MXPA06009847A - BETA-AMINOACID-DERIVATIVES AS FACTOR Xa INHIBITORS - Google Patents

Abstract

The present invention relates to compounds of the Formula (I), in which R°;R1;R2;R3;R4;R5;R6;Q;V;G and M have the meanings indicated in the claims. The compounds of the formula I are valuable pharmacologically active compounds. They exhibit a strong antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of cardiovascular disorders like thromboembolic diseases or restenoses. They are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and/or factor VIIa (FVIIa), and can in general be applied in conditions in which an undesired activity of factor Xa and/or factor VIIa is present or for the cure or prevention of which an inhibition of factor Xa and/or factor VIIa is intended. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

Description

BETA-AMINO ACIDS DERIVATIVES AS INHIBITORS OF THE XA FACTOR The present invention relates to the compounds of the formula I, where R °, R1, R2, R3, R4, R5, R6, Q, V, G and M mean as indicated below. The compounds of the formula I are valuable pharmacologically active compounds. They show a strong antithrombotic effect and are suitable, for example, in the treatment and prophylaxis of cardiovascular disorders such as thromboembolic diseases or restenosis. They are reversible inhibitors of the blood coagulation enzymes factor Xa (FXa) and / or Vlla (FVlla) and, in general, can be applied in diseases in which there is an undesired activity of factor Xa and / or Vlla factor, or when it is intended to cure or prevent by inhibiting factor Xa and / or factor Vlla. Furthermore, the invention relates to the processes for preparing the compounds of the formula I, their use, in particular as ingredients in the drugs and in the pharmaceutical preparations comprising them. Normal hemostasis is the result of a complex balance between the procedures of initiation of coagulation, formation and dissolution of clots. The complex interactions between blood cells, Specific proteins of the plasma and vascular surface maintain fluidity of the blood unless a wound or hemorrhage occurs (EP-A-987274). Many significant disease states are related to abnormal hemostasis. For example, the formation of the local thrombus that is due to the rupture of an atherosclerotic plaque is an important cause of acute myocardial infarction and unstable angina. The treatment of a coronary thrombus obliterans by both thrombolytic therapy and percutaneous angioplasty may be accompanied by a new thrombolytic closure of the affected vessel. Safe and effective therapeutic anticoagulants are still needed to limit or prevent the formation of thrombi. It is more desirable to develop drugs that inhibit coagulation without directly inhibiting thrombin but by inhibiting other stages in the coagulation cascade, such as factor Xa activity and / or factor Vlla. It is now believed that factor Xa inhibitors carry a lower risk of hemorrhage than thrombin inhibitors (A. E. P. Adang &J. B. M. Rewinkel, Drugs of the Future 2000, 25, 369-383). Inhibitors of factor Xa-specific and low molecular weight blood clots have been described that are effective but do not cause undesirable side effects, for example, in WO-A-95/29189. However, in addition to being an effective factor Xa blood clot inhibitor, it is desirable that such inhibitors also have more advantageous properties, for example, stability in plasma and liver, and selectivity to other serine proteases whose inhibition is not pursued, such as thrombin. There is a progressive need for more inhibitors of blood clots specific to low molecular weight factor Xa, which are effective and also have the above advantages. Specific inhibition of the catalytic factor factor Vlla / tissue factor using monoclonal antibodies (WO-A-92/06711) or a protein such as factor Vlla inactivated with chloromethyl ketone (WO-A-96/12800, WO-A-97 / 47651) is a very effective means of controlling the formation of thrombi caused by acute arterial injury or thrombotic complications related to bacterial septicemia. There is also experimental evidence to suggest that inhibition of Vlla factor / tissue factor activity inhibits restenosis after balloon angioplasty. Mandrel hemorrhage studies have been performed and indicate that the inhibition of the Vlla factor / tissue factor complex has the widest window of safety in relation to therapeutic efficacy and with the risk of hemorrhage from any proven anticoagulant approach., among them the inhibition of thrombin, thrombocytes and factor Xa. Some Vlla factor inhibitors have already been described. EP-A-987274, for example, describes the compounds containing a tripeptide unit, which inhibit factor Vlla. However, the profile of the properties of these compounds is still not ideal and there is a progressive need for more inhibitors of low molecular weight inhibitor blood clots of factor Vlla. The present invention satisfies the above needs by providing new compounds of the formula I, which show a better inhibitory activity of factor Xa and / or Vlla factor and that are favorable drugs with great bioavailability. Thus, the present invention relates to the compounds of the formula I, R ° is 1) a heterocyclyl extracted from the group of acridinyl, azabenzimidoazolyl, azaspirodecanyl, azepinyl, azetidinyl, aziridinyl, benzimidazolyl, 1,3-benzodioxoyl, benzofuranyl, benzothienyl, benzothiofu-ranyl, benzothiophenyl, benzoxazolyl, benzothiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 4,5-dihydrooxa-zolinyl, dioxazolyl, dioxazinyl, 1,3-dioxolanyl, 1,3-dioxolyl, 6H-1, 5,2- dithiazinyl, dihydrofuro [2,3-b] -tetrahydrofuranyl, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, indanyl, 1 H-indazolyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, sochromanyl, isoindazolyl, isoindolinyl, isoindolyl , isoquinolinyl, isothiazolyl, isothiazolidinyl, isothiazolinyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, 2-isoxazolinium, cetopiperazinyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, or xadiazolyl, 1, 2,3-oxadiazolyl, 2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,4-oxadiazoliol, 1,2-oxa-tetrapanyl, 1,2-oxathiolanyl, 1,4 -oxazepanyl, 1,4-oxazepinium, 1,2-oxazinyl, 1,3-oxazinyl, 1,4-oxazinyl, oxazolidinyl, oxazolinyl, oxazolyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phenylpyridyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridoimidazolyl, pyridooxazolyl, pyridopyrimidinyl, pyridothiazolyl, pyridothienyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinolyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, 1, 4,5,6-tetrahydropyridazinium, tetrahydropyranyl, tetrahydropyridinyl, tetrahydrothiophenyl, tetrazinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolium, thianthrenyl, 1,2-thiazolinyl, 1,3-thiazinyl, 1,4- thiazinyl, 1,3-thiazolyl, thiazolyl, thiazolidinyl, thiazolidyl, thienyl, thietanyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thietanyl, thiomorpholinyl, thiophenolyl, thiophenyl, thiopyranyl, 1,2,3-triazinyl, 1,4-triazinyl, 1,3,5-triazinyl, 1, 2,3-triazoyl, 1, 2,4-triazolyl, 1,2,5-triazolyl, 1,4-triazolyl and xanthenyl, wherein said heterocyclyl is unsubstituted or mono-, di- or trisubstitutes independently from each other, by R8 or 2) an aryl of 6 to 14 members which are obtained from the phenyl, naphthyl, biphenylyl, 2-biphenylyl, 3-biphenylyl, 4-biphenylyl, anthryl or fluorenyl group, in which the aryl is mono- or di-substituted independently of one another by R8, R8 is a halogen, carbamimidoyl, -N02, -CN, -C (0) -NH2, -OH, -NH2, -O-CF3, -O- (C? -C8) -alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by a halogen, NH2, -OH or a methoxy, or - (C? -C s) -alkyl moiety, in which the alkyl is unsubstituted or mono-, di- or trisubstituted independently of others by a halogen, NH2, -OH or a methoxy moiety, or -SO2-CH3 or -SO2-CF3, provided that R8 is at least one halogen, -C (O) -NH2 or a -O- moiety (C ? -C8) -alkyl, Q is a direct bond, - (C0-C2) -alkyl-C (O) - (Co-C2) -alkyl, - (CrC6) -alkylene, - (C0-C3) -alkylene -S (O) 2- or - (C0-C2) -alkylene-NR10-C (O) -O- (Co-C2) -alkylene, wherein R10 is as defined below, and wherein the Alkylene moieties are unsubstituted or mono-, di- or trisubstituted independently from one another by a halogen, -NH2, -OH or - (C3-C6) -cycloalkylene, in which the cycloalkylene is unsubstituted or mono- , di- or trisubstitutes independently of each other by a halogen, -NH2 or -OH; R1 is a hydrogen atom, - (C? -C4) -alkyl, wherein the alkyl is unsubstituted or substituted one to three times by R13; - (C1-C3) -alkyl-C (O) -NH-R °, - (C? -C3) -alkylene-C (O) -O-R10, an aryl with 6 to 14 members that are obtained from the group phenyl, naphthyl, biphenylyl, 2-biphenylyl, 3-biphenylyl, 4-biphenylyl, anthryl or fluorenyl, in which the aryl is mono-, di- or trisubstituted independently from each other by R8, - (C0-C4) -aIquilen -heterocyclyl, wherein the heterocyclyl is as defined above and is unsubstituted or mono-, di- or trisubstituted independently from each other by R 14, - (C? -C3) -perfluoroalkyl, - (C? -C3) -alkylene-S (O) - (C? -C4) -alkyl, - (C1-C3) -alkylene-S (O) 2- (C? -C3) -alkyl, - (C1-C3) -alkylene- S (O) 2-N (R4 ') - R5', - (C1-C3) -alkylene-O- (C? -C4) -alkyl or - (Co-C3) -alkylene- (C3-C8) - cycloalkyl, R4 and R5 are independently one of the other, are identical or different and are a hydrogen atom or - (C? -C4) -alkyl, R2 is a direct bond or - (CrC4) -aIquinene or R1-N-R2-V forms a cyclic group of 4 to 10 members which are obtained from the group azepine, azetidine, dioxazole, dioxazine, 1,2-diazepine, 1, 3-diazepine, 1, 4-diazepine, 2,3 dihydroindole, imidazole, imidazoline, imidazolidine, indole, isothiazole, isothiazolidine, isothiazoline, isoxazoline, isoxazolidine, 2-isoxazoIina, ketopiperazine, morpholine, 1, 4-oxazepam, 1 , 2-oxa-tiepan, 1, 2-oxathiolane, 1, 2-oxazine, 1, 3-oxazine, 1, 4-oxazine, oxazole, piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyrrole, pyrrolidine, pyrrolidinone , pyrroline, tetrahydropyridine, thiazolidine, thiazoline or thiomorpholine, wherein said cyclic group is unsubstituted or mono- or independently di- trisustituye one another by R14, V is 1) a heterocyclyl as defined for R °, on the said heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently by R 14 or 2) an aryl as defined for R °, wherein the aryl is mono-, di- or trisubstituted independently of others by R14, R14 is a halogen, -OH, = O, - (CrC8) -alkyl, - (C? -C) -alkoxy, -NO2, - (C0-C4) -alkyl-C (O) -O-R18, -CN, - (C0-C4) -alkyl-N (R18) -R21, - (C0-C4) -alkyl-O-R18, - (Co-C4) -alkylene-heterocyclic , wherein the heterocyclyl is as defined above and wherein the heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R 13, - (C0-C8) -alkyl-SO2- (C? -C4) -alkyl, -S-R18, - (Co-C8) -alkyl-S? 2- (C1-C3) -perfluoroaIlkyl, - (C0-C8) -alkyl-SO2-N (R18) -R21, -CF3, -C (O) -N (R18) -R21, -NR ^ -CIOJ-NH-id-C ^ -alkyl, - (C0-C3) -Ilkyl- (C? -C3) -perfluoroalkyl, or -NR18-C (O) -N - [(C? -C8) -alkyl] 2, wherein R18 and R21 are independently from each other, hydrogen atom, - (C0-C6) -aIquiN (R22) -R23, - (C0-C6) -alkyl-O-R22, - (C0-C6) ) -alkyl-heterocyclyl, wherein the heterocyclyl is as defined above and wherein the heterocyclyl is unsubstituted or is mono-, di- or trisubstituted independently from each other by R 13, - (C0-C6) -alkyl- N (R22) -C (O) -N (R22) -R23, - (C-C6) -Ilkyl-C (O) -O-R22, - (dC ^ -alkyl, - (C0-C6) - alkyl-C (O) -N (R22) -R23, - (C0-C6) -alkyl-SO2-R22 or - (C? -C3) -perfluoroalkyl, wherein R22 and R23 are independently from each other hydrogen, - (C? -C3) -perfluoroalkyl, - (C3-C6) - cycloalkyl or - (Ci-C? J-alkyl, G is a direct bond, - (CH2) m-NR10-SO2-NR10- (CH2) n-, - (CH2) m- CH (OH) - (CH2) n-, - (CH2) m-, - (CH2) mO- (CH2) n-, - (CH2) m C (O) -NR10 _ (CH2) n-, - (CH2) -SO2- (CH2) n-, - (CH2) m-NR10-C (O) -NR10- (CH2) n-, - (CH2) m-NR10-C (O) - (CH2) n-, - (CH2) mC (O) - (CH2) n-, - (CH2) -S- (CH2) n-, - (CH2) m-SO2-NR10- (CH2) ) n-, - (CH2) m-NR10-SO2- (CH2) n-, - (CH2) m-NR10-, - (CH2) mOC (O) -NR10 - (CH2) n- or - (CH2) m-NR10-C (O) -O- (CH2) n-, n and m are independently identical or different and are the integers zero, 1, 2, 3, 4 , 5, or 6, M is 1) an aryl of 6 to 14 members obtained from the phenyl, naphthyl, biphenylyl, 2-biphenylyl, 3-bifeniIiIo, 4-biphenylyl, anthryl or fluorenyl, wherein the aryl is unsubstituted or mono-, di- or independently trisustituye one another by R14, or 2) a monocyclic or bicyclic heterocyclyl of 3 to 15 members obtained from the group acridinyl, azaindole (1H-pyrrolopyridinyl), azabencimidoazolilo, azaspirodecanilo, azepinyl, azetidinyl, aziridinyl, azirinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxathiolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, carbazolyl, 4aH-carbazoyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 1,4-diazepanyl, 1,2-diazepinium, , 3-diazepinyl, 1,4-diazepinyl, diaziridinyl, diazirinyl, dihidroimidazolonilo, 4,5-dihidrooxazolinilo, dioxazolyl, dioxazinyl, dioxolyl, 1, 3-dioxoIanilo, 1,3-dioxolnilo, 3,3-dioxo- (1 3,4) oxathiazine, 6H-1, 5,2-dithiazinyl, dihydrofuro [2,3-b] -tetrahydrofuranyl, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolinyl, indolizinyl, indolyl, 3H-indole, sobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl (benzimidazolyl), isothiazolyl, isothiazolidinyl, isothiazolinyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, 2-isoxazolinyl, cetomorpholinyl, cetopiperazinyl, morpholinyl, naphthyridinyl , octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, [1,3,4] oxathiazine 3,3-dioxidyl , 1,2-oxa-triestanyl, 1,2-oxathiolanyl, 1,4-oxazepanyl, 1,4-oxazepinyl, 1,2-oxazinyl, 1,3-oxazinyl, 1,4-oxazinyl, oxazolidinyl, oxazolidinonyl, oxazolinyl , oxazolonyl, oxazolyl, oxetanyl, oxiranyl, oxocanyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxyntinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperazin-2-onyl, piperidinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazin-2-on -yl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridinon-yl, pyridooxazolyl , pyridoimidazolyl, pyridothiazolyl, pyridyl, pyrimidinyl, pyrimidine-2,4-dion-yl, pyrrolidinyl, pyrrolidinonyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydropyridinyl, tetrahydrothiophenyl, tetrazinyl, tetrazolyl, 6H-1,2,5-thiadiazinium, 1, 2,3-thiadiazolium, 1,2,4-thiadiazolium, 1, 2,5-thiadiazolyl, 1, 3, 4-thiadiazolium, thianthrenyl, 1,2-thiazolinium, 1,3-thiazinyl, 1,4-thiazinyl, 1,3-thiazolyl, thiazolyl, thiazolidinyl, thiazoylinyl, thienyl, thietanyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thietanyl, thiomorpholinyl, thiomorpholine 1, 1-dioxidyl, thiophenolyl, thiophenyl, thiopyranyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1, 2,3-triazolyl, 1, 2,3 -triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1, 3,4-triazoly and xanthenyl, wherein the heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R14, as long as M contains or is substituted with at least one oxo- moiety, R3, R4, R5 or R6 are independent of each other and are identical or different and are 1) hydrogen atom 2) halogen 3) - (C ^ -C4) -alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, 4) - (C? -C3) -perfluoroalkyl, 5) phenyl, wherein the phenyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, 6) - (Co-C4) -alkylene-O-R19, wherein R19 is a) hydrogen atom b) - (C? -C) -alkyl , wherein the alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, or c) phenyl, wherein the phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R13, d) -CF3, oe) -CHF2 7) -N02, 8) -CN, 9) - SOs-R11, wherein s is 1 or 2, 10) -SOfN (R11) -R12 > wherein t is 1 or 2, 11) - (C0-C4) -alkylene-C (O) -R11, 12) - (C0-C4) -alkylene-C (O) -O-R11, 13) - (C0-C4) -alkylene-C (O) -N (R11) -R12, 14) - (C0-C4) -alkyl-N (R11) -R12, 15) -NR11-SO2-R12, 16) - S-R10, 17) - (C0-C2) alkylene-C (O) -O- (C2-C4) -alkylene-OC (O) - (C? -C4) -alkyl, 18) -C (O) -OC (R15, R16) -OC (O) -R17, 19) - (C0-C2) alkylene-C (O) -O- (C2-C4) -alkylene-OC (O) -O- (C? -C6) -alkyl, 20) -C (O) -O-C (R15, R16) -OC (O) -O-R17, 21) - (C? -C4) -alkylene- (C6-C? 4 ) -aryl, in which the aryl is mono-, di- or trisubstituted independently from each other by R 3, 22) - (C? -C4) -alkylene- (C -Ci5) -heterocyclyl, in which the heterocyclyl it is not substituted or it is mono-, di- or trisubstituted independently of one another by R 13, 23) - (C? -C) -alkylene- (C 3 -C 8) -cycloalkyl, wherein the cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R 13 , 24) - (C? -C4) -alkylhene-het, in which het is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, 25) - (C0-C4) -alkylene-O -CH2- (C? -C3) -perfluoroalkyl-CH2-O- (C0-C4) -alkyl, 26) -SOw-N (R11) -R13, wherein w is 1 or 2.27) - (C0-C4) -alkylene-N (R) -C (O) -R12, 28) - (C0-C4) -alkylene-N (R1) -C (O) -O-R12 or 29) a residue from the following list if two residues -OR19 are linked to adjacent atoms they can form together with the atoms with which they are linked a ring of 5 or 6 members, which is not replaced or is replaced one, two, three or four times by R13, as long as the rest -NH-CH2 (R) -R3, which is part of the formula I, is not one of the following residues of the bond -NH-CH2 (R4) -N- or -N- CH2 (R4) -O-, wherein R4 is as defined above, or R3 and R4 or R5 and R6 together with the carbon atom to which they are attached form a ring of 3 to 8 members which are obtained from the azetidine, azocane group, azocan-2-one, cyclobutyl, cycloheptyl, cyclohexyl, cyclooctane, cyclooctene, cyclopropyl, 1,4-diazepam, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, [1,4] diazocane, [ 1,2] diazocan-3-one, [1,3] diazocan-2-one, dioxazine, [1,4] dioxocane, dioxol, cetopiperazine, morpholine, 1,2-oxa-tiepan, 1,4-oxacepan, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, [1,4] oxazocane, [1, 3] oxazocan-2-one, oxetane, oxocane, oxocan-2-one, piperazine, piperidine, pyrano, 5,6,7,8-tetrahydro-1H-azocin-2-one, thiomorpholine or tetrahydrofuran, wherein said ring is unsubstituted or mono-, di- or trisubstituted independently from each other by R 13, or R 3 and R 5 or R 4 and R 6 together with the carbon atoms to which they are bound form a ring of 4 to 8 members which are obtained from the group azetidine, azocan, azocan-2-one, cyclobutyl, cycloheptyl, cyclohexyl, cyclooctane, cyclooctene, cyclopropyl, 1,4-diazepam, 1,2-diazepine, 1,3-diazepine , 1, 4-diazepine, [1,4] diazocane, [1,2] diazocan-3-one, [1,3] diazocan-2-one, dioxazine, [1,4] dioxocane, dioxole, cetopiperazine, morpholine , 1,2-oxa-tiepan, 1,4-oxacepan, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, [1,4] oxazocane, [1, 3] oxazocan-2-one , oxetane, oxocane, oxocan-2-one, piperazine, piperidine, pyrano, 5,6,7,8-tetrahydro-1H-azocin-2-one, thiomorpholine or tetrahydrofuran, in that said ring is unsubstituted or mono-, di- or trisubstituted independently of one another by R13, R11 and R12 are independently identical or different from each other and are 1) hydrogen atom 2) - (C? -C6) -alkyl, in which the alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13, 3) - (Co-C6) -alkyl- (C3-C8) -cycloalkyl, 4) -SOt -R10, wherein t is 1 or 2, 5) - (Co-C6) -alkyl- (C6-C? 4) -aryl, in which the alkyl and the aryl independently of each other are not substituted or mono-, di- or trisubstituted by R13, 6) - (C? -C3) -perfluoroalkyl, 7) -O-R17, or 8) - (Co-C6) -a! quil- (C -Ci5) -heterocyclic ilo as defined for R °, wherein alkyl and heterocyclyl independently of each other are unsubstituted or mono-, di- or trisubstituted by R13, or R11 and R12 together with the nitrogen atom to which they are attached can form a 4- to 8-membered monocyclic heterocyclic ring, which, in addition to the nitrogen, may contain one or two identical or different ring heteroatoms which are selected from oxygen, sulfur or nitrogen, wherein said heterocyclic ring is unsubstituted or mono-, di- or trisubstituted independently of each other by R13, R13 is Halogen, -NO2, -CN, = O, -OH, -CF3, -C (O) -O-R10, -C (O) - N (R10) -R20, -N (R10) -R20, - (C3-C8) -cycloalkyl, - (C0-C3) -alkylen-O-R10, -Si- (CH3) 3, -N (R10) -S (O) u-R10, wherein u is 1 or 2, -S-R10, -SOrR10, wherein r is 1 or 2, -S (O) vN (R10) -R20, wherein v is 1 or 2, -C (O) -R10, - (d-C8) -alkyl, - (d- C8) -alkoxy, phenyl, phenyloxy-, - (C? -C3) -perfluoroalkyl, - (C0-C4) -alkyl-C (O) -O-C (R15, R16) -OC (O) -R17, -O-R15, -NH-C (O) -NH-R10, -O- CF3, - (C0-C4) -alkyl- C (O) -OC (R15, R16) -OC (O) -O-R17, -NH-C (O) -O-R10, or a residue of the following list R10 and R20 are independently from each other hydrogen, halogen, - (d-C6) -alkyl, - (C0-C4) -alkyl-OH, - (Co-C) -alkyl-O- (C? -C4) - alkyl or - (C? -C3) -perfluoroalkyl, R15 and R16 are independently of each other hydrogen, - (C1-Ce) -alkyl, or together with the carbon atom to which they are attached they can form a carbocyclic ring of 3 to 6 members which is unsubstituted or substituted one to three times by R10, and R17 is- (C? -C6) -alkyl, - (d-C6) -alkyl-OH, - (d-C6) -alkyl- O- (C? -C6) -alkyl, - (C3-C8) -cycloalkyl, - (C? -C6) -alkyl-O- (C? -8) -alkyl- (C3-C8) -cycloalkyl , - (d-C6) -alkyl- (C3-C8) -cycloalkyl, wherein said ring of cycloalkyl is unsubstituted or is replaced one, two or three times by -OH, -O- (C? -C4) -alkyl or R10, in all its steroisomeric forms and mixtures thereof in any proportion, and their physiologically tolerable salts. XXX2) The present invention also relates to the compounds of the formula I, wherein R ° is 1) phenyl or naphthyl, wherein the phenyl or the naphthyl is mono-, di- or trisubstituted independently from each other by R8 , 2) a heterocyclyl of the acridinyl group, azabenzimidoazolyl, azaspirodecanyl, azepinyl, azetidinyl, aziridinyl, benzimidazoiyl, 1,3-benzodioxolyl, benzofuranyl, benzothienyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, carbazolyl, is obtained. , 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 4,5-dihydrooxa-zolinyl, dioxazolyl, dioxazinyl, 1,3-dioxolanyl, 1,3-dioxolyl, 6H-1, 5,2-dithiazinyl, dihydrofide [2,3-b] -tetrahydrofuranyl, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, indanyl, 1H-indazolyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, sochromanyl, isoindazolyl, isoindolini isoindolyl, isoquinolinyl, isothiazolyl, isothiazolidinyl, isothiazolinyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, 2-isoxazolinyl, cetopiperazinyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,3-oxadiazolyl, 1,4-oxadiazolyl, , 2,5-oxadiazolyl, 1,4-oxadiazolyl, 1,2-oxa-tetrapanyl, 1,2-oxathiolanyl, 1,4-oxazepanyl, 1,4-oxazepinyl, 1,2-oxazinyl, 1,3 -oxazinyl, 1,4-oxazinyl, oxazolidinyl, oxazolinyl, oxazolyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phenylpyridyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridoimidazolyl, piridooxazolilo, pyridopyrimidinyl, piridotiazolilo, pyridothienyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinolyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, 1, 4,5,6-tetrahydropyridazinyl, tetrahydropyranyl, tetrahydropyridinyl, tetrahydrothiophenyl, tetrazinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1, 2,5-thiadiazolyl, 1,4-thiadiazolyl, thiantrenyl, 1,2-thiazinyl, 1, 3-thiazinyl, 1, 4-thiazinyl, 1, 3-tiazoliIo, thiazolyl, thiazolidinyl, thiazolinyl, thienyl, thietanyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thietanyl, thiomorpholinyl, thiophene lilo, thiophenyl, thiopyranyl, 1,2,3-triazinyl, 1,4-triazinyl, 1, 3,5-triazinyl, 1,2,3-triazolyl, 1,4-triazolyl, 1, 2, 5-triazolyl, 1,4-triazolyl and xanthenyl, wherein said heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R8, R8 is halogen, carbamimidoyl, -NO2, -CN, -C (O) -NH2, -OH, -NH2, -O-CF3, -O- (C? -8) -alkyl, wherein the alkyl is unsubstituted or mono- or di-substituted independently of one another by halogen, NH2, -OH or a methoxy, or - (C? -8) -alkyl moiety, in which the alkyl is unsubstituted or mono- , di- or trisubstitutes independently from each other by halogen, NH2, -OH or a methoxy moiety, or - SO2-CH3 or -SO2-CF3, provided that R8 is at least one halogen, -C (O) -NH2 or a residue -O- (C? -C8) -alkyl, Q is - (C0-C2) -alkylene-C (O) - (Co-C2) -alkylene- or -SO2-, wherein the alkylene moiety is unsubstituted or mono-, di- or trisubstituted independently of others by halogen, -NH2, -OH or - (C3-C6) -cycloalkylene, in which the cycloalkylene is unsubstituted or mono-, di- or trisubstituted independently from each other by halogen, -NH2 or -OH; R1 is a hydrogen atom, - (C? -C4) -alkyl, in which the alkyl is unsubstituted or is substituted one to three times by R13; - (C1-C3) -alkylene-C (O) -NH-R °, - (C? -C3) -alkylene-C (O) -O-R10, an aryl of the phenyl, naphthyl, biphenylyl, anthryl or fluorenyl, in which the aryl is mono-, di- or trisubstituted independently from each other by R8, - (d-C3) -perfluoro-alkyl, - (C? -C3) -alkylene-S (O) - (C1 -C4) -alkyl, - (d-C3) -alkylene-S (O) 2- (C? -C3) -alkyl, - (d-C3) -alkylene-S (O) 2-N (R4 ') -R5 ', - (C1-C3) -alkylene-O- (C1-C4) -alkyl, - (Co-C3) -alkylene- (C3-C8) -cycloalkyl or - (C0-C3) -alkylene-het wherein het is a residue eobtiene the group azepine, azetidine, aziridine, azirine, 1, 4-diazapan, 1, 2-diazepine, 1, 3-diazepine, 1,4-diazepine, diaziridine, diazirine, dioxazole , dioxazine, dioxole, 3-dioxolno, 1, 3-dioxolane, furan, imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, ketopiperazine, morpholine, 1, 4-oxazepam, 1, 2-oxa-tiepan, 1,2-oxathioanane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazole, oxaziridine, oxirane, piperaz ina, piperidine, pyran, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tetrazine, tetrazole, thiadiazine, thiadiazole, 1,2-thiazine, 1, 3-thiazine, 1,4-thiazine, 1,3-thiazole, thiazole, thiazolidine, thiazoline, thienyl, tietan, thiomorpholine, thiopyran, 1,2,3-triazine, 1,4-triazine, 1, 3,5-triazine, 1,2,3-triazole or 1,4-triazole, wherein het is unsubstituted or mono-, di- or independently trisustituye one another by R14, R4 and R5 are independently of one another identical or different and are hydrogen atom or - (CrC) -aIquilo, R2 is a direct bond or - (C? -C4) -alkylene, or R1-N-R2-V form a cyclic group of 4 to 10 members which are obtained from the azepine, azetidine, dioxazole, dioxazine, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine group, , 3-dihydroindole, imidazole, imidazoline, imidazolidine, indole, isothiazole, isothiazolidine, isothiazoline, isoxazoline, isoxazolidine, 2-isoxazoline, cetopiperazine, morpholine, 1,4-oxacepan, 1,2-oxa-tiepan, 1,2-oxathiolane , 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazole, piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, thiazolidine, thiazoline or thiomorpholine, in wherein said cyclic group is unsubstituted or mono- or di-substituted independently of one another by R 14, V is 1) a heterocyclyl as defined for R °, wherein said heterocyclyl is unsubstituted or mono-, di- - or independently replaces one another by R 14 or 2) an aryl as defined for R °, wherein the aryl is mono-, di- or trisusti independently of one another by R14, R14 is halogen, -OH, = O, - (d-C8) -alkyl, - (C? -C4) -alkoxy, -NO2, - (C0-C4) -alkyl C ( O) -O-R18, -CN, - (C0-C4) -alkyl-N (R18) -R21, - (C0-C4) -alkyl-O-R18, - (Co-C) -alkylene-heterocyclyl, in which the heterocyclyl is a residue that is selected from azetidine, azetidinone, piperidine, piperazine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, 1,2,3-triazine, 1,4-triazine, 1,3-triazine, 1,2,3-triazole , 1, 2,4-triazole, tetrazine, tetrazole, 1,4-diazepam, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, azepine, cetopiperazine, 1,4-oxacepan, oxazole, isoxazole , isoxazolidine, 2-isoxazoline, morpholine, thiazole, isothiazole, thiadiazole or thiomorpholine, - (C0-C8) -alkyl-SO2- (C? -C4) -alkyl, - (C0-C8) -alkyl-SO2- (C? -C3) -perfluoroalkyl, -CF3, - (C0-C8) -alkyl-SO2-N (Ri8) -R21, -C (O) -N (R18) -R21, -NR18-C (O) -NH- (d-C8) -alkyl, -S-R18, - (C0-C3) -alkyl- (C? -C3) -perfluoroalkyl, or -NR18-C (O) -NH - [(d-C8 ) -alkyl] 2, wherein R18 and R2 are independently from each other hydrogen atom, - (C0-C6) -alkyl-N (R22) -R23, - (C0-C6) -alkyl-O-R22, - (C0-C6) -alkyl-heterocyclyl, wherein the heterocyclyl is a moiety selected from azetidine, azetidinone, piperidine, piperazine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, , 2,3-triazine, 1, 2,4-triazine, 1, 3,5-triazine, 1,2,3-triazole, 1,2,4-triazole, tetrazine, tetrazole, 1,4-diazepam, 1 , 2-diazepine, 1,3-diazepine, 1,4-diazepine, azepine, cetopiperazine, 1,4-oxacepan, oxazole, isoxazole, isoxazolidine, 2-isoxazoline, morpholine, thiazole, isothiazole, thiadiazole or thiomorpholine, and in that the heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13, - (C0-C6) -alkyl-N (R22) -C (O) -N (R22) -R23, - ( C0-C6) -alkyl-C (O) -O-R22, - (d-C6) -alkyl, - (C0-C6) -alkyl-C (O) -N (R22) -R23, - (C0-) C6) -alkyl-SO2-R22o - (C? -C3) -perfluoroalkyl, wherein R22 and R23 are independently from each other a hydrogen atom, - (d-C3) -perfluoroalkyl, - (C3-C6) - cycloalkyl or - (d-Cß) -alkyl, G is a direct bond, - (CH2) m-NR10-SO2-NR10- (CH2) n-, (CH2) m-, - (CH2) mC (O) -NR10 _ (CH2) n-, - (CH2) ) -SO2- (CH2) n -, - (CH2) m NR10-C (O) -NR10- (CH2) n-, - (CH2) m-NR10-C (O) - (CH2) n-, - (CH2) mC (O) - (CH2) n-, - (CH2) m-SO2-NR10- (CH2) n-, - (CH2) m-NR10-SO2- (CH2) n-, n and m are independently one of other identical or different and are the integers zero, 1, 2, 3, 4, 5 or 6. M is heterocyclyl, in which the heterocyclyl is a residue of the group that can be derived from azepam, azepine, 1, 4- diazepam, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, dihydropyrimidinone, dihydroimidazolone, 3,3-dioxo- (1, 3,4) oxathiazine, imidazole, imidazolidinone, isothiazole, isoxazole, isoxazolidine, 2-isoxazoline, ketomorpholine, cetopiperazine, morpholine, morpholinone, oxazole, oxazolone, oxazolidinone, [1,4] -oxacepan, piperazine, piperazinone, piperidine, piperidinone, pyrazine, pyridazine, pyridazinone, pyridine, pyridone, pyrimidine-2,4- dione, pyrimidine, pyrimidinone, pyrimidinedione, pyrrolidine, pyrrolidinone, tetrahydropyran, 1, 4,5,6-tetrahydro-pyridazinyl, tetrahydro-pyrimidinone, tetrazine, tetrazole, thiadiazole, thiazole, thiophene, thiomorpholine, 1,1-dioxido-thiomorpholine, pyrazinone, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,4-triazole, wherein said heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently of each other by R 14, provided that M contains or is substituted with less an oxo-, R3, R4, R5, or R6 residue are independently identical or different from each other and are 1) hydrogen atom, 2) halogen, 3) - (C? -C4) -alkyl, in which the alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R13, 4) - (C? -C3) - perfluoroalkyl, 5) phenyl, in which the phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13, 6) - (C0-C4) -alkylene-O-R19, wherein R19 is a) hydrogen atom b) - (C? -C4) -alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, or c) phenyl, wherein the phenyl it is unsubstituted or mono-, di- or trisubstituted independently of one another by R13, d) -CF3, e) -CHF2, 7) -NO2) 8) -CN, 9) -SOs-R11, wherein is 1 or 2, 10) -SOt-N (R11) -R12, wherein t is 1 or 2, 11) - (C0-C4) -alkylene-C (O) -R11, 12) - (C0-) C4) -alkylene-C (O) -O-R11, 13) - (C0-C4) -alkylene-C (O) -N (R11) -R12, 14) - (C0-C4) -alkylene-N ( R11) -R12, 15) -NR11-SO2-R12, 16) -S-R10, 17) - (Co-C2) alkylene-C (O) -O- (C2-C4) -alkylene-OC (O) - (d-C4) -alkyl, 18) -C (O) -OC (R15, R16) -OC (O) -R17, 19) - (C0-C2) alkylene-C (O) -O- (C2-C4) -alkylene-OC (O) -O- (C? -Ci-alkyl, 20) -C (O) -O-C (R15, R16) -OC (O) -O-R17, 21) - (C? -C) -alkylene- (C6-Ci4) -aryl, wherein the aryl is mono-, di- or trisubstituted independently of one another by R13, 22) - (C? -C) -alkyl- (C4-Ci5) -heterocyclyl, in which the heterocyclyl is unsubstituted or mono- di - or tris replaces independently of each other by R13. 