) d 2.23 (s, 3H), 3.62 (s, 2H), 3.94 (s, 2H), 4.20 (s, 2H), 4.51 (s, 2H), 6.17 (d, 1H), 7.39 (d, 1H), 7.40-7. 43 (m, 1H), 7.54- 7.62 (m, 3H), 7.86 (d, 1H), 8.46-8.50 (m, 2H). MS m / z 460 (M + H) + (xxxix)? / - (1 H -benzimidazol-6-ylmethyl) -2-. { 4-methyl-2-oxo-1- [(pyridin-3-ylmethyl) amino] -1,2-dihydropyridin-3-yl} acetamide The compound of Example 1 (xxxiii) above (38 mg, 0.059 mmol) was reacted with TFA: water: thioanisole: 1,2-ethanedithiol (2 mL of 35: 2: 2: 1) for 3 hours. Acetic acid was added to the reaction mixture before the solvent evaporated under reduced pressure. The residue was triturated with diethyl ether and the crude product was purified by preparative HPLC in order to provide the base compound. NMR with 1H (500 MHz, CD3OD) d 2.24 (s, 3H), 3.64 (s, 2H), 4.16 (s, 2H), 4.51 (s, 2H), 6.16 (d, 1H), 7. 24 (d , 1H), 7.35 (d, 1H), 7.38 (dd, 1H), 7.54-7. 58 (m, 2H), 7.78 (d, 1H), 8.13 (s, 1H), 7.44_7. 46 (m, 2H). MS m / z 403 (M + H) + (xl)? / - [(5-aminopyridin-2-yl) methyl] -2-. { 4-methyl-2-oxo-1 - [(pyridin-3-yl-methyl) amino] -1,2-dihydropyridin-3-yl} acetamide It was prepared according to the procedure described in Example 2 (xxvi) above. NMR with 1H (500 MHz, CD3OD) d 8.91 (s, 1H), 8.82 (d, 1H), 8.68 (d, 1H), 8.05-8. 09 (m, 2H), 7.73 (dd, 1H), 7.67 (d, 1H), 7. 58 (d, 1H), 6.28 (d, 1H), 4.58 (s, 2H), 4.49 (s, 2H) , 3.62 (s, 2H), 2.25 (s, 3H) (xli)? / - [2- (aminomethyl) -5-chlorobenzyl] -2-. { 1 - [(2,2-difluoro-2-p i ridin-2-ylethyl) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} Acetamide was prepared according to the procedure described in Example 2 (xxvi) above. NMR with 1H (500 MHz, CD3OD) d 8.73 (m, 1H), 8.21 (m, 1H), 7.95 (m, 1H), 7.73 (m, 1H), 7.45 (m, d, 1H), 7.40-7.44 (m, 2H), 7.35 (dd, 1H), 6.23 (dd, 1H), 4.42 (s, 2H), 4.26 (s, 2H), 3.90 (m, 2H), 3.59 (s, 2H), 2.23 ( s, 3H). MS m / z 474 (M + H) + (xli i)? / - [2- (aminomethyl) -5-chlorobenzyl] -2- (1- {[[2,2-difluoro-2- (1- Oxido-pyridin-2-yl) ethyl] amino.} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetamide. It was prepared according to the procedure described in Example 2 (xxvi) above. NMR with 1H (500 MHz, CD3OD) d 8. 26 (d, 1H), 7.92 (dd, 1H), 7.60-7. 70 (m, 2H), 7.49 (d, 1H), 7.36-7. 43 (m, 2H), 7.16 (d, 1H), 6.05 (d, 1H), 4.43 (s, 2H), 4.26 (s, 2H), 4.20 (m, 2H), 3.54 (s, 2H), 2.20 (s, 3H). MS m / z 492 (M + H) + (xliii)? / - [2- (aminomethyl) -5-chlorobenzyl] -2- (4-met l-2-oxo-1 -. {[[(2-oxo-l, 2-dihydro pyridin) acetate -3-yl) methyl] amino.} -1, 2- dihydro pyridin -3-yl) acetamide It was prepared from the compound of Example 1 (xxvi) using General Method B above and using an extended reaction time. The titled compound was isolated by preparative HPLC. NMR with 1H (500 MHz, CD3OD) d 7.51 (d, 1H), 7.43 (dd, 1H), 7.34-7. 44 (m, 3H), 7.30 (d, 1H), 6.28 (t, 1H), 6.22 (d, 1H), 4.38 (s, 2H), 4.14 (s, 2H), 3.97 (s, 2H), 3.50 (s, 2H), 2.21 (s, 3H), 1.90 (s, 3H). MS m / z 442 (M + H) + EXAMPLE 3 Compounds (i) to (xiii) which are presented below were prepared according to the following General Method. The relevant esters (obtained from Preparation 4 above) were dissolved in THF (4 mL). Aqueous LiOH (2.5 mL of 0.5 M, 1.3 mmol) was added to the resulting solution. The reaction mixtures were stirred at room temperature for 5 to 25 hours. The solvent was then evaporated under reduced pressure to give the corresponding carboxylic acids as lithium salts, which were stored at -80 ° C and used without further purification.

The crude carboxylic acid salts were dissolved in DMF (1 mL) and / V-methylmorpholine (88 μL, 0.8 mmol) was added. TBTU (192 mg, 0.6 mmol) was dissolved in 0.5 mL of DMF and added to each reaction mixture, and then the reaction mixtures were stirred at room temperature for 30 min. Then a solution of 2- [2- (aminomethyl) -4-chlorophenoxy] - / V-ethylacetamide (1 mol equiv, see List 5 above) in DMF (1 mL) was added to each reaction mixture. The reaction mixtures were stirred at room temperature overnight before being filtered and evaporated to dryness. The crude mixtures were purified by preparative HPLC (see above General Experiment Details) to give the amides listed below as oils or solids. The yields after three steps for these amides were from 7 to 29% (Purity> 85%; UV at 215 nm). (i) 2-. { 4-chloro-2 - [( { [1- (isobutylamino) -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl] acetyl} amino) methyl] phenoxy} -? / - ethylacetamide NMR with 1H (500 MHz, DMSO-d6) d 8.29 (t, 1H), 8.04 (t, 1H), 7.56 (d, 1H), 7.26 (m, 2H), 6.92 (d, 1H) ), 6.42 (t, 1H), 6.11 (d, 1H), 4.46 (s, 2H), 4.33 (d, 2H), 3.47 (s, 2H), 3.10 (q, 2H), 2.71 (t, 2H) , 2.12 (s, 3H), 1.68 (m, 1H), 0.99 (t, 3H), 0.92 (d, 6H). MS m / z 463.4 (M + H) + (ii) 2- [4-chloro-2- ( { [(4-methyl-2-oxo-1- { [(1-phenyl-1H- pyrazol-5-yl) methyl] amino.} -1,2-dihydro-pyridin-3-yl) to ce ti I] amino} methyl) f enoxy] -N-ethylacetamide. NMR with 1H (500 MHz, DMSO-d6) d 8.28 (t, 1H), 8.04 (t, 1H), 7.60 (d, 1H), 7.51 (m, 4H), 7.42 (t, 1H), 7.26 (m, 2H), 7.19 (d, 1H), 6.91 (m, 2H), 6.35 (d, 1H) ), 5.99 (d, 1H), 4.46 (s, 2H), 4.32 (d, 2H), 4.22 (d, 2H), 3.44 (s, 2H), 3.09 (q, 2H), 2.09 (s, 3H) , 0.98 (t, 3H). MS m / z 563. (M + H) + (iii) 2-. { 4-chloro-2 - [( { [1- ( { [2,5-dimethyl-1- (4H-1,2,4-triazol-4-yl) -1H-pyrrol-3-yl ] methyl.} amino) -4-methyl-2-oxo-1,2-dihydro pyridin-3-yl] acetyl} amino) methyl] phenoxy} -? / - ethylacetamide. 1 H NMR (500 MHz, DMSO-d 6) d 9.01 (s, 2 H), 8. 32 (t, 1 H), 8.04 (t, 1 H), 7.42 (d, 1 H), 7.26 (m, 2 H), 6.92 (d, 1H), 6.37 (t, 1H), 6.10 (d, 1H), 5.97 (s, 1H), 4.46 (s, 2H), 4.33 (d, 2H), 3.83 (d, 2H), 3.48 (s, 2H), 3.10 (q, 2H), 2.13 (s, 3H), 1.91 (s, 3H), 1.77 (s, 1H), 0.99 (t, 3H). MS m / z 581.5 (M + H) + (i) 2- (1-. {[[(4-benzoyl-1-methyl-1 H -pyrrol-2-yl) methyl] amino.} -4- methyl-2-oxo-1,2-dihydro-pyridin-3-yl) - -. { 5-Ro-2- [2- (et i lamino) -2-oxoethoxy] benzyl} acetamide. NMR with 1H (500 MHz, DMSO-d6) d 8.31 (t, 1H), 8.05 (t, 1H), 7.70 (d, 2H), 7.58 (m, 1H), 7.47 (m, 3H), 7.29 (m, 3H), 6.92 (d, 1H), 6.70 (t, 1H), 6.30 (s, 1H) ), 6.05 (d, 1H), 4.47 (s, 2H), 4.33 (d, 2H), 4.10 (d, 2H), 3.76 (s, 3H), 3.49 (s, 2H), 3.11 (q, 2H), 2.12 (s, 3H), 1.00 (t, 3H). MS / 77 / z 604.5 (M + H) + (v) 2- (4-chloro-2-. {[[( { 1 - [(2,3-dihydro-1-benzofura? / - 5- il meti l) amino] -4meti l-2-oxo-1,2-dihydropyridin-3- il} acetyl) amino] methyl} phenoxy) -? / - ethylacetamide. NMR with 1H (500 MHz, DMSO-d6) d 8.29 (t, 1H), 8.05 (t, 1H), 7.40 (d, 1H), 7.26 (m, 2H), 7.20 (s, 1H), 7.00 (d, 1H), 6.92 (d, 1H), 6.68 (d, 1H), 6.59 (t, 1H), 6.04 (d, 1H), 4.50 (m, 4H), 4.33 (d, 2H), 3.96 (d, 2H), 3.48 (s, 2H) ), 3.12 (m, 4H), 2.11 (s, 3H), 1.00 (t, 3H). MS m / z 538.8 (M + H) + (vi) 2- [4-chloro-2- ( { [(1- { [(2,4-DimetiI-1,3-thiazole-5- il) methyl] am i no.} -4met i l-2-oxo-1,2-dihydropyridin-3-yl) acetyl] amino} methyl) phenoxy] -? / - ethylacetamide. NMR with 1H (500 MHz, DMSO-d6) d 8.29 (t, 1H), 8.05 (m, 1H), 7.28 (m, 2H), 7.22 (d, 1H), 6.92 (d, 1H), 6.84 (t, 1H), 6.01 (d, 1H), 4.47 (s, 2H), 4.33 (d, 2H) ), 4.19 (d, 2H), 3.48 (s, 2H), 3.11 (q, 2H), 2.55 (s, 3H), 2.11 (s, 3H), 2.03 (s, 3H), 1.00 (t, 3H). MS m / z 532.2 (M + H) + (vii) 2- [4-chloro-2- (1 [(1-1 [(1,5-d.methyl-1H-pyrazol-4-yl) methyl] amino.} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetyl] amino} methyl) phenoxy] -? / - ethylacetamide. NMR with H (500 MHz, DMSO-d6) d 8.29 (t, 1H), 8. 05 (m, 1H), 7.36 (s, 1H), 7.36 (d, 1H), 7.26 (m, 2H), 7.20 (s, 1H), 6.92 (d, 1H), 6.39 (t, 1H), 6.05 (d, 1H), 4.47 (s, 2H), 4.33 (d, 2H), 3.86 (d, 2H), 3.67 (s, 3H), 3.48 (s, 2H), 3.11 (q, 2H), 2.13 (s, 3H), 2.12 (s, 3H), 1.00 (t, 3H). MS m / z 514.8 (M + H) + (viii) 2-. { 4-chloro-2 - [( { [4-methyl-2-oxo-1- ( { [1- (phenylsulfonyl) - 1H-pyrrol-2-yl] methyl} amino) -1,2-dihydropyridin-3-yl] acetyl} amino) methyl] -phenoxy} -A / -eti lace t amide NMR with 1H (500 MHz, DMSO-d6) d 8.26 (t, 1H), 8. 04 (t, 1H), 7.96 (d, 2H), 7.27 (t, 1H), 7.61 (t, 2H), 7.43 (dd, 1H), 7.25 (m, 2H), 6.93 (m, 2H), 6.78 (t, 1H) ), 6.23 (t, 1H), 6.10 (m, 1H), 5.96 (d, 1H), 4.47 (s, 2H), 4.32 (d, 2H), 4.23 (d, 2H), 3.44 (s, 2H), 3.10 (q, 2H), 2.08 (s, 3H), 0.99 (t, 3H). MS m / z 626.4 (M + H) + (ix) 2- [4-chloro-2- ( { [(1-. {[[(3,5-dimethylisoxazol-4-yl) methyl] am i No. 4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetyl] amino.} methyl) phenoxy] -? / - ethylacetamide. NMR with 1H (500 MHz, DMSO-d6) d 1.01 (t, 3H), 2.10 (s, 3H), 2.12 (s, 3H), 2.16 (s, 3H), 3.12 (p, 2H), 3.47 (s) , 2H), 3.89 (d, 2H), 4.32 (d, 2H), 4.48 (s, 2H), 6.02 (d, 1H), 6.67 (t, 1H), 6.93 (d, 1H), 7.21-7.31 ( m, 3H), 8.05 (t, 1H), 8.31 (t, 1H). MS m / z 516.4 (M + H) + (x) 2- [4-chloro-2- ( { [(1- { [(4-chloro-2-phenyl-1W-imidazole-5- il) methyl] amino.} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetyl] amino.} methyl) phenoxy] -? / - ethylacetamide. NMR with 1H (500 MHz, DMSO-d6) d 1.01 (t, 3H), 2.11 (s, 3H), 3.13 (p, 2H), 3.49 (s, 2H), 4.12 (d, 2H), 4.33 (d, 2H), 4.48 (s, 2H), 6.02 (d, 1H), 6.91-6.95 (m , 1H), 6.98 (t, 1H), 7.20 (d, 1H), 7.25-7.28 (m, 2H), 7.37 (t, 1H), 7.46 (t, 2H), 7.90 (d, 2H), 8.05 ( t, 1H), 8.31 (t, 1H), 12.98 (s, 1H). MS m / z 539.4 (M + H) + (xi) 2-. { 1 - [(2,1,3-benzoxadiazol-5-ylmethyl) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} -? / -. { 5-Chloro-2- [2- (ethylamino) -2-oxoethoxy] benzyl} -acetamide NMR with 1H (500 MHz, DMSO-d6) d 1.00 (t, 3H), 2.09 (s, 3H), 3.10 (p, 2H), 3.46 (s, 2H), 4.25 (d, 2H), 4.32 (d, 2H), 4.48 (s, 2H), 6.02 (d, 1H), 6.93 (d, 1H), 7.14 (t, 1H), 7.24-7. 28 (m, 2H), 7.45 (d, 1H), 7.68 (d, 1H), 7.83 (s, 1H), 8.00-8. 07 (m, 2H), 8. 28 (t, 1H). MS m / z 539.4 (M + H) + (xii) 2- (4-chloro-2-. {[[(. {4-meti-l-2-oxo-1 - [(pirazi / V-2- ilmethyl) amino] -1,2-dihydropyridin-3-yl}. acetyl) amino] methyl.}. phenoxy) - / \ - ethylacetamide MS m / z 499.4 (M + H) + (xiii) 2- (4 -chloro-2- { [( { 1 - [(cyclopentylmethyl) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl.} acetyl) amino] methyl. phenoxy) -? / ~ ethylacetamide. NMR with 1H (500 MHz, DMSO-d6) d 1.00 (t, 3H), 1.18-1.26 (m, 2H), 1.43-1.59 (m, 4H), 1.69-1.77 (m, 2H), 1.91-1.99 (m, 1H), 2.12 (s, 3H), 2.83 (t, 2H), 3.10 (p , 2H), 3.47 (s, 2H), 4.32 (d, 2H), 4.46 (s, 2H), 6.12 (d, 1H), 6.39 (t, 1H), 6.92 (d, 1H), 7.24-7.28 ( m, 2H), 7.57 (d, 1H), 8.03 (t, 1H), 8.29 (t, 1H). MS m / z 489.4 (M + H) + EXAMPLE 4 Compounds (i) through (xxix) below were prepared according to the following General Method.