23) - (C? -C) -alkylene- (C3-C8) -cycloalkyl, in which the cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R13. 24) - (C? -C) -alkylene-het, in which het is unsubstituted or mono-, di- or trisubstituted independently of one another by R13. 25) - (C0-C3) -alkylene-O-CH2- (d-C3) -perfluoroalkylene-CH2-O- (Co-C3) -alkyl, 26) -SOw-N (R1) -R13, wherein w is 1 or 2, 27) - (C0-C4) -alkylene-N (R 1) -C (O) -R 12, 28) - (C 0 -C 4) -alkylene-N (R 11) -C (O) -O-R12 or 29) a remainder of the following list It is me, or if two residues -OR19 are linked to the adjacent atoms, they can form together with the atoms with which they are linked a ring of 5 to 6 members, which is not substituted or is replaced one, two, three or four times by R13, always and when the residue -NH-CH2 (R4) -R3, which is part of the formula I, is not of the following linking moieties -NH-CH2 (R4) -N- or -N-CH2 (R4) -O- , wherein R4 is as defined above, or R3 and R4 or R5 and R6 together with the carbon atom to which they are attached can form a 3 to 8 member ring that is selected from the group azetidine, azocan, azocan 2-one, cyclobutyl, cycloheptyl cyclohexyl, cyclooctane, cyclooctene, cyclopropyl, 1,4-diazepam, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, [1,4] diazocane, [1, 2 ] diazocan-3-one, [1, 3] diazocan-2-one, dioxazine, [1, 4] dioxocane, dioxol, cetopiperazine, morpholine, 1,2-oxa-tiepan, 1,4-oxacepan, 1,2 -oxazine, 1,3-oxazine, 1,4-oxazine, [1,4] oxazocane, [1,3] oxazocan-2-one, oxetane, oxocane, oxocan-2-one, piperazine, pipe Rhyme, pyrano, 5,6,7,8-tetrahydro-1H-azocin-2-one, thiomorpholine or tetrahydrofuran, in that said ring is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, where R13 is defined below, or R3 and R5 or R4 and R6 together with the carbon atoms to which they are attached; they can form a 4 to 8 member ring that is obtained from the group azetidine, azocan, azocan-2-one, cyclobutyl, cycloheptyl cyclohexyl, cyclooctane, cyclooctene, cyclopropyl, 1,4-diazepam, 1,2-diazepine, 1, 3-diazepine, 1,4-diazepine, [1,4] diazocane, [1,2] diazocan-3-one, [1, 3] diazocan-2-one, dioxazine, [1,4] dioxocane, dioxole, cetopiperazine, morpholine, 1,2-oxa-tiepan, 1,4-oxacepan, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, [1,4] oxazocane, [1, 3] oxazocan- 2-one, oxetane, oxocane, oxocan-2-one, piperazine, piperidine, pyrano, 5,6,7,8-tetrahydro-1H-azocin-2-one, thiomorpholine or tetrahydrofuran, wherein said ring is unsubstituted or is mono-, di- or trisubstituted independently from each other by R 3, wherein R 13 is as defined below, R 11 and R 12 are independently of one another identical or different and are 1) hydrogen atom 2) - (C? -C6) -alkyl, wherein the alkyl is unsubstituted or is mono-di-o or trisubstituted independently from each other by R13, 3) - (C0-C6) -acyl- (C3-C8) -cycloalkyl, 4) -SOt-R10, where t is 1 or 2.5) - (Co-C6) -alkyl- (C6) -C? 4) -aryl, in which the alkyl and aryl independently of each other are unsubstituted or mono-di- or they are substituted by R, 6) - (C? -C3) -perfluoroalkyl, 7) -O-R17, or 8) - (Co-C6) -alkyl- (C4-C? 5) -heterocyclyl as defined for R °, wherein alkyl and heterocyclyl are as defined above, and independently of one another, are not substituted or mono-, di- or trisubstituted by R13, or R11 and R12 together with the nitrogen atom at which join together form a heterocyclic ring of the azepine group, azetidine, dioxazole, dioxazine, 1,4-diazepam, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine, -isoxazoline, cetopiperazine, morpholine, [1,4] oxapentane, 1,4-oxazepine, oxazole, piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tetrazine, tetrazole, thiazole, thiadiazole, thiazolidine, thiazoline, thiomorpholine, thiophene, 1,2,3-triazine, 1,4-triazine, 1, 3,5-triazine, 1, 2,3-triazole or 1, 2,4-triazole, wherein said heterocyclic ring is unsubstituted or mono-, di- or trisubstituted independently of each other by R13, R13 is halogen, -NO2, -CN, = O, -OH, -CF3, -C (O) -O-R10, -C (O) -N (R10) -R20, -N (R10) -R20, - (C3-C8) -cycloalkyl, - (C0-C3) -alkylen -O-R10, -Si- (CH3) 3, -N (R10) -S (O) u-R10, wherein u is 1 or 2, -S-R10, -SOr-R10, wherein it's 1 or 2 , -S (O) v N (R 10) -R 20, wherein v is 1 or 2, -C (O) -R 10, - (C C 8) -alkyl, - (d-C 8) -alcoxy, phenyl, phenyloxy-, -O-CF3, - (C0-C4) -alkyl-C (O) -OC (R15, R16) -OC (O) - R17, - (C? -C4) -alkoxy-phenyl, - (C0-C4) -alkyl-C (O) -OC (R15, R16) -OC (O) -O-R17, - (C? -C3 ) -perfluoroalkyl, -O-R15, -NH-C (O) -NH-R10, -NH-C (O) -O-R10, or a remainder of the following list R10 and R20 are independently from each other, hydrogen, - (C6-C6) -alkyl, - (C0-C4) -alkyl-OH, halogen, - (C0-C4) -alkyl- (C? -C) -alkyl or - (C? -C3) -perfluoroalkyl, R15 and R16 are independently of each other, hydrogen, - (d-C6) -alkyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, in which each ring is unsubstituted or it is substituted one to three times by R10, and R17 is - (C? -C6) -alkyl, - (C? -C6) -alkyl-OH, - (d-C6) -alkyl- (C1-C6) ) -alkyl, - (C3-C8) -cycloalkyl, - (C? -C6) -alkyl-O- (C? -8) -acyl- (C3-C8) -cycloalkyl, - (CrC6) -alkyl- ( C3-C8) -cycloalkyl, wherein said cycloalkyl ring is unsubstituted or is replaced one, two or three times by -OH, -O- (d-C4) -alkyl or R10, in all its stereoisomeric forms and their mixtures in any proportion and their physiologically tolerable salts. 3) The present invention also relates to the compounds of the formula I, wherein R ° is 1) a mono- or bicyclic aryl of 6 to 14 members of the naphthyl or phenyl group, wherein the aryl is mono-, di- or trisubstitutes independently from each other by R 8, 2) a heterocyclyl of the azabenzimidoazolyl, benzimidazolyl, 1,3-benzodioxolyl, benzofuranyl, benzoxazolyl, benzothiazolyl, benzothiophenyl, cinnolinyl, chromanyl, furyl, midazolyl, indanyl, indazolyl, indolyl, isochromanyl, isoindolyl, imidazolyl, isoquinolinyl, isothiazolyl, imidazolyl, isoxazolyl, oxazolyl, phenylpyridyl, phthalazinyl, pteridinyl, purinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyridoimidazolyl, pyridopyridinyl, pyridopyrimidinyl, pyridothienyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinolyl, quinoxalinyl, tetrahydropyranyl, 1, 4,5,6-tetrahydro-pyridazinyl, tetrazolyl, thiazolyl, thiadiazolyl or thienyl, wherein said heterocyclyl is unsubstituted is or is mono-, di- or trisubstituted independently from each other by R8, or R8 is fluorine, chlorine, bromine, halogen, carbamimidoyl, -NO2, -CN, -C (O) -NH2, -OH, -NH2, -O-CF3, -O- (C1-C8) -alkyl, wherein the alkyl is not substituted or mono-, di- or trisubstituted independently from each other by halogen, NH2, -OH or a methoxy moiety, or - (CrC8) -alkyl, in which the alkyl is not substituted or mono-, di- or trisubstituted independently from each other by halogen, NH2, -OH or a methoxy moiety, or -SO2-CH3? -SO2-CF3, provided that R is at least one halogen, -C (O) -NH2 or a radical -O- (C? -C8) -alkyl, Q is a - (C0-C2) -alkyllene-C ( O) - (C0-C2) -aikylno-, -SO2-, in which the alkylene moiety is not substituted or mono-, di- or trisubstituted independently from each other by halogen, -NH2 or -OH; or - (C3-C6) -cycloalkylene, in which the cycloalkylene is not substituted or mono-, di- or trisubstituted independently from each other by halogen, -NH2 or -OH; R1 is a hydrogen atom, - (C? -C) -alkyl, in which the alkyl is not substituted or substituted one to three times by R13, - (C1-C3) -alkylene-C (O) - NH-R °, - (d-C2) -alkylene-C (O) -O-R10, - (d-C3) -perfluoro-alkyl, - (dC ^ -alkylene-SiOHd-C ^ -alkyl, - ( C? -C3) -alkylene-S (O) 2- (C? -C3) -alkyl, - (d-C3) -alkylene-S (O) 2-N (R4 ') - R5', - (C ? -C3) -alkyllene-O- (dC) -alkyl, - (Co-C3) -alkylene- (C3-C8) -cycloalkyl, or - (Co-C3) -alkylene-het, in which het is a residue obtained from the group azepine, azetidine, aziridine, azirine, 1,4-diazepam, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, diaziridine, diazirine, dioxazole, dioxazine, dioxole, 1,3-dioxolne, 1,3-dioxolane, furan, imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-oxazoline, cetopiperazine, morpholine, 1, 2-oxa-tiepan, 1,2-oxathiolane, 1,4-oxacepan, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazole, oxaziridine, oxirane, piperazine, piperidine, pyran, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tetrazine, tetrazole, thiadiazine thiadiazole, 1,2-thiazine, 1,3-thiazine, 1,4-thiazine, 1,3-thiazole, thiazole, thiazolidine, thiazoline, thienyl, thietan, thiomorpholine, thiopyran, 1,2,3-triazine, 1, 2, 4-triazine, 1,3,5- triazine, 1,2,3-triazole or 1,2,4-triazole, in which het is not replaced or mono-, di- or trisubstituted independently from each other by R 14, R 4 and R 5. independently of each other, they are identical and are a hydrogen atom or - (C? -C4) -acyl, R2 is a direct bond or - (C? -C) -alkylene, R1-N-R2-V form a cyclic group of 4 to 10 members which are obtained from the group azepine, azetidine, dioxazole, dioxazine, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, 2,3-dihydroindole, midazole, imidazoline, imidazolidine, idol, isothiazole, isothiazolidine, Siathiazoline, isoxazoline, isoxazolidine, 2-isoxazoline, cetopiperazine, morpholine, 1,4-oxacepan, 1,2-oxa-tiepan, 1,2-oxathiolane, 1,2-oxazine, 1,3-oxazine, 1, 4 -oxazine, oxazole, piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, thiazolidine, thiazoline or thiomorpholine, wherein said cyclic group is not substituted or mono-, di- or tris replaces independ Each of the others by R 14, R 3, R 4, R 5 or R 6 are independent of each other, are identical or different and are 1) hydrogen atom 2) fluorine, chlorine or bromine, 3) - (C 4 -C 4) alkyl , wherein the alkyl is not substituted or mono-, di- or trisubstituted independently from each other by R13, 4) - (C? -C3) -perfluoroalkyl, 5) phenyl, wherein the phenyl is not substituted or is mono-, di- or trisubstituted independently from each other by R13, 6) - (C0-C4) -alkylene-O-R19, wherein R19 is a) hydrogen atom, b) - (C? -C) -alkyl, wherein the alkyl is not substituted mono-, di- or trisubstitutes independently from each other by R 13, c) phenyl, in which the phenyl is not substituted is mono-, di- or trisubstituted independently from each other by R 13, d) -CF 3 e) -CHF 2 7) -NO 2 , 8) -CN, 9) -SOs-R11, where s is 1 or 2, 10) -SOt-N (R1) -R12, where t is 1 or 2, 11) - (C0-C4) ) -alkylene-C (O) -R11 12) - (C0-C4) -alkylene-C (O) -O-R11, 13) - (C0-C4) -alkylene-C (O) -N (R11) -R12, 14) - (C0-C4) -alkylene-N (R11) -R12, 15) -NR10-SO2-R10, 16) -S-R10, 17) - (C0-C2) alkylene-C (O ) -O- (C2-C4) -alkylene-OC (O) - (C? -C4) -alkyl, 18) -C (O) -OC (R15, R16) -OC (O) -R17, 19) - (C0-C2) alkylene-C (O) -O- (C2-C4) -alkylene-OC (O) -O- (d- C6) -alkyl, 20) -C (O) -O-C ( R 1'5 °, 21) - (C0-C4) -alkylene-N (R11) -C (O) -R12, 22) - (C? -C4) -alkylene- (C4-Ci5) -heterocyclyl, in which the heterocyclyl is not it substitutes or mono-, di- or trisubstitutes independently of each other by R13 23) - (C? -C4) -alkylene- (C3-C8) -cycloalkyl, in which the cycloalkyl is not substituted or mono-, di- or is independently substituted by R 13, 24) - (CrC 4) -alkylene-het, in which het is not substituted or mono-, di- or trisubstituted independently of one another by R > 113 ) - (C0-C4) -alkylene-N (R1) -C (O) -O-R12 or 26) a remainder of the following list Bte is methyl, or if two residues -OR19 are linked to the adjacent atoms they can form together with the atoms to which they are linked a 1,3-dioxole ring or a 2,3-dihydro- [1,4] dioxin ring, which is replaced one, two, three or four times for R13, as long as the rest -NH-CH2 (R4) -R3, which is part of the Formula I, is not one of the following linking moieties -NH-CH2 (R4) -N- or -N- CH2 (R4) -O-, wherein R4 is as defined above, or R3 and R4 or R5 and R6 together with the carbon atom to which they are attached form a ring of 3 to 8 members which are obtained from the group azetidine, azocan, azocan-2-one, cyclobutyl, cycloheptyl, cyclohexyl, cyclooctane, cyclooctene, cyclopropyl, 1,4 -diazepan, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, [1,4] diazocane, [1,2] diazocan-3-one, [1,3] diazocan-2-one, dioxazine, [1, 4] dioxocane, dioxol, cetopiperazine, morpholine, 1,2-oxa-tiepan, 1,4-oxacepan, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, [1, 4] oxazocan, [1, 3] oxazocan-2-one, oxetane, oxocane, oxocan-2-one, piperazine, piperidine, pyrano, 5,6,7,8-tetrahydro-1H-azocin-2-one, thiomorpholine or tetrahydrofuran, in which said ring is not replaced or mono -, di- or trisubstitutes independently one of the other by R13, in which R13 is defined below, or R3 and R5 or R4 and R6 ', together with the carbon atoms to which they are bound, form a ring of 4 to 8 members obtained from the group azetidine, azocano, azocano-2-one, cyclobutyl, cycloheptyl, cyclohexyl, cyclooctane, cyclooctene, cyclopropyl, 1,4-diazepam, 1,2-diazepine, 1,3-diazepine, 1,4- diazepine, [1,4] diazocane, [1,2] diazocan-3-one, [1, 3] diazocan-2-one, dioxazine, [1,4] dioxocane, dioxole, cetopiperazine, morpholine, 1,2- oxa-tiepan, 1,4-oxacene, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, [1,4] oxazocane, [1, 3] oxazocan-2-one, oxetane, oxocane, oxocan-2-one, piperazine, piperidine, pyran, 5,6,7,8-tetrahydro-1H-azocin-2-one, thiomorpholine or tetrahydrofuran, wherein said ring is not substituted or no-, di- or tris replace independently of one another by R 13, wherein R 13 is defined below, V is 1) a heterocyclyl of the azaindole group (1 H-pyrrolopyridine), azepine, azetidine, aziridine, azirine, 1,4-diazepam, 1,2-diazepine , 1,3-diazepine, 1,4-diazepine, diaziridine, diazirine, dioxazole, dioxazine, dioxole, 1,3-dioxole, 1,3-dioxolane, furan, imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole , isoxazoline, isoxazolidine, 2-isoxazoline, cetopiperazine, morpholine, 1,2-oxa-tiepan, 1,2-oxathiolane, 1,4-oxacepan, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine , oxazole, oxaziridine, oxirane, piperazine, piperidine, pyran, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tetrazine, tetrazole, thiadiazine, thiadiazole, 1,2-thiazine , 1,3-thiazine, 1,4-thiazine, 1,3-thiazole, thiazole, thiazolidine, thiazoline, thienyl, tietan, thiomorpholine, thiopyran, 1,2,3-triazine, 1, 2,4-triazine, 1, 3,5-triazine, 1,2,3-triazole or 1,4-triazole, which is as defined above and, in which, the het is not replaced or is mono-, di- or trisubstituted independently from each other by R 14, or 2) phenyl, wherein the phenyl is not substituted or mono-, di- or trisubstituted independently of one another by R 14 R 14 is fluorine, chlorine, bromine, -OH, = O, - (C? -C8) -alkyl, - (C1-C4) -alkoxy, -NO2, -CN, -NH2, -C (O) -O-R18, - (C0-) C8) -alkyl-SO2- (d-C4) -alkyl, - (C0-C8) -alkyl-SO2- (d-C3) -perfluoroalkyl, - (C0-C8) -alkyl-SO2-N (R18) - R21, -C (O) -N (R18) -R21, -NR18-C (O) -NH- (d-C8) -alkyl, -S-R18, - (Co-dHalquiKd-Cs) -perfluoroalkyl, or -NR18-C (O) -NH - [(C1-C8) -alkyl] 2, wherein R18 and R21 are independently from each other hydrogen atom, - (C0-C4) -alkyl-N (R22) - R23, - (C0-C4) -alkyl-O-R22, - (C0-C4) -alkyl- heterocyclyl, in which the heterocyclyl is a residue obtained from azetidine, azetidinone, piperidine, piperazine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, 1,2,3-triazine, 1,2,4-triazine, 1,3, 5-triazine, 1, 2,3-triazole, 1,2,4-triazole, tetrazine, tetrazole, 1,4-diazepam, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, azepine, cetopiperazine, 1,4-oxapacline, oxazole, isoxazole, isoxazolidine, 2-isoxazoline, morpholine, thiazole, isothiazole, thiadiazole or thiomorpholine, and wherein the heterocyclic is not substituted or mono-, di- or trisubstituted independently of each other by R13, - (C0-C4) -alkyl-N (R22) -C (O) -N (R22) -R23, - (C0-C4) -alkyl-C (O) -O-R22, - (d -C4) -alkyl, - (C0-C4) -alkyl-C (O) -N (R22) -R23, - (C0-C4) -alkyl-SO2-R22 or - (C? -C3) -perfluoroalkyl, wherein R22 and R23 are independently of any other hydrogen atom, - (C -? - C3) -perfluoroalkyl, - (C3-C6) -cycloalkyl or - (C? -C) -alkyl, G is a direct bond, - (CH2) m-NR10-SO2-NR10- (CH2) n-, - (CH2) m-CH (OH) - (CH2) n-, - ( CH2) m-, - (CH2) mO- (CH2) n-, - (CH2) mC (O) -NR10 _ (CH2) n-, - (CH2) -SO2- (CH2) n-, - (CH2) ) m-NR10-C (O) -NR10- (CH2) n-, - (CH2) m -NR10-C (O) - (CH2) n-, - (CH2) mC (O) - (CH2) n -, - (CH2) -S- (CH2) n-, - (CH2) m-SO2-NR10- (CH2) n-, - (CH2) m-NR10-SO2- (CH2) n-, - (CH2) ) m-NR10-, - (CH2) mOC (O) -NR10- (CH2) n- or - (CH2) m-NR10-C (O) -O- (CH2) n-, n and m are independently one of other, identical or different and are the integers zero, 1, 2, 3, 4, 5 or 6, M is 1) phenyl or naphthyl, in which the phenyl or naphthyl are not substituted or mono-, di- or independently replace each other by R14, 2) heterocyclyl, wherein the heterocyclyl is a group moiety that can be derived from azepam, azepine, 1,4-diazepam, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, dihydropyrimidinone, dihydroimidazolone , 3,3-dioxo- (1,3,4) oxathiazine, midazole, imidazolidinone, isothiazole, isoxazole, isoxazolidine, 2-isoxazoline, ketomorpholine, cetopiperazine, morpholine, morpholinone, oxazole, oxazolone, oxazolidinone, [1, 4] -oxacepan, piperazine, piperazinone, piperidine, piperidinone, pyrazine, pyridazine, pyridazinone, pyridine, pyridone, pyrimidine-2,4-dione, pyrimidine, pyrimidinone, pyrimidinedione, pyrrolidine, pyrrolidinone, tetrahydropyran, 1, 4,5,6-tetrahydro-pyridazinyl, tetrahydro-pyrimidinone, tetrazine, tetrazole, thiadiazole, thiazole, thiophene, thiomorpholine, 1,1-thiomorpholine dioxide, pyrazinone, 1,2,3-triazine, 1, 2 , 4-triazine, 1, 3,5-triazine, 1, 2,3-triazole or 1,2,4-triazole, wherein said heterocyclyl is not substituted or mono-, di- or trisubstituted independently of each other by R14, as long as M contains or is substituted with at least one oxo- moiety, R11 and R12, are independently of each other, identical or different and are 1) hydrogen atom, 2) - (Ci-CβJ-alkyl, wherein the alkyl is not substituted or mono-, di- or trisubstituted independently from each other by R13, 3) - (C? -C3) -perfluoroalkyl, 4) (Co-C6) -alkyl- (C3-C6) ) -cycloalkyl, 5) - (Co-C 1 J -alkyl-phenyl, wherein phenyl is as defined above and wherein alkyl and phenyl independently of one another are not replace or be mono-, di- or trisubstituted by R13, or 6) - (Co-C6) -alkyl- (C4-Ci5) -heterocyclyl as defined for R °, wherein the alkyl and the heterocyclyl are as defined above and independently from each other are not replaced or mono-, di- or trisustituyen by R13, or R11 and R12 together with the nitrogen atom to which they bind may form a ring obtained from group azepine , azetidine, 1, 4-diazepane, dioxazole, dioxazine, 1, 2-diazepine, 1,3-diazepine, 1, 4-diazepine, imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2 -isoxazoIina, ketopiperazine, morpholine, [1, 4] oxazepam, 1, 4-oxazepine, oxazole, piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tetrazine, tetrazole, thiazole, thiadiazole, thiazolidine, thiazoline, thiomorpholine, thiophene, 1,2,3-triazine, 1,4-triazine, 1,3,5-triazine , 1, 2,3-triazole or 1,4-triazole, which is not substituted or mono-, di- or trisubstituted independently from each other by R13, R13 is fluorine, chlorine, bromine, iodine, -NO2, -CN, = O, -OH, -CF3, -C (O) -O-R10, C (O) -N (R10) -R20, -N (R10) -R20, - (C0-C3) -alkylene -O-R10, -Si- (CH3) s, -N (R10) -S (O) 2 -R10, -S-R10, -SO2-R10, -S (O) 2-N (R10) -R20 , -C (O) -R10 '- (C? -C8) -alkyl, - (d-C8) -alcoxy, phenyl, phenyloxy-, -O-CF3, - (C? -C3) -perfluoroalkyl, - (C0-C4) -alkyl-C (O) -OC (R15, R16) -OC (O) -R17, - (C? -C4) -alkoxy-phenyl, - (C0-C4) -alkyl-C ( O) -OC (R15, R16) -OC (O) -O-R17, -O-R15, -NH-C (O) -NH-R10, -NH-C (O) -O-R10, or a rest of the following list R10 and R20 are, independently of one another, hydrogen, - (d-C6) alkyl, - (C0-C4) -alkyl-OH, halogen, - (Co-C4) -alkyl-O- (d-C4) - alkyl or - (? C -C3) perfluoroalkyl, R15 and R 6 are, independently of one another, hydrogen, - (d-C6) -alkyl, or together form a cyclopropyl ring, cyclobutyl, cyclopentyl or ciciohexilo in that each ring is not replaced or replaced one to three times by R10, and R17 is (C? -C6) -alkyl, - (d-C6) -alkyl-OH, - (d-C6) -alkyl- O- (C?-C6) -alkyl- (C3-C8) -cycloa-alkyl, - (C?-C6) -alkyl-O- (C?-C8) -alkyl- (C3-C8) -cycloalkyl, - (C? -C6) -alkyl- (C3-C8) -cycloa-alkyl, wherein said cycloaikyl ring is not replaced or is replaced one, two or three times by -OH, -O- (dC) -alkyl or R10, in all its stereoisomeric forms and their mixtures in any proportion, and their physiologically tolerable salts. 4) The present invention also relates to the compounds of the formula I, wherein R ° is 1) phenyl, where the phenyl is unsubstituted or mono-, di- or independently trisustituye one another by R8, 2) a heterocyclyl group of benzimidazolyl, 1, 3-benzodioxolyl, benzofuranyl, benzoxazolyl, benzothiazolyl , benzothiophenyl, cinnolinyl, chromanyl, furyl, imidazolyl, indanyl, indazolyl, indolyl, isochromanyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, phenylpyridyl, phthalazinyl, pteridinyl, purinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyridoimidazolyl, pyridopyridinyl, pyridopyrimidinyl , pyrimidinyl, pyrrolyl, quinazolinyl, quinolyl, quinoxalinyl, tetrahydropyranyl, 1, 4,5,6-tetrahydro-pyridazinyl, thiazolyl, thiadiazolyl, thienyl, triazolyl or tetrazolyl, wherein said heterocyclyl is unsubstituted or mono-, di- or independently replaces one another by R8, R8 is F, Cl, Br, carbamimidoyl, -C (O) -NH2, - (C? -C4) -alkyl, wherein said heterocyclyl is unsubstituted or mono-, di- - or trisu independently of one another by halogen, -OH or a methoxy moiety, or -O- (C? -C4) -alkyl, wherein the alkyl is not substituted or mono-, di- or trisubstituted independently from each other by halogen or a methoxy moiety, provided that R8 is at least one F, Cl, Br, or -C (O) -NH2 or a residue of -O- (C? -C4) -alkyl, Q is- (C0-) C2) -alkylene-C (O) - (C0-C2) -alkylene-, -SO2-, R1 is hydrogen atom, - (C? -C2) -alkyl, - (d-C3) -alkylene-C ( O) -NH-R °, - (d-C3) -perfluoroalkyl, - (d-C2) -alkylene-C (O) -O-R10, - (d-C3) -alkylene-S (O) 2- (C? -C3) -alkyl or - (C? -C3) -alkylene-S (O) 2-N (R4 ') -R5', wherein R4 and R5 are independent of each other, are identical or different and they are hydrogen atom or - (CC) -alkyl, R2 is a direct bond or - (C? -C2) -alkylene, R1-N-R2-V form a cyclic group of 4 to 10 members of the azetidine group, azetidinone, 2, 3 dihydroindole, indole, piperidine, piperazine, pyridine, pyrrole, pyrazole, pyrimidine, pyrrolidine, pyrrolidinone, 1,2,3-triazine, 1,4-triazine, 1, 3,5-triazine, 1, 2,3 -triazole, 1,4-triazole, tetrazine, tetrazole, 1,4-diazepam, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, azepine, cetopiperazine, 1,4-oxacepan, oxazole , isoxazole, soxazolidine, 2-isoxazoline, morpholine, thiazole, isothiazole, thiadiazole or thiomorpholine, wherein said cyclic group is not substituted or mono-, di- or trisubstituted independently of each other by R14, V is 1) a cyclic moiety of the group containing the compounds that are derived from azaindole (1 H-pyrrolopyridine), aziridine, azirine, azetidine, azetidinone, 1,4-diazepam, pyrrole, pyrrolidine, pyridonyl, imidazole, pyrazole, 1,2,3- triazole, 1,2,4-triazole, tetrazole, pyridine, py imidine, pyridazine, pyrazine, 1,2,3-triazine, 1, 2,4-triazine, 1, 3,5-triazine, tetrazine, tetrazole, azepine, diazirine, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, pyridine, pyrazine, pyrimidine, pyridazine, piperidine, piperazine, pyrrolidinone, cetopiperazine, furan, pyran, dioxole, 1,4-oxacepan, oxazole, soxazole, 2-isoxazoline, isoxazolidine, morpholine, oxirane, oxaziridine , 1,3-dioxole, 1,3-dioxolane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxaziridine, thiophene, thiopyran, thietane, thiazole, isothiazole, isothiazoline, isothiazolidine, 1, 2 -oxatiolan, thiadiazole, thiopyran, 1,2-thiazine, 1,3-thiazole, 1,3-thiazine, 1,4-thiazine, thiadiazine or thiomorpholine, wherein said cyclic moiety is not substituted or mono- or trisitute independently of each other by R14, or 2) phenyl, in which the phenyl is not substituted or mono- or di-substituted independently of each other by R 14, R 14 is fluorine, chlorine, -OH, = O, - (d-C 8) -alkyl, -C (O) -O-R18, -NH2, -C (O) -N (R18) R21, -CF3, -CN, - (C0-C?) -alkyl- (d-C3) -perfluoroalkyl or -N ( R18) -R21, wherein R18 and R21 are independently of each other hydrogen atom, - (C0-C4) -alkyl-N (R22) -R23, - (C0-C4) -alkyl-O-R22, - (C0-C4) -alkyl-heterocyclyl, in which the heterocyclyl is azetidinyl and in which the heterocyclyl is not substituted or mono-, di-o or trisubstitutes independently of each other by R13, - (C0-C4) - alkyl-N (R22) -C (O) -N (R22) -R23, - (C0-C4) -alkyl-C (O) -O-R22, - (d-C4) -alkyl, - (C0-) C4) -alkyl-C (O) -N (R22) -R23, - (C0-C4) -alkyl-SO2-R22 or - (C? -C3) -perfluoroalkyl, wherein R22 and R23 are independently of each another hydrogen atom, - (C? -C3) -perfluoroalkyl, - (C3-C6) -cycloalkyl or - (C? -C) -alkyl, G is a direct bond, - (CH2) m-, - (CH2 ) mO (O) -NR10 _ (CH2) n-, - (CH2) mC (O) - (CH2) n- or - (CH2) m-NR10- n and m are independently identical or different from each other and are the integers zero, 1, 2, 3 or 4, M is heterocyclyl, wherein the heterocyclyl is a residue of the group that can be derived from azepam, azepine, 1,4-diazepam, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, dihydropyrimidinone, dihydroimidazolone, 3,3 - dioxo- (1, 3,4) oxathiazine, imidazole, imidazolidinone, siathiazole, soxazole, isoxazolidine, 2-oxazoline, cetomorpholine, cetopiperazine, morpholine, morpholinone, oxazole, oxazolone, oxazolidinone, [1,4] -oxacepan , piperazine, piperazinone, piperidine, piperidinone, pyrazine, pyridazine, pyridazinone, pyridine, pyridone, pyrimidine-2,4-dione, pyrimidine, pyrimidinone, pyrimidinedione, pyrrolidine, pyrrolidinone, tetrahydropyran, 1,4,6,6-tetrahydropyridazinyl, tetrahydropyrimidinone, tetrazine, tetrazole, thiadiazole, thiazole, thiophene, thiomorpholine, 1,1-thiomorpholine dioxide, pyrazinone, 1,2,3-triazine, 1,4-triazine, 1, 3,5-triazine, 1,2,3 -triazole or 1,2,4-triazole, wherein said heterocyclyl is not substituted or mono-, di- or trisubstituted independently from each other by R 14, provided that M contains or is substituted with at least one oxo- , R3, R4, R5 or R6 are independent of each otherare identical or different and are 1) hydrogen atom, 2) fluorine, chlorine or bromine, 3) - (C? -C) -alkyl, in which the alkyl is not substituted or mono-, di- or trisubstituted independently from each other by R 13, 4) - (d-C 3) -perfluoroalkyl, 5) phenyl, wherein the phenyl is not substituted or mono- or trisubstituted independently from each other by R 13, 6) - (C 0) -C4) -alkylene-O-R19, wherein R19 is a) hydrogen atom, b) - (C? -C) -alkyl, wherein the alkyl is not substituted or mono-di- or trisubstituted independently from one another by R 13, c) phenyl, in which the phenyl is not substituted or mono-, di- or trisubstituted independently of one another by R 13, d) -CF3 oe) -CHF2, 7) -NO2, 8) -CN, 9) -SOs-R11, wherein s is 1 or 2.10) -SOt-N (R11) -R12, in the that t is 1 or 2, 11) - (Co-C4) -alkylene-C (O) -R11, 12) - (C0-C4) -alkylene-C (O) -O-R11, 13) - (C0) -C4) -acykylene-C (O) -N (R11) -R12, 14) - (C0-C4) -alkylene-N (R1) -R12, 15) -NR10-SO2-R10, 16) -S -R10, 17) - (C0-C2) alkylene-C (O) -O- (C2-C4) -alkylene-OC (O) - (C1-C4) -alkyl, 18) -C (O) -OC (R15, R16) -OC (O) -R17, 19) - (C0-C2) alkylene-C (O) -O- (C2-C4) -alkyl ene-OC (O) -O- (C? -CJ) -alkyl, 20) -C (O) -O- C (R15, R6) -OC (O) -O-R17, 21) - (C0-C) -alkylene-N (R11) -C (O) -R12, 22) - (C? -C4) -alkylene- (C4-Ci5) -heterocyclyl, in which the heterocyclyl is not substituted or mono-, di- or trisubstituted independently of one another by R13, 23) - (C? -C) -alkylene- (C3-C8) -cycloalkyl, wherein the cycloalkyl is not substituted or mono-, di- or trisubstituted independently from each other by R13, 24) - (C? -C) -alkylene-het, in which the het is not replaced or mono-, di- or trisubstituted independently from each other by R13, 25) - (C0- C4) -alkylene-N (R11) -C (O) -O-R12 or 26) a remainder of the following list It is me, or if two residues of -OR19 are linked to adjacent atoms, they can form together with the atoms to which they are bound a 1,3-dioxole ring or a 2,3-dihydro- [1,4] dioxin ring, which is substitute one, two, three or four times for R13, as long as the rest -NH-CH2 (R4) -R3, which is part of formula I, is not one of the following-NH-CH2-bonding moieties (R4) ) -N- or -N-CH2 (R4) -O-, wherein R4 is as defined above, or R11 and R12 are. independently of one another, identical or different and are 1) hydrogen atom 2) - (C? -C6) -alkyl, in which the alkyl is not substituted or mono- or di-substituted independently from each other by R13, 3) - (C? -C3) -perfluoroalkyl, 4) - (Co-C3) -alkyl- (C3-C6) -cycloalkyl, 5) - (Co-CβJ-alkyl-phenyl, wherein the phenyl is as defined above and wherein the alkyl and the phenyl are independently of one another or mono- or di-substituted by R13, or 6) - (Co-C6) -alkyl- (C -Ci5) -heterocyclyl as defined for R °, wherein the alkyl and the heterocyclyl are as defined above and independently of one another are not substituted or mono- or trisubstituted by R-? 3, or R11 and R12 together with the nitrogen atom to which they are attached can form a ring which is obtained of the azepine group, azetidine, 1,4-diazepam, dioxazole, dioxazine, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, cetopiperazine, morpholine, [1, 4] -oxapan, 1,4-oxazepine, oxazole, piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tetrazine, tetrazole, thiazole, thiazolide, thiazolidine , thiazoline, thiomorpholine, thiophene, 1,2,3-triazine, 1,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, in which said ring is not substituted or mono- or trisubstituted independently of each other by R13, R13 is fluorine, chlorine, -NO, -CN, = O, -OH, -CF ", -C (O) -O -R1 °, -C (O) - N (R1 °) -R20, -NYRlOj-RSO, - (Co-C3) -acykylene-O-RlO, -Si- (CH3) 3, -N (R10).