The relevant esters (obtained from Preparation 4 above) were dissolved in THF (4mL). Aqueous LiOH (2.5 mL of 0.5 M, 1.3 mmol) was added to the resulting solution. The reaction mixtures were stirred at room temperature for 5 to 25 hours. The solvent was then evaporated under reduced pressure to give the corresponding carboxylic acids as lithium salts, which were stored at -80 ° C and then used without further purification. The crude carboxylic acid salts were dissolved in DMF (1 mL) and? / -methylmorphoin (88 μL, 0.8 mmol) was added. TBTU (192 mg, 0.6 mmol) was dissolved in 0.5 mL of DMF and added to each reaction mixture, and then the reaction mixtures were stirred at room temperature for 30 min. Then a solution of the specific amine (1 mol equiv, see List 5 above) in DMF (1 mL) was added to each reaction mixture. The reaction mixtures were stirred at room temperature overnight before being filtered and evaporated to dryness. The resulting residues (amides protected with Boc) were dissolved in TFA (1.5 mL), stirred at room temperature for 1 hour and then concentrated in vacuo. The crude mixtures were purified by preparative HPLC (see General Details of the above Experiment) to give the amides listed below as oils or solids, the yields after four steps for these amides were from 2 to 47% (Purity> 87%; UV at 215 nm). (i)? / - [2- (aminomethyl) -5-chlorobenzyl] -2- (4-methyl-2-oxo-1-. [(5-pyridin-2-yl-2-thienyl) methyl] amino} -1,2-dihydro pyridin-3-yl) to ce tamide. NMR with H (500 MHz, DMSO-d6) d 2.11 (s, 3H), 3.48 (s, 2R), 3.83 (s, 2H), 4.27-4.35 (m, 4H), 6.03 (d, 1H), 6.91 (d, 1H), 7.03 (t, 1H), 7.24-7.29 (m, 2H), 7.30 (s, 1H), 7.38-7.42 (m, 2H), 7.60 (d, 1H), 7.81 (dt, 1H) ), 7.86 (d, 1H), 8.38 (t, 1H), 8.51 (d, 1H). MS m / z 508.4 (M + H) + (ii)? / - [2- (aminomethyl) -5-chlorobenzyl] -2- (1- { [(5-cioro-1,3-di meti 1 -1 H-pyrazol-4-yl) methyl] amino.} -4-methyl-2-oxo-1,2-dihydro pyridin-3-yl) acetamide NMR with 1H (500 MHz, DMSO-d6) d 2.04 (s, 3H), 2.13 (s, 3H), 3.48 (s, 2H), 3.67 (s, 3H), 3.72 (s, 2H), 3.88 (d, 2H), 4.29 (d, 2H), 6.02 (d, 1H), 6.61 (t, 1H) ), 7.17 (d, 1H), 7.24-7.28 (m, 2H), 7. 39 (d, 1H), 8.32 (t, 1H). MS m / z 476.7 (M + H) + (iii)? / - [2- (aminomethyl) -5-chlorobenzyl] -2- (1- {[[6-cyclo-1,3-benzo dioxol] -5-yl) methyl] amino.} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) -acetamide. NMR with 1H (400 MHz, CDCl 3) d 8.32 (t, 1H), 7.35-7. 41 (m, 2H), 7.24-7.29 (m, 2H), 7.04 (s, 1H), 7.01 (s, 1H), 6.87 (t, 1H), 6.06 (m, 3H), 4.29 (d, 2H) , 4.10 (d, 2H), 3.73 (s, 2H), 3.47 (s, 2H), 2.13 (s, 3H). MS m / z 502.7 (M + H) + (v)? / - [(6-amino-2,4-dimethylpyridin-3-yl) metii] -2- (4-metiI-1- { [ (1-methyl-1H-imidazol-2-yl) methyl] amino.} -2-oxo-1,2-dihydropyridin-3-yl) -acetamide. 1 H NMR (500 MHz, DMSO-d 6) d 7.79 (t, 1 H), 7.18 (d, 1 H), 7.09 (s, 1 H), 6.80 (t, 1 H), 6.74 (s, 1 H), 6.10 (s) , 1H), 5.99 (d, 1H), 5.62 (s, 2H), 4.11 (m, 4H), 3.66 (s, 2H), 2.27 (s, 3H), 2.13 (s, 3H), 2.09 (s, 3H). MS m / z 409.8 (M + H) + (v) A / - [(6-am i no-2,4-dimethyl pyrid i n-3-i l) methyl] -2-. { 1 - [(cyclohexyl-methyl) amin or] -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl} acetamide. 1 H NMR (500 MHz, DMSO-d 6) d 7.76 (t, 1 H), 7.52 (d, 1 H), 6. 41 (t, 1 H), 6.09-6.13 (m, 2 H), 5.65 (s, 2 H) , 4.10 (d, 2H), 3.39 (s, 2H), 2.71 (t, 2H), 2.25 (s, 3H), 2.11 (s, 6H), 1.77 (d, 2H), 1.57-1.71 (m , 3H), 1.39 (m, 1H), 1.10-1.25 (m, 3H), 0.88-0. 98 (m, 2H). MS m / z 412.4 (M + H) + (vi)? / - [(6-amino-2,4-dimethyl pyrid i n-3-yl) methyl] -2- (4-methy1-) { [(4-methyl-3,4-dihydro-2H-1,4-benzoxazyl? / - 7-yl) methyl] amino] -2-oxo-1,2-dihydro pyridine -3- il) acetamide MS m / z 477.5 (M + H) + (vii)? - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2-. { 1 - [(4-Cyano-benz I) am i no] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} acetamide NMR with 1H (500 MHz, DMSO-d6) d 7.74-7.80 (m, 3H), 7. 51 (d, 2H), 7.33-7.37 (m, 1H), 7.06 (t, 1H), 6.10 (s, 1H), 6.00 (d, 1H), 5.63 (s, 2H), 4.15 (d, 2H) , 4.11 (d, 2H), 3.38 (s, 2H), 2.26 (s, 3H), 2.13 (s, 3H), 2.08 (s, 3H). MS m / z 430.8 (M + H) + (viii)? / - [(6-amino-2-methylpyridin-3-yl) methyl] -2-. { 4-metiI-2- oxo-1 - [(2-phenoxybenzyl) amino] -1,2-dihydropyridin-3-yl} acetamide NMR with 1H (500 MHz, DMSO-d6) d 7.95 (t, 1H), 7.45 (d, 1H), 7.25-7.36 (m, 4H), 7.08-7.19 (m, 3H), 6.96 (t, 1H), 6.89 (d, 1H), 6.81 (d, 1H), 6.21 (d, 1H), 6.00 (d, 1H), 5.69 (s, 2H), 4.13 (d, 2H), 4.03 (d, 2H), 3.36 (s, 2H), 2.21 (s, 3H), 2.09 (s, 3H) MS m / z 484.4 (M + H) + (x)? / - [2- (aminomethyl) -5-chlorobenzyl] -2 - (1- {[[1-ethyl-3-methyl-1 H -pyrazol-4-yl) methyl] amino} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl ) -acetamide NMR with 1H (500 MHz, DMSO-d6) d 8.33 (t, 1H), 7.46 (s, 1H), 7.21-7.41 (m, 4H), 6.45 (t, 1H), 6.05 (d, 1H) ), 4.29 (d, 2H), 3.97 (q, 2H), 3.88 (d, 2H), 3.72 (s, 2H), 3.48 (s, 2H), 2.13 (s, 3H), 2. 08 ( s, 3H), 1.28 (t, 3H). MS m / z 456.8 (M + H) + (x)? / - [2- (aminomethyl) -5-chlorobenzyl] -2- (4-methyl-1- { [(4-m ethyl-1 H -imidazol-5-yl) methyl] amino.} -2-oxo-1, 2-d I hydro pyridin-3-yl) acetamide MS m / z 428.8 (M + H) + (xi)? / - [ 2- (aminomethyl) -5-chlorobenzyl] -2- (1- {[[(5-chloro-1-methyl-3-phenyl-1 H -pyrazol-4-yl) methyl] amino} -4 -methyl-2-oxo-1,2-dihydropyridin-3-yl) acetamide. NMR with 1H (500 MHz, DMSO-d6) d 2.11 (s, 3H), 3.46 (s, 2H), 3.73 (s, 2H), 3.80 (s, 3H), 4.05 (d, 2H), 4.30 (d, 2H), 5.97 (d, 1H), 6.85 (t, 1H), 7.08 (d, 1H) ), 7.26 (s, 2H), 7.36-7.41 (m, 3H), 7.44 (t, 1H), 7.78 (d, 2H), 8.33 (t, 1H). MS m / z 538.8 (M + H) + (xii)? / - [2- (aminomethyl) -5-chlorobenzyl] -2- (4-methyl-1- { [(2- morpholino-4-ylpyridin -3-yl) methyl] amino.} -2-oxo-1, 2-dihydro pyridin-3-yl) acetamide. NMR with H (500 MHz, DMSO-d6) d 2.13 (s, 3H), 3.08 (t, 4H), 3.46 (s, 2H), 3.66-3.76 (m, 6H), 4.12 (d, 2H), 4.30 (d, 2H), 6.07 (d, 1H), 6.97-7.04 (m, 2H), 7.23-7.29 (m, 2H), 7.40 (t, 2H), 7.69 (dd, 1H), 8.21 (dd, 1H) ), 8.33 (t, 1H) MS m / z 510.8 (M + H) + (xii i)? / - [2- (aminomethyl) -5-c! Orobenzyl] -2-. { 1 - [(3,3-dimethylbutyl) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} acetamide. NMR with 1H (500 MHz, DMSO-d6) d 0.86 (s, 9H), 1.36 (t, 2H), 2.14 (t, 3H), 2.86-2. 96 (m, 2H), 3.48 (s, 2H), 3.80 (s, 2H), 4.30 (d, 2H), 6.16 (d, 1H), 6.36 (t, 1H), 7.22-7. 29 (m, 2H), 7.39 (d, 1H), 7.60 (d, 1H), 8.37 (t, 1H). MS m / z 419.4 (M + H) + (xiv) A / - [2- (to my nom ethyl) -5-cl benzyl gold] -2- (1- { [(5-cl oro- 2-thienyl) methyl] amino.} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetamide MS m / z 464.7 (M + H) + (xv)? / - [2- (amomethyl) -5-chlorobenzyl] -2-1 - [(3-cyano-4-fluorobenzyl) -amin or] -4-methyl-2-oxo-1,2-dihydro pyridin-3-yl} to ceta mida. NMR with 1H (500 MHz, DMSO-d6) d 2.11 (s, 3H), 3.46 (s, 2H), 3.74 (s, 2H), 4.14 (d, 2H), 4.29 (d, 2H), 6.05 (d, 1H), 7.02 (t, 1H), 7.15-7.20 (m, 1H), 7.22-7.30 (m, 2H), 7.36-7.49 (m, 3H), 7.67- 7. 74 (m, 1H), 7.88 (dd, 1H), 8.32 (t, 1H) MS m / z 467.7 (M + H) + (xvi)? / - [2- (aminomethyl) -5-chlorobenzyl] -2 - (4-Methyl-1- {[[5-methyl-3-phenylisoxazol-4-yl) methyl] amino} -2-oxo-1,2-dihydropyridin-3-yl) -acetamide NMR with 1H (500 MHz, DMSO-d6) d 2.12 (s, 3H), 2.17 (s, 3H), 3.46 (s, 2H), 3.73 (s, 2H), 4.00 (d, 2H), 4.30 (d, 2H) ), 5.99 (d, 1H), 6.87 (t, 1H), 7.14 (d, 1H), 7.24-7.29 (m, 2H), 7.39 (d, 1H), 7.49-7.56 (m, 3H), 7.79- 7.85 (m, 2H), 8.37 (t, 1H). MS m / z 505.8 (M + H) + (xvi i) / V- [2- (aminomethyl) -5-chlorobenzyl] -2- (4-methyl-2-oxo-1- { [3- ( trifluoromethoxy) benzyl] amino.} -1, 2-dihydropyridin-3-yl) acetamide. 1 H NMR (500 MHz, DMSO-d 6) d 2.11 (t, 3 H), 3.47 (s, 2 H), 3.83 (s, 2 H), 4.16 (d, 2 H), 4.30 (d, 2 H), 6.04 (d , 1H), 6.96 (t, 1H), 7.23-7.37 (m, 6H), 7.38-7.49 (m, 4H), 8.38 (t, 1H). MS m / z 509.4 (M + H) + (xviii)? / - [2- (aminomethyl) -5-chlorobenzyl] -2-. { 1 - [(5-chloro-2-fluoro-benzyl) to ino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} acetamide NMR with 1H (500 MHz, DMSO-d6) d 2.12 (s, 3H), 3.46 (s, 2H), 3.86 (s, 2H), 4.14 (d, 2H), 4.29 (d, 2H), 6.07 ( d, 1H), 6.98 (t, 1H), 7.22 (t, 1H), 7.25-7.29 (m, 2H), 7.35-7.44 (m, 3H), 7.49 (dd, 1H), 8.35 (t, 1H) . MS m / z 477.3 (M + H) + (xix)? / - [2- (aminomethyl) -5-chlorobenzyl] -2- (4-methyl-1-. {[[(2-met i 1-1 H-imidazol-5-yl) methyl] amino.} -2-oxo-1,2-dihdropiridin-3- il) acetamide. NMR with 1H (500 MHz, DMSO-d6) d 2.12 (s, 3H), 2.22 (s, 3H), 3.48 (s, 2H), 3.72 (s, 2H), 3.92 (d, 2H), 4.29 (d , 2H), 6.05 (d, 1H), 6.64 (t, 1H), 6.71 (s, 1H), 7.24-7.27 (m, 2H), 7.37-7.41 (m, 2H), 8.32 (t, 1H). MS m / z 428.8 (M + H) + (xx)? / - [2- (aminomethyl) -5-chlorobenzyl] -2-. { 1 - [(2-Fluoro-5-methoxy-benzyl) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} acetamide NMR with 1H (500 MHz, DMSO-d6) d 2.12 (s, 3H), 3.47 (s, 2H), 3.69 (s, 3H), 3. 83 (s, 2H), 4.13 (d, 2H), 4.30 (d, 2H), 6.04 (d, 1H), 6.83-6.87 (m, 1H), 6.90-6.94 (m, 2H), 7.07 (t, 1H), 7.26-7.31 (m, 2H), 7.36 ( d, 1H), 7.40 (d, 1H), 8.38 (t, 1H). MS m / z 473.4 (M + H) + (xxi) / V- [2- (aminomethyl) -5-ciorobenzyl] -2-. { 4-methyl-1 - [(2-morpholino-4-ylbenzyl) amino] -2-oxo-1,2-dihydropyridin-3-yl} acetamide MS m / z 509.8 (M + H) + (xxii) / V- [2- (aminomethyl) -5-chlorobenzyl] -2- (1- {[[(1,3-dimethyl-5-morpholino- 4-yl-1H-pyrazol-4-yl) metii] amino.} -4-methyl-2-oxo-1,2-dihydro pyridin-3-yl) to keta mide. NMR with 1H (500 MHz, DMSO-d6) d 1.94. (s, 3H), 2.14 (s, 3H), 2.98-3.02 (m, 4H), 3.50 (s, 2H), 3.55 (s, 3H), 3.65-3. 69 (m, 4H), 3.72 (s, 2H), 3.91 (d, 2H), 4.29 (d, 2H), 6.05 (d, 1H), 6.41 (t, 1H), 7.23-7.27 (m, 2H) , 7.29 (d, 1H), 7.39 (d, 1H), 8.35 (t, 1H). MS m / z 527.8 (M + H) + (xxiii)? / - [2- (aminomethyl) -5-chlorobenzyl] -2-. { 4-methyl-2-oxo-1 - [(quinolin-8-ylmethyl) amino] -1,2-dihydropyridin-3-yl} acetamide. MS m / z 475.8 (M + H) + (xxiv) / V- [2- (aminomethyl) -5-chlorobenzyl] -2- [4-met i-2-oxo-1- ( { [5 - (2-thienyl) isoxazol-3-yl] methyl.} Amino) -1,2-dihydropyridin-3-yl-acetamide. NMR with 1H (500 MHz, DMSO-d6) d 2.11 (s, 3H), 3.47 (s, 2H), 3.72 (s, 2H), 4.23 (d, 2H), 4.28 (d, 2H), 6.05 (d , 1H), 6.91 (s, 1H), 7.14 (t 1H), 7.22-7.27 (m, 3H), 7.39 (d, 1H), 7.46 (d, 1H), 7.69 (d, 1H), 7.82 (d , 1H), 8.33 (t, 1H). MS m / z 497.7 (M + H) + (xxv)? / - [2- (aminomethyl) -5-fluorobenzyl] -2-. { 4-methyl-2-oxo-1 - [(2-phenylpropyl) amino] -1,2-dihydropyridin-3-yl} acetamide. NMR with 1H (400 MHz, CDCl 3) d 1.25 (d, 3H), 2.13 (s, 3H), 2.86-2.92 (m, 1H), 3.03-3.09 (m, 1H), 3.13-3.19 (m, 1H) , 3.46 (s, 2H), 3.75 (s, 2H), 4.30 (d, 2H), 6.11 (d, 1H), 6.38 (t, 1H), 6.99-7.05 (m, 2H), 7.18-7.32 (m , 5H), 7.37 (dd, 1H), 7.48 (d, 1H), 8.35 (t, 1H). MS m / z 437.5 (M + H) + (xxvi)? / - [2- (aminomethyl) -5-methylbenzyl] -2-. { 1 - [(bicyclo [2.2.1] hept-5-eN-2-i I methy1) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} acetamide MS m / z 421.4 (M + H) + (xxvii) / V- [2- (aminomethyl) -5-methylbenzyl] -2- [1- (3 - [(2-chloro-1,3-thiazole- 5-yl) methoxy] benzyl.} Am i no) -4-methyl-2-oxo-1,2-dihydropyridin-yl] acetamide MS m / z 552.4 (M + H) + (xxviii) N- [2- (Aminomethyl) -5-methyl enzoyl] -2- (4-methyl-1-. {[[(3-methyl-5-phenylisoxazol-4-yl) methyl] amino}. -2-oxo-1, 2-dihydro pyridin-3-i I) -acetamide. NMR with 1H (500 MHz, DMSO-d6) d 2.09 (s, 3H), 2.19 (s, 3H), 2.24 (s, 3H), 3.42 (s, 2H), 3.76 (s, 2H), 4.06 (d , 2H), 4.28 (d, 2H), 5.99 (d, 1H), 6.91 (t, 1H), 7.03 (d, 1H), 7.07 (s, 1H), 7.23 (d, 1H), 7.25 (d, 1H), 7.49-7.56 (m, 3H), 7.76 (d, 1H), 7.80 (d, 1H), 8.36 (t, 1H). MS m / z 486.5 (M + H) + (xxix) A / - [2- (aminomethyl) -5-methylbenzyl] -2- (1- { [(1,3-dimethyl-5-morpholino-4 -yl-1 H-pyrazol-4-yl) methyl] amino.} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetamide MS m / z 508.5 (M + H) + EXAMPLE 5 The following compounds were prepared, from appropriate intermediates (such as those described herein above), according to or by analogy with the methods described herein: (1) A / - [(6-amino-2-methylpyridin -3-yl) methyl] -2- (4-methyl-1-. {[[(3-methyl-5-phenylisoxazol-4-yl) methyl] amino.} -2-oxo-1,2-dihydropyridine -3-yl) -acetamide; (2)? / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2-. { [(5-Cioro-2-thienyl) methyl] amino} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetamide; (3)? / - [2- (aminomethyl) -5-chlorobenzyl] -2- (1- {[[5-chloro-2-phenyl-1-imidazol-4-yl) methyl] amino} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetamide; (4)? / - [2- (aminomethyl) -5-chlorobenzyl] -2- (1- [. {(1,5-dimethyl-1 H -pyrazol-4-yl) methyl] amino}. 4-methyl-2-oxo-1, 2-d ih id ro pyrid i n-3-yl) acetamide; (5) 2- [4-chloro-2- ( { [(4-methyl-1- {[[4-methyl-1H-imidazol-5-yl) -methyl] -amino} - 2-oxo-1,2-dihydropyridin-3-yl) acetyl] amino.} Methyl) phenoxy] - / V-ethylacetamide; (6) 2- (4-chloro-2-. {[[(4-metii-2-oxo-1 - [(pyridin-2-ylmethyl) amino] -1,2-dihydropyridin-3-yl}. acetyl) amino] methyI} phenoxy) - / V-ethylacetamide; (7) 2- [4-Chloro-2- ( { [(4-methyl-1. {[[(2-methyl-1-imidazol-2-yl) methyl] -amino}. 2-oxo-1,3-dihydroxpyridin-2-yl) acetyl] amino.} Methyl) phenoxy] -? / - ethiacetamide; (8) 2- (1- { [(6-chloro-1,3-benzodioxoI-5-yl) methyl] amino.} -4-methyl-2-oxo-1,2-dihydropyridin-3- il) -? / -. { 5-Chloro-2- [2- (ethylamino) -2-oxo-ethoxy] -benzyl} to ceta mida; (9) 2- [4-chloro-2- ( { [(4-methyl-1- { [(2-methyl-1H-imidazol-5-yl) methyl] -amino.} -2 -oxo-1,2-dihydropyridin-3-yl) acetyl] amino.}. methyl) phenoxy] -? / - ethylacetamide; (10) 2- (4-chloro-2-. {[[( { 4-meti I-2-OXO-1 - [(2-phenoxybenzyl) -amino] -1,2-dihydropyridin-3 -yl.}. acetyl) amino] methyl.}. phenoxy) -? / - ethylacetamide; (11) 2-. { 4-chloro-2 - [( { [1- ( { 3 - [(2-chloro-1,3-thiazol-5-yl) methoxy] benci l} -amino) -4-methy! -2-oxo-1,2-dihydro pyridin-3-yl] a ceil} amino) - methyl] -phenoxy} -? / - eti ceta mida; (12) / V- [2- (Aminomethyl) -5-fluorobenzyl] -2- (4-methyl-1-. {[[(2-morpholino-4-ylpyridin-3-yl) methyl] amino}. -2-oxo-1, 2-dihydropyridin-3-yl) acetamide; (13)? / - [2- (aminomethyl) -5-methylbenzyl] -2- (1- {[[(5-chloro-1,3-di-methyl-1H-pyrazol-4-yl) methyl]] amino.} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) -acetamide; (14) / v * - [2- (aminomethyl) -5-fluorobenzyl] -2- (4-methy1-2-oxo-1- { [(1-phenyl-1 H-pyrazole-5- il) methyl] amino.} -1, 2-dihydropyridin-3-yl) acetamide; (15)? - [2- (aminomethyl) -5-fluorobenzyl] -2- (4-methyl-1-. {[[(1-methyl-1 H-imidazol-2-yl) methyl] amino}. -2-oxo-1, 2-dihydro pyridin-3-yl) acetamide; (16) / V- [2- (aminomethyl) -5-fiuorobenzyl] -2-. { 1 - [(3-Cyano-4-fluorobenzyl) -amino] -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl} to ceta mida; (17) N- [2- (aminomethyl) -5-methylbenzyl] -2- (1- {[[(1,3-dimethyl] -5-morpholino-4-yl-1H-pyrazol-4-yl ) methyl] amino.} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetamide; * (18)? - [(2-aminomethyl) -5-methylbenzyl] -2- [4-methyI-2-oxo-1- ( { [5- (2-thienyl) isoxazol-3-yl] methyl .}. amino) -1,2-dihydropyridin-3-yl] acetamide; (19)? / - [2- (aminomethyl) -5-methylbenzyl] -2-. { 1 - [(4-cyanobenzyl) amino] -4-methyl-l-2-oxo-1,2-dihydropyridin-3-yl} to ceta mida; (20) 2- [4-chloro-2- ( { [(1- { [(1,3-dimethyl-5-morpholino-4-yl-1 V- pyrazol-4-yl) methyl] amino} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetyl] ami no} - meti I) phenoxy] -? / - ethylacetamide; (21)? / - [(6-amino-2,4-dimethyl pyridin-3-yl) methyl] -2- (1- {[[(1,3-dimethyl-5-morpholino-4-yl)] -1 W-pyrazol-4-yl) methyl] amino.} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetamide; (22)? / - [2- (aminomethyl) -5-methylbenzoyl] -2- (1- {[[(1,5-dimethyl-1 H -pyrazol-4-yl) methyl] amino}. -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) -acetamide; (23)? / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2- (1- {[[(1,5-dimethyl-1 H -pyrazol-4-yl)] methyl] amino.} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) -acetamide; (24)? / - [(6-amino-2-methylpyridin-3-yl) methyl] -2- (1- { [(1,5-di met i 1-1 H-pyrazol-4-yl) ) methyI] amino.} -4-metii-2-oxo-1,2-dihydropyridin-3-yl) -acetamide; (25) 2- [4-chloro-2- ( { [(1- {[[1-ethyl-3-methyl-1H-pyrazol-4-yl) methyl] -amino}. 4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetyl] amino.} Methyl) -phenoxy] -W-ethylacetamide; (26)? / - [2- (aminomethyl) -5-fluorobenzyl] -2- (1- {[[1-ethyl-3-methyl-1H-pyrazole -4 -i I) methyl] amino} -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl) -acetamide; (27)? / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2- (1- {[[1-ethyl-3-methyl-1H-pyrazole -4] - i I) methyl] amino.} -4-methyl-2-oxo-1,2-di-idro-pyridin-3-yl) acetamide; (28)? Í - [(6-amino-2-methylpyridin-3-yl) methyl] -2- (1-. {[[(1-ethyl-3-methyl-1H-pyrazol-4-yl) methyl] ] amino.} -4-methyl-2-oxo-1,2-dihydropyridin-3- il) -acetamide; (29)? / - [2- (aminomethyl) -5-chlorobenzyl] -2- (4-methyl-1-. {[[(1-methy1H-imidazol-2-yl) methyl] amino} -2-oxo-1,2-dihydro pyridin-3-yl) acetamide; (30)? / - [(6-amino-2-methylpyridin-3-yl) methyl] -2- (4-methyl-1-. {[[(1-methyl-1H-imidazol-2-yl) methyl] ] amino.} -2-oxo-1,2-dihydropyridin-3-yl) acetamide; (31)? / - [2- (aminomethyl) -5-chlorobenzyl] -2- (4-meth) 1-2-0X0-1 - { [(1-f-enyl-1-pyrazol- 5-yl) methyl] amino.} -1, 2-dihydro pyridin-3-yl) acetamide; (32)? / - [(6-amino-2,4-dimethyl-3-yl) methyl] -2- (4-methyl-2-oxo-1- { [(1-phenyl-1H-pyrazole -5-yl) methyl] amino.} -1, 2-dihydropyridin-3-yl) -acetamide; (33)? / - [(6-amino-2-methylpyridin-3-yl) methyl] -2- (4-methyl-2-oxo-1 - { [(1-f in i 1-1 H -pyrazol-5-yl) met il] amino.} -1, 2-dihydropyridin-3-yl) acetamide; (34)? / - [2- (aminomethyl) -5-chlorobenzyl] -2-. { 1 - [(2,1,3-Benzoxadiazol-5-yl-methyl) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} acetamide; (35)? / - [2- (aminomethyl) -5-methylbenzyl] -2-. { 1 - [(2,1,3-benzoxadiazol-5-ylmethyl) amin or] -4-met] 1-2-0X0-1, 2-dihydro pyridin-3-yl} acetamide; (36)? / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2-1 - [(2,1,3-benzoxadiazol-5-methyl) amino] -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl} acetamide; (37)? / - [(6-amino-2-methylpyridin-3-yl) methyl] -2-. { 1 - [(2,1,3-benzoxadiazol-5-yl-methyl) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} acetamide; (38)? / - [2- (aminomethyl) -5-chlorobenzyl] -2- (1- {[[(2,4-dimethyl-1, 3-ti azo l-5-i I) meti I] am i no.}. 4-methyl-2-oxo-1,2-dihydro-pyridyl-3-yl) acetamide; (39)? / - [2- (aminomethyl) -5-fluorobenzyl] -2- (1- {[[(2,4-dimethyl-1,3-thiazol-5-yl) methyl]] ami No.} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetamide; (40)? - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2- (1- {[[(2,4-dimethyl-1,3-thiazol-5-yl)] meth] I] amino.} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) -acetamide; (41)? / - [(6-amino-2-methylpyridin-3-yl) methyl] -2- (1- {[[(2,4-dimethyl-1,3-thiazol-5-yl) methyl] ] amino.} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) -acetamide; (42) 2- (4-chloro-2-. {[[( { 1 - [(2-chloro-5-fluorobenzyl) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3 -iI.}. acetyl) amino] methyl.}. phenoxy) -? / - ethylacetamide; (43)? / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2-. { 1 - [(2-Chloro-5-fluorobenz I) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} acetamide; (44) - [2- (aminomethyl) -5-fluorobenzyl] -2-. { 1 - [(2-chloro-5-fIuorobenzyl) -amin or] -4-methyl -2-0X0-1, 2-dihydropyri din-3-yl} to ceta mida; (45)? / - [(6-amino-2-methylpyridin-3-yl) methyl] -2-. { 1 - [(2-Chloro-5-fluoro-benzyl) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} acetamide; (46) 2- (4-chloro-2-. {[[( { 1 - [(2-fluoro-5-methoxybenzyl) amino] -4-met i l-2-oxo-1,2-dihydropyridin -3-yl.}. Acetyl) amino] methyl.}. Phenoxy) - / V-ethyl-acetamide; (47) A / - [2- (aminomethyl) -5-methylbenzyl] -2-. { 1 - [(2-Fluoro-5-methoxy-benzyl) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} acetamide; (48)? - [(6-amino-2,4-dimethyl pyrid in-3-i I) methyl] -2-. { 1 - [(2-fluoro-5-methoxybenzyl) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} acetamide; (49) A / - [(6-amino-2-methylpyridin-3-yl) methyl] -2-. { 1 - [(2-Fluoro-5-methoxy-benzyl) amin or] -4-met-1-2-0X0-1, 2-dihydropyridin-3-yl} acetamide; (50) A / - [(6-amino-2-methylpyridin-3-yl) methyl] -2- (1- {[[(2-methoxypyridin-3-yl) methyl] amino} -4- methyl-2-oxo-1,2-dihydropyridin-3-yl) acetamide; (51) 2- (1-. {[[(2-methoxypyridin-3-yl) methyl] amino.} -4-methyl-2-oxo-1,2-dihi-ropyridin-3-yl) -? - [2- (1 / -tetrazol-1-yl) benzyl] acetamide; (52)? / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2- (4-methyl-1- { [(2-methyl-1H-imidazol-5-yl) ) methyl] amino.} -2-oxo-1,2-dihydropyridin-3-yl) -acetamide; (53)? / - [(6-amino-2-methylpyridin-3-yl) methyl] -2- (4-methyl-1- { [(2-m ethyl-1 H- imidazol-5-yl) ) mefU] amino.} -2-oxo-1,2-dihydro pyridin-3-yl) acetamide; (54) 2 - [( { 4-Methyl-1 - [(2-morpholino-4-ylbenzyl) amino] -2-oxo-1,2-dihydropyridin-3-yl.} Acetyl) amino] methyl } phenoxy) -? / - ethylacetamide; (55)? / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2-. { 4-methyl-1- [(2-morph or lino-4-ylbenzyl) amin or] -2-oxo-l, 2-dihydro pyridin-3-yl} acetamide; (56)? / - [(6-amino-2-methylpyridin-3-yl) methyl!] - 2-. { 4-methyl-1 - [(2-morpholino-4-ylbenzyl) amino] -2-oxo-1,2-dihydropyridin-3-yl} acetamide; (57) 2- [4-Cioro-2- ( { [(4-methyl-1- { [(2-morpholino-4-ylpyridin-3-yl) methyl] -amino.} -2 -oxo-1, 2-dihydropyridin-3-yl) acetyl] amino.}. methyl) phenoxy] -? / - ethylacetamide; (58)? / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2- (4-methyl-1- { [(2-morpholino-4-ylpyridin-3 -iI) methyl] amino.} -2-oxo-1,2-dihydropyriin-3-yl) -acetamide; (59)? / - [(6-amino-2-methylpyridin-3-yl) methyI] -2- (4-methyl-1-. {[[(2-morpholino-4-ylpyridin-3-yl) methyl] ] amino.} -2-oxo-1,2-dihydropyridin-3-yl) -acetamide; (60)? / - [2- (aminomethyl) -5-chlorobenzyl] -2-. { 4-methyl-2-oxo-1 - [(2-phenoxybenzyl) amino] -1,2-dihydropyridin-3-yl} acetamide; (61)? / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2-. { 4-Methyl-2-oxo-1 - [(2-f-enoxy-benzyl) amino] -1,2-dihydropyridin-3-yl} acetamide; (62)? / - [2- (ami nometi I) -5-methylbenzyl] -2-. { 4-methyl-2-oxo-l - [(2-phenoxybenzyl) amino] -1,2-dihydropyridin-3-yl} acetamide; (63) / V- [2- (aminomethyl) -5-chlorobenzyl] -2- (1- ({(3,5-dimethylisoxazol-4-yl) methyl] amino.} -4-methyl-2- oxo-1, 2-dihydropyridin-3-yl) acetamide; (64)? / - [2- (aminomethyl) -5-methiibenzyl] -2- (1- {[[(3,5-dimethyl-isoxazol-4-yl) methyl] amino} -4-methyl -2-oxo-1,2-dihydropyridin-3-yl) acetamide; (65)? / - [(6-amino-2-methylpyridin-3-yl) methyl] -2- (1-. {[[(3,5-di-methyl-isoxazole-4-i) methyl]] amino.} -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl) -acetamide; (66)? / - [2- (aminomethyl) -5-chlorobenzyl] -2-. { 1 - [(3-methoxybenthyl I) am i no] -4-met i l-2-oxo-1,2-dihydropyridin-3-yl} acetamide; (67)? / - [2- (aminomethyl) -5-methylbenzyl] -2-. { 1 - [(3-methoxy-benzyl) amino] -4-methyl-2-oxo-1,2-d-hydro pyridin-3-yl} to ceta mida; (68)? / - [(6-amino-2,4-dimethyl-pyridin-3-yl) methyl] -2-. { 1 - [(3-methoxy-benzyl) -amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} acetamide; (69)? / - [(6-amino-2-methylpyridin-3-yl) methyl] -2-. { 1 - [(3-methoxybenzyl) -amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} acetamide; (70) A / - [2- (aminomethyl) -5-chlorobenzyl] -2- (4-methyl-1-. {[[(3-methyl-5-phenylisoxazol-4-yl) methyl] amino}. -2-oxo-1, 2-dihydropyridin-3-yl) -acetamide; (71) 2- [4-Cioro-2- ( { [4-methyl-1-. {[[(3-methyl-5-phenylisoxazol-4-yl) -methyl] amino} -2- oxo-1,2-dihydropyridin-3-yl) acetyl] amino} methyl) -phenoxy] -? / - ethylacetamide; (72)? / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2- (4-methyl-1- { [(3-methyl-5-phenylisoxazoI-4-yl) ) methyl] amino.} -2-oxo-1,2-dihydropyridin-3-yl-acetamide; (73)? / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2- ( 4-methyl-1- { [(4-methyl-1? TY-imidazol-5-yl) methyl] amino.} -2-oxo-1,2-dihydro-pyridin-3-yl) -acetamide; (74) A / - [(6-amino-2-methylpyridin-2-yl) methyl] -2- (4-methyI-1-. {[[(4-met i 1-1 H-imidazole-5 -yl) methyl] amino.}. -2-oxo-1,2-dihydropyridin-3- il) acetamide; (75)? / - [(6-amino-2-methylpyridin-3-yl) methyl] -2- (4-methyl-1 - [(4-methyl-3,4-dihydro-2H-1,4- benzoxazin-7-yl) methyl] amino.} -2-oxo-1,2-dihydro-pyridin-3-yl) -acetamide; (76) 2- [4-chloro-2- ( { [(1- {[[5-chloro-1,3-dimethyl-1H-pyrazol-4-yl) methyl] -amino} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetyl] amino} methyl] -phenoxy] - / V-ethyl acetamide; (77)? / - [(6-amino-2,4-dimethyl pyridin-3-yl) methyl] -2- (1 - [(5-chloro-1,3-dimethyl-1 H-pyrazole-4 -yl) methyl] amino.} -4-methyl-2-oxo-1,2-dihydro-pyri din-3-yl) to keta mide; (78)? / - [(6-amino-2-methylpyridin-3-y) methyl] -2- (1- {[[5-chloro-1,3-dimethyl-1 H-pyrazole-4 -yl) methyl] amino.} -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl) acetamide; (79) 2- [4-chloro-2- ( { [(1- { [(5-chloro-1-methyl-3-phenyl-1H-pyrazol-4-yl) -methyl] amino} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetyl] amino.} - methyl) phenoxy] -? / - ethylacetamide; (80)? / - [2- (aminomethyl) -5-fluorobenzyl] -2- (1- {[[5-chloro-1-methyl-3-phenyl-1H-pyrazol-4-yl) methyl] amino.} -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl) acetamide; (81) / V - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2- (1- {[[5-chloro-1-methyl-3-phenyl-1 H-pyrazol-4-yl) methyl] amino.} -4-methyl-2-oxo-1,2-dihydro pyridin-3-yl) acetamide; (82)? / - [(6-amino-2-methylpyridin-3-yl) methyl] -2- (1- {[[5-chloro-1-methyl-3-phenyl-1 H-pyrazole- 4-yl) methyl] amino.} -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl) acetamide; (83) 2- (4-chloro-2-. {[[( { 1 - [(5-chloro-2-fluorobenzyl) amino] -4-met i l-2-oxo-1,2-dihydropyridin -3-yl.}. Acetyl) amino] methyl.}. Phenoxy) -? / - ethylacetamide; (84)? / - [2- (aminomethyl) -5-methylbenzyl] -2-. { 1 - [(5-Chloro-2-fluorobenzyl) -amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} acetamide; (85)? / - [(6-amino-2,4-dimethylpyridin-3-ii) methyl] -2-. { 1 - [(5-chloro-2-fluorobenzyl) ami no] -4- me ti l-2-oxo-1,2-dihydropyridin-3-yl} acetamide; (86)? / - [(6-amino-2-methylpyridin-3-yl) methyl] -2-1 - [(5-chloro-2-fluoro-benzyl) to my no] -4-methyl- 2-oxo-1,2-dihydropyridin-3-yl} acetamide; (87)? / - [2- (amomethyl) -5-methyl-benzyl] -2- (1 - [(5-chloro-2-phenyl-1H-imidazol-4-yl) methyl] amino}. -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) -acetamide; (88)? / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2- (1- {[[5-chloro-2-phenyl-1 H-imidazole-4-] il) methyl] amino.} -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl) acetamide; (89)? / - [(6-amino-2-methylpyridin-3-yl) methyl] -2- (1- { [(5-chloro-2-phenyl-1 H-imidazol-4-yl) methyl] amino.} -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) -acetamide; (90) 2- [4-chloro-2- ( { [(1- {[[(5-chloro-2-thienyl) methyl] amino} -4-met i-2-oxo- 1,2-dihydropyridin-3-yl) acetyl] amino.} Methyl) phenoxy] -W-ethyl-acetamide; (91)? / - [(6-amino-2-methylpyridin-3-yl) methyl] -2- (1 - [(5-cyoro-2-thienyl) -methyl] amino.} -4-methyl- 2-oxo-1,2-dihydro-pyridin-3-yl) acetamide; (92) 2- [4-chloro-2- ( { [(4-methyl-1- { [(5-methyl-3-phenylisoxazole-4- il) -methyl] amino} -2-oxo-1,2-dihydropyridin-3-yl) acetyl] amino} methyl) -phenoxy] -? / - ethylacetamide; (93)? / - [(6-ami-2, 4-dimethyl pyrid i n-3-yl) methyl] -2- (4-methi 1-1 -. {[[(5-metii-3- phenylisoxazol-4-yl) methyl] amino.} -2-oxo-1,2-dihydro pyridin-3-yl) acetamide; (94)? - [(6-amino-2-methylpyridin-3-yl) methyl] -2- (4-methyl-1 - [(5-methyl-3-phenylisoxazol-4-yl) methyl] amino.} -2-oxo-1, 2-dihydropyridin-3-yl) -acetamide; (95) 2- [4-chloro-2- ( { [(4-methyl-2-oxo-1-. {[[(5-pyridin-2-yl-2-thienyl) -methyl] amino] } -1, 2-dihydropyridin-3-yl) acetyl] amino] methyl) phenoxy] -ethylacetamide; (96)? / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2- (4-methyl-2-oxo-1 - { [(5-pyridin-2- il-2-thienyl) methyl] ami no.