S (O) 2-R 10, -S-R 10, -SO 2 -R 10, -S (O) 2-N (R 10) -R 20 I -C (O) -R 10, - (C < , - (C -? - C8) -alkoxy, phenyl, phenyloxy-, -O-CF3, - (C <] -C3) -perfluoroalkyl, or - NH-C (O) -NH-R10, - ( C0-C4) -alkyl-C (O) -OC (R15, R16) -OC (O) -R17, - (C < | -C4) -alkoxy-phenyl, - (C0-C4) -alkyl-C (O) -OC (R15, R16) -OC (O) -O-R17, -O-R15, -NH-C (O) -O-R10, or a remainder of the following list methyl, R10 and R20 are, independently of one another, hydrogen, - (C-C6) -alkyl, - (Co-C4) -alkyl-OH, fluorine, - (Co-C4) -alkyl-O- (C ? -C4) -alkyl or - (C? -C3) -perfluoroalkyl, R15 and R16 are, independently of one another, hydrogen, - (Cj-C6) -alkyl, or together form a ring of the cyclopropyl, cyclobutyl, cyclopentyl group or cyclohexyl, wherein each ring is not substituted or substituted one to three times by R10, and R17 is - (C? -C6) -alkyl, - (C? -C6) -alkyl-OH, - (d -C6) -alkyl-O- (d- C6) -alkyl, - (C3-C8) -cycloa-alkyl, - (d-CeJ-alkyl-O-id-Cf -alk Cs-Cs) -cycloalkyl, - (d -C6) -alkyl- (C3-C8) -cycloalkyl, wherein said cycloalkyl ring is not replaced or is replaced one, two or three times by -OH, -O- (d-C4) -alkyl or R10, in all its stereoisomeric forms and their mixtures in any proportion and their physiologically tolerable salts. 5) The present invention also relates to the compounds of the formula I, wherein R ° is a residue of the phenyl, pyridyl or thienyl group, wherein said heterocyclyl is not substituted or mono-, di- or trisubstituted independently of each other by R8, R8 is F, Cl or carbamimidoyl, provided that R8 is at least one F or Cl, Q is -C (O) - or -SO2-, R1 is hydrogen atom, -CH2-C (O) -O-R10 or -CH2-CF2, R2 is a direct bond or - (C? -C2) -alkylene, or R1-N-R2-V forms a cyclic group of the group 2.3 dihydroindole or indole, wherein said cyclic group is not substituted or mono-, di- or trisubstituted independently of each other by R14, V is a cyclic moiety of the phenyl or pyridyl group, wherein said cyclic moiety is not substituted or mono-, di- or trisubstitutes independently of each other by R14, R14 is fluorine, - (C? -C3) -perfluoroalkyl, -C (O) -O-R18, -CF3 or = O, R18 is hydrogen atom or - (C ? -C4) -alkyl, G is a direct bond M is a heterocyclyl of the group that can be derived from 3,3-dioxo- (1, 3,4) oxathiazine, imidazole, morpholine, pyrazine or pyridine, wherein said heterocyclyl is not substituted or mono-, di- or trisubstituted independently of each other by R14, as long as M contains or is substituted with at least one oxo- moiety, R3, R4, R5 or R6 are independent of each other, are identical or different and are hydrogen atom, fluorine, -NR11-SO2-R12, - (C0-C4) -alkylene-N (R11) -C (O) -R12, - (C0-C4) -alkylene-N ( R11) -R12 or - (C0-C) -alkylene-N (R11) -C (O) -O-R12, R11 and R12 are, independently of one another, identical or different and are 1) hydrogen atom, ) - (Ci-CβJ-alkyl, wherein the alkyl is not substituted or mono-, di- or trisubstituted independently of one another by R13, 3) indanyl, piperidinyl, tetrahydropyranyl, or 4) - (Co-C3) -alkyl- (C3-C6) -cycloalkyl, 5) - (C? -C3) -perfluoroalkyl, 6) - (C0-C6) -alkyl-phenyl, wherein the phenyl is as defined above and wherein alkyl and phenyl, independently of each other, are not substituted or mono- or trisubstituted by R13, R13 is fluorine, chlorine, -S-R10, - (d-C4) -aiquillo u = O, R10 is hydrogen atom, fluorine or - (d-C4) -alkyl, in all its stereoisomeric forms and their mixtures and their physiologically tolerable salts. 6) The present invention also relates to the compounds of the formula, they are. { 2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -etl} 5-cyclo-thiophene-2-carboxylic acid amide. { 2- [4- (2-Oxo-2H-pyrazin-1-yl) -phenylcarba-minyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide "4-chloro-N-. { 2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -etl} -benzamide,. { 3-oxo-3- [5- (2-oxo-2H-pyrazin-1-yl) -2,3-dihydroindol-1-yl] -propiI} 5-chloro-thiophene-2-carboxylic acid amide. { 3-oxo-3- [5- (2-oxo-2H-pyrazin-1-yl) -indol-1-yl] -propyl} 5-chloro-thiophene-2-carboxylic acid amide. { 2- [2-fluoro-4- (2-oxo-2H-pyrazin-1-yl) -phenylcarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- (2,2-difluoro-ethylamino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -etiI} -5-chloro-thiophene-2-carboxylic acid amide, 3- (5-chloro-thiophene-2-sulfonylamino) -N- [4- (3-oxo-morpholin-4-yl) -phenyl] -propionamide ,. { 2- [4- (3,3-dioxo- [1,3,4] oxathiazin-4-yl) -phenylcarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { 2,2-difluoro-2- [4- (2-oxo-2H-pyrazin-1-yl) -phenylcarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { 2,2-difluoro-2- [4- (3-oxo-morfoin-4-yl) -phenylcarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, 3-carbamimidoyl-N-. { 2- [4- (2-Oxo-2H-pyrazin-1-yl) -phenylcarbaminyl] -ethyl} -benzamide, methyl ester of 5- acid. { 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionylamino} -2- (3-Oxo-morpholin-4-yl) -benzoic acid, 5- acid. { 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionylamino} -2- (3-oxo-morfoin-4-yl) -benzoic acid,. { 2- [6- (3-Oxo-morpholin-4-yl) -pyridin-3-ylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { 2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide. { 2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, 2- acid. { 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionylamino} -5- (3-oxo-morpholin-4-yl) - benzoic acid methyl ester 2-. { 3 - [(5-Chloro-thiophene-2-carbonyl) -amino] -propionylamino} -5- (2-Oxo-2H-pyridin-1-yl) -benzoic acid, 2- acid. { 3 - [(5-Chloro-thiophene-2-carbonyl) -amino] -propionylamino} -5- (2-Oxo-2H-pyridin-1-yl) -benzoic acid,. { 2- [4- (4-Oxo-4H-pyridin-1-yl) -phenylcarbaminyl] -ethyl} 5-Chloro-thiophene-2-carboxylic acid amide, 4-chloro-N-. { 2- [4- (4-Oxo-4H-pyridin-1-yl) -phenylcarbaminyl] -ethyl} -benzamide, methyl ester of acid. { . { 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionyl} - [4- (3-Oxo-morpholin-4-yl) -pheni] -amino} -acetic, acid. { . { 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionyl} - [4- (3-oxo-morpholin-4-yl) -phenyl] -amino} -acetic, (2- {(2,2-difluoro-ethyl) - [4- (3-oxo-morpholin-4-yl) -phenyl] -carbamoyl} -ethyl) -amide of 5- chloro-thiophene-2-carboxylic acid benzyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbaminyl] -ethyl} -carbamic, terbutyl ester of acid. { 2- (2S) - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} -carbámico,. { 2- (2S) -amino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { 2- (2S) -dicic-isopropylamino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl} -5-chloro-thiophene-2-carboxylic acid amide, [2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -2- (2S) - (tetrahydro-pyrano-4-ylamino) ) -ethyl-5-chloro-thiophene-2-carboxylic acid amide. { 2- (2S) - (1-isopropyl-piperidin-4-ylamino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { 2- (2S) - (indan-2-ylamino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { 2- (2,2-Dimethyl-propylamino) -2- (2S) - [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { 2- (2S) -cyclobutylamino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl} -amide of 5-acid chloro-thiophene-2-carboxylic acid,. { 2- (2S) -cyclohexylamino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { 2- (2S) - (2,2-difluoro-ethylamino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { 2- (2S) - (2,2-difluoro-acetylamino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl} -5-chloro-thiophene-2-carboxylic acid amide, [2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -2- (2S) - (2,2,3,3 5-Chloro-thiophene-2-carboxylic acid, -tetrafluoro-propionylamino) -ethyl] -amide, [2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -2- (2S) - 5-Chloro-thiophene-2-carboxylic acid (2,2,2-trifluoro-ethanesulfonylamino) -eti) -amide. { 2- (2R) - (2,2-difluoro-ethylamino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { 2- [Cyclopropylmethyl- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { 2- (2R) - [Cyclobutyl- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, terbutyl acid ester. { 2- (2S) - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -etl} -carbámico,. { 2- (2S) -amino-2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenocarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { 2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -2- (2S) -isopropylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { 2- (2S) -ethylamino-2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { 2-Cyclobutylamino-2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid ". { 2 (2S) - (4-pentafluorothio-benzoylamino) -2- [4- (3-oxo-morfoin-4-yl) -phenylcarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, or. { 2- (2R) - (2,2-difluoro- acetylamino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -etl} 5-doro-thiophene-2-carboxylic acid amide,. As used in the present invention, the term "alkyl" should be understood in the broadest sense to mean that the hydrocarbon moieties can be linear, namely, a linear, or branched chain and which may be acyclic or cyclic residues or comprise any combination of acyclic and cyclic subunits. In addition, the term alkyl, as used in the present invention, expressly includes saturated groups as well as unsaturated groups, in which these latter groups contain one or more, for example, one, two or three, double and / or triple bonds links, provided that the double bonds are not within a cyclic alkyl group in such a way as to give rise to an aromatic system. All these statements also apply if an alkyl group is generated as a substituent in another moiety, for example, in an alkyloxy moiety, an alkyloxycarbonyl moiety or an arylalkyl moiety. Examples of "- (CrCs) -alkyl" or "- (d-C8) -alkylene" are alkyl radicals containing 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms, methyl, methylene, ethyl , ethylene, propyl, propylene, butyl, butylene, pentyl, pentylene, hexyl, heptyl or octyl, the n-isomers of all these residues, isopropyl, isobutyl, 1-methylbutyl, isopentyl, neopentyl, 2,2-dimethylbutyl, 2- methylpentyl, 3-methylpentyl, isohexyl, sec-butyl, tBu, ferc-pentyl, sec-butyl, tertiary butyl or pentyl. The term "- (Co-Cι-alkyl" or "- (Co-C 8) -alkylene" is an alkyl moiety containing 1, 2, 3, 4, 5, 6, 7, or 8 carbon atoms. "-Co-alkyl" or "-Co-alkylene" is a covalent bond, unsaturated alkyl radicals are, for example, alkenyl radicals. as vinyl, 1-propenyl, 2-propenyl (= allyl), 2-butenyl, 3-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 5-hexenyl or 1,3-pentadiene, or Alkynyl radicals such as ethynyl, 1-propynyl, 2-propynyl (= propargyl) or 2-butynyl. Remains alkyl can also be unsaturated when they are replaced. Examples of cyclic alkyl radicals of - (C3-C8) -cycloalkyl are cycloalkyl radicals containing 3, 4, 5, 6, 7 or 8 ring carbon atoms such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl, which also they can be replaced and / or unsaturated. A bond can be formed through any carbon atom of unsaturated cyclic alkyl groups and unsaturated cycloalkyls groups such as, for example, cyclopentenyl or cyclohexenyl. The terms "monocyclic or bicyclic aryl of 6 to 14 members" or "- (C6-C14) -aryl" are understood to refer to aromatic hydrocarbon radicals containing from 6 to 14 carbon atoms in the ring. Examples of radicals - (C6-d4) -aryl are phenyl, naphthyl, for example, 1-naphthyl and 2-naphthyl, biphenylyl, for example, 2-biphenylyl, 3-biphenylyl and 4-biphenylyl, anthryl or fluorenyl. Preferred aryl radicals are biphenyl radicals, naphthyl radicals and, in particular, phenyl radicals. The terms "4- to 5-membered mono- or bicyclic heterocyclyl" or "heterocyclyl" refer to heterocyclyls in which one or more of the 4 to 15 ring carbon atoms have been replaced by heteroatoms such as nitrogen, oxygen or sulfur. Examples are acridinyl, azaindole (1 H-pyrrolopyridinyl), azabenzimidoazolyl, azaspirodecanyl, azepinyl, azetidinyl, aziridinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 4,5-dihidrooxazolinilo, dioxazolyl, dioxazinyl, 1, 3- dioxolanyl, 1,3-dioxolyl, 3,3-dioxo [1, 3,4] oxathiazinyl, 6H-1, 5,2-dithiazinyl, dihydrofuro [2,3-b] -tetrahydrofuranyl, furanyl, furazanyl, imidazolidinyl,! midazolinyl, imidazolyl, indanyl, 1 H-indazolyl, ndolinyl, indolizinyl, indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl (benzimidazolyl), isothiazolyl, isothiazolidinyl, isothiazolinyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, -isoxazolinyl, cetopiperazinyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,3-oxadiazoyl, 1,4-oxadiazolyl, 1, 2,5-oxadiazoyl, 1,4-oxadiazoyl, 1,2-oxa -Typanyl, 1,2-ox atiolanyl, 1,4-oxazepanyl, 1,4-oxazepinyl, 1,2-oxazinyl, 1,3-oxazinyl, 1,4-oxazinyl, oxazolidinyl, oxazolinyl, oxazolyl, oxetanyl, oxocanyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, piridooxazolilo, pyridoimidazolyl, piridotiazolilo, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydropyridinyl, tetrahydrothiophenyl, tetrazinyl, tetrazolyl, 6H-1, 2,5-thiadiazinyl, 1, 2,3-thiadiazolyl, 1, 2,4-thiadiazolyl, 1, 2,5-thiadiazolyl, 1,4-thiadiazolyl, thiantrenyl, 1,2-thiazinyl, 1,3-thiazinyl, 1,4-thiazinyl, 1,3-thiazolyl, thiazolyl, thiazolidinyl, thiazolidyl, thienyl, thietanyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thietanyl, thiomorpholinyl, thiophenolyl, thiophenyl, thiopyranyl, 1,2,3-triazinyl, 1,4-triazinyl, 1,3,5-triazinyl, 1,2,3-triazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1, 2,5-triazolyl, 1,3,4-triazolyl and xanthenyl. Heterocyclics are also preferred, such as benzimidazolyl, 1,3-benzodioxolyl, benzofuranyl, benzothiazolyl, benzothiophenyl, benzoxazolyl, chromanyl, cinnolinyl, 2-furyl, 3-furyl, imidazolyl, indolyl, indazolyl, isochromanyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, phthalazinyl , pteridinyl, purinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridoimidazolyl, pyridopyridinyl, pyridopyrimidinyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrimidinyl, pyrrolyl; 2-pyrrolyl, 3-pyrrole, quinolinyl, quinazolinyl, quinoxalinyl, tetrazolyl, thiazolyl, 2-thienyl and 3-thienyl. Also preferred: The terms "het" or "a cyclic radical of 3 to 7 members, containing up to 1, 2, 3 or 4 heteroatoms" refer to the structures of the heterocycles that can be derived from compounds such as azepine, azetidine, aziridine, azirine, 1,4 diazepam, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, diaziridine, diazirine, dihydroimidazolone, dioxazole, dioxazine, dioxole, 1, 3-dioxolno, 1,3-dioxolane, furan, imidazole, imidazoline, imidazolidine, imidazolidinone, isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, cetomorfolina, ketopiperazine, morpholine, 1, 2- oxa-tiepan, 1,2-oxathiolane, 1,4-oxacepan, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazolone, oxazole, 3,3-dioxide [1, 3,4 ] oxathiazinane, oxaziridine, oxazolidinone, oxetan, oxirane, piperazine, piperidine, pyran, pyrazine, pyrazole, pyrazin-2-one, piperazin-2-one, pyrazoline, pyrazolidine, pyridazine, pyridine, pyridinone, pyrimidine, pyrimidine-2,4 -dione, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydrofuran, tetrahydropyran, tetrahydropyridine, tetrazine, tetrazole, thiadiazole thiadiazine, 1, 2-thiazine, 1, 3-thiazine, 1, 4-thiazine, 1, 3-thiazole, thiazole, thiazolidine, thiazoline, thienyl, thietane, thiomorpholine, 1,1-thiomorpholine dioxide, thiopyran, 1,2,3-triazine, 1,4-triazine, 1, 3,5-triazine, 1, 2,3- triazole or 1, 2,4-triazole. The term "R1-N-R2-V can form a cyclic group of 4 to 10 members" or "R11 and R2 together with the nitrogen atom to which they join can form a monocyclic or bicyclic heterocyclic ring of 4 to 8 members that, in addition to the nitrogen atom may contain one or two identical or different ring heteroatoms that are chosen from oxygen, sulfur and nitrogen "refers to the structures of the heterocycles that can be derived from compounds such as azepam, azepine, azetidine , dioxazole, dioxazine, 1, 4-diazepane, 1,2-diazepine, 1, 3-diazepine, 1, 4-diazepine, 2,3-dihydroindole, imidazole, midazolina, imidazolidine, indole, isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, cetopiperazine, morpholine, [1,4] oxacepan, oxazole, piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tetrazine, tetrazole, thiazole, thiadiazole, thiazolidine, thiazoline, thiomorpholine, 1, 2,3-triazine, 1, 2,4-triazine, 1, 3,5-triazine, 1,2,3-triazole or 1, 2,4-triazole. The term "R15 and R16 together with the carbon atom to which they are attached can form a 3-6 membered carbocyclic ring" refers to structures that can be derived from compounds such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. The term "R3 and R4 or R5 and R6 together with the carbon atom to which they are attached can form a 3- to 8-membered ring, which contains zero, 1, 2, 3 or 4 heteroatoms which are selected from nitrogen, sulfur or oxygen "refers to structures of carbocycles or heterocycles which can be derived from compounds such as azetidine, azocane, azocane-2-one, cyclobutyl, cycloheptyl, ciciohexilo, cyclooctane, cyclooctene, cyclopropyl, 1,4-diazepane, 1 , 2-diazepine, 1,3-diazepine, 1,4-diazepine, [1,4] diazocane, [1,2] diazocan-3-one, [1, 3] diazocan-2-one, dioxazine, [1 , 4] dioxocane, dioxol, cetopiperazine, morpholine, 1,2-oxa-tiepan, 1,4-oxacepan, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, [1,4] oxazocane, [1,3] oxazocan-2-one, oxetane, oxocane, oxocan-2-one, piperazine, piperidine, pyran, 5,6,7,8-tetrahydro-1H-azocin-2-one, thiomorpholine or tetrahydrofuran. The term "R3 and R5 or R4 and R6 together with the carbon atoms to which they are attached can form a 4- to 8-membered ring, containing 0, 1, 2, 3 or 4 heteroatoms which are selected from nitrogen, sulfur or oxygen "refers to carbocyclic or heterocyclic structures that can be derived from compounds such as azetidine, azocan, azocan-2-one, cyclobutyl, cycloheptyl, cyclohexyl, cyclooctane, cyclooctene, 1,4-diazepam, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, [1,4] diazocane, [1,2] diazocan-3-one, [1] 3] diazocan-2-one, dioxazine, [1,4] dioxocane, dioxol, cetopiperazine, morpholine, 1,2-oxa-tiepan, 1,4-oxacepan, 1,2-oxazine, 1,3-oxazine, 1 , 4-oxazine, [1,4] oxazocane, [1, 3] oxazocan-2-one, oxetane, oxocane, oxocan-2-one, piperazine, piperidine, pyrano, 5,6,7, 8-tetrahydro-1H -azocin-2-one, thiomorpholine or tetrahydrofuran. The term "oxo moiety" or "= O" refers to moieties such as carbonyl (-C (O) -) or nitroso (-N = O). The term "- (C? -C3) -perfluoryl" is a partially or fully fluorinated alkyl moiety, which may be derived from moieties such as -CF3, -CHF2, -CH2F, -CHF-CF3, -CHF-CHF2 , -CHF-CH2F, -CH2-CF3, -CH2-CHF2, -CH2-CH2F, -CF2-CF3, -CF2-CHF2, -CF2-CH2F, -CH2-CHF-CF3, -CH2-CHF-CHF2, -CH2-CHF-CH2F, -CH2-CH2-CF3, -CH2-CH2-CHF2, -CH2-CH2-CH2F, -CH2-CF2-CF3, -CH2-CF2-CHF2, -CH2-CF2-CH2F, - CHF-CHF-CF3, -CHF-CHF-CHF2, -CHF-CHF-CH2F, -CHF-CH2-CF3, -CHF-CH2-CHF2, -CHF-CH2-CH2F, -CHF-CF2-CF3, -CHF -CF2-CHF2, -CHF-CF2-CH2F, -CF2-CHF-CF3, -CF2-CHF-CHF2, -CF2-CHF-CH2F, -CF2-CH2-CF3, -CF2-CH2-CHF2, -CF2- CH2-CH2F, -CF2-CF2-CF3, -CF2-CF2-CHF2 or -CF2-CF2-CH2F. The term "- (C? -C3) -perfluorylene" is a partially or fully fluorinated alkylene moiety, which may be derived from moieties such as -CF2-, CHF-, -CHF-CHF2-, -CHF-CHF-, - CH2-CF2-, -CH2-CHF-, -CF2-CF2-, -CF2-CHF-, -CH2-CHF-CF2-, -CH2-CHF-CHF-, -CH2-CH2-CF2-, -CH2- CH2-CHF, -CH2-CF2-CF2-, -CH2-CF2-CHF-, -CHF-CHF-CF2-, -CHF-CHF-CHF-, -CHF- CH2-CF2-, -CHF-CH2-CHF-, -CHF -CF2-CF2-, -CHF-CF2-CHF-, -CF2-CHF-CF2-, -CF2-CHF-CHF-, -CF2-CH2-CF2-, -CF2-CH2-CHF-, -CF2-CF2 -CF2-, or -CF2-CF2- CHF. Halogen is fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or iodine, particularly preferably chlorine or fluorine. The optically active carbon atoms present in the compounds of the formula I can have, independently of each other, an R or S configuration. The compounds of the formula I can be present in the form of pure enantiomers or in the form of pure diastereomers or in form of mixtures of enantiomers and / or diastereomers, for example, in the form of racemic mixtures. The present invention relates to pure enantiomers and mixtures of enantiomers as well as to pure diastereomers and mixtures of diastereomers. The invention comprises mixtures of two or more of two stereoisomers of the formula I and comprises all the proportions of the stereoisomers in the mixtures. In case the compounds of the formula I can be present as E isomers or Z isomers (or cis isomers or trans isomers), the invention relates to both the pure isomers E and the pure isomers Z and the mixtures of E / Z in all proportions. The invention also encompasses all tautomeric forms of the compounds of the formula I. The diastereomers, including the E / Z isomers, can be separated into the individual isomers, for example, by chromatography. The racemic mixtures in the two enantiomers can be separated by the customary methods, for example, by chromatography in chiral phases or by resolution, for example, by crystallization of the diastereomeric salts that are obtained with optically active acids or bases. Stereochemically uniform compounds of the formula I can also be obtained by the use of stereochemically uniform starting materials or by the use of stereoselective reactions. The physiologically tolerable salts of the compounds of the formula I are non-toxic salts which are physiologically acceptable, in particular pharmacologically usable salts. Such salts of the compounds of formula I which contain acidic groups, for example a carboxylic group COOH, are, for example, alkali metal salts or alkaline earth metal salts such as sodium salts, potassium salts, magnesium salts and salts of calcium, and also salts with physiologically tolerable quaternary ammonium ions such as tetramethylammonium or tetraethylammonium, and salts by the addition of acid with ammonium and physiologically tolerable organic amines, such as methylamine, dimethylamine, trimethiamine, ethylamine, triethylamine, ethanolamine or tris- (2- hydroxyethyl) amine. The basic groups which occur in the compounds of the formula I, for example, amino group or guanidino groups, form salts by the addition of acid, for example, with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid or acid. phosphoric, or with organic carboxylic acids and sulfonic acids such as formic acid, acetic acid, oxalic acid, citric acid, lactic acid, malic acid, succinic acid, malonic acid, benzoic acid, maleic acid, fumaric acid, tartaric acid, methanesulfonic acid and p-toluenesulfonic acid. Compounds of the formula I, which simultaneously contain a basic group and an acid group, for example, a guanidino group and a carboxyl group, can also appear as zwitterions (betaines) which are also included in the present invention. Salts of the compounds of the formula I can be obtained by the usual methods known to those skilled in the art, for example, by combining a compound of the formula I with an inorganic or organic acid or base in a solvent or dispersant, or other salts by the exchange of cations or anions. The present invention also includes all salts of the compounds of the formula I which, due to their low physiological tolerability, they are not suitable for direct use in drugs but are suitable, for example, as intermediates to carry out further chemical modifications of the compounds of the formula I or as starting substances in the preparation of the Physiologically tolerable salts. In addition, the present invention includes all solvates of the compounds of the formula I, for example, hydrates or adducts with alcohols. The invention also includes derivatives and modifications of the compounds of the formula I, for example, prodrugs, protected forms and other physiologically tolerable derivatives, as well as the active metabolites of the compounds of the formula I. The invention relates, in particular, to to the prodrugs and protected forms of the compounds of the formula I, which can be converted into the compounds of the formula I in physiological conditions. Suitable prodrugs of the compounds of the formula I are known to those skilled in the art, namely the chemically modified derivatives of the compounds of the formula I having properties that have been improved in a desired manner, for example, in connection with the solubility, bioavailability or duration of the action. More detailed information about prodrugs is found in standard literature, such as, for example, Design of Prodrugs, H. Bundgaard (ed.), Elsevier, 1985; Fleisher et al., Advanced Drug Delivery Reviews 19 (1996) 115-130; or H. Bundgaard, Drugs of the Future 16 (1991) 443, all incorporated in the present invention by reference. Suitable prodrugs of the compounds of the formula I are especially the acylated prodrugs and the carbamates of prodrugs of the groups containing acylated nitrogen, such as the amino groups and the guanadine group and also esters of prodrugs and amides of prodrugs of the groups carboxylic acids that can appear in the compounds of the formula I. In the acylated prodrugs and in the prodrug carbamates, one or more, for example one or two, hydrogen atoms in nitrogen atoms in such groups are replaced with an acyl group or carbamate, preferably a group - (C6C6) -alkyloxycarbonyl. Suitable acyl groups and the carbamate groups of the acylated prodrugs and the prodrug carbamates are, for example, the groups Rp1-CO- and Rp2O-CO-, wherein Rp1 is hydrogen, (C -C? 8) - alkyl, (C3-C8) -cycloalkyl, (C3-C8) -cycloalkyl- (d-C4) -alkyl-, (Ce-C? 4) -aryl, Het-, (C6-C? 4) -aryl- (C? -C4) -alkyl- or Het- (d-C4) -alkyl- and wherein Rp2 has the meanings indicated in Rp1 with the exception of hydrogen.