} - 1, 2-dihydropyridin-3-yl) -acetamide; (97)? / - [2- (aminomethyl) -5-fluorobenzyl] -2- (4-methyl-2-oxo-1- [(5-pyridin-2-yl-2-thienyl) methyl] amino.} -1, 2-dihydropyridin-3-yl) acetamide; (98) A / - [(6-amino-2-methylpyridin-3-yl) methyl] -2- (4-methyl-2-oxo-1- { [(5-pyridin-2-yl-2) -thienyl) methyl] amino.}. -1,2-dihydropyridin-3-yl) acetamide; (99) A / - [2- (aminomethyl) -5-fluorobenzyl] -2- (1- {[[6-chloro-1,3-benzo-dioxol-5-yl) methyl] amino}. -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) -acetamide; (100)? / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2- (1-. {[[(6-chloro-1,3-benzodioxol-5-yl) methyl] ] amino.} -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl) -acetamide; (101)? / - [(6-amino-2-methylpyridin-3-yl) methyl] -2- (1- {[[(6-chloro-1,3-benzodioxol-5-yl) methyl] amino] .) -4-methyl-2-oxo-l, 2-dihydropyridin-3-yl) -acetamide; (102) 2- [4-chloro-2- ( { [(4-methyl-2-oxo-1- { [3- (trifluoromethoxy) -benzyl] -amino.} -1, 2 -dihydropyridin-3-yl) acetyl] amino.} methyl) phenoxy] - / V-ethyl-acetamide; (103)? - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2- (4-methyl-2-or xo-1- { [3- (trif luoro m ethoxy) b ene il] amino.} -1, 2-dihydropyridin-3-yl) acetamide; (104)? / - [2- (aminomethyl) -5-fluorobenzyl] -2- (4-methyl-2-oxo-1- { [3- (trifluoromethoxy) benzyl] amino.} -1, 2 -dihydropyridin-3-yl) acetamide; (105)? / - [(6-amino-2-methylpyridin-3-yl) methyl] -2- (4-methyI-2-oxo-1- {[[3- (trifluoromethoxy) benzyl] amino} -1, 2-dihydro pyridin-3-yl) acetamide; (106) 2-. { 4-chloro-2 - [( { [4-methyl-2-oxo-1- ( { [5- (2-thienyl) isoxazol-3-yl] -methyl} amino) -1, 2-dihydropyridin-3-yl] acetyl} amino) methyl] phenoxy} -? - eíi the ceta mida; (107)? / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2- [1- ( { 3 - [(2-chloro-1,3-thiazole-5- il) methoxy] benzyl.} amino) -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl] acetamide; (108)? / - [(6-amino-2-methyl-pyridin-3-ii) methyl] -2- [1- (. {3 - [(2-chloro-1,3-thiazol-5-yl)] methoxy] benzylamino) -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl] acetamide; (109)? / - [2- (aminomethyl) -5-chlorobenzyl] -2- (1- {[[(1R, 4S) -bicyclo [2.2.1] -hept-5-en-2-ylmethyl]] amino.} -4-methyl-2-oxo-1,2-dihydro- pyridin-3-yl) -acetamide; (110)? / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2- (1- { [(1R, 4S) -bicyclo [2.2.1] hept-5- en-2-ylmethyl] amino.} -4-methyl-2-oxo-1,2-dihydro-pyridin-3-yl) acetamide; (111) 2- (4-chloro-2-. {[[( { 1 - [(cyclohexylmethyl) amino] -4-methyl-2-oxo-1, 2-d¡h¡drop¡r¡din -3-.1.) Acetyl) amino] methyl.}. Phenoxy) - / V-ethylacetamide; (112)? / - [2- (aminomethyl) -5-ciorobenzyl] -2-. { 1 - [(Cyclohexyl-methyI) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} acetamide; (113)? / - [2- (aminomethyl) -5-fluorobenzyl] -2-. { 1 - [(cyclohexyl-methyl) amino] -4-methyl-2-oxo-1, 2-d i hidropyro din-3-yl} acetamide; (114)? / - [(6-amino-2-methylpyridin-3-yl) methyl] -2-. { 1 - [(Cyclohexylmethyl) -amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} acetamide; (115)? / - [2 (aminomethyl) -5-methylbenzyl] 2-. { 1 - [(cyclopentyl-methyl-1) -amino-4-m-ethyl-2-oxo-1,2-d-hydrohydridin-3-yl) acetamido; (116)? / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] 2-. { 1 - [(cyclopenti I meti I) -am and no] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetamide; (117) N - [(6-amino-2-methylpyridin-3-yl) methyl] 2-. { 1 - [(cyclopenethylmethyl) -amyl] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl) acetamide; (118) / V - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] 2-. { 4-methyl-2-oxo-1 - [(pyridin-2-ylmethyl) amino] -1,2-dihydropyridin-3-yl) acetamide; (119) A / - [(6-amino-2-methylpyridin-3-yl) methyl] 2-. { 4-Methyl-2-oxo-1 - [(pyrid-n-2-ylmethyl) to mino] -1,2-dihydropyridin-3-yl) to ketameth; (120)? / - [2- (amin omethyl) -5-chlorob in cyl] -2-. { 4-methyl-2-oxo-1 - [(pyridin-3-ylmethyl) amino] -1,2-dihydropyridin-3-yl} acetamide; (121) 2- (4-chloro-2-. {[[( { 4-methyl-2-oxo-1 - [(pyridin-3-ylmethyl) amino] -1,2-dihydropyridin-3-yl! l.}. acetyl) amino] methyl.}. phenoxy) - / V-ethylacetamide; (122)? / - [2- (aminomethyl) -5-methylbenzyl] -2-. { 4-methyl-2-oxo-l - [(pyridin-3-ylmethyl) amin or] -1,2-dihydropyridin-3-yl} acetamide; (123)? / - [2- (am inometi I) -5-f I uorobenci I] -2-. { 4-methyl-2-oxo-1 - [(pyridin-3-ylmethyl) amin or] -1,2-dihydro-pyridin-3-yl} to ce tamida; (124)? / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2-4-methyl-2-oxo-1 - [(pyridin-3-ylmethyl) amino] -1, 2-dihydropyridin-3-yl} acetamide; (125)? / - [(6-amino-2-methylpyridin-3-yl) methyl] -2-. { 4-Methyl-2-oxo-1 - [(pyridin-3-ylmethyl) amino] -1,2-dihydropyridin-3-yl} acetamide; (126)? / - [2- (aminomethyl) -5-methylbenzyl] -2-. { 4-Methyl-2-oxo-1 - [(quinolin-8-ylmethyl) amino] -1,2-dihydropyridin-3-yl} acetamide; (127) 2- (4-chloro-2-. {[[( { 4-methyl-2-oxo-1 - [(quinolin-8-ylmethyl) amino] -1,2-dihydropyridin-3-yl. .}. acetyl) amino] methyl.}. phenoxy) -? / - ethylacetamide; (128)? / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2-. { 4-methyl-2-oxo-1 - [(quinolin-8-ylmethyl) amino] -1,2-dihydropyridin-3-yl} acetamide; (129) 2- [4-chloro-2- ( { [(1- {[[2,2-difluoro-2- (1-oxidopyridin-2-yl) ethyl] -amino} -4 -methyl-2-oxo-1,2-dihydropyridin-3-yl) acetyl] amino.} methyl) -phenoxy] -A- -ethylacetamide; (130) 2- (4-chloro-2-. {[[( { 1 - [(2,2-difluoro-2-pyridin-2-yethyl) amino] -4-methyl-2-oxo-1 , 2-dihydropyridin-3-yl} acetyl) amino] methyl.} - fen oxy) -? / - ethyl acetate; (131)? / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2-. { 1 - [(2,2-difluoro-2-pyridin-2-ylethyl) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} - acetamide; (132) A / - [2- (aminomethyl) -5-methyIbenzyl] -2-. { 4-methyl-2-oxo-1- [(2-phenylethyl) amino] -1,2-dihydro-pyridin-3-yl-acetamide; (133)? / - [2- (aminomethyl) -5-methoxybenzyl] -2-. { 4-Methyl-2-oxo-1 - [(2-phenylethyl) amino] -1,2-dihydro pyridine-3-l} to ce tamida; (134) 2- (4-chloro-2-. {[[(. {4-methyl-2-oxo-1 - [(2-phenylethyl) amino] -1,2-dihydropyridin-3-yl.} acetyl) amino] methyl.}. phenoxy) -? / - ethylacetamide; (135)? / - [(6-amin or-2,4-dimethyl pyrid i n-3-yl) methyl] -2-. { 4-methi I-2-oxo-l - [(2-f-enylethyl) amino] -1,2-dihydropyridin-3-yl} acetamide; (136)? / - [(6-amino-2-methyl-pyridin-3-yl) methyl] -2-. { 4-methyl-2-oxo-1 - [(2-phenylethyl) amino] -1,2-dihydropyridin-3-yl} acetamide; (137)? / - [2- (aminomethyl) -5-chlorobenzyl] -2-. { 4-meth yl-oxo-1- [(2-phenylpropyl) amino] -1,2-dihydropyridin-3-yl} acetamide; (138) 2- (4-chloro-2- { [( { 4-metll-2-oxo-1 - [(2-phenylpropyl) -amino] -1,2-dihydropyridin-3-yl} acetyl) amino] methyl.}. phenoxy) - / V-ethylacetamide; (139)? / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2-. { 4-methyl-2-oxo-l - [(2-f in ylpropyl) amino] -1,2-dihydropyridin-3-yl} acetamide, • (140)? / - [(6-amino-2-methylpyridin-3-yl) methyl] -2-. { 4-methyl-2-oxo-1 - [(2-phenylpropyl) amino] -1,2-dihydropyridin-3-yl} acetamide; (141)? / - [(6-amino-2-methylpyridin-3-yl) methyl] -2- (4-metii-2-oxo-1 - { [(2-oxo-1,2-dihydropyridin -3-yl) methyl] amino.} -1, 2-dihydropyridin- 3-l) -acetamide; (142) 2- (4-cyoro-2-. {[[( { 1 - [(3,3-dimethylbutyl) amino] -4-methyl-2-oxo-1, 2- ihydropyridin-3-yl. .}. acetyl) amino] methyl.}. phenoxy) -? / - ethylacetamide; (143)? / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl) -2-. { 1 - [(3,3-dimethylbutyl) amin or] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} acetamide; (144) 2- (4-chloro-2-. {[[( { 1 - [(4-cyanobenzyl) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} acetyl) amino] methyl.}. phenoxy) -? / - ethylacetamide; (145)? / - [2- (aminomethyl) -5-chlorobenzyl] -2-. { 1 - [(4-Cyanobenz I) amino] -4-methyl I-2-oxo-1,2-dihydropyridin-3-yl} acetamide; (146) 2- (4-chloro-2-. {[[( { 1 - [(3-cyano-4-fluorobenzyl) amino] -4-methyl-2-oxo-1,2-dihydropyridin-3 -l.} Acetyl) amino] methyl.}. Phenoxy) -? / - ethyl acetamide; (147) A / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2-. { 1 - [(3-cyano-4-fluoro enci I) am i no] -4-met i l-2-oxo-1,2-dihydropyridin-3-yl-acetamide; (148)? / - [(6-ami no-2-methyl pyrid in -3-1) methyl] -2-1 - [(3-cia no-4-fl or oro-be nci I) am ino ] -4-methyl-2-oxo-1,2-dihydropyridin-3-yl} acetamide; (149) 2- [1- (benzylamine and no) -4-methyl-2-oxo-1,2-dihydropyridin-3-yl] -? / -. { 5-Chloro-2- [2- (ethylamino) -2-oxoethoxy] benzyl} to ceta mida; (150)? / - [2- (aminomethyl) -5-fluorobenzyl] -2- [1- (benzylamino) -4-methyl-2-oxo-1,2-dihydropyridin-3-yl] acetamide; (151) A / - [(6-amino-2,4-dimethylpyridin-3-yl) methyl] -2- [1- (benzylamino) -4-methyl-2-oxo-1,2-dihydropyridin-3- il] acetamide; (152)? / - [2- (aminomethyl) -5-chlorobenzyl) -2- [1- (isobutylamino) -4-methyl-2-oxo-1,2-dihydropyridin-3-yl] acetamide; (153)? / - [2- (aminomethyl) -5-methyl-enyl] -2- [1- (isobutyl-amino) -4-methyl-2-oxo-1,2-dihydropyridin-3-yl] a-keta measure; and (154)? / - [(6-amino-2,4-d.methylpyridin-3-yl) methyl] -2- [1- (isobutylamino) -4-met-1-2-0X0-1, 2-dihydropyridin-3-yl] acetamide.