Especially preferred compounds of the formula I are those in which two or more residues are defined as indicated above in the preferred compounds of the formula I, or the residues may have one or more of the specific denotations of the residues given in their general definitions or preferred definitions of preferred compounds of the above. All possible combinations of the definitions given of the preferred definitions and the specific denotations of the remains are, explicitly, subject of the present invention. Also, in relation to all the compounds of the formula I, all their stereoisomeric forms and their mixtures in any proportion and their physiologically acceptable salts are, explicitly, object of the present invention, as well as their prodrugs. Similarly, also in all preferred compounds of formula I, all residues that appear more than once in the molecule are independent of each other and may be identical or different. The compounds of formula I can be prepared using the methods and techniques, which, as such, are well known and appreciated by those skilled in the art. The person skilled in the art will be able to easily dispose of the starting substances or of the molecular blocks necessary for use in the general synthetic processes that can be applied to prepare compounds of the formula I. In many cases, they are commercially available or have been described in the literature. Otherwise, they can be prepared from readily available precursor compounds analogously to the procedures described in the literature, or through the procedures or analogously to the procedures described in this application. In general, compounds of formula I can be prepared, for example, in the course of a convergent synthesis, by linking two or more retrosinthetically derivable fragments of formula I. More specifically, β-derivatives are used. starting amino acids which are suitably substituted as molecular blocks for the preparation of the compounds of the formula I. If they are not commercially available, these ß-amino acid derivatives can be prepared according to well-known standard procedures for the formation of β-amino acids. By choosing the appropriate precursor molecules, these ß-amino acid syntheses allow introducing a variety of substituents in the different positions of the ß-amino acid system, which can be chemically modified to finally reach the molecule of the formula I that has the adequate replacement pattern. Some of the exhaustive compilations in which you can find numerous details and references to the literature on the chemistry of ß-amino acids and on the synthetic procedures for their preparation are Juaristi, E. (ed.), Enantioselective Synthesis of ß-Amino Acids 1st ed. Wiley-VCH: New York, 1997; Cole, D. C, Recent Stereoselective Synthetic Approaches to ß-Amino Acids. Tetrahedron 1994, 50, 9517-9582; Abele, S. and Seebach, D., Eur. J. Org. Chem. 2000, 1-15; Juaristi, E. and López-Ruiz, H., Recent Advances in the Enantioselective Syntheses of ß-Amino Acids. Curr. Med. Chem. 1999, 6, 983-1004. If the derivatives of the ß-amino acids are not available commercially and they have to be synthesized, it can be carried out, for example, according to the syntheses of well-known β-amino acids mentioned above. In the following methods of particular interest of the embodiment of this invention, they are briefly listed and referenced; however, they are standard procedures that are discussed exhaustively in the literature and well known to the person skilled in the art. Although not always explicitly shown, in certain cases, the isomers will be produced during the synthesis of the reactions mentioned below. However, such mixtures of isomers can be separated by modern separation techniques, such as, for example, preparative HPLC. 1) Arndt-Eistert homologation of β-amino acids (see, for example, Plucinska, K. and Liberek, B., Tetrahedron 1987, 43, 3509-3517; Cassal, J.-M., Fürst, A. and Meier , W., Helv. Chim. Acta 1976, 59, 1917-1924): 2) From aspartic acid, asparagine and derivatives, p. eg, by transformation into homoserin derivatives and treatment with an "R35Cu" cuprate reagent. (EI Marino, A., Roumestant, M.L., Viallefont, P. Razafindramboa, D., Bonato, M. and Follet, M., Synthesis 1992, 1104-1108) 3) By the addition of Michael of amines to acrylates and their derivatives: see, for example, Kwiatkowski, S., Jeganathan, A., Tobin, T. and Watt, D.S., Synthesis 1989, 946-949 or Woster, P.M. & Murray, WJ, J.Med.Chem .; 29; 5; 1986; 865-868 (cyclic acrylates): or, for example, by the addition of lithium amides derivatives of chiral secondary amines to the crotonate esters (Davies, S. G. and Ichihara, O., Tetrahedron: Asymmetry 1991, 2, 183-186) 4) By hydrogenation of 3-amino acrylates (see, for example, Lubell, WD, Kitamura, M. and Noyori, R., Tetrahedron: Asymmetry 1991, 2, 543-554; Achiwa, K. and Soga, T ., Tetradedron Lett., 1978, 28, 1119-1120) OR « 0R ) Nucleophilic addition to the double bond equivalents C = N, p. eg, addition of enolates to chiral sulfimines (Tang, T. P. and Ellmann, J. A., J.

Org. Chem. 2002, 67, 7819-7832, and references cited therein): In addition, to obtain the desired substituents of the β-amino acid system of the formula I, the functional groups introduced into the ring system can be chemically modified during the synthesis of the β-amino acid. Above all, the groups present in the system of ß-amino acid can be modified by a variety of reactions and thus obtain the desired residues R1a, R1b, R1c, R1d. The hydroxymethyl groups as well as the formyl groups linked to the β-amino acid system can be transformed into a variety of functional groups, for example, into the corresponding carboxylic acid or carboxylic ester by many oxidative reactions well known to those skilled in the art. . In addition, for example, a nitrile group linked to the ß-amino acid can be easily converted to the desired acid under acidic, basic or reducing conditions. In addition, the carboxylic acid groups and the acetic acid groups can be converted into their homologs by the reactions usual for the extension of the carboxylic acid chain. The halogen atoms can be introduced into the side chains, for example, according to procedures similar to the following described in the literature. For fluorination, N-fluoro-2,4,6-trimethylpyridinium triflate is the reagent of choice [T. Umemoto, S. Fukami, G. Tomizawa, K. Harasawa, K. Kawada, K. Tomita, J. Am. Chem. Soc. (1990) 112, 8563 see also K. Manko et al., J. Fluor Chem. (1988) 39, 435; R. Storer et al. Nucleosides Nucleotides (1999) 18; 203]; however, other suitable fluorination reagents may also be employed where appropriate. Chlorination, bromination or iodination of the aromatic side chains can be carried out by reacting them with elemental halogens or with the use of NCS, NBS or NIS and many other reagents that are well known to those skilled in the art. Depending on the reaction conditions, the reactants, the stoichiometry and the substitution pattern, the halogen is introduced into the different positions of the aromatic side chain of the β-amino acid. By selective halogen / metal exchange or metallation by selective hydrogen / metal exchange and subsequent reaction with a wide range of electrophiles, several substituents can be introduced into the aromatic nucleus [M. R. Grimmett, Heterocycies (1994) 37, 2087; V. D. Gardner et al., J. Heterocycl. Chem. (1984) 21, 121; D. Butler et al., J. Org. Chem. (1971) 36, 2542]. Halogens or hydroxy groups (by their tríflatos or nonaflatos) - or the primary amines (by means of their diazonium salts) present in the side chain of the ß-amino acid - can be converted directly, or after the interconversion in the corresponding tin or acid boronic, in a variety of other functional groups such as, for example, -CN, -CF3, -2F5, ethers, acids, amides, amines, alkyl or aryl groups mediated by transition metals, namely palladium or nickel catalysts or copper salts and reagents, for example, referred to below. [F. Diederich, P. Stang Metal-catalyzed Cross-coupling Reactions, Wiley-VCH, 1998; or M. Beller, C Bolm, Transition Metals for Organic Synthesis, Wiley-VCH, 1998; J. Tsuji Palladium Reagents and Catalysts, Wiley, 1996; J. Hartwig, Angew. Chem (1998) 110, 2154; B. Yang, S. Buchwald, J. Organomet. Chem. (1999) 576 125; T. Sakamoto, K. Ohsawa, J. Chem. Soc. Perkin Trans I (1999) 2323 D. Nichols, S. Frescas, D. Marona-Lewicka, X. Huang, B. Roth, G. Gudelsky J. Nash, J. Med. Chem. (1994) 37, 4347; P. Lam, C. Clark, S. Saubern J. Adams, M. Winters, D. Chan, A. Combs, Tetrahedron Lett. (1998) 39, 2941 D. Chan, K. Monaco, R. Wang, M. Winters, Tetrahedron Lett. (1998) 39, 2933 V. Fariña, V. Krishnamurthy, W. Scott, The Stille Reaction, Wiley, 1994 F. Qing et al. J. Chem. Soc. Perkin Trans. I (1997) 3053; S. Buchwald et al J. Am. Chem Soc. (2001) 123, 7727; S. Kang et al. Synlett (2002) 3, 427 S. Buchwald et al. Organic Lett. (2002) 4, 581; T. Fuchikami et al. Tetrahedron Lett. (1991) 32, 91; Q. Chen et al. Tetrahedron Lett. (1991) 32, 7689]. For example, the nitro groups can be reduced to amino groups by the various reducing agents, such as sulfides, dionites, complex hydrides or by catalytic hydrogenation. It is also possible to carry out the reduction of a nitro group as a subsequent step of the synthesis of a compound of the formula I, and a reduction of a nitro group to an amino group can also be simultaneously produced with a reaction carried out in another functional group, for example, when a group is reacted as a cyano group with hydrogen sulfide or when a group is hydrogenated. In order to introduce the radicals R a, R 1b, R 1c, R 1d, the amino groups can be modified according to standard alkylation processes, for example by reacting with the (substituted) alkyl halides or by reductive amination of the carbonyls, according to standard methods of acylation, for example, by reaction with activated carboxylic acid derivatives, such as chlorides, anhydrides, activated esters or others, or by reacting them with carboxylic acids in the presence of an activating agent or according to standard procedures of sulfonylation, for example, by reaction with sulfonyl chlorides. The ester groups present in the β-amino acid can be hydrolyzed to the corresponding carboxylic acids which, after activation, can be reacted with amines or alcohols under standard conditions to obtain amides or alcohols, respectively. The ester groups present in the β-amino acid can be converted to other esters by transesterification. The carboxylic acids linked to a suitable β-amino acid can also be alkylated to obtain esters. Ester groups present in the β-amino acid, for example, the benzyloxy groups or other easily cleavable ester groups, can be cleaved to obtain hydroxy groups which can then be reacted with a variety of agents, for example, with etherification or activating agents that allow the hydroxy group to be replaced by other groups. Sulfur-containing groups can be reacted analogously.

During the course of the synthesis to modify the R50 or R8 groups linked to the ß-amino acid system by the application of the parallel synthesis methodology, a variety of reactions, including, for example, palladium catalysis, can be very useful. nickel or copper. Such reactions are described, for example, in F. Diederich, P. Stang, Metal-catalyzed Cross-coupling Reactions, Wiley-VCH (1998); or M. Beller, C. Bolm, Transition Metals for Organic Synthesis, Wiley-VCH (1998); J. Tsuji, Palladium Reagents and Catalysts, Wiley (1996); J. Hartwig, Angew. Chem. (1998), 110, 2154; B. Yang, S. Buchwaid, J. Organomet. Chem. (1999), 576, 125; P. Lam, C. Clark, S. Saubern, J. Adams, M. Winters, D. Chan, A. Combs, Tetrahedron Lett. (1998), 39, 2941; D. Chan, K. Monaco, R. Wang, M. Winters, Tetrahedron Lett. (1998), 39, 2933; J. Wolfe, H. Tomori, J. Sadight, J. Yin, S. Buchwaid, J. Org. Chem. (2000), 65, 1158; V. Fariña, V. Krishnamurthy, W. Scott, The Stille Reaction, Wiley, (1994); S. Buchwaid et al., J. Am. Chem. Soc. (2001), 123, 7727; S. Kang et al., Synlett (2002), 3, 427; S. Buchwaid et al., Org. Lett. (2002), 4, 581. In addition, the reactions mentioned previously to convert the functional groups are described, in general, extensively in organic chemistry textbooks such as M. Smith, J. March, March's Advanced Organic Chemistry, Wiley- VCH, 2001 and in treatises like Houben-Weyl, "Methoden der Organischen Chemie" (Methods of Organic Chemistry), Georg Thieme Verlag, Stuttgart, Germany, or "Organic Reactions", John Wiley & Sons, New York, or R. C. Larock, "Comprehensive Organic Transformations", Wiley-VCH, 2nd ed (1999), B. Trost, I. Fleming (eds.) Comprehensive Organic Synthesis, Pergamon, 1991; A. Katritzky, C. Rees, E. Scriven Comprehensive Heterocyclic Chemistry II, Elsevier Science, 1996), in which you can find details about the reactions and the original literature. Due to the fact that, in the present case, the functional groups are linked to the ß-amino acid, in some cases it may be necessary to adapt the reaction conditions specifically or to choose specific reagents from a variety of reagents which, in principle, can be use in a conversion reaction or otherwise, take specific measures to achieve a desired conversion, for example, to use group protection techniques. However, in these cases, the person skilled in the art will have no problem finding suitable reaction variants and reaction conditions. The structural elements present in the residues linked to the β-amino acid in the compounds of the formula I and in the group COR8 present in the β-amino acid can be introduced into the β-amino acid derivative which is obtained as outlined above by steps of consecutive reactions using synthesis methodologies such as those described below using procedures that, by themselves, are well known to those skilled in the art. 8 'The radicals R which can be introduced into the formula 2, for example, by condensation of the corresponding carboxylic acid of the formula 2 with a compound of the formula HR, namely with an amine of the formula HN (R) R '-VGM to obtain a compound of formula 3. The compound of formula 3 thus obtained may already contain the final groups 8 '. , The desired groups, namely, the groups R and R can be the groups -N (R) -R-V- or GM and R -Q- that were defined in the formula I, or optionally in the 8 '50 compound of the formula 3 thus obtained the residue or the radicals R and the radical R 1 2 0 are subsequently converted to the radicals -N (R) R -VGM and R -Q- respectively, to obtain the desired compound of the formula I . formula Thus, the residues R8 and the residues R1 and R2 | -VGM contained therein may have the denotations of R1 and R2-VGM, respectively, offered above or additionally in the residues R1 ', and the functional groups R2'-VGM may also be appear in the form of groups which, subsequently, can be transformed into the final groups R1 and R2-VGM, namely, the functional groups can appear in the form of the precursor or derivative groups, for example, in protected form. In the course of the preparation of the compounds of the formula I, it may generally be advantageous or necessary to introduce the functional groups which reduce or prevent undesirable reactions or side reactions in the respective synthesis step, in the form of precursor groups which, more late, they become the desired functional groups, or temporarily block the functional groups through a suitable group protective strategy for the synthesis problem. Those strategies are well known to those skilled in the art (see, for example, Greene and Wuts, Protective Groups in Organic Synthesis, Wiley, 1991, or P. Kocienski, Protecting Groups, Thieme 1994). As examples of precursor groups, cyano groups and nitro groups may be mentioned. At a later stage, the cyano group can be converted into carboxylic acid derivatives or by reduction into aminomethyl groups, or the nitro groups can be transformed by reduction, such as catalytic hydrogenation, into amino groups. The protecting groups can also serve as a solid phase and cleave from the solid phase supports to remove the protecting group. The use of such techniques is known to those skilled in the art. (Burgess K (Ed.) Solid Phase Organic Synthesis, New York, Wiley, 2000). For example, a hydroxyphenolic group can be linked to a trityl-polystyrene resin, which serves as a protecting group, and the molecule of this resin is cleaved by a treatment with TFA at a later stage of the synthesis. The rest R50 in the compounds of formulas 2 and 3 can denote the group -Q-R ° as defined above, which will eventually be present in the desired target molecule of formula I, or may denote a group which, subsequently, can be transformed into the group -QR °, for example, a precursor group or a derivative of the group -QR °, in that the functional groups appear in protected form, or R50 can denote a hydrogen atom or a protecting group of the nitrogen atom of the ß-amino acid. Similarly, the residues R1a, R1b, R1c, R1d in formulas 2 and 3 have the corresponding definitions of R3, R4; R5, R6 in formula I as defined higher; however, for the synthesis of the compounds of the formula I, initially, these residues can appear in the step of the condensation of a compound of the formula 2 with a compound of the formula HR8 ', which gives a compound of the Formula 3 in the form of precursor groups or in protected form. The R49 moieties in the compounds of the formula 2, which may be identical or different, may be, for example, hydroxy or (dC4) -ayloxy, namely, the COR49 groups present in the compounds of the formula 2 may be , for example, without the carboxylic acids or esters thereof as alkyl esters, as the COR8 groups can be in the compounds of the formula I. The groups COR49 can also be any other activated derivative of a carboxylic acid which allows the amide formation, ester formation or thioester formation with a compound of formula HR8 '. The group COR49 can be, for example, an acid chloride, an activated ester such as a substituted phenyl ester or an N-hydroxysuccinimide or a hydroxybenzotriazole ester, an azolide such as an imidazolide, an azide or a mixed anhydride, for example a mixed anhydride with an ester of carbonic acid or with a sulfonic acid, which derivatives can be prepared from the carboxylic acid by standard procedures and can be reacted with an amine, an alcohol or a mercaptan of the formula HR8 'under the conditions standards A carboxylic acid group COOH representing COR49 in a compound of formula 2 can be obtained, for example, from a β-amino acid ester group by standard hydrolysis procedures. It can also be obtained, for example, by the hydrolysis of a nitrile group that is introduced into the ß-amino acid during the synthesis of the ß-amino acid. Compounds of the formula I in which a COR8 group is an ester group can also be prepared from the compounds of the formula 2 in which COR49 is a carboxylic acid group, by common esterification reactions as, for example, by reacting the acid with an alcohol in an acid catalysis or an alkylation of a carboxylic acid salt with an electrophile such as an alkyl halide, or by the transesterification of another ester. Compounds of the formula I in which a group COR8 is an amide group can be prepared from the amines and the compounds of the formula 2, wherein COR49 is a carboxylic acid group or an ester thereof by amination reactions common. Especially for the preparation of the amides, the compounds of the formula 2, in which COR49 is a carboxylic acid group, can be condensed under standard conditions, with compounds of the formula HR8 which are amines by means of common coupling reagents which are used in the synthesis of peptides. Such coupling reagents are, for example, carbodiimides such as dicyclohexylcarbodiimide (DCC) or diisopropylcarbodumide, carbonyldiazoles such as carbonyldiimidazole (CDI) and similar reagents, propylphosphonic anhydride, O - ((cyano- (ethoxycarbonyl) -methylene) amino) -NNN tetrafluoroborate. '^' - tetramethyluronium (TOTU), diethylphosphoryl cyanide (DEPC) or and bis- (2-oxo-3-oxazolidinyl) -phosphoryl chloride (BOP-CI) and many others. If the remainder of -Q-R ° present in a β-amino acid of formula I or the rest R50 present in a β-amino acid of formula 2, or a residue in the that the functional groups within the QR or R50 moiety appear in protected form or in the form of a precursor group, has not been introduced yet during an earlier stage, for example, during a synthesis of the β-amino acid, these residues can be introduced, for example, in the ß-amino acid system by the conventional procedures of the literature for N-alkylation, reductive amination, N-arylation, N-acylation or N-sulfonylation of the nitrogen atoms of the ß-ring - amino acid, which is well known to the person skilled in the art. The N-acylation of a nitrogen atom can be carried out, for example, by standard conditions by means of common coupling reagents used in the synthesis of peptides. Such coupling reagents are, for example, carbodiimides such as dicyclohexylcarbodiimide (DCC) or diisopropylcarbodiimide, carbonyldiazoles such as carbonyldiimidazole (CDI) and similar reagents, propylphosphonic anhydride, O - ((cyano- (ethoxycarbonyl) -methylene) amino) -NNN tetrafluoroborate. 'N'-tetramethyluronium (TOTU), diethylphosphoryl cyanide (DEPC) or bis- (2-oxo-3-oxazolidinyl) -phosphoryl chloride (BOP-CI) and many others. The N-alkylation of a nitrogen atom can be carried out, for example, under standard conditions, preferably in the presence of a base such as K2C03, Cs2CO3, NaH or KOlBu, using an alkylating compound of the formula LG-Q-R0 or of the formula R50-LG, in which the atom in the group Q or in the group R50 linked to the group LG in this case is an aliphatic carbon atom of an alkyl radical and LG is a leaving group, for example, halogen as chlorine, bromine or iodine, or a sulfonyloxy group such as tosyloxy, mesyloxy or trifluoromethylsulfonyloxy. You can control the regioselectivity of the N- alkylation by choosing the base, the solvent and the reaction conditions. However, mixtures of positional isomers can be separated by modern separation techniques such as, for example, flash chromatography, crystallization or preparative HPLC. Preferred methods include, but are not limited to, those described in the examples. The compounds of the present invention are inhibitors of serine proteases, which inhibit the activity of the enzymatic factors of blood coagulation Xa and / or Vlla. In particular, they are very active inhibitors of factor Xa. They are specific inhibitors of serine protease since they do not substantially inhibit the activation of other proteases whose inhibition is not desired. The activity of the compounds of the formula I can be determined, for example, in the assays described below or in other assays known to those skilled in the art. In relation to the inhibition of factor Xa, a preferred embodiment of the invention comprises the compounds having a Ki < 1 mM for the inhibition of factor Xa, as determined in the assay described below, with or without the concomitant inhibition of factor Vlla and which, preferably, does not substantially inhibit the activity of other proteases involved in coagulation and fibrinolysis, whose inhibition is not desired (using the same inhibitor concentration). The compounds of the invention inhibit the catalytic activity of factor Xa directly, within the prothrombinase complex or as a soluble subunit, or indirectly, by inhibiting the assembly of factor Xa in the prothrombinase complex.

As inhibitors of factor Xa and / or factor Vlla, the compounds of formula I and their physiologically tolerable salts and their prodrugs are generally suitable for the treatment and prophylaxis of conditions in which the activity of factor Xa and / or the factor Vlla performs a function or has an undesirable effect or that may be favorably influenced by inhibiting factor Xa and / or factor Vlla or by reducing its activities, or when the physician wishes a prevention, relief or cure that requires the inhibition of factor Xa and / or factor Vlla or a reduction in its activity. As the inhibition of factor Xa and / or factor Vlla influences blood coagulation and fibrinolysis, generally, the compounds of formula I and their physiologically reactive salts and their prodrugs are suitable for reducing blood coagulation or for the treatment and prophylaxis of conditions in which the activity of the blood coagulation system is important or undesirable in scope, or which may be favorably influenced by reducing blood coagulation or for the prevention, relief or cure of which the doctor wishes a reduction in the activity of the blood coagulation system. Thus, a specific object of the present invention is the reduction or inhibition of unwanted blood coagulation, in particular in an individual, by administration of an effective amount of a compound, a physiologically tolerable salt or a prodrug thereof. , as well as also pharmaceutical preparations thereof. The present invention also relates to the use of the compounds of the formula I and / or their physiologically tolerable salts and / or their prodrugs to produce drugs to inhibit factor Xa and / or factor Vlla or to influence blood coagulation, the inflammatory response or fibrinolysis, or for the treatment or prophylaxis of the diseases mentioned above or below, by example, for the production of drugs for the treatment and prophylaxis of cardiovascular disorders, thromboembolic diseases or restenosis. The invention also relates to the use of the compounds of the formula I and / or their physiologically tolerable salts and / or their prodrugs for the inhibition of factor Xa and / or factor Vlla or for influencing blood coagulation or fibrinolysis or for the treatment or prophylaxis of the diseases mentioned above or below, for example, for use in the treatment and prophylaxis of cardiovascular disorders, thromboembolic diseases or restenosis, and to treatment methods that pursue such purposes, including methods for such treatments and prophylaxis. The present invention also relates to pharmaceutical preparations (or pharmaceutical compositions) containing an effective amount of at least one compound of the formula I and / or its physiologically tolerable salts and / or its prodrugs in addition to a usual pharmaceutically acceptable excipient, know, one or more pharmaceutically acceptable carrier substances or excipients and / or auxiliary substances or additives. The invention also relates to the treatment of disease states such as abnormal thrombus formation, acute myocardial infarction, unstable angina, thromboembolism, acute associated vessel occlusion. to thrombolytic therapy or to percutaneous transluminal coronary angioplasty (PTCA), transient ischemic attacks, stroke, intermittent claudication or peripheral or coronary artery bypass, narrowing of vessel lumen, postcoronary restenosis or venous angioplasty, maintenance of vascular permeability in the patients on hemodialysis for a long time, anatomopathological thrombus formation that occurs in the veins of the lower extremities after abdominal, knee or hip surgery, risk of pulmonary thromboembolism or dissemination of the systemic intravascular coagulopathy that occurs in the Vascular systems during a septic shock, certain viral infections or cancer. The compounds of the present invention can also be used to reduce an inflammatory response. Examples of specific disorders for the treatment or prophylaxis against which the compounds of the formula I can be used are coronary heart disease, myocardial infarction, angina pectoris, vascular restenosis, for example, restenosis after angioplasty as PTCA, adult acute dyspnoea syndrome, multiorgan failure and dissemination of intravascular coagulation disorder. Examples of related complications associated with surgery are thrombosis such as deep vein thrombosis and thrombosis of the nearest vein, which occurs after surgery. The compounds of the formula I and their physiologically tolerable salts and their prodrugs can be administered to animals, preferably to mammals, and in particular to humans, as drugs for treatment or prophylaxis. They can be administered by themselves or in mixtures with another or in the form of pharmaceutical preparations, which allow enteral or parenteral administration. The drugs can be administered orally, for example, in the form of pills, tablets, coated tablets, coated tablets, granules, hard and soft gelatin capsules, solutions, syrups, emulsions, suspensions, or aerosol mixtures. The administration, however, can also be performed rectally, for example in the form of suppositories, or parenterally, for example by the intravenous, intramuscular or subcutaneous routes, in the form of injectable solutions or infusible solutions, microcapsules, implants or splints, or percutaneously or topically, for example, in the form of ointments, solutions or tinctures, or in other ways, for example, in the form of aerosols or nasal sprays. The pharmaceutical preparations according to the invention are prepared in a manner known per se and familiar to the person skilled in the art, using inert inorganic and / or organic pharmaceutically acceptable excipients in addition to the compound (s) of the formula I and / or its / s salt / is physiologically tolerable / s and / or his / her prodrugs. For the manufacture of pills, tablets, coated tablets and hard gelatine capsules it is possible to use, for example, lactose, corn starch or derivatives thereof, talc, stearic acid or its salts, etc. Excipients for soft gelatine capsules and suppositories are, for example, fats, waxes, semi-solid and liquid polyols, natural or solidified oils, etc. Excipients suitable for the production of the solutions, for example, injectable solutions, or of emulsions or syrups are, for example, water, saline solutions, alcohols, glycerol, polyols, sucrose, hydrogenated sugar, glucose, vegetable oils, etc. Suitable excipients for microcapsules, implants or splints are, for example, copolymers of glycolic acid and lactic acid. Normally, the pharmaceutical preparations contain approximately between 0.5% and 90% by weight of the compounds of the formula I and / or their physiologically tolerable salts and / or their prodrugs. The amount of the active component of the formula I and / or its physiologically tolerable salts and / or its prodrugs in the pharmaceutical preparations is usually about 0., 5 mg to about 1000 mg, preferably from about 1 mg to about 500 mg. In addition to the active ingredients of the formula I and / or their physiologically acceptable salts and / or prodrugs and the substances of the excipient, the pharmaceutical preparations may contain additives such as, for example, fillers, disintegrants, binders, lubricants, humectants, stabilizers, emulsifiers, preservatives, sweeteners, colorants, odorants, flavorings, thickeners, diluents, buffer substances, solvents, solubilizers, agents to achieve a prolonged effect, salts to alter the osmotic pressure, coating agents or antioxidants. They may also contain two or more compounds of the formula I, and / or their physiologically tolerable salts and / or their prodrugs. In the case that a pharmaceutical preparation contains two or more compounds of the formula I, the selection of the individual compounds can point to a profile pharmacological specific of the pharmaceutical preparation. For example, a very powerful compound with a short duration can be combined with a long-lasting compound of lower power. The flexibility allowed in relation to the choice of substituents in the compounds of formula I allows a great control over the biological and physicochemical properties of the compounds, and thus, allows the selection of such desirable compounds. In addition, on at least one compound of the formula I and / or its physiologically tolerable salt and / or its prodrug, the pharmaceutical preparations may also contain one or more therapeutically or prophylactically active ingredients. By using the compounds of formula I, the dose may vary within wide limits and, as is usual and known to the physician, must be adjusted to the conditions of the patient in each particular case. It depends, for example, on the specific compound used, on the nature and severity of the disease to be treated, on the mode and administration regimen, or on whether an acute or chronic disease is treated or if prophylaxis is carried out. An adequate dosage can be established using clinical approaches well known in medical practice. In general, the daily dose to achieve the desired results in an adult with a weight around 75 kg is from 0.01 mg / kg to 100 mg / kg, preferably from 0.1 mg / kg to 50 mg / kg, in particular from 0.1 mg / kg to 10 mg / kg (in each case, in milligrams per kilogram of body weight). The daily dose can be divided into several, in particular in the case of the administration of relatively large amounts, for example, in administrations in 2, 3 or 4 fractions. Usually, according to the individual behavior, it may be necessary to divert the indicated daily dose to the high or low. A compound of the formula I can also advantageously be used as an anticoagulant outside of an individual. For example, an effective amount of a compound of the invention can be contacted with a sample of freshly taken blood to prevent coagulation of the blood sample. In addition, a compound of formula I or its salts can be used for the purpose of diagnosis, for example, in in vitro diagnostics, and as an aid in biochemical investigations. For example, a compound of formula I can be used in an assay to identify the presence of factor Xa and / or factor Vlla or to isolate factor Xa and / or factor Vlla in a substantially pure form. A compound of the invention can be labeled with, for example, a radioisotope and then, the labeled compound linked to factor Xa and / or factor Vlla is detected using a routine method useful for detecting particular labeling. Thus, a compound of formula I or a salt thereof can be used as a probe to detect the location or amount of factor Xa activity and / or factor Vlla in vivo, in vitro or ex vivo. In addition, the compounds of the formula I can be used as synthesis intermediates for the preparation of other compounds, in particular other pharmaceutically active ingredients, which can be obtained from the compounds of the formula I, for example, with the introduction of substituents or modification of functional groups. The general synthesis sequences to prepare the compounds that are useful in the present invention are outlined in the examples given below. Both the explanation of, and the actual procedure for, the various aspects of the present invention are described where appropriate. The following examples are intended to be merely illustrative of the present invention and not limiting thereof neither by its scope nor by its spirit. Those skilled in the art will readily understand that known variations of the conditions and methods described in the examples can be used to synthesize the compounds of the present invention. It is understood that changes that do not substantially affect the activity of the different embodiments of this invention are included within the invention described herein. Thus, the following examples are intended to illustrate but not limit the present invention.

EXAMPLES When in the final stage of the synthesis of a compound an acid such as trifluoroacetic acid or acetic acid is used, for example when trifluoroacetic acid is used to remove a tBu group or when a compound was purified by chromatography using an eluent that contained such acid, in some cases, depending on the development procedure, for example the details of a lyophilization process, the compound was obtained, partially or completely, in the form of a salt of the acid used, for example in the form of a salt of the acetic acid or an acid salt trifluoroacetic or a salt of hydrochloric acid. Abbreviations used: Terbutil tBu 2,2'-Bis (diphenylphosphino-1,1-biphenyl) Binap Bis- (oxo-3-oxazolidinyl) -phosphoryl chloride BOP-CI Dibenzylideneacetone dba Dichloromethane DCM Dicyclohexylcarbodiimide DCC Diethylphosphoryl cyanide DEPC Diisopropylethylamine DIPEA 4-Dimethylaminopyridine DMAP N, N-Dimethylformamide DMF Dimethylsulfoxide DMSO 1, 1 '-Bis (diphenylphosphino) ferrocene DPPF O- (7-Azabenzotriazol-1-yl) -N, N, N', N'-tetramethyluronium-hexafluorophosphate HATU N-Bromosuccinimide NBS N -Chlorosuccinimide NCS N-Yodosuccinimide NIS N-Ethylmorpholine NEM Methanol MeOH Ambient temperature, from 20 ° C to 25 ° C RT Saturated sat. Tetrahydrofuran THF Trifluoroacetic acid TFA Tetrafluoroborate O - ((ethoxycarbonyl) cyanoethyleneamino) -N, N, N ', N'-tetramethyluronium TOTU Example 1: . { 2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide, (i) 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionic acid tertbutyl ester A solution was stirred at room temperature for 12 h of 340 mg of 5-chloro-thiophene-2-carboxylic acid, 362 mg of 3-amino-propionic acid terbutyl ester, 785 mg of TOTU and 0.66 ml of triethylamine in 10 ml of DMF. 20 ml of water were added and the organic phase was extracted twice with ethyl acetate. The solvent was dried over MgSO and removed in vacuo. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 484 mg MS (ES +): m / e = 290, chlorine standard. (ii) 3 - [(5-Chloro-thiophene-2-carbonyl) -amino] -propionic acid A solution of 484 mg of 3 - [(5-chloro-thiophene-2-carbonyl) tert-butyl ester was stirred for 12 h. ) -amino] -propionic in 50 ml of CH2CI2 and 15 ml of trifluoroacetic acid. The solvent was removed in vacuo. The product was recrystallized from diisopropyl ether. Yield: 190 mg MS (ES +): m / e = 234, chlorine standard. (iii) 4- (4-Nitro-phenyl) -morpholine A mixture of 24.5 g of morpholine and 13.3 g of 1-fluoro-4-nitrobenzene in 30 ml of DMSO was heated at 100 ° C for 4 h. . The solution was poured into 300 ml of water and the resulting precipitate was collected by filtration to produce a bright yellow crystalline product, which was dried in vacuo. Yield: 19.7g. (iv) 4- (4-Nitro-phenyl) -morpholin-3-one 32 g of benzyltriethylammonium chloride and 22.7 g of potassium permanganate (325 mesh) were carefully added to RT at RT. g of 4- (4-nitro-phenyl) -morpholine in 200 ml of DCM. After stirring for 1 h at RT, the reaction mixture was heated to reflux for 10 h.

Then, a solution of 95 g of a2S? 3 in 450 ml of water was added under ice cooling and with vigorous stirring. The mixture was filtered through a pad of celite and the filtrate was concentrated in vacuo. The yellow solid was stirred with 250 ml of water and the precipitated product was collected by filtration.

This crude product was purified by chromatography on silica gel using a gradient of 100% DCM / MeOH up to 50% as eluent. The fractions containing the product were combined and the solvent was evaporated in vacuo. Yield: 2.6 g. (v) 4- (4-Amino-phenyl) -morpholin-3-one 13.2 g of SnCl2 dihydrate was added to a solution of 2.6 g of 4- (4-Nitro-phenyl) -morpholin-3- ona in 350 ml of ethyl acetate and 17 ml of ethanol. Then, after cooling to RT, the mixture was stirred for 16 h. He The precipitated product was collected by filtration and was sufficiently pure to be used in the next reaction step. Yield: 2.07 g. (saw) . { 2- [4- (3-Oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl} 5-Chloro-thiophene-2-carboxylic acid amide. A solution of 185 mg of 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionic acid, 160 mg of 4 mg, was stirred for 4 h. - (4-amino-phenyl) -morpholin-3-one, 312 mg of TOTU and 0.26 ml of triethylamine in 10 ml of DMF. Water was added and the precipitate was collected by filtration. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 202 mg MS (ES +): m / e = 408, chlorine standard.

Example 2: { 2- [4- (2-Oxo-2H-pyrazin-1-yl) -phenylcarbaminyl] -ethyl} 5-Chloro-thiophene-2-carboxylic acid amide, (i) 1- (4-Nitro-phenyl) -1 H -pyrazin-2-one A mixture of 720 mg was stirred at 35 ° C for 16 h. 1-fluoro-4-nitro-benzene, 632 mg of sodium salt of 1 H-pyrazin-2-one and 3.3 g of Cs2CO3 in 13 ml of DMF. Water was added and the mixture was stirred for 1 h. The precipitate was collected by filtration. The product was pure enough to be used without further purification. Yield: 545 mg MS (ES +): m / e = 218. (ii) 1- (4-Amino-phenyl) -1 H -pyrazin-2-one 2.7 g of SnCl 2 dihydrate was added to a solution of 520 mg of 1- (4-nitro-phenyl) -1H-pyrazin-2-one in 26 ml of ethyl acetate and 13 ml of ethanol. The mixture was refluxed for 6 h. The precipitate was collected by filtration and the product was pure enough to be used without further purification. Yield: 450 mg MS (ES +): m / e = 188. (ii). { 2- [4- (2-Oxo-2H-pyrazin-1-yl) -phenylcarbaminyl] -ethyl} 5-Chloro-thiophene-2-carboxylic acid amide. A solution of 218 mg of 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionic acid, 262 mg of 1%, was stirred for 6 h. - (4-amino-phenyl) -1H-pyrazin-2-one, 367 mg of TOTU and 0.31 ml of triethylamine in 10 ml of DMF. Water was added and the precipitate was collected by filtration. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 212 mg MS (ES +): m / e = 403, chlorine standard.

Example 3: 4-chloro-N-. { 2- [4- (3-Oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl} -benzamide (i) 3- (4-chloro-benzoylamino) -propionic acid terbutyl ester A solution of 3-amino-propionic acid terbutyl ester in 5 ml of CH2Cl2 was slowly added over 5 minutes to an ice solution of 384 mg of 4-chloro-benzoyl chloride and 0.6 ml of triethylamine in 25 ml of ice. CH2Cl2. After 1 h, the reaction solution was washed 2 times with water and the organic solvent was dried over MgSO. After removing the solvent in vacuo, the residue was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a colorless oil. Yield: 451 mg MS (ES +): m / e = 284, chlorine standard. (i) 3- (4-Chloro-benzoylamino) -propionic acid 450 mg of 3- (4-chloro-benzoylamino) -propionic acid terbutyl ester was dissolved in a mixture of 70 ml of CH2Cl2 and 30 ml of trifluoroacetic acid. After 12 h, the solvent was removed in vacuo and the residue was purified by preparative HPLC (C 8 reverse phase column, elution with a gradient of H 2 O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 360 mg MS (ES +): m / e = 228, chlorine standard. (iii) 4-Chlorine-N-. { 2- [4- (3-Oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl} -benzamide A solution of 180 mg of 3- (4-chloro-benzoylamino) -propionic acid, 311 mg of TOTU, 160 mg of (4-amino-phenyl) -morpholin-3-one and stirred was stirred for 3 h at room temperature. 0.26 ml of triethylamine in 10 ml of DMF. 5 ml of water were added and the precipitate was collected by filtration. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid.

Yield: 302 mg MS (ES +): m / e = 402, chlorine standard.

Example 4: { 3-oxo-3- [5- (2-oxo-2H-pyrazin-1-yl) -2,3-dihydro-indol-1-yl] -propyl} 5-Chloro-thiophene-2-carboxylic acid amide, (i) 5-Bromo-2,3-dihydro-indole-1-carboxylic acid terbutyl ester 992 mg of di-fer-butyl-carbonate was slowly added to a solution of 600 mg of 5-bromo-2,3-dihydro-1 H-indole and 37 mg of 4-dimethylaminopyridine in 30 ml of acetonitrile. After 2 h at 50 ° C, the solvent was removed in vacuo. The residue was dissolved in 50 ml of ethyl acetate and washed with water. The organic solvent was dried over MgSO and the solvent was removed in vacuo. The product was used without further purification. Yield: 712 mg MS (ES +): m / e = 299. (i) 5- (2-Oxo-2H-pyrazin-1-yl) -2,3-dihydro-indole-1-carboxylic acid terbutyl ester degassed in an argon atmosphere a mixture of 712 mg of 5-bromo-2,3-dihydro-indole-1-carboxylic acid terbutyl ester, 338 mg of 1H-pyrazin-2-one sodium salt, 363 mg of carbonate potassium, 173 mg of 8-hydroxyquinoline and 227 mg of copper iodide (I) in 10 ml of DMF. The reaction mixture was heated at 120 ° C for 6 h. 4 ml of a 14% NH3 solution was added and the mixture was stirred for 1 h. 20 ml of water was added and the mixture was extracted with ethyl acetate. The organic phase was dried over MgSO and the solvent was removed in vacuo. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a H2O / MeCN gradient with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 237 mg MS (ES +): m / e = 314. (iii) 1 - (2,3-Dihydro-1 H -indoI-5-yl) -1 H-pyrazin-2-one 237 mg of 5- (2-Oxo-2H-pyrazin-1-yl) -2,3-dihydro-indole-1-carboxylic acid terbutyl ester in a mixture of 60 ml of CH2Cl2 and 40 ml of trifluoroacetic acid. After 12 h, the solvent was removed in vacuo and the residue was purified by preparative HPLC (reversed phase column 18, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 150 mg MS (ES +): m / e = 214. (iv). { 3-oxo-3- [5- (2-oxo-2H-pyrazin-1-yl) -2,3-dihydro-indol-1-yl] -propyl} 5-chloro-thiophene-2-carboxylic acid amide. A solution of 150 mg of 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionic acid, 270 mg of 1 mg, was stirred for 5 h. (2,3-dihydro-1H-indol-5-yl) -1H-pyrazin-2-one, 253 mg of TOTU and 0.32 ml of triethylamine in 3 ml of DMF. Water was added and the precipitate was collected by filtration. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 100 mg MS (ES +): m / e = 429, chlorine standard.