EXAMPLE 6 The compounds of the Examples in test B above were tested and found to have IC50TT values of less than 50 μM. Undoubtedly, it was found that the compounds of examples 2 (xi) and 2 (xii) had IC 50 values of 92.2 nM and 0.62 μM, respectively.

ABBREVIATIONS ac. = aqueous AUC = area under the curve Boc = urea-butyloxycarbonyl BSA = bovine serum albumin d = (in relation to NMR) DCC duplex = dicyclohexyl-carbodiimide DCE = 1,2-dichloroethane DCM = dichloromethane DIPEA = diisopropylethylamine DMAP = 4- (? /,? / - dimethyl amino) pyridine DMF = dimethylformamide DMSO = dimethyl sulfoxide DVT = deep vein thrombosis EDC = 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride Et = ethyl Ether = diethyl ether Et3N = triethylamine EtOAc = ethyl acetate EtOH = ethanol Et2O = diethyl ether = hour (s) HATU = O- (azabenzotriazol-1-yl) hexafluorophosphate, N, N ', / V'-tetramethyluronium HBTU = [? /,? /,? /' Hexafluorophosphate, / V'-tetramethyl-O- (benzotriazole-li) -O-uronium] HCl = hydrochloric acid, gas hydrogenated chloride or hydrochloride salt (depending on context) HOAt = 1-hydroxy-7-azabenzotriazole HOBt = 1-hydroxybenzotriazole HPLC = high performance liquid chromatography LC = liquid chromatography mCPBA = meta-chloroperbenzoic acid Me = methyl MeOH = methanol min = minute (s) MS = mass spectroscopy NADH = nicotinamide adenine dinucleotide, reduced form NADPH = nicotinamide adenine dinucleotide phosphate, reduced form NBS =? / - bromosuccinimide NIH = National Institute of Health (USA) NIHU = National units US Institute of Health OAc = PCC acetate = pyridinium chlorochromate Ph = phenyl Pr = propyl PyBOP = (benzotriazol-1-yloxy) tripyrrolidinphosphonium hexafluorophosphate rt / RT = room temperature SOPs = standard operating procedures TBME = methyl ester of éri -butyl TBTU = [tetrafluoroborate of? /, / V,? / ', A /' - tetramethyl-O- (benzotriazol-1-yl) uronium] TEA = triethylamine TFA = trifluoroacetic acid THF = tetrahydrofuran The prefixes n, s, i and t have their usual meanings: normal, secondary, iso and tertiary. The prefix c means cycle.