Example 5: { 3-oxo-3- [5- (2-oxo-2H-pyrazin-1-yl) -indol-1-yl] -propyl} - 5-chloro-thiophene-2-carboxylic acid amide, (i) 1- (1 H-indol-5-yl) -1 H-pyrazin-2-one A mixture of 700 mg of 5-bromine was carefully degassed -1 H-indole, 506 mg of sodium salt of 1 H-pyrazin-2-one, 543 mg of potassium carbonate, 259 mg of 8-hydroxyquinoline and 340 mg of copper iodide (I) in 9 ml of DMF in one argon atmosphere. The reaction mixture was heated at 120 ° C for 6 h. 4 ml of an NH3 solution was added and the mixture was stirred for 1 h. 20 ml of water was added and the mixture was extracted with ethyl acetate. The organic phase was dried over MgSO4 and the solvent was removed in vacuo. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 259 mg MS (ES +): m / e = 212. (ii). { 3-oxo-3- [5- (2-oxo-2H-pyrazin-1-yl) -indol-1-yl] -propyl} 5-chloro-thiophene-2-carboxylic acid amideA solution of 60 mg of 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionic acid, 84 mg of 1- (1H-indol-5-yl) -1H- was stirred for 5 h. pyrazin-2-one, 101 mg of TOTU, 35 mg of hydroxybenzotriazole and 0.13 ml of triethylamine in 3 ml of DMF. Water was added and the aqueous phase was extracted with ethyl acetate. The organic phase was dried over MgSO and the solvent was removed in vacuo. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to yield a white solid. Yield: 10 mg MS (ES +): m / e = 427, chlorine standard.

Example 6:. { 2- [2-fluoro-4- (2-oxo-2H-pyrazin-1-yl) -phenylcarbaminyl] -ethyl} 5-Chloro-thiophene-2-carboxylic acid amide, (i) 1- (4-Amino-3-fluoro-phenyl) -1 H-pyrazin-2-one A mixture of 2 g of 2- fluoro-4-iodo-phenylamine, 1 g of sodium salt of 1H-pyrazin-2-one, 1.3 g of potassium carbonate, 612 mg of 8-hydroxyquinoline and 804 mg of copper iodide (I) in 20 ml of DMF in an argon atmosphere. The reaction mixture was heated to 130 ° C in a microwave reactor for 120 min. 10 ml of an NH 3 solution was added and the mixture was stirred for 1 h. 20 ml of water was added and the mixture was extracted with ethyl acetate. The organic phase was dried over MgSO4 and the solvent was removed in vacuo. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 180 mg MS (ES +): m / e = 206. (ii). { 2- [2-fluoro-4- (2-oxo-2H-pyrazin-1-yl) -phenylcarbaminyl] -ethyl} 5-Chloro-thiophene-2-carboxylic acid amide. A solution of 120 mg of 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionic acid, 164 mg of 1 mg, was stirred for 12 h. - (4-amino-3-fluoro-phenyl) -1 H-pyrazin-2-one, 202 mg of TOTU and 0.26 ml of triethylamine in 3 ml of DMF. Water was added and the aqueous phase was extracted with ethyl acetate. The organic phase was dried over MgSO and the solvent was removed in vacuo. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 9 mg MS (ES +): m / e = 421, chlorine standard.

Example 7: { (R) -2- (2,2-difluoroethylamino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, (i). { 2-amino-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbaminyl] -ethyl} - (R) -5-Chloro-thiophene-2-carboxylic acid amide 30% HBr in acetic acid (7 ml) was added dropwise at 0 ° C to benzyl acid ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamate] -ethyl} -carbamic (327 mg). The mixture was stirred for 10 min at 0 ° C and then for 1 h at RT after which it was concentrated in vacuo. The residue was triturated with a saturated solution of sodium bicarbonate after which it was extracted with DCM. The combined organic phases were washed with water, dried over MgSO 4 and concentrated to give 271 mg of. { 2-amino-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbaminyl] -ethyl} acid (f?) - 5-chloro-thiophene-2-carboxylic acid which was used directly in the next step. (I) { (f?) - 2- (2,2-difluoro-ethylamino) -2- [4- (3-oxo-morpholin-4-yl) -3- trifluoromethyl-phenylcarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide To a solution of the above crude amine (103 mg) in THF (3 ml) was added DIPEA (96 μl) and then 1,1-difluoro-2- trifluoromethanesulfonyl-ethane (29 mg). The mixture was stirred for 20 h at RT after which it was concentrated. The residue was purified by preparative RP-HPLC to give. { (R) -2- (2,2-difluoroethylamino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, in the form of its trifluoroacetate salt (15 mg). MS (ES +): m / e = 555 [M + H] +, chlorine standard.

Example 8: 3- (5-chloro-thiophene-2-sulfonylamino) -N- [4- (3-oxo-morpholin-4-yl) -phenyl] -propionamide (i) 3- (5-) tert-butyl ester chloro-thiophene-2-sulfonylamino) -propionic acid To a solution of 1.33 g of 3-amino-propionic acid terbutyl ester and 2.8 g of diisopropylethylamine in 33 ml of CH2Cl2 was added slowly to 0 ° C the solution of 1.6 g of 5-chloro-thiophene-2-sulfonyl chloride in 5 ml of CH2Cl2. The reaction mixture was allowed to reach room temperature and was stirred for 3 h. The organic phase was washed with water, dried over MgSO and the solvent was evaporated in vacuo. The crude product was purified by column chromatography (silica gel, elution with a gradient of ethyl acetate / heptane). The fractions containing the product were evaporated to produce a colorless oil. Yield: 2.37 g MS (ES +): m / e = 326, chlorine standard. (ii) 3- (5-Chloro-thiophene-2-sulfonylamino) -propionic acid 2.37 mg of 3- (5-chloro-thiophene-2-sulfonylamino) -propionic acid butyric acid ester were dissolved in a mixture of 120 ml of CH2Cl2 and 40 ml of trifluoroacetic acid. After 12 h, the solvent was removed in vacuo and the residue was purified by preparative HPLC (reversed phase column 18, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 1.96 g MS (ES +): m / e = 270, chlorine standard. (iii) 3- (5-Chloro-thiophene-2-sulfonylamino) -N- [4- (3-oxo-morpholin-4-yl) -phenyl] -propionamide A solution of 160 mg of acid was stirred for 12 h. 3- (5-chloro-thiophene-2-sulphonyl) -propionic acid, 120 mg of 4- (4-amino-phenyl) -morpholin-3-one, 234 mg of TOTU and 0.20 ml of triethylamine in 3 ml of DMF. Water was added and the precipitate was collected by filtration. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 60 mg MS (ES +): m / e = 444, chlorine standard.

Example 9: { 2- [4- (3,3-dioxo- [1,3,4] oxathiazinan-4-yl) -phenylcarba-minyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, (i) N-Benzyl-C-chloro-N- (2-hydroxy-ethyl) -methanesulfonamide A solution of 4.9 g of chloro- methanesulfonyl in 50 ml of THF was slowly added to an ice-cooled solution of 5 g of 2- benzylamino-ethanol and 11.2 mL of diisopropopylethylamine in 180 mL of THF. The reaction mixture was slowly allowed to warm to room temperature. The solvent was removed in vacuo. The residue was dissolved in 100 ml of ethyl acetate and washed with water. The organic phase was dried over MgSO4 and the solvent was removed in vacuo. The product was pure enough to be used without further purification. Yield: 8.7 g MS (ES +): m / e = 264. (ii) 4-Benzyl- [1, 3,4] oxathiazinone dioxide A mixture of 8.7 g of N-benzyl-C-chloro- N- (2-hydroxy-ethyl) -methanesulfonamide and 21.5 g of Cs 2 CO 3 in 100 ml of DMF was heated at 80 ° C for 15 h. Water was added and the solution was extracted with ethyl acetate. The organic phase was dried over MgSO4 and the solvent was removed in vacuo. The product was purified by column chromatography (silica gel, elution with a gradient of ethyl acetate / heptane). The fractions containing the product were evaporated to produce a colorless oil. Yield: 7.5 g. MS (ES +): m / e = 228. (iii) 3,3-Dioxide of [1, 3,4] oxathiazinone A mixture of 6.3 g of 3,3-dioxide-4-benzyl- [1, 3 , 4] oxathiazinone and 0.6 g of Pd / C in 150 ml of THF and 1.5 ml of acetic acid was stirred under a hydrogen atmosphere (6 bar / 45 ° C). After 6 h, the reaction vessel was carefully purged with nitrogen, the catalyst was removed by filtration and the solvent was removed in vacuo. The product was pure enough to be used without further purification. Yield: 3.8 g MS (ES +): m / e = 138. (iv) 3,3-4- (4-Nitro-phenyl) - [1,4] oxathiazinone. A mixture of 2.2 g of 1-fluoro-4 was heated at 50 ° C. for 7 h. Nitro-benzene, 2.1 g of 3,3-dioxide [1, 3,4] oxathiazine and 10.0 g of Cs 2 CO 3 in 15 ml of DMF. Water was added and the precipitate was collected by filtration. The crude product was purified by column chromatography (silica gel, elution with a gradient of ethyl acetate / heptane). The fractions containing the product were evaporated to produce a slightly yellow oil. Yield: 3.0 g. MS (ES +): m / e = 259. (v) 4- (3,3-Dioxo- [1,4-] oxathiazin-4-yl) -phenylamine Was stirred under a hydrogen atmosphere (1 bar / RT). ) a mixture of 600 mg of 4- (4-nitro-phenyl) - [1,3,4] oxathiazine-3,3-dioxide and 8 g of Raney-Ni in 100 ml of NH 3 / methanol. After 4 h, the reaction vessel was carefully purged with nitrogen, the catalyst was removed by filtration and the solvent was removed in vacuo. The crude product was purified by column chromatography (silica gelElution with a gradient of ethyl acetate / heptane). The fractions containing the product were evaporated to produce a slightly yellow oil. Yield: 404 mg MS (ES +): m / e = 229. (vi). { 2- [4- (3,3-dioxo- [1, 3,4] oxathiazinan-4-yl) -phenylcarbaminyl] -ethyl} 5-Chloro-thiophene-2-carboxylic acid amide. A solution of 200 mg of 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionic acid, 195 mg of 4 mg, was stirred for 4 h. - (3,3-dioxo-3-yl- [1, 3,4] oxathiazin-4-yl) -phenylamin, 337 mg of TOTU and 0.29 ml of DMF. Water was added and the precipitate was collected by filtration. The gross product is purified by preparative HPLC (C18 reverse phase column, gradient elution of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 318 mg MS (ES +): m / e = 444, chlorine standard.

Example 10: { 2,2-difluoro-2- [4- (2-oxo-2H-pyrazin-1-yl) -phenylcarba-minyl] -ethyl} 5-Chloro-thiophene-2-carboxylic acid amide, (i) 3 - [(5-Chloro-thiophene-2-carbonyl) -amino] -2,2-difluoro-propionic acid ethyl ester stirred at room temperature environment for 6 h in a solution of 650 mg of ethyl ester of 3-Amino-2,2-difluoro-propionic acid (prepared according to Cheguillaume et al, Tetrahedron Letters 44 (2003) 2375-2377), 415 mg of 5- chloro-thiophene-2-carboxylic acid, 958 mg of TOTU and 1.2 mg of triethylamine in 10 ml of DMF. 100 ml of ethyl acetate and 50 ml of water were added, the phases were separated and the organic phase was dried over MgSO. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 445 mg MS (ES +): m / e = 298, chlorine standard, (ii) 3 - [(5-Chloro-thiophene-2-carbonyl) -amino] -2,2-difluoro-propionic acid Was stirred for 4 h a solution of 445 mg of ethyl ester of 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -2,2-d-fluoro-propionic acid and 71 mg of LiOH in 7.5 ml of THF and 7.5 ml of Water. The organic phase was removed in vacuo and 1N hydrochloric acid was added. The aqueous phase was extracted twice with ethyl acetate and the organic phase was dried over MgSO4. The solvent was removed in vacuo. The product was pure enough to be used without further purification. Yield: 330 mg MS (ES +): m / e = 270, chlorine standard. (iii). { 2,2-difluoro-2- [4- (2-oxo-2H-pyrazin-1-yl) -phenylcarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide A solution of 160 mg of 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -2,2-difluoro-propionic acid was stirred for 3 h. , 166 mg of 1- (4-amino-phenyl) -1H-pyrazin-3-one, 233 mg of TOTU and 0.20 ml of triethylamine in 5 ml of DMF. Water was added and the precipitate was collected by filtration. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 210 mg MS (ES +): m / e = 439, chlorine standard.

Example 11: { 2,2-difluoro-2- [4- (3-oxo-morpholin-4-yl) -phenylcarba-minyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. A solution of 160 mg of 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -2,2-difluoro- acid was stirred for 3 h. propionic, 137 mg of 4- (4-amino-phenyl) -morpholin-3-one, 234 mg of TOTU and 0.20 ml of triethylamine in 5 ml of DMF. Water was added and the precipitate was collected by filtration. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 239 mg MS (ES +): m / e = 444, chlorine standard.

Example 12: 3-Carbamimidoyl-N-. { 2- [4- (2-Oxo-2H-pyrazin-1-yl) -phenylcarbaminyl] -ethyl} -benzamide (i) 3-Cyano-N-. { 2- [4- (2-Oxo-2H-pyrazin-1-yl) -phenylcarbaminyl] -ethyl} -benzamide A solution of 198 mg of 3- (3-cyano-benzoylamino) -propionic acid, 339 mg of 4- (4-amino-phenyl) -morpholin-3-one, 356 mg of TOTU and 0.3 ml of triethylamine in 3 ml of DMF. Water was added and the aqueous phase was extracted with ethyl acetate. The organic phase was dried over MgSO and the solvent was removed in vacuo. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 105 mg MS (ES +): m / e = 388. (ii) 3-Carbamimidoyl-N-. { 2- [4- (2-Oxo-2H-pyrazin-1-yl) -phenylcarba-minyl] -ethyl} - benzamide A solution of 105 mg of 3-cyano-N- was dissolved. { 2- [4- (2-Oxo-2H-pyrazin-1-yl) -phenylcarbamino] -ethyl} -benzamide in 1.5 ml of methanol and 1.5 ml of CH2Cl2. Acetyl chloride (1.5 ml) was added and the solution was stirred for 3 d at 5 ° C. Diethyl ether was added and the precipitate was collected by filtration. The solid was dissolved in methanol / NH3 and heated at 65 ° C for 4 h. The solvent was removed in vacuo and the crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 15 mg MS (ES +): m / e = 405.

Example 13: Methyl ester of 5- acid. { 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionylamino} -2- (3-oxo-morpholin-4-yl) -benzoic acid (i) 2-Morpholin-4-yl-5-nitro-benzoic acid methyl ester A mixture of sodium hydroxide was heated at 100 ° C. for 4 h. 1.3 g of morpholine and 3 g of 2-fluoro-5-nitro-benzoic acid methyl ester in 20 ml of DMSO. The solution was poured into 300 ml of water and the resulting precipitate was collected by filtration to produce a bright yellow crystalline product, which was dried in vacuo. Yield: 3.8 g. (I) 5-Nitro-2- (3-oxo-morpholin-4-yl) -benzoic acid methyl ester. 9.5 g of benzyltriethylammonium chloride and 6.6 g were carefully added to RT. of potassium permanganate (325 mesh) to a solution of 3.7 g of 2-morpholin-4-yl-5-nitro-benzoic acid methyl ester in 50 ml of CH2Cl2. After stirring for 1 h at RT, the reaction mixture was heated to reflux for 6 h. A saturated solution of Na2SO3 was added and the mixture it was filtered through a pad of celite and the filtrate was concentrated in vacuo. The yellow solid was stirred with 100 ml of water and the precipitated product was collected by filtration. This crude product was purified by chromatography on silica gel using a gradient of 100% DCM / MeOH up to 50% as eluent. The fractions containing the product were combined and the solvent was evaporated in vacuo. Yield: 0.9 g. (iii) 5-Amino-2- (3-oxo-morpholin-4-yl) -benzoic acid methyl ester 3.2 g of SnCl2 dihydrate was added to a solution of 0.8 g of 5-methyl-5-methyl ester Nitro-2- (3-oxo-morpholin-4-yl) -benzoic acid in 20 ml of ethyl acetate and 7 ml of ethanol, and the reaction mixture was heated to reflux for 2 h. Then, after cooling to RT, the mixture was stirred for 16 h. The precipitated product was collected by filtration and was sufficiently pure to be used in the next reaction step. Yield: 0.7 g. (iv) 5- methyl acid ester. { 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionylamino} -2- (3-Oxo-morpholin-4-yl) -benzoic acid A solution of 0.7 g of 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionic acid was stirred for 4 h, 0.8 mg of 5-amino-2- (3-oxo-morpholin-4-yl) -benzoic acid methyl ester, 1.3 mg of TOTU and 1.1 ml of triethylamine in 7.5 ml of DMF. Water was added and the precipitate was collected by filtration. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with TFA 0.1%). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 0.9 g. MS (ES +): m / e = 466, chlorine standard.

Example 14: Acid 5-. { 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionylamino} -2- (3-Oxo-morpholin-4-yl) -benzoic acid To a solution of 110 mg of 5-methyl ester. { 3 - [(5-Chloro-thiophene-2-carbonyl) -amino] -propionylamino} -2- (3-Oxo-morpholin-4-yl) -benzoic acid in methanol (10 ml) was added 0.35 ml of a 1 M NaOH solution. The mixture was heated at 50 ° C for 6 h. The solvent was evaporated in vacuo, acidified and extracted with ethyl acetate. The organic phase was dried over MgSO4 and the solvent was evaporated in vacuo. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 76 mg MS (ES +): m / e = 452, chlorine standard.Example 15:. { 2- [6- (3-Oxo-morpholin-4-yl) -pyridin-3-ylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, (i) 4- (5-Nitro-pyridin-2-yl) -morpholine A mixture of 1.6 g of morpholine was heated at 100 ° C for 4 h. , 9.2 g of CsCO3 and 3 g of 2-chloro-5-nitro-pyridine in 20 ml of DMF. The solution was poured into 300 ml of water and the resulting precipitate was collected by filtration to produce a bright yellow crystalline product, which was dried under vacuum. Yield: 3.9 g. (ii) 4- (5-Nitro-pyridin-2-yl) -morpholin-3-one 10.5 g of benzyl-triethyl-ammonium chloride and 7.2 g of potassium permanganate were carefully added to RT ( 325 mesh) to a solution of 3.2 g of 4- (5-nitro-pyridin-2-yl) -morpholine in 60 ml of CH2Cl2. After stirring for 1 h at RT, the reaction mixture was heated to reflux for 6 h.

A saturated Na 2 S 3 solution was added and the mixture was filtered through a pad of celite and the filtrate was concentrated in vacuo. The yellow solid was stirred with 100 ml of water and the precipitated product was collected by filtration.

This crude product was purified by chromatography on silica gel using a gradient of 100% DCM / MeOH up to 50% as eluent. The fractions containing the product were combined and the solvent was evaporated in vacuo. Yield: 80 mg (ni) 4- (5-Amino-pyridin-2-yl) -morpholin-3-one A mixture of 80 mg of 4- (5-nitride-pyridine) was hydrogenated at room temperature for 3 h. -2-yl) -morpholin-3-one and 95 mg of Pd / C in 30 ml of methanol. The catalyst was removed by filtration and the solvent was removed in vacuo. The product was sufficiently pure for the next reaction step Yield: 69 mg (iv). { 2- [6- (3-Oxo-morpholin-4-yl) -pyridin-3-ylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid, A solution of 70 mg of 3 - [(5-chlorothiophene-2-carbonyl) -amino] -propionic acid, 85 mg of 4- (4-amino-phenyl-2-yl) was stirred for 4 h. -morpholin-3-one, 142 mg of TOTU and 0.12 ml of triethylamine in 3 ml of DMF. Water was added and the precipitate was collected by filtration. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 49 mg MS (ES +): m / e = 409, chlorine standard.

Example 16:. { 2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl} 5-Chloro-thiophene-2-carboxylic acid amide, (i) 4- (2-Chloro-4-nitro-phenyl) -morpholine A mixture of 4.4 g of morpholine was heated at 100 ° C for 8 h. , 24.5 g of CsCO3 and 8 g of 1,2-difluoro-4-nitro-benzene in 60 ml of DMF. The solution was poured into 300 ml of water and the resulting precipitate was collected by filtration to produce a bright yellow crystalline product, which was dried in vacuo. Yield: 10.7 g. (ii) 4- (4-Nitro-2-fluoro-phenyl) -morpholin-3-one 30.2 g of benzyltriethylammonium chloride and 20.9 g of potassium permanganate (325 mesh) were carefully added to RT. ) to a solution of 10 g of 4- (2-fluoro-4-nitro-phenyl) -morfoin in 115 ml of CH2Cl2. After stirring for 1 h at RT, the reaction mixture was heated to reflux for 6 h. A saturated solution of Na2SO3 was added and the mixture was filtered through a pad of celite and the filtrate was concentrated in vacuo. The solid The yellow was stirred with 100 ml of water and the precipitated product was collected by filtration. This crude product was purified by chromatography on silica gel using a gradient of 100% DCM / MeOH up to 50% as eluent. The fractions containing the product were combined and the solvent was evaporated in vacuo. Yield: 1.2 g. (iii) 4- (4-Amino-2-fluoro-phenyl) -morfoin-3-one A mixture of 1.2 g of 4- (4-nitro-2-fluoro-phenyl) was hydrogenated at room temperature for 3 h. ) -morpholin-3-one and 0.35 g of Pd / C in 100 ml of methanol. The catalyst was removed by filtration and the solvent was removed in vacuo. The product was sufficiently pure for the next reaction step. Performance: 1, 0 g. (iv). { 2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. A solution of 1 g of 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionic acid, 1.2 mg was stirred for 4 h. of 4- (4-amino-2-fluoro-phenyl) -morpholin-3-one, 1.9 g of TOTU and 1.7 ml of triethylamine in 20 ml of DMF. Water was added and the precipitate was collected by filtration. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 1.4 g. MS (ES +): m / e = 426, chlorine standard. Example 17: { 2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] - ethyl} 5-Chloro-thiophene-2-carboxylic acid amide, (i) 4- (4-Nitro-2-trifluoromethyl-1-phenyl) -morpholine A mixture of 1 was heated at 100 ° C for 4 h. 25 g of morpholine and 9.3 g of CsCO3 and 3 g of 1-fluoro-4-nitro-2-trifluoromethyl-benzene in 20 ml of DMF. The solution was poured into 300 ml of water and the resulting precipitate was collected by filtration to produce a bright yellow crystalline product, which was dried in vacuo. Yield: 3.2 g. (ii) 4- (4-Nitro-2-trifluoromethyl-phenyl) -morpholin-3-one 7.9 g of benzyltriethylammonium chloride and 5.5 g of potassium permanganate (325 mesh) were carefully added at RT. ) to a solution of 3.2 g of 4- (4-nitro-2-trifluoromethyl-phenyl) -morpholine in 50 ml of CH2Cl2.

After stirring for 1 h at RT, the reaction mixture was heated to reflux for 6 h. A saturated solution of Na2SO3 was added and the mixture was filtered through a pad of celite and the filtrate was concentrated in vacuo. The yellow solid was stirred with 100 ml of water and the precipitated product was collected by filtration. This crude product was purified by chromatography on silica gel using a gradient of 100% DCM / MeOH up to 50% as eluent.

The fractions containing the product were combined and the solvent was evaporated in vacuo. Yield: 660 mg (iii) 4- (4-Amino-2-trifluoromethyl-phenyl) -morpholin-3-one A mixture of, 66 g of 4- (4-nitro-2-) was hydrogenated at room temperature for 3 h. trifluoromethyl-phenyl) -morpholin-3-one and 0.24 g of Pd / C in 0 ml of methanol. The catalyst was removed by filtration and the solvent was removed at empty. The product was sufficiently pure for the next reaction step. Yield: 0.56 g. (iv). { 2- [4- (3-Oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamyl] -etl} 5-Chloro-thiophene-2-carboxylic acid amide. A solution of 0.5 g of 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionic acid, 0, was stirred for 4 h. 55 g of 4- (4-amino-2-trifluoromethyl-phenyl) -morpholin-3-one, 0.84 g of TOTU and 0.71 ml of triethylamine in 6 ml of DMF. Water was added and the precipitate was collected by filtration. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 184 mg MS (ES +): m / e = 476, chlorine standard.

Example 18: 2- methyl acid ester. { 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionylamino} -5- (3-Oxo-morpholin-4-yl) -benzoic acid (i) Methyl ester of 5-morpholin-4-yl-2-nitro-benzoic acid A mixture of 4.0 was stirred at room temperature for 2 h. g of morpholine and 9.2 g of 5-fluoro-2-nitro-benzoic acid methyl ester in 60 ml of DMF. The solution was poured into 300 ml of water and the resulting precipitate was collected by filtration to produce a bright yellow crystalline product, which was dried in vacuo. Yield: 11, 9 g.

(I) 2-Nitro-5- (3-oxo-morpholin-4-yl) -benzoic acid methyl ester 8.9 g of benzyltriethylammonium chloride and 6.2 g of potassium permanganate (325 mesh) were added carefully to RT to a solution of 3.5 g of 5-morpholin-4-yl-methyl ester. 2-nitro-benzoic in 60 ml of CH2Cl2. After stirring for 1 h at RT, the reaction mixture was heated to reflux for 6 h. A saturated solution of Na 2 SO 3 was added and the mixture was filtered through a pad of celite and the filtrate was concentrated in vacuo. The yellow solid was stirred with 100 ml of water and the precipitated product was collected by filtration. This crude product was purified by chromatography on silica gel using a gradient of 100% DCM / MeOH up to 50% as eluent. The fractions containing the product were combined and the solvent was evaporated in vacuo. Yield: 320 mg. (ni) 2-Amino-5- (3-oxo-morpholin-4-yl) -benzoic acid methyl ester A mixture of sodium hydroxide was hydrogenated at room temperature for 3 h. 300 mg of 2-nitro-5- (3-oxo-morpholin-4-yl) -benzoic acid methyl ester and 114 mg of Pd / C in 50 ml of methanol. The catalyst was removed by filtration and the solvent was removed in vacuo. The product was sufficiently pure for the next reaction step. Yield: 256 mg. (iv) 2- methyl acid ester. { 3 - [(5-chloro-thiophene-5-carbonyl) -amino] -propionylamino} -5- (3-Oxo-morpholin-4-yl) -benzoic acid. 51 mg of triphosgene was slowly added to a solution of 115 mg of 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionic acid and 179 mg of 2,4,6-trimethylpyridine in 8 ml of CH 2 Cl 2 at 0 ° C. After 5 min, 123 mg of 2-amino-5- (3-oxo-morpholin-4-yl) -benzoic acid methyl ester were added. The mixture was stirred for 6 h. The solvent was removed in vacuo and the crude product was purified by preparative HPLC (reverse phase column 18, elution with a gradient of H O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 47 mg MS (ES +): m / e = 466, chlorine standard.

Example 19: 2- methyl acid ester. { 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionylamino} -5- (3-Oxo-morpholin-4-yl) -benzoic acid (i) 2-Nitro-5- (2-oxo-2H-pyridin-1-yl) -benzoic acid methyl ester stirred at room temperature during 2 h a mixture of 1.1 g of 3-hydroxypyridine and 2 g of 5-fluoro-2-nitro-benzoic acid in 15 ml of DMF. The solution was poured into 300 ml of water and the resulting precipitate was collected by filtration to produce a bright yellow crystalline product, which was dried in vacuo. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 1.3 g. (ii) 2-Amino-5- (2-oxo-2H-pyridin-1-yl) -benzoic acid methyl ester A mixture of 1.3 g of 2-nitro-5- (3-oxo-2H-pyridin-4-yl) -benzoic acid methyl ester and 160 mg of catalyst CF1082 BV / W was hydrogenated at room temperature for 3 h. (Pt V / C) in 100 ml of methanol and 0.5 ml of acetic acid. The catalyst was removed by filtration and the solvent was removed in vacuo. The product was sufficiently pure for the next reaction step. Yield: 1, 1 g. (iii) 2- methyl acid ester. { 3 - [(5-chloro-thiophene-5-carbonyl) -amino] -propionylamino} -5- (2-Oxo-2H-pyridin-1-yl) -benzoic acid A solution of 260 mg of 3- [(5-chloro-thiophene-2, carbonyl) -amino was stirred at 60 ° C for 8 h. ] -propionic, 249 mg of 5-amino-2- (3-oxo-2H-pyridin-4-yl) -benzoic acid methyl ester and 425 mg of dichlorotriphenyl-nylphosphorane in 10 ml of CHCl3. The solvent was removed in vacuo and the crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2 / / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 50 mg MS (ES +): m / e = 460, chlorine standard.