Claims

1. A compound of the formula I where the dotted line is absent or represents a link; A represents C (O), S (O) 2, C (O) O (in the latter group the portion O is linked to R1), C (O) NH, S (O) 2NH (in these last two groups the NH portion is attached to R1) or alkylene of 1 to 6 carbon atoms; R represents (a) alkyl of 1 to 10 carbon atoms, alkenium of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms (these last three groups are optionally substituted by one or more substituents selected from halo, CN, cycloalkyl of 3 to 10 carbon atoms (optionally substituted by one or more substituents selected from halo, OH, = O, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms and aryl), OR a, S (O) nR4b, S (O) 2N (R4c) (R4d), N (R4e) S (O) 2R4f, N (R49) (R4h), B1-C (O) -B2-R4i, aryl and He1) , (b) cycloalkyl of 3 to 10 carbon atoms or cycloalkynyl of 4 to 10 carbon atoms, the last two groups of which are optionally substituted by one or more substituents selected from halo, = O, CN, alkyl of 1 to 10 carbon atoms , cycloalkyl of 3 to 10 carbon atoms (optionally substituted by one or more substituents selected from halo, OH, = O, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms and aryl), OR4a, S (O) nR4b, S (O) 2N (R4c) (R4d), N (R e) S (O) 2R4f, N (R4g) (R4h), B3-C (O) -B4-R i, aryl and Het2, (c) aryl, or (d) Het3; R4a to R4i independently represent, in each case, (a) H, (b) Alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms (the last three groups of which are optionally substituted by one or more substituents selected from halo, OH, alkoxy of 1 to 6 carbon atoms, aryl and Het4), (c) Cycloalkyl from 3 to 10 carbon atoms, cycloalkenyl of 4 to 10 carbon atoms (the latter of which groups is optionally substituted by one or more substituents selected from halo, OH, = O, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, aryl and Het5), (d) aryl or (e) Het6, provided that R4 does not represent H when n is 1 or 2; the group -DE- (a) when the dotted line represents a bond, represents -C (R5a) = C (R5b) -, or (b) when the dotted line is absent, represents -C (R6a) (R6) - C (R7a) (R7b) -; R5a and R5b independently represent H, halo, OH, alkyl of 1 to 4 carbon atoms, (CH2) 0. O (alkyl of 1 to 3 carbon atoms) (the latter two groups of which are optionally substituted by an OH group or one or more F atoms); R6a, R6b, R7a and R7b independently represent H, F or methyl; or R5a and R5 together represent n-alkylene of 2 to 4 carbon atoms; or one of R6a and R6b, together with one of R7a and R7b represents n-alkylene of 1 to 4 carbon atoms; R2 represents (a) H, (b) halo; (c) alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms (whose last four groups are optionally substituted by one or more substituents selected from halo, OH, CN, alkoxy of 1 to 4 carbon atoms, C (O) OH, C (O) O-alkyl of 1 to 4 carbon atoms and OC (O) -alkyl of 1 to 4 carbon atoms) or (d) together with R3a, R2 represents n-alkylene of 2 to 3 carbon atoms, T1- (n-alkylene of 1 to 2 carbon atoms) or (n-alkylene of 1 to 2 carbon atoms) -T1, whose last three groups are optionally substituted by halo, or (e) together with R3a and R3b, R2 represents T2- [C (H) =], where T2 is attached to the carbon atom to which the R2 group is attached; R and R, 3óbD independently represent H, F or methyl (whose last group is optionally substituted by one or more atoms of F), or (a) together with R2, R3a represents n-alkylene of 2 to 3 carbon atoms, (n-alkylene of 1 to 2 carbon atoms) - or (N-alkylene of 1 to 2 carbon atoms) -T1, whose last three groups are optionally substituted by halo, or (b) together with R2, R3a and R3b represent T2- [C (H) =], wherein T2 is attached to the carbon atom to which the group is attached R2; T1 and T2 independently represent O, S, N (H) or N (alkyl of 14 carbon atoms); G represents (a) -C (O) N (R8a) - [CH (C (O) R9)] 0 -? - alkylene of 0 to 3 carbon atoms- (Q1) a-, (b) -C ( O) N (R8b) -alkenylene of 2 to 3 carbon atoms- (Q1) a-, (c) R represents H or an aromatic heterocyclic group of 5 to 10 members containing one or two rings and containing, as the hetero atom (s), a sulfur atom or an oxygen atom, and / or one or more nitrogen atoms, the heterocyclic group of which is optionally substituted by one or more selected substituents halo and alkyl of 1 to 6 carbon atoms; Q1 represents O, NR10a, [N (H)] 0-? C (O) -alkylene of 0 to 2 carbon atoms, C (O) NHNHC (O), or -N = C (R10b) -; a represents 0 or 1; Q2 & It represents Q represents L represents (a) alkylene of 0 to 6 carbon atoms-Ra, (b) alkylene of 0 to 2 carbon atoms-CH = CH-alkylene of 0 to 2 carbon atoms-Ra, (c) alkylene of 0 to 2 carbon atoms-C = C-alkylene of 0 to 2 carbon atoms-Ra, (d) (and) where the dotted line represents an optional double bond, or Ar represents phenyl or naphthyl; Het represents a heterocyclic group of 5 to 10 members that includes one or two rings, and which contains, as heteroatom (s), a sulfur or oxygen atom and / or one or more nitrogen atoms; R 11a represents H or one or more substituents selected from halo, OH, CN, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms (the latter two groups of which are optionally substituted by one or more substituents selected from halo , OH, alkoxy of 1 to 4 carbon atoms, C (O) OR 2a and C (O) N (R12b) R12c) and S (O) 0-2R12d; Rnb and Rnc independently represent H or one or more substituents selected from halo, OH, CN, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms (the latter two groups of which are optionally substituted by one or more substituents selected halo, OH, alkoxy of 1 to 4 carbon atoms, C (O) OR12a and C (O) N (R12b) R12c), S (O) 0-2R12d, = O, = NH, = NOH y = N -CN; R12a to R12c independently represent H, alkyl of 1 to 6 carbon atoms or cycloalkyl of 3 to 7 carbon atoms (the latter two groups of which are optionally substituted by an OH or N (R12e) R12f group or by one or more halogen atoms ); R 12d represents, independently in each case, alkyl of 1 to 6 carbon atoms optionally substituted by an OH or N (R12e) R12f group or by one or more halogen atoms; Ri2e and Ri2f represent, independently in each case, H or alkyl of 1 to 4 carbon atoms optionally substituted by one or more halogen atoms; Ra up Rd independently represent (to) (b) (c) (d) (and) (g) Hetx or Rb to Rd can also represent H; Q3 represents O, N (R10c), S (O) 2, S (O) 2NH, C (O) or -CH = N-; Q4 represents O, S or CH2; a represents 0 or 1; Hetx represents a 5-6 membered heterocyclic group containing one to four heteroatoms selected from oxygen, nitrogen and / or sulfur, said heterocyclic group may be substituted by one or more substituents selected from halo, = O, alkyl from 1 to 6 carbon and alkoxy atoms of 1 to 6 carbon atoms (the latter two groups of which are optionally substituted by one or more halogen atoms); R 3a to R 13c independently represent (a) H, (b) CN, (c) NH 2, (d) OR 15 or (e) C (O) OR 16; R 5 represents (a) H, (b) alkyl of 1 to 10 carbon atoms, alkenyl of 3 to 10 carbon atoms, alkynyl of 3 to 10 carbon atoms, (c) cycloalkyl of 3 to 10 carbon atoms, cycloalkenyl of 4 to 10 carbon atoms , whose last two groups are optionally substituted by one or more substituents selected from halo and alkyl of 1 to 6 carbon atoms, or (d) alkyl of 1 to 3 carbon atoms, whose last group is optionally interrupted by oxygen, and is substituted by aryl or by -O-aryl; R16 represents (a) alkyl of 1 to 10 carbon atoms, alkenyl of 3 to 10 carbon atoms, alkynyl of 3 to 10 carbon atoms, the last three groups of which are optionally interrupted by one or more oxygen atoms, or (b) ) cycloalkyl of 3 to 10 carbon atoms, cycloalkenyl of 4 to 10 carbon atoms, the latter two groups of which are optionally substituted by one or more substituents selected from halo and alkyl of 1 to 6 carbon atoms, or (c) alkyl of 1 to 3 carbon atoms, whose last group is optionally interrupted by oxygen, and is substituted by aryl or -O-aryl; R8a to R8c, R10a to R10c and R14a to R149 independently represent (a) H or (b) alkyl of 1 to 4 carbon atoms (whose last group is optionally substituted by one or more substituents selected from halo and OH), or R14a and R1b independently represent C (O) O- alkyl of 1 to 6 carbon atoms (the alkyl part of which the latter group is optionally substituted by aryl and / or one or more halogen atoms), or R14c represents (a) alkyl of 1 to 4 carbon atoms substituted by cycloalkyl of 3 to 7 carbon atoms or aryl, (b) cycloalkyl of 3 to 7 carbon atoms , (c) C (O) O-alkyl of 1 to 6 carbon atoms (the alkyl part of which the latter group is optionally substituted by aryl and / or one or more halogen atoms), (d) C (O ) alkyl of 1 to 6 carbon atoms, (e) C (O) N (H) -alkyl of 1 to 6 carbon atoms (the alkyl part of which the latter group is optionally substituted by aryl and / or one or more halogen atoms) or (f) S (O) 2-Alkyl of 1 to 6 carbon atoms (the alkyl part of which the latter group is optionally substituted by aryl) lo and / or one or more halogen atoms), or R14c and R14d together represent n-alkylene of 3 to 6 carbon atoms optionally interrupted by O, S, N (H) or N (alkyl of 1 to 4 carbon atoms ) and / or substituted by one or more alkyl groups of 1 to 4 carbon atoms; each aril represents independently a group carbocyclic aromatic of 6 to 10 carbon atoms, said group may contain either one or two rings, and may be substituted by one or more substituents selected from (a) halo, (b) CN, (c) alkyl from 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms (whose last three groups are optionally substituted by one or more substituents selected from halo, OH, alkoxy of 1 to 6 carbon atoms, C (O) OH, C (O) O-alkyl of 1 to 6 carbon atoms, phenyl (whose last group is optionally substituted by halo) and Het7), (d) cycloalkyl of 3 to 10 carbon atoms, cycloalkenyl of 4 to 10 carbon atoms (the latter two groups of which are optionally substituted by one or more substituents selected from halo, OH, = O, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, phenyl (the latter group of which is optionally substituted by halo) and Het8), (e) OR17a, (f) S (O) pR17b, (g) S (O 2N (R17c) (R17d), (h) N (R17e) S (O) 2R17f,. (i) N (R17g) (R17h), (j) B5-C (O) -B6-R17i, (k) phenyl (whose last group is optionally substituted by halo), (I) Het9 and (m) Si (R18a) (R18b) (R18c); R17a to R17 'independently represent, in each case, (a) H, (b) alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms (the last three groups of which are optionally substituted by one or more substituents selected from halo, OH, alkoxy of 1 to 6 carbon atoms, phenyl (the latter group of which is optionally substituted by halo) and Het10), (c) cycloalkyl of 3 to 10 carbon atoms, cycloalkenyl of 4 to 10 carbon atoms (the latter two groups of which are optionally substituted by one or more substituents selected from halo, OH, = O, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, phenyl ( whose last group is optionally substituted by halo) and Het11), (d) phenyl (whose last group is optionally substituted by halo) or (e) Het12, provided that R17b does not represent H when p is 1 or 2; Het1 to Het12 independently represent heterocyclic groups of 4 to 14 members containing one or more heteroatoms selected from oxygen, nitrogen and / or sulfur, whose heterocyclic groups may contain one, two or three rings, and may be substituted by one or more substituents selected from (a) halo, (b) CN, (c) alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms (the last four groups of which are optionally substituted by one or more substituents selected from halo, OH, alkoxy of 1 to 6 carbon atoms, C (O) OH, C (O O-alkyl of 1 to 6 carbon atoms, phenyl (whose last group is optionally substituted by halo) and Heta), (d) cycloalkyl of 3 to 10 carbon atoms, cycloalkenyl of 4 to 10 carbon atoms (the latter two groups of which are optionally substituted by one or more substituents selected of halo, OH, = O, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, phenyl (whose last group is optionally substituted by halo) and Hetb), (e) = O, (f) OR19a (g) S (O) qR19b (h) S (O) 2N (R19c) (R19d), (i) N (R19e) S (O) 2R19f, (j) N (R199) (R19h), (k ) B7-C (O) -B8-R19i, (I) phenyl (whose last group is optionally substituted or halo), (m) Hetc and (n) Si (R20a) (R20b) (R20c); R19a to R19 'independently represent, in each case, (a) H, (b) alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms (the last three groups of which are optionally substituted by one or more substituents selected from halo, OH, alkoxy of 1 to 6 carbon atoms, phenyl (the latter group of which is optionally substituted by halo) and Hetd), (c) cycloalkyl of 3 to 10 carbon atoms, cycloalkenyl of 4 to 10 carbon atoms (the latter two groups of which are optionally substituted by one or more substituents selected from halo, OH, = O, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, phenyl ( whose last group is optionally substituted by halo) and Hete), (d) phenyl (whose last group is optionally substituted by halo) or (e) Hetf, provided that R19b does not represent H when q is 1 or 2; Heta to Hetf independently represent 5- or 6-membered heterocyclic groups containing from one to four heteroatoms selected from oxygen, nitrogen and / or sulfur, whose heterocyclic groups may be substituted by one or more substituents selected from halo, = O and alkyl of 1 to 6 carbon atoms; B1 to B8 independently represent a direct link, O, S or NH; n, p and q independently represent 0, 1 or 2; R18a, R18b, R18c, R20a, R20b and R20c independently represent alkyl of 1 to 6 carbon atoms or phenyl (the latter group of which is optionally substituted by halo or alkyl of 1 to 4 carbon atoms); unless otherwise specified (i) the alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, alkylene and alkenylene groups as well as the alkyl part of the alkoxy groups may be substituted by one or more halogen atoms, and (ii) the cycloalkyl and cycloalkenyl groups may contain one or two rings, and additionally they may be fused to the ring in one or two phenyl groups; or a derivative thereof acceptable for pharmaceutical use.