Example 20: 2- Acid. { 3 - [(5-chloro-thiophene-5-carbonyl) -amino] -propionylamino} -5- (2-Oxo-2H-pyridin-1-yl) -benzoic acid To a solution of 481 mg of methyl ester of 2- acid. { 3 - [(5-chloro-thiophene-5-carbonyl) -amino] -propionylamino} -5- (3-Oxo-2H-pyridin-1-yl) -benzoic acid in methanol (30 ml) was added with 2.0 ml of a solution of 1 M NaOH. The mixture was stirred for 4 h at room temperature. The solvent was evaporated in vacuo, acidified and extracted with ethyl acetate. The organic phase was dried over MgSO4 and the solvent was evaporated in vacuo. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 107 mg MS (ES +): m / e = 446, chlorine standard.

Example 21: { 2- [4- (4-Oxo-4H-pyridin-1-yl) -phenylcarbamyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, (i) 1- (4-Nitro-phenyl) -1 H-pyridin-4-one A mixture of 10 g of 1 g was stirred at room temperature for 2 h. H-pyridin-4-one and 10.1 g of 1-fluoro-4-nitro-benzene in 30 ml of DMF. The solution was poured into 300 ml of water and the resulting precipitate was collected by filtration to produce a bright yellow crystalline product, which was dried in vacuo. Yield: 11.2 g. (ii) 1- (4-Amino-phenyl) -1 H-pyridin-4-one 52 g of SnCl 2 dihydrate were added to a solution of 10 g of 1- (4-nitro-phenyl) -1H-pyridin-4-one in 510 ml of ethyl acetate and 26 ml of ethanol and the reaction mixture was heated to reflux for 6 h. Then, after cooling to RT, the solvent partially evaporated. The precipitated product was collected by filtration and was sufficiently pure to be used in the next reaction stage. Yield: 3.3 g. (iii). { 2- [4- (4-Oxo-4H-pyridin-1-yl) -phenylcarbamide] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. A solution of 233 mg of 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionic acid was stirred for 3 h at room temperature, 260 mg of 1- (4-amino-phenyl) -1 H-pyridin-4-one, 391 mg of TOTU and 0.33 ml of triethylamine in 3 ml of DMF. Water was added and the precipitate was collected by filtration. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 220 mg MS (ES +): m / e = 402, chlorine standard.

Example 22: The 4-chloro-N-. { 2- [4- (4-Oxo-4H-pyridin-1-yl) -phenylcarb-binyl] -ethyl} -benzamide was prepared in an analogous manner. MS (ES +): m / e = 396, chlorine standard.

Example 23: Acid methyl ester. { . { 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionyl} - [4- (3-oxo-morpholin-4-yl) -phenyl] -amino} -acetic (i) [4- (3-Oxo-morpholin-4-yl) -phenylamino] -acetic acid methyl ester A mixture of 500 mg of 4- (4-amino-phenyl) was stirred at room temperature for 24 h. ) -morpholin-3-one, 438 mg of acid methyl ester bromoacetic and 395 mg of K2CO3 in 10 ml of DMF. Water was added and the precipitate was collected by filtration. The product was sufficiently pure for the next reaction step Yield: 490 mg (ii) Methyl acid ester. { . { 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionyl} - [4- (3-Oxo-morpholin-4-yl) -phenyl] -amino} -acetic A solution of 200 mg of 3 - [(5-chloro-thiophene-2, carbonyl) -amino] -propionic acid, 177 mg of methyl ester of acid [4- (3) was stirred at 60 ° C for 8 h. -oxo-morpholin-4-yl) -phenylamino] -acetic acid and 303 mg of dichlorotriphenylphosphorane in 7.5 ml of CHCl3. The solvent was removed in vacuo and the crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 116 mg MS (ES +): m / e = 480, chlorine standard.

Example 24: Acid. { . { 3 - [(5-chloro-thiophene-2-carbonyl) -aminoj-propionyl} - [4- (3-Oxo-morpholin-4-yl) -phenyl] -amino} -acetic 0.5 ml of 1 M NaOH was added to a solution of 96 mg of acid. { . { 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propioniI} - [4- (3-oxo-morpholin-4-yl) -phenyl] -amino} -acetic in 15 ml of methanol. The mixture was stirred for 10 h, acidified and extracted with ethyl acetate. The organic phase was dried over MgSO4 and the solvent was evaporated in vacuo. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2 / / MeCN with 0.1% TFA). The fractions containing the The product was evaporated and lyophilized to produce a white solid. Yield: 20 mg MS (ES +): m / e = 466, chlorine standard.

Example 25: (2- ({(2,2-difluoro-ethyl) - [4- (3-oxo-morpholin-4-yl) -phenyl] -carbamoyl.} -ethyl) -amide of 5- cyclo-thiophene-2-carboxylic acid, (i) 4- [4- (2,2-D-fluoro-ethylamino) -phenyl] -morpholin-3-one A mixture of 199 mg of ethyl acetate was stirred at room temperature for 24 h. 4- (4-amino-phenyl) -morfoin-3-one, 214 mg of 2,2-difluoroethyl methanesulfonic acid ester and 1.5 ml of diisopropylethylamine in 15 ml of THF. The solvent was removed, water was added and the mixture was extracted with ethyl acetate. The organic phase was dried over MgSO4 and the solvent was removed in vacuo. The product was sufficiently pure to be used in the next reaction stage. Yield: 660 mg (ii) (2- {(2,2-difluoro-ethyl) - [4- (3-oxo-morpholin-4-yl) -phenyl] -carbamoyl.} -ethyl) -amide of 5-chloro-thiophene-2-carboxylic acid, A solution of 50 mg of 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionic acid, 55 mg of 4- [4- (2,2-) was stirred at 60 ° C for 8 h. difluoro-ethylamino) -phenyl] -morpholin-3-one and 71 mg of dichlorotriphenylphosphorane in 5 ml of CHCl3. The solvent was removed in vacuo and the crude product was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 29 mg MS (ES +): m / e = 472, chlorine standard.

Example 26: Benzyl acid ester. { (/?) - 2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbaminyl] -ethyl} - carbamic (i) 4- (Nitro-2-trifluoromethyl-phenyl) -morpholin-3-one To sodium hydride (0.93 g, 60% in mineral oil) in THF (20 ml) was added a solution of 1 , 93 g of morpholin-3-one (US Patent No. 5 349 045) in a mixture of THF (5 ml) and DMF (5 ml). The mixture was stirred durfante 1 h at 60 ° C and then cooled to RT. A solution of 1-fluoro-4-nitro-2-trifluoromethyl-benzene (4.37 g) in THF (10 ml) was slowly added. The reaction mixture was stirred for 1 h at RT after which it was cautiously quenched by the addition of a 0.5 N potassium hydrogensulfate solution, diluted with water and extracted with ethyl acetate. The combined organic phases were washed with water and salt water, dried (MgSO) and concentrated. The residue was triturated with n-heptane to remove the mineral oil and then extracted with MTBE. The combined ether extracts were concentrated and the residue was purified by RP-HPLC to yield 1.14 g of 4- (4-nitro-2-trifluoromethyl-phenyl) -morpholin-3-one. (ii) 4- (4-Amino-2-trifluoromethyl-phenyl) -morpholin-3-one 10% palladium on carbon (50 mg) was added to a solution of 4- (4-nitro-2-trifluoromethyl) phenyl) -morpholin-3-one (560 g) in ethanol (35 ml). The mixture was stirred for 90 min at RT in a hydrogen atmosphere. The catalyst was removed by filtration and the filtrate was concentrated in vacuo to give the 4- (4-Amino-2-trifluoromethyl-phenyl) -morpholin-3-one crude (511 mg). (iii) (R) -2-Benzyloxycarbonylamino-3 - [(5-chloro-thiophene-2-acid carbonyl) -amino] -propionic To a solution of 5-chloro-thiophene-2-carboxylic acid (162 mg) in a mixture of THF (2 ml) and DMF (1 ml) was added carbonyl-diimidazole (89 mg) in one portion. The mixture was stirred for 30 min at 45 ° C and then cooled to RT. (R) -3-Amino-2-benzyloxycarbonylamino-propionic acid (102 mg) was added followed by trylamine (0.3 ml). The mixture was stirred for 1 h at 50 ° C whereupon it was concentrated. The residue was purified by RP-HPLC to give 127 mg of (/) -2-benzyloxycarbonylamino-3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionic acid. (iv) Benzyl acid ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbaminyl] -ethyl} -carbamic Previous acid (661 mg) in DMF (8 ml) was added 4- (4-amino-2-trifluoromethyl-phenyl) -morpholin-3-one (346 mg), DIPEA (697 μl) and HATU (532 mg). The mixture was stirred for 90 min at RT and for 3 h at 50 ° C after which it was concentrated. The residue was subjected to a preparative HPLC (gradient of CH3CN / H2O + 0.05% TFA) to give benzyl acid ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbaminyl] -ethyl } -carbamate as its trifluoroacetic salt (327 mg). MS (ESI +): m / e = 625 [M + H] +, chlorine standard.

Example 27: Terbutyl acid ester. { 2- (2S) - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic (i) 2- (2S) -ferc-butoxycarbonylamino-3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionic acid At RT, 1.6 g of 1,1'-carbonyldiimidazole was added to a solution of 1.6 g of 5-chloro-thiophene-2-carboxylic acid in 40 ml of THF and stirred for 2 h. Then 2.0 g of 3- (3S) -amino-2-fer-butoxycarbonylamino-propionic acid and 2.8 ml of NEt3 were added and the solution was stirred for 16 h. The reaction mixture was adjusted to pH 4 by adding 20 ml of aqueous phosphate buffer, then saturated with sodium chloride and extracted with ethyl acetate (2 times with 150 ml each). The combined organic phases were dried over MgSO, filtered and concentrated in vacuo. The crude solid product was used in subsequent reactions without further purification. Yield: 3.5 g. (ii) Terbutyl acid ester. { 2- (2S) - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} -carbamm 402 mg of 4- (4-amino-phenyl) -morpholin-3-one were added at 0 ° C., 532 mg of BOP-CI and 1.2 ml of NEt3 to a solution of 730 mg of 2- (2S) -ferc-butoxycarbonylamino-3 - [(5-chloro-thiophene-2-carbonyl) -am acid. No] -proponic in 20 ml of DCM. Then, the mixture was slowly warmed to RT and stirred for 16 h. The reaction mixture was diluted with 150 ml of ethyl acetate and washed twice with salt water. The organic phase was dried over MgSO, filtered and concentrated to yield the pure solid product. Yield: 537 mg MS (ES +): m / e = 523, chlorine standard.

Example 28: { 2- (2S) -amino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamo] -ethyl} 5-Chloro-thiophene-2-carboxylic acid amide, 1.8 ml of TFA was added at RT to a solution of 900 mg of TFA. terbutycyl ester of acid. { 2- (2S) - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic in 10 ml of DCM and the reaction mixture was stirred for 16 h. Then 150 ml of toluene was added and the solvents were removed in vacuo. The residue was purified by chromatography on silica and eluted with ethyl acetate. Yield: 620 mg MS (ES +): m / e = 423, chlorine standard.

Example 29: 2- (2S) -diciciropylamino-2- [4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-Chloro-thiophene-2-carboxylic acid amide. 500 mg of a 3A molecular sieve was added to a solution of 180 mg of. { 2- (2S) -amino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, in 1.7 ml of methanol and 20 μl of acetic acid, and then 0.5 ml of (l-ethoxy-cyclopropoxy) -trimethyl-silane and , 9 ml of NaBH 3 (CN) (1 M in THF). The reaction mixture was heated to 80 ° C, then cooled to RT, diluted with 100 mL of ethyl acetate and filtered through a pad of celite. After removing the solvents in vacuo, the residue was purified by chromatography on silica and eluted with a gradient of ethyl acetate / heptane. Yield: 190 mg MS (ES +): m / e = 503, chlorine standard.

Example 30: [2- [4- (3-Oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (2S) - (tetrahydro-pyrano-4-ylamino) -ethyl] -amide of 5- chloro-thiophene-2-carboxylic acid, The title compound was prepared analogously to Example 29 with the difference that tetrahydro-pyran-4-one was used instead of (1-ethoxy). cyclopropoxy) -trimetyl-silan. MS (ES +): m / e = 507, chlorine standard.

Example 31:. { 2- (2S) - (1-isopropyl-piperidin-4-ylamino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, The title compound was prepared analogously to Example 29 with the difference that isopropyl-piperidin-4-one was used in place of (1-ethoxy-cyclopropoxy) -trimethyl-silane. MS (ES +): m / e = 548, chlorine standard.

Example 32:. { 2- (2S) - (indan-2-ylamino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-Chloro-thiophene-2-carboxylic acid amide The title compound was prepared analogously to Example 29 with the difference that 1-lndedan-2-one was used instead of (1-ethoxy-cyclopropoxy) -trimethyl-silane. MS (ES +): m / e = 539, chlorine standard.

Example 33: { 2- (2,2-dimethyl-propylamino) -2- (2S) - [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-Chloro-thiophene-2-carboxylic acid amide The title compound was prepared analogously to the example 29 with the difference that 2,2-dimethyl-propionic aldehyde was used in place of (1-ethoxy-cyclopropoxy) -trimethyl-silane. MS (ES +): m / e = 493, chlorine standard.

Example 34:. { 2- (2S) -cyclobutylamino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-Chloro-thiophene-2-carboxylic acid amide The title compound was prepared analogously to Example 29 with the difference that cyclobutane was used in place of (1-ethoxy-cyclopropoxy) -trimethyl-silane. MS (ES +): m / e = 477, chlorine standard.

Example 35: { 2- (2S) -cyclohexylamino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-Chloro-thiophene-2-carboxylic acid amide The title compound was prepared analogously to the example 29 with the difference that cyclohexanone was used in place of (1-ethoxy-cyclopropoxy) -trimethyl-silane. MS (ES +): m / e = 505, chlorine standard.

Example 36:. { 2- (2S) - (2,2-difluoro-ethylamino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-Chloro-thiophene-2-carboxylic acid amide, 1 g of MgSO, 2 ml of NEt3 and 1.1 g of trifluoro-methanesulfonic acid 2,2-difluoroethyl ester were added at RT to a solution of 780 mg from . { 2- (2S) -amino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide in 25 ml acetonitrile. The reaction mixture was stirred for 16 h and then treated with 1 ml of a concentrated ammonia solution. After removing the solvents in vacuo, the residue was filtered through a pad of silica and eluted with ethyl acetate and concentrated. The residue was purified by preparative HPLC (C18 reverse phase column, Elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. The product was obtained as its trifluoroacetic salt. Yield: 293 mg MS (ES +): m / e = 487, chlorine standard.

Example 37: { 2- (2S) - (2,2-difluoro-acetylamino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etl} -amide of 5-chloro-thiophene-2-carboxylic acid, 3.6 g of BOP-CL and 5 ml of NEt3 were added at RT to a solution of 1.8 g of difluoroacetic acid in 10 ml of DMF. After 30 min, 795 mg of. { 2- (2S) -amino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, dissolved in 15 ml of DFM and the reaction mixture was stirred for 16 h. The reaction mixture was then diluted with 100 ml of DCM and 100 ml of water. After the organic phase was separated, the aqueous phase was extracted with DCM (2 times with 100 ml each time) and the combination of the organic phases was dried over MgSO.

After removing the solvents in vacuo, the residue was purified by chromatography on silica with ethyl acetate as eluent. The fractions containing the product were evaporated and the residue was then purified by Preparative HPLC (C19 reversed phase column eluted with a gradient of H2O / MeCN in 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 336 mg MS (ES +): m / e = 501, chlorine standard.

Example 38: [2- [4- (3-Oxo-morpholin-4-yl) -phenocarbamoyl] -2- (2S) - -Chloro-thiophene-2-carboxylic acid (2,2,3,3-tetrafluoro-propionylamino) -ethyl] -amide The title compound was prepared analogously to example 37 with the difference that acid was used 2,2,3,3-tetrafluoro-propionic instead of difluoroacetic acid. MS (ES +): m / e = 551, chlorine standard.

Example 39: [2- [4- (3-Oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (2S) - (2,2,2-trifluoro-ethanesulfonylamino) -ethyl] -amide of 5- chloro-thiophene-2-carboxylic acid, 715 mg of 2,2,2-trifluoro-ethanesulfonyl chloride was added at 0 ° C to a solution of 800 mg of. { 2- (2S) -amino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, and 0.9 ml of NEt3 in 10 ml of DMF. The reaction mixture was stirred for 16 h at RT and then concentrated in vacuo. The residue was filtered through a pad of silica, with ethyl acetate as eluent. After removing the solvents, the residue was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA).

The fractions containing the product were evaporated and lyophilized to produce a white solid. The product was obtained as its trifluoroacetic salt. Yield: 256 mg MS (ES +): m / e = 569, chlorine standard.

Example 40: { 2- (2R) - (2,2-difluoro-ethalamine) -2- [4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, The title compound was prepared by a sequence of reactions similar to that used in Example 36 with the difference that 3- (3f?) - amino-2-tert-butoxycarbonylamino-propionic acid was used instead of 3- ( 3S) -amino-2-yerc-butoxycarbonyl-propionic acid. MS (ES +): m / e = 487, chlorine standard.

Example 41: { 2- [Cyclopropylmethyl- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-Chloro-thiophene-2-carboxylic acid amide. 100 mg of a molecular sieve of 3 A was added to a 50 mg solution of. { 2- (2f?) - (2,2-difluoro-ethylamino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, in 0.5 ml of methanol and 20 μl of acetic acid, and then 43 mg of cyclopropanecarbaldehyde and 0.4 ml of NaBH3 (CN) ( THF). The reaction mixture was heated at 80 ° C for 8 h, then cooled to RT, diluted with 20 ml of ethyl acetate and filtered through a pad of celite. After removing the solvents in vacuo, the residue was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. The product was obtained as its trifluoroacetic salt. Yield: 5 mg MS (ES +): m / e = 541, chlorine standard.

Example 42: { 2- (2f?) - [Cyclobutyl- (2,2-difluoro-ethyl) -amino] -2- [4- (3- oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide The title compound was prepared analogously to example 41 with the difference that cyclobutanone was used instead of cyclopropanecarbaldehyde. MS (ES +): m / e = 541, chlorine standard.

Example 43: Terbutyl acid ester. { 2- (2S) - [(5-chloro-thiophene-2-carbonyl) -amino] -1 - [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic (i) 4- (4-Amino-3-fluoro-phenyl) -morpholin-3-one A mixture of 10 g of 2-fluoro-4-iodo-phenylamine, 7.1 g of morpholin-3-one [prepared by adapting a procedure described by Vieles, P., Seguín, J. Bull. Soc. Chim. Fr. (1953), 287-9 and US-5 349 045], 3.2 g Cul, 1.8 ml of N, N'-dimethyl-ethane-1,2-diamine and 23.3 g of Cs 2 CO 3 in dioxane were heated at 120 ° C for 16 h. The reaction mixture was concentrated in vacuo and the residue was triturated several times with DCM and filtered. The combined filtrates were concentrated and the residue was purified by chromatography on silica and eluting with a gradient of ethyl acetate / heptane to yield the desired product as a yellow solid. Yield: 8.7 g. (I) Terbutyl acid ester. { 2- (2S) - [(5-chloro-thiophene-2-carbonyl) -amino] -1 - [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic 2.3 g of 2.3 g 4- (4-amino-3-fluoro-phenyl) -morpholin-3- were added One, 3.0 g of HOAT and 11.1 g of DIPEA to a solution of 3.7 g of 2- (2S) -ferc-butoxycarbonyl-3 - [(5-chloro-thiophene-2-carbonyl) - amino] -propionic in 50 ml of DCM. The mixture was cooled to 0 ° C, then 10.1 g of PyBrop was added and the reaction was stirred for 16 h. Subsequently, the reaction was diluted with 50 ml of water and the aqueous layer was extracted with DCM (2 times with 150 ml each time). The combined organic phases were dried over MgSO 4, filtered and concentrated. The residue was purified by chromatography on silica and eluted with a gradient of ethyl acetate / heptane. The fractions containing the product were evaporated to produce a white solid. Yield: 2.5 g MS (ES +): m / e = 541, chlorine standard.

Example 44: { 2- (2S) -amino-2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide The title compound was prepared analogously to example 28 with the difference that acid terbutyl ester was used. { 2- (2S) - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbámico instead of. { 2- (2S) -amino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. MS (ES +): m / e = 441, chlorine standard.

Example 45: { 2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (2S) -isopropylamino-ethyl} 5-Chloro-thiophene-2-carboxylic acid amide. 500 mg of a 3A molecular sieve was added to a 200 mg solution of. { 2- (2S) -amino-2- [2-fluoro-4- (3-oxo-morpholin-4-yl) - phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide in 1 ml of methanol and 20 μl of acetic acid, and then 50 μl of acetone and 0.4 ml of NaBH 3 (CN) (1 M in THF) were added. . The reaction mixture was heated at 80 ° C for 1 h, then cooled to RT, diluted with 100 ml of ethyl acetate and filtered through a pad of celite. After removing the solvents in vacuo, the residue was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. The product was obtained as its trifluoroacetic salt. Yield: 14 mg MS (ES +): m / e = 483, chlorine standard.

Example 46:. { 2- (2S) -ethylamino-2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide The title compound was prepared analogously to example 45 with the difference that acetaldehyde was used instead of acetone. MS (ES +): m / e = 469, chlorine standard.

Example 47: { 2-Cyclobutylamino-2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-Chloro-thiophene-2-carboxylic acid amide The title compound was prepared analogously to the example 45 with the difference that cyclobutanone was used instead of acetone. MS (ES +): m / e = 495, chlorine standard.

Example 48: { 2 (2S) - (4-pentafluorothio-benzoylamino) -2- [4- (3-oxo- morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, 9 μl of pyridine and 38 mg of 4- (pentafluorothio) benzoyl chloride were added to a 50 mg solution of. { 2- (2S) -amino-2- [4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide, dissolved in 1 ml of THF and the reaction mixture was stirred for 16 h. Then, the reaction mixture was concentrated in vacuo and the residue was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2O / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 13 mg MS (ES +): m / e = 653, chlorine standard.

Example 49:. { 2- (2R) - (2,2-difluoro-acetylamino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-Chloro-thiophene-2-carboxylic acid amide The title compound was prepared analogously to the example 37 with the difference that it was used. { 2- (2?) - amino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, instead of. { 2- (2S) -amino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, MS (ES +): m / e = 501, chlorine standard.

Example 50: Terbutyl acid ester. { 2- (2SJ - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl.} - carbamic (i) 5-Bromo-2-nitro-benzaldehyde 20 g of 3-bromo-benzaldehyde were added dropwise at 0 ° C to a mixture of 8 ml of HNO3 (63%) and 60 ml of H2SO4 (98%) . Then, the mixture was slowly heated to RT and stirred for 4 h at this temperature. The solution was poured over crushed ice and the precipitated product was collected by filtration. The product was dried under vacuum and used in subsequent reactions without further purification. Yield: 24 g. (I) 4-Bromo-2-difluoromethyl-1-nitro-benzene. 16.3 ml of [bis (2-methoxyethyl) amino] sulfide trifluoride (BAST) was added at 0 ° C to a solution of 12 g. g of 5-bromo-2-nitro-benzaldehyde in 120 ml of DCM and 0.1 ml of ethanol in a Teflon container.

At 30 min, the reaction mixture was heated at 40 ° C for 3 h, then cooled to RT, diluted with 150 ml of DCM and cautiously quenched with saturated aqueous NaHC 3. The organic layer was separated and the aqueous layer was extracted with DCM (2 times with 150 ml each time). The combined organic phases were dried over MgSO 4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica and eluted with an ethyl acetate / heptane 1: 2 The fractions containing the product were evaporated to produce a white solid. Yield: 11 g. (iii) 4- (3-D-fluoro-methyl-4-nitro-phenyl) -morpholin-3-one A mixture of 1.6 g of 4-bromo-2-difluoromethyl-1-nitro-benzene, 1 g of morpholin-3-one [prepared by adapting a procedure described by Vieles, P., Seguin, J. Bul !. Soc. Chim. Fr. (1953), 287-9 and US-5 349 045], 498 mg of Cul, 231 mg of N, N'-dimethyl-ethane-1,2-diamine and 1.3 g of K2CO3 in 50 ml of toluene were heated at 120 ° C for 16 h. Then, the mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica and eluted with a 1: 5 ethyl acetate / heptane (with 1% NEt3). The fractions containing the product were evaporated to yield a yellow solid. Yield: 830 mg (iv) 4- (4-Amino-3-d-fluoro-methyl-phenyl) -morpholin-3-one 100 mg of Pd / C (10%) was added to a solution of 830 mg of sodium - (3-bifluoromethyl-4-nitro-phenyI) -morpholin-3-one in 87 ml of ethyl acetate and 0.3 ml of acetic acid, and the mixture was purged with argon for 10 min. Then, the mixture was stirred under a hydrogen atmosphere for 16 h at RT. After adding 100 ml of ethyl acetate, the reaction mixture was filtered through a pad of celite. The residue was purified by chromatography on silica and eluted with a 1: 1 ethyl acetate / heptane (with NEt.3 1%). The fractions containing the product were evaporated to yield a yellow solid. Yield: 320 mg (v) Terbutyl acid ester. { 2- (2S) - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic 34 mg 4- (4-amino-3-difluoromethyl-phenol) -morpholin-3-one, 29 mg of HOAT, 106 μl of DIPEA and 100 mg of PyProb were added to a solution of 50 mg of 2- (2S) -ferc-butoxycarbonylamino-3 - [(5-chloro-thiophene-2-carbonyl) - amino] -propionic in 1 ml of DCM. Then, the reaction mixture was concentrated and the residue was purified by preparative HPLC (C18 reverse phase column, elution with a gradient of H2 / / MeCN with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to produce a white solid. Yield: 1 mg MS (ES +): m / e = 555 [M + H] +, chlorine standard.

Example 51: 2- (2S) -amino-2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -eti} 5-Chloro-thiophene-2-carboxylic acid amide The title compound was prepared analogously to the example [. { 2- (2S) -amino-2- [4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,] with the difference that terbutyl acid ester was used. { 2- (2S - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl.} - carbamic instead of. {2- (2S) -amino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide 5-chloro-thiophene-2-acid carboxylic Example 52: 2- (2S) -dicyclopropylamino-2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, The title compound was prepared analogously to example [. { 2- (2S) -d-cyclopropylamino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, with the difference that it was used. { 2- (2S) ~ amino-2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, instead of. { 2- (2S) -amino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-cyclo-thiophene-2-carboxylic acid.

Example 53: { 2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcar-bamoyl] -2- (2S) -ethylamino-ethyl} 5-Chloro-thiophene-2-carboxylic acid amide The title compound was prepared analogously to Example 51 with the difference that acetaldehyde was used in place of (1-ethoxy-cyclopropoxy) -trimethyl-silane.

Example 54: { 2- (2S) - (cyclopropylmethyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} 5-Chloro-thiophene-2-carboxylic acid amide The title compound was prepared analogously to Example 52 with the difference that cyclopropanecarbaldehyde was used in place of (1-ethoxy-cyclopropoxy) -trimethyl-silane.

Example 55: { 2- (2S) -cyclobutylamino-2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, The title compound was prepared analogously to Example 52 with the difference that cyclobutanone was used in place of (1-ethoxy-cyclopropoxy) -trimethyl-silane.