2. A compound as described in claim 1, which is a compound of the formula le, Id or le, wherein X1 represents CH or N; when X1 represents CH (a) Rx represents Rb as defined in claim 1, and (b) Ry represents R11a as defined in claim 1; r represents 1 to 3; s represents 2 to 4; t represents 1 to 3; u and v independently represent 0 to 2, the sum of u and v is 1 or 2; and R1, R2, R3a, R3b, R11a, R1c, R13a, R13b, R1a, R14b, Rb, Rd and A are as defined in claim 1.

3. A compound as defined in claim 2, which is a compound of the formula le, wherein A represents CH (CH3) CH2 (in which latter group the unit CH (CH3) is linked to R1) or CH2, (CH2) 2 or CF2CH2 (in which latter group the unit CF2 is attached to R1); R1 represents (a) isopropyl or urea-butyl, (b) cyclopentyl, cyclohexyl or bicyclo [2.2.1] hept-5-ene, (c) phenyl optionally substituted by one or two substituents selected from halogen, CN, methyl, CF3 , methoxy, OCF3, phenoxy, morpholino-4-yl or O-CH2- (2-chlorothiazol-5-yl), (d) imidazolyl optionally substituted by one to three substituents selected from Cl, methyl and phenyl, (e) isoxazolyl optionally substituted by one or two substituents selected from methyl, phenyl and 2-thienyl, (f) thiazolyl optionally substituted by one or two methyl groups, (g) thienyl optionally substituted by Cl or pyridinyl (h) pyrazolyl optionally substituted by one to three substituents selected from Cl, methyl, ethyl, phenyl and morpholino-4-yl, (i) pyrrolyl optionally substituted by one to three substituents selected from methyl, S (O) 2-phenyl, C (O) phenyl and 1,4-triazol-1-yl, (j) pyridinyl optionally substituted by OH, methoxy or morpholino-4-yl, and optionally in the form of an N-oxide, (k) pyridonyl, (I) pyrazinyl, (m) benzodioxolyl optionally substituted by halo, (n) benzomorpholinyl optionally substituted by methyl; (o) 2,1, 3-benzoxadiazolyl, (p) 2,3-dihydrobenzofuranyl, or (q) quinolinyl; R5 and R6 represent both H; r represents 1; the group It represents R ° represents H, F, Cl, OH, methyl, tetrazol-1-yl, OCH2C (O) N (H) R12b or CH2N (H) R14c, R12 represents H or alkyl of 1 to 3 carbon atoms optionally substituted by N (CH3) 2; R14c represents C (O) O-tert-butyl, H, Ethyl, CH2CF3 or cyclopentyl; Rm represents H, methyl, CF3, methoxy, F or Cl; and Rya represents H or, particularly, methyl.

4. A pharmaceutical formulation containing a compound as defined in any one of claims 1 to 3, or a pharmaceutically acceptable derivative thereof, in admixture with an adjuvant, diluent or carrier acceptable for pharmaceutical use.

5. A compound as defined in any one of claims 1 to 3, or a derivative thereof acceptable for pharmaceutical use, for use as a pharmaceutical compound.

6. The use of a compound as defined in any one of claims 1 to 3, or a derivative thereof acceptable for pharmaceutical use, as an active ingredient for the manufacture of a medicament for the treatment of a condition wherein the Thrombin inhibition is beneficial.

7. A method or treatment of a condition wherein the inhibition of thrombin is beneficial, which method comprises administering a therapeutically effective amount of a compound as defined in any of claims 1 to 3, or a derivative thereof acceptable for pharmaceutical use, to a person suffering from such a condition, or who is susceptible to it.

8. A process for the preparation of a compound of the formula I as defined in claim 1, which comprises: (a) for the compounds of the formula I in which the group G represents (i) C (O) ) N (R8a) - [CH (C (O) R9)] 0-1-alkylene of 0 to 3 carbon atoms- (Q1) a-, (ii) C (O) N (R8b) -a! Quenylene of 2 to 3 carbon atoms- (Q1) a-, (iii) C (O) N (R8) -alkynylene of 2 to 3 carbon atoms- (Q1) a-, (iv) (v) wherein Q2a represents N or NHCH, coupling a compound of formula II, wherein the dotted line, R1, R2, R3a, R3b, A, D and E are as defined in claim 1, with a compound of the formula III, H-Ga-L wherein L is as defined in claim 1 and Ga represents (i) -N (R8a) - [CH (C (O) R9)] 0 -? - alkylene of 0 to 3 carbon atoms- (Q1) a-, (ii) -N (R8b) -alkenylene of 2 to 3 carbon atoms- (Q1) a- (iii) -N (R8b) -alkynylene of 2 to 3 carbon atoms- (Q1) a- (iv) (v) where Q * 2 ^ aa represents N or NHCH and Raa, RBD, R8C, Rs, Q, Q and a are as defined in claim 1 (b) for the compounds of the formula I in which G represents and L represents La, whose last group represents L as defined in claim 1, except that it does not represent C 0 -Calkylene-Ra, cyclization of a compound of formula IV, wherein La is as defined above, and the dotted line, R1, R2, R3a, R3b, A, D and E are as defined in claim 1; (c) for the compounds of the formula I in which Ra, Rb, Rc or Rd represents -C (= NH) NH2, -C (= NNH2) NH2 or -C (= NOH) NH2, reaction of a compound of the formula V, wherein Lb represents L as defined in claim 1, except that Ra, Rb, Rc or Rd (as appropriate) is replaced by a cyano group or -C (= NH) O-alkyl of 1 to 4 carbon atoms carbon, and the dotted line, R1, R2, R3a, R3b, A, D, E, and G are as defined in claim 1, with an appropriate source of ammonia, hydrazine or hydroxylamine; (d) for the compounds of the formula I in which R13a, R13b or R13c represents H, deprotection of a corresponding compound of the formula I in which R13a, R13b or R13c, (as appropriate) represents C (O) O -CH2aryl; (e) for the compounds of the formula I in which R14c represents H, deprotection of a corresponding compound of the formula I in which R14c represents C (O) O-alkyl of 1 to 6 carbon atoms; (f) reaction of a compound of formula VI, wherein the dotted line, R2, R3a, R3b, A, D, E, G and L are as defined in claim 1, with a compound of the formula VIL R1-A-Lg1 VI wherein Lg1 represents a suppressive group and R1 and A are as defined in claim 1; (g) for the compounds of the formula I in which A represents C (O) NH, the reaction of a compound of the formula VI, as defined above, with a compound of the formula VIII, R1_N = C = O VI wherein R1 is as defined in claim 1; (h) for the compounds of the formula I in which A represents alkylene of 1 to 6 carbon atoms, the reaction of a compound of the formula VI, as defined above, with a compound of the formula IX, R1-alkylene of O to 5 carbon atoms-CHO IX wherein R1 is as defined in claim 1, followed by reduction in the presence of a reducing agent; or (i) for the compounds of the formula I in which Ra, Rb, Rc or Rd represents -C (= NCN) NH2, reaction of a corresponding compound of the formula I in which Ra, Rb, RQ or Rd, respectively, represents -C (= NH) NH2 with cyanogen bromide.

9. A compound of formula II, as defined in claim 8, or a derivative protected therefrom.

10. A compound of formula IV, as defined in claim 8, or a derivative protected therefrom.

11. A compound of formula VI, as defined in claim 8, or a derivative protected therefrom.