Example 56: [2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcar-bamoyl] -2- (2S) - (2,2-dimethyl-propylamino) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid, The title compound was prepared analogously to the example 52 with the difference that 2,2-dimethyI-propionaldehyde was used in place of (1-ethoxy-cyclopropoxy) -trimethylsilane.

The following compounds can also be prepared in a similar manner: 2-dimethylaminoethyl 2-ester. { 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionlamino} -5- (3-oxo-morpholin-4-yl) -benzoic acid,. { 2- [2- (1-methyl-azetidin-3-ylcarbamoyl) -4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide [2-. { 3 - [(5-chloro-thiophene-2-carbonyl) -amino] -propionylamino} -5- (3-oxo-morpholin-4-yl) -benzoylamino-acetic,. { 2- [2- (2,2-difluoro-ethylcarbamoyl) -4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -etiI} -amide of 5-chloro-thiophene-2-carboxylic acid,,. { 2- [2- (2-dimethylamino-etiIcarbamoyl) -4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2-amino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2-amino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2-amino-2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2-amino-2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2-amino-2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2-amino-2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2-amino-2- [3-difluoromethyl] -4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2-amino-2- [3-difluoromethyl-4- (3-oxo- morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2-amino-2- [2-d.fluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} - 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-amino-2- [2-d-fluoro-methyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,,. { (S) -2-amino-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2-amino-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} -amide of 5-cyclo-thiophene-2-carboxylic acid ". { (S) -2-amino-2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2-amino-2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2-amino-2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2-amino-2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2-amino-2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2-amino-2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarba-moyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [bis- (2,2-difluoro-etl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Bis- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Bis- (2,2-difluoro-ethyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [b] s- (2,2-difluoro-ethyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl- 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [bis- (2,2-difluoro-ethyl) - amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amido-5-thiophene-2-carboxylic acid amide. { (R) -2- [bis- (2,2-difluoro-ethyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Bis- (2,2-difluoro-ethyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Bis- (2,2-difluoro-ethyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Bis- (2,2-difluoro-ethyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarba -moyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide. { (R) -2- [bis- (2,2-d.fluoro-ethyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Bis- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Bis- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl } 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [b.s- (2,2-d.fluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [bis- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenol lcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Bis- (2,2-difluoro-ethyl) -amino] -2- [3-d.fluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Bis- (2,2-difluoro-ethyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarba -moyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Bis- (2,2-difluoro-ethyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [bis- (2,2-difluoro-etiI) - amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) - (2,2,2-trifluoro-etl) -amino] -2- [4- (3-oxo-morpholin-4-yl) phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-d.fluoro-ethyl) - (2,2,2-tr.fluoro-ethyl) -amino] -2- [4- (3-oxo-morfoIin-4- il) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) - (2,2,2-trifluoro-etl) -amino] -2- [2-fluoro-4- (3-oxo-morpholine- 4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) - (2,2,2-trifluoro-etl) -amino] -2- [2-fluoro-4- (3-oxo-morfoiin- 4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) - (2,2,2-trifluoro-ethyl) -amino] -2- [3-fluoro-4- (3-oxo-morfoin- 4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) - (2,2,2-trifluoro-ethyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholine- 4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) - (2,2,2-trifluoro-ethyl) -amino] -2- [3-d.fluoromethyl-4- (3-oxo-morpholine- 4-yl) -phenylcarbamoyl] -ethyl} -amido-5-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) - (2,2,2-trifluoro-ethyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-) il) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-etl) - (2,2,2-trifluoro-ethyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholine- 4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) - (2,2,2-trifluoro-ethyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-) il) -phenylcarbamoyl] -ethyl} - 5-cyclo-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-d.fluoro-ethyl) - (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) - (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) - (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morfoin-4-yl) - 2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-d.fluoro-ethyl) - (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid ". { (S) -2 - [(2,2-d.fluoro-ethyl) - (2,2,2-trifluoro-et.l) -amino] -2- [3-difluoromethoxy-4- (3- oxo-morphoyl-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) - (2,2,2-trifluoro-etl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholine- 4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) - (2,2,2-trifluoro-et.l) -amino] -2- [2-d.fluoromethoxy-4- (3-oxo- morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) - (2,2,2-trifluoro-ethyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-) il) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) -methyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2 - [(2,2-difluoro-ethyl) -methyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-d.fluoro-ethyl) -methyl-amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenyl-carbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) -methyl-amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) -methyl-amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) -methyl-amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-acidamide carboxylic, { (S) -2 - [(2,2-difluoro-ethyl) -methyl-amino] -2- [3-d] -fluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - etl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) -methyl-amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -eti} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) -methyl-amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-etl) -methyl-amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) -methyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) -methyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) -methyl-amino] -2- [4- (3-oxo-morfo-lin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) -methyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl } 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) -methyl-amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-d.fluoro-ethyl) -methyl-amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-d.fluoro-ethyl) -methyl-amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcar- bamoil] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) -methyl-amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) -ethyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amid 5-chloro- thiophene-2-carboxylic acid,. { (R) -2 - [(2,2-difluoro-ethyl) -ethyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [(2, 2-difluoro-ethyl) -ethyl-amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) -etiI-amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-etiI) -ethyl-amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-etl) -etl-amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl) ] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-etl) -etl-amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) - phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) -ethyl-amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) -ethyl-amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2 - [(2,2-difluoro-ethyl) -ethyl-amino] -2- [2-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) -ethyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) -ethyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-d.fluoro-et.l) -ethyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl ] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-D-Fluoro-ethyl) -ethyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarba-moyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro- ethyl) -ethyl-amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) -ethyl-amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2 - [(2,2-difluoro-ethyl) -ethyl-amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) -ethyl-amino] -2- [2-difluoro-methoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl } 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutyl- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutyl- (2,2-d-fluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcar-bamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutyl- (2,2-d.fluoro-et.l) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl) ] -etiI} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutyl- (2,2-difluoro-ethyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutyl- (2,2-difluoro-ethyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -eti l} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutyl- (2,2-difluoro-ethyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutyl- (2,2-d-fluoro-ethyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutyl- (2,2-difluoro-ethyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutyl- (2,2-difluoro-ethyl) -amino] -2- [2-difluoromethyl] -4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-acidamide carboxylic, { (R) -2- [Cyclobutyl- (2,2-difluoro-ethyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutyl- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutyl- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] - ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- [Cyclobutyl- (2,2-d-fluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl } 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutyl- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -etl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- [Cyclobutyl- (2,2-difluoro-ethyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutyl- (2,2-difluoro-ethyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclobutyl- (2,2-d.fluoro-et.l) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbam L] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutyl- (2,2-difluoro-ethyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl ester } 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropyl- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropyl- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [CyclopropyI- (2,2-difluoro-ethyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [cyclopropyl- (2,2-difluoro- etl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- [cyclopropyl- (2, 2-difluoro-ethyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -eti} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropyl- (2,2-difluoro-ethyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -eti l} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- [Cyclopropyl- (2,2-difluoro-ethyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropyl- (2,2-difluoro-ethyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropyl- (2,2-difluoro-ethyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropyl- (2,2-difluoro-ethyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [cyclopropyl- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -eti l} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2- [Cyclopropyl- (2,2-d-fluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl- phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- [Cyclopropyl- (2,2-difluoro-etl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropyl- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- [Cyclopropyl- (2,2-d-fluoro-ethyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropyl- (2,2-d.fluoro-etiI) -amino] -2- [3-difluoromethoxy-4-] (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropyl- (2,2-difluoro-ethyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -et L} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropyl- (2,2-difluoro-ethyl) -amino] -2- [2-d.fluoromethoxy-4- (3-oxo-morpholin-4-yl) -fen Lcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [cyclopropylmethyl- (2,2-difluoro-etyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - etl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropylmethyl- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropylmethyl- (2,2-difluoro-ethyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropylmethyl- (2,2-difluoro-ethyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropylmethyl- (2,2-difluoro-ethyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2- [Cyclopropylmethyl- (2,2-difluoro-ethyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [cyclopropylmethyl- (2,2-d-fluoro-ethyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropylmethyl] - (2,2-d.-fluoro-ethyl) -amino] -2- [3-d.fluoromethyl-4- (3-oxo-morpholin-4-) il) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropylmethyl- (2,2-difluoro-ethyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropylmethyl- (2,2-difluoro-ethyl) -amino] -2- [2-d.fluoromethyl-4- (3-oxo-morpholin-4-) il) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropylmethyl- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropylmethyl- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenycarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropylmethyl- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoro-methyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropylmethyl] - (2,2-d-fluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoro-methyl-phenylcarbamoyl ] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropylmethyl- (2,2-difluoro-ethyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [cyclopropylmethyl- (2,2-d.fluoro-ethyl) -amino] -2- [3-d.fluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl ] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropylmethyl] - (2,2-difluoro-ethyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropylmethyl] - (2,2-d-fluoro-ethyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenicarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- [Cyclobutylmethyl- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarba -moyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutylmethyl- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,,. { (S) -2- [Cyclobutylmethyl- (2,2-difluoro-ethyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutylmethyl- (2,2-difluoro-ethyl) -amino] -2- [2-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-acid amide thiophene-2-carboxylic acid ". { (S) -2- [Cyclobutylmethyl- (2,2-difluoro-ethyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutylmethyl- (2,2-difluoro-ethyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutylmethyl- (2,2-difluoro-ethyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutylmethyl- (2,2-difluoro-ethyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- [Cyclobutylmethyl- (2,2-difluoro-ethyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl } 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutylmethyl- (2,2-difluoro-ethyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutylmethyl- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutylmethyl- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- [Cyclobutylmethyl- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid ". { (R) -2- [Cyclobutylmethyl- (2,2-difluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutylmethyl- (2,2-difluoro-etl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl ] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2- [Cyclobutylmethyl- (2,2-difluoro-ethyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl ] -ethyl} -amide of 5-acid chloro-thiophene-2-carboxylic acid,. { (S) -2- [Cyclobutylmethyl- (2,2-difluoro-ethyl) -amino] -2- [2- d.fluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2- [Cyclobutylmethyl- (2,2-difluoro-ethyl) -amino] -2- [2- d.fluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2 - [(2,2-difluoro-ethyl) - (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl ] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) - (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) - (2,2-dimethyl-propyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) - (2,2-dimethyl-propyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) - (2,2-dimethyl-propyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-d.fluoro-ethyl) - (2,2-dimethyl-propyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4- il) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) - (2,2-dimethyl-propyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-d.fluoro-et.l) - (2,2-d.methyl-propyl) -amino] -2- [3-difluoromethyl-4 - (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) - (2,2-dimethyl-propyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) phenylcarbamoyl] -etl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2 - [(2,2-difluoro-ethyl) - (2,2-dimethyl-propyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide . { (S) -2 - [(2) 2-d.phiuoro-ethyl) - (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morfoin-4-yl) -3 - trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-d.fluoro-ethyl) - (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-d.fluoro-ethyl) - (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-etiI) - (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-tr Fluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) - (2,2-dimethyl-propyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) - (2,2-dimethyl-propyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) - (2,2-dimethyl-propyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) phenylcarbamoyl] -ethyl} 5-Cio-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) - (2,2-dimethyl-propyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) -isobutyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) -isobutyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) -isobutyl-amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) -isobutyl-amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) -isobutyl-amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) -isobutyl-amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) -isobutyI-amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) -isobutyl-amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) -isobutyl-amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) -isobutyl-amino] -2- [2-difluoromethyl] -4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) -isobutyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) -isobutyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) -isobutyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-etiI) -isobutyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) -isobutyl-amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) -isobutyl-amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-Cio-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-difluoro-ethyl) -isobutyl-amino] -2- [2-difluoromethoxy-4- (3- oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-difluoro-ethyl) -isobutyl-amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Bis- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [bis- (2,2,2-Trifluoro-etl) -amino] -2- [4- (3-oxo-morfoin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [bis- (2,2,2-trifluoro-ethyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl } 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Bis- (2,2,2-trifluoro-ethyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Bis- (2,2,2-trifluoro-ethyl) -amino] -2- [3-fluoro-4- (3-oxo-morfo-lin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [b1s- (2,2,2-Trifluoro-ethyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl ] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide. { (S) -2- [Bis- (2,2,2-trifluoro-ethyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Bis- (2,2,2-trifluoro-ethyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Bis- (2,2,2-trifluoro-ethyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Bis- (2,2,2-trifluoro-ethyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [bis- (2,2,2-Trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [bis- (2,2,2-Trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Bis- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Bis- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [bis- (2,2,2-trifluoro-ethyl) -amino] -2- [3-difluoromethoxy] -4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl } 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Bis- (2,2,2-trifluoro-ethyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Bis- (2,2,2-trifluoro-ethyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [bis- (2,2,2-trifluoro-ethyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Methyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Methyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [methyl- (2,2,2-trifluoro-ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [methyl- (2,2,2-trifluoro-ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [methyl] - (2,2,2-trifluoro-ethyl) -amino ] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [methyl- (2,2,2-tri- fluoro-ethyl) -amino] - ethyl} -amide -chloro-thiophene-2-carboxylic acid,,. { (S) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [methyl- (2,2,2-rifluoro-ethyl) -amino] -ethyl} 5- Chloro-thiophene-2-carboxylic acid amide. { (R) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [methyl- (2,2,2-trifluoro-ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [methyl- (2,2,2-trifluoro-ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [2-difluorometl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [methyl- (2,2,2-trifluoro-ethyl) -amino] - ethyl} -amido-5-thiophene-2-carboxylic acid amide. { (S) -2- [Methyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Methyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Methyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl ] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Methyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [methyl- (2,2,2-trifluoro-ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [methyl- (2,2,2-trifluoro-ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [methyl- (2,2,2-trifluoro-ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [methyl- (2,2,2-trifluoro-ethyl) -amino] -ethyl} 5-chloro-acid amide thiophene-2-carboxylic acid ". { (S) -2- [Ethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Ethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [etiI- (2,2,2-trifluoro-ethyl) -amino] -2- [2-fIuoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -eti l} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Ethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Ethyl- (2,2,2-trifluoro-etiI) -amino] -2- [3-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide. { (R) -2- [Ethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [ethyl- (2,2,2-trifluoro-etiI) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [ethyl- (2,2,2-trifluoro-etiI) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [ethyl- (2,2,2-trifluoro-ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [ethiI- (2,2,2-trifluoro-ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Ethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Ethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Ethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} -amide of 5-acid chloro-thiophene-2-carboxylic acid,. { (R) -2- [Ethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [ethyl- (2,2,2-trifluoro-ethyl) -amino] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [ethyl- (2,2,2-trifluoro-ethyl) -amino] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [ethyl- (2,2,2-trifluoro-ethyl) -amino] - ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [ethyl- (2,2,2-trifluoro-ethyl) -amino] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutyl- (2,2,2-trifluoro-ethyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutyl- (2,2,2-trifluoro-ethyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [cyclobutyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutyl- (2, 2,2-trifluoro-ethyl) -amino] -2- [2-d.fluoromethyl] -4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutyl- (2,2,2-trifluoro-ethyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [CyclobutyI- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] 5-Chloro-thiophene-2-carboxylic acid methyl-amide,. { (S) -2- [Cyclobutyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-d.fluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutyl- (2,2,2-trifluoro-ethyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutyl- (2,2,2-trifluoro-ethyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [cyclopropyl- (2,2,2- trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,,. { (S) -2- [Cyclopropyl- (2,2,2-trifluoro-ethyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [CyclopropyI- (2,2,2-trifluoro-ethyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropyl- (2,2,2-trifluoro-ethyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropyl- (2,2,2-trifluoro-ethyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropyl- (2,2,2-trifluoro-etiI) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropyl- (2,2,2-trifluoro-etl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl ] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2- trifluoromethyl-phenylcarbamoyl] -eti} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-d-fluoro-methoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl ] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropyl- (2,2,2-trifluoro-ethyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] - ethyl} 5-cyclo-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropyl- (2,2,2-trifluoro-ethyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -etiI} 5-cyclo-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [2-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -etiI} -amido 5-doro-thiophene-2-carboxylic acid,. { (R) -2- [Cyclopropylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [2-fIuoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-fIuoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl) ] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropylmethyl- (2,2,2-trifluoro-etl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholine- 4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [cyclopropylmethyl- (2, 2,2-trifluoro-ethyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl } 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclopropylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclopropylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [CyclobutyImethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) - phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutymethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [2-fluoro-4- (3-oxo-morfoyl-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl ] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutymethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-d.fluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} 5-cyclo-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morfoin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2- trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [Cyclobutylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [2-d.fluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - etl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [Cyclobutylmethyl- (2,2,2-trifluoro-ethyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-dimethyl-propyl) - (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-dimethyI-propyl) - (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenycarbamoyl ] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-dimethyl-propyl) - (2,2,2-trifluoro-ethyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholine- 4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-dimethyl-propyl) - (2,2,2-trifluoro-ethyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4- il) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-dimethyl-propyl) - (2,2,2-trifluoro-ethyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4- L) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-dimethyl-propyI) - (2,2,2-trifluoro-ethyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4- il) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) - (2,2,2-trifluoro- ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [3-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) - (2,2,2-trifluoro-ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) - (2,2,2-trifluoro- ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [(2,2-dimethyl-propyl) - (2,2,2-trifluoro- etl) -amino] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-dimethyl-propyl) - (2,2,2-trifluoro-etiI) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3 -trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-dimethyl-propyl) - (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3 -trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2 - [(2,2-dimethyl-propyl) - (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2 -trifluoromethyl-phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide. { (R) -2 - [(2,2-dimethyl-propyl) - (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morfoin-4-yl) -2 -trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) - (2,2,2-trifluoro- ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) - (2,2,2-trifluoro- ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) - (2,2,2-trifluoro- ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) - (2,2,2-trifluoro- ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [isobutyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide . { (R) -2- [isobutyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl-ethyl-acid-5-amide chloro-thiophene-2-carboxylic acid,. { (S) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [isobutyl- (2,2,2-trifluoro-ethyl) -amino] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [2-Fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [isobutyl- (2,2,2-trifluoro-ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [isobutyl- (2,2,2-trifluoro-ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [3-Fluoro-4 (3-oxo-morfoin-4-yl) -phenyicarbamoyl] -2- [isobutyl- (2,2,2-trifluoro-ethyl) -amino] -ethyl} -amido 5-doro-thiophene-2-carboxylic acid,,. { (S) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [isobutyl- (2,2,2-trifluoro-ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [isobutyl- (2,2,2-trifluoro-ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [isobutyl- (2,2,2-trifluoro-ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- [isobutyl- (2,2,2-trifluoro-ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [isobutyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide. { (R) -2- [isobutyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [isobutyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [isobutyl- (2,2,2-trifluoro-ethyl) -amino] -2- [4- (3-oxo- morfoin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -2- [isobutyI- (2,2,2-trifluoro-ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -2- [isobutyl- (2,2,2-trrfluoro-ethyl) -amino] -ethyl} -amido 5-doro-thiophene-2-carboxylic acid,. { (S) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -2- [isobutyl- (2,2,2-trifluoro-ethyl) -amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -2- [isobutyl- (2,2,2-trifluoro-ethyl) -amino] -ethyl} -amido 5-doro-thiophene-2-carboxylic acid,,. { (S) -2-dimethylamino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2-dimethylamino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amido 5-doro-thiophene-2-carboxylic acid,. { (S) -2-dimethylamino-2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2-dimethylamino-2- [2-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2-dimethylamino-2- [3-fIuoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide. { (R) -2-dimethylamino-2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [3-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -2-dimethylamino-ethyl} -5-Chloro-thiophene-2-carboxylic acid amide ". { (R) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-dimethylamino-ethyl} : 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-dimethylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [2- difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -2-dimethylamino-ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2-dimethylamino-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Dimethylamino-2- [4- (3-oxo-morfoin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-Dimethylamino-2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-dimethylamino-2- [4- (3-oxo-morfoin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} - 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- [3-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -2-dimethylamino-ethyl]} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-dimethylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-d-methylamino-etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -2-dimethylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (ethyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (ethyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- (ethyl-methyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (ethyl-methyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (ethyl-methyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-Cio-thiophene-2-carboxylic acid amide,. { (R) -2- (ethyl-methyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4- iI) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid, [(S) -2- [3- difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (ethyl- 5-Chloro-thiophene-2-carboxylic acid amide, [(R) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamate] L] -2- (ethyl-methyl-amino) -etiI] -amide of 5-chloro-thiophene-2-carboxylic acid, [(S) -2- [2-difluoromethyl-4- (3-oxo-morpholine 4-yl) -phenylcarbamoyl] -2- (ethyl-methyl-amino) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid, [(R) -2- [2-difluoromethyl-4- ( 5-Chloro-thiophene-2-carboxylic acid 3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (ethyl-methyI-amino) -etiI] -amide. { (S) -2- (ethyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (ethyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (ethyl-methy1-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (ethyl-methyl-amino) -2- [4- (3-oxo-morfoin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, [(S) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (ethyl-methyl- amino) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid, [(R) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- 5-Chloro-thiophene-2-carboxylic acid (ethyl-methyl-amino) -ethyl] -amide, [(S) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) - Phenylcarbamoyl] -2- (ethyl-methyl-amino) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid, [(R) -2- [2-difluoromethoxy-4- (3-oxo-morpho- 4-yl) -phenylcarbamoyl] -2- (ethyl-methyl-amino) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- (Cyclobutyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclobutyl-methyl-amino) -2- [4- (3-oxo- morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-methyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-methyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-methyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-methyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-methyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-methyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-methyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclobutyl-methyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-methyl-amino) -2- [4- (3-oxo-morfoin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} -amido 5-doro-thiophene-2-carboxylic acid,. { (R) -2- (Cyclobutyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -etl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- (Cyclobutyl-methyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclobutyl-methyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-methyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-methyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-methyl-amino) -2- [2-fIuoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropyl-methyl-amino) -2- [2-fIuoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-methyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropyl-methyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclopropy1-methy1-amino) -2- [3-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropy1-methyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-methyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropylmethylamino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-methyl-amino) -2- [4- (3-oxo: morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2- (Cyclopropyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -eti} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-methyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-- (cyclopropyl-methyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclopropyl-methyl-amino) -2- [2-d.fluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2- (Cyclopropyl-methylamino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} - 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethylmethylamino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-methyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-methyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-methyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropymethyl-methyl-amino) -2- [3-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclopropylmethylmethyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2- (cyclopropylmethyl-methyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-methyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-methyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclopropylmethyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -etiI} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclopropylmethyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropylmethyl-methyl-amino) -2- [4- (3-oxo-morfoin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-methyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-methylene-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-methyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethylmethylamino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutymethyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etl} - 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-methyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-methyl-amino) -2- [2-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-methyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-methyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- (Cyclobutylmethyl-methyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amido 5-doro-thiophene-2-carboxylic acid,. { (R) -2- (Cyclobutylmethyl-methyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-methyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-methyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclobutylmethylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-methyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-methylene-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-methyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-methyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2 - [(2,2-dimethyl-propyl) -methyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2 - [(2,2-dimethyl-propyl) -methyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2 - [(2,2-dimethyl-propyl) -methyl-amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2 - [(2,2-dimethyl-propyl) -methyl-amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2 - [(2,2-Dimethyl-propyl) -methyl-amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2 - [(2,2-dimethyl-propyl) -methyl-amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) -methyl-amine] - etiI} -amid acid 5- chloro-thiophene-2-carboxylic acid,. { (R) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) -methyl-amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) -methyl-amino] -ethyl} -amido 5-doro-thiophene-2-carboxylic acid,. { (R) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) -methyl-amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2 - [(2,2-dimethyl-propyl) -methyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2 - [(2,2-dimethyl-propyl) -mef? L-amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2 - [(2,2-dimethyl-propyl) -methyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2 - [(2,2-Dimethyl-propyl) -methyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) -methyl-amino] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -2 - [(2,2-dimethyl-propyl) -methyl-amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) -methyl-amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) -methyl-amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (isobutyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (isobutyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide, [(S) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (isobutyl-methyl- 5-Chloro-thiophene-2-carboxylic acid amine) -ethyl] -amide, [(R) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - 2- (Chloro-thiophene-2-carboxylic acid) 2- (isobutyl-methyl-amino) -ethyl] -amide, [(S) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (isobutyl-methyl-amino) -ethyl] -amide of 5-chloro- thiophene-2-carboxylic acid, [(R) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (butynyl-methyl-amino) -ethyl] -5-Chloro-thiophene-2-carboxylic acid amide, [(S) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -2- (isobutylmethyl) amino) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid, [(R) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - 2- (Chloro-thiophene-2-carboxylic acid, 5- (2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -2- (isobutyl-methyl-amino) -ethyl] -amide. ) -phenylcarbamoyl] -2- (isobutyl-methyl-amino) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid, [(R) -2- [2-difluoromethyl-4- (3- oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (isobutyl-methylamino) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- (isobutyI-methyl-amino) -2- [4- (3-oxo-morfoin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (isobutyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Sobutyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (isobutyl-methyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, [(S) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (isobutyl-methyl) -amino) -etl] -amido of 5-chloro-thiophene-2-acid carboxylic acid, [(R) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (isobutyl-methyl-amino) -etl] -amide acid 5-chloro-thiophene-2-carboxylic acid, [(S) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (isobutyl-methyl-amino) -ethyl ] - 5-chloro-thiophene-2-carboxylic acid amide, [(R) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (isobutyl) 5-cyclo-thiophene-2-carboxylic acid methylamine) -ethyl] -amide ,. { (S) -2-diethylamino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-diethylamino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} - 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-diethylamino-2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-diethylamino-2- [2-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-diethylamino-2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2-diethylamino-2- [3-fIuoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-diethylamino-2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-diethylamino-2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-diethylamino-2- [2-difluoromethyl-4- (3-oxo-morfo! In-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-diethylamino-2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-diethylamino-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-diethylamino-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl- phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- diethylamino-2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-diethyl-amino-2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-diethylamino-2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-diethylamino-2- [3-d-fluoro-methoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-diethylamino-2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-diethylamino-2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclobutyl-ethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-ethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -eti} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-ethyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-ethyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-ethyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2- (Cyclobutyl-ethyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- (Cyclobutyl-ethyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-ethyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-acid chloro-thiophene-2-carboxylic acid,. { (S) -2- (Cyclobutyl-ethyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-ethyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-ethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-ethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-ethylamino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclobutyl-ethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-ethyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-ethyl-amino) -2- [3-d-fluoro-methoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-ethyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-ethyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- (cyclopropyl-ethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropyl-ethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-ethylamino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2- (cyclopropyl-ethyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) - phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-ethyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropyl-ethyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-ethyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropyl-ethyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-ethyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropyl-ethyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-ethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropyl-ethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-ethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropyl-ethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-ethyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2- (cyclopropyl-ethyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-ethyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-y) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-acidamide carboxylic, { (R) -2- (cyclopropyl-ethyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-ethyl-amino) -2- [4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-etl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-ethyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-ethyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-eti-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-ethyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-ethyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-ethyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-ethyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-ethyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-ethyl-amino) -2- [4- (3-oxo-morfoin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-ethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-ethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropylmethyl-ethylamino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-ethyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-ethyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-ethyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-eti-amino) -2- [2-d-fluoro-methoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- (Cyclobutylmethyl-ethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-ethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-ethyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-ethyl-amine) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-ethyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-ethyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-ethyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, . { (R) -2- (Cyclobutylmethyl-ethyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- (Cyclobutylmethyl-ethyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-ethyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclobutylmethyl-ethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-ethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-ethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-ethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-ethyl-amino) -2- [3-d-fluoro-methoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-ethyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-ethyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-ethyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2 - [(2,2-dimethy1-propyl) -ethyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2 - [(2,2-dimethyl-propyl) -etiI-amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2 - [(2,2-dimethyl-propyl) -ethyl-amino] -2- [2-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -etiI} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2 - [(2,2-Dimethyl-propyl) -ethyl-amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2 - [(2,2-dimethyl-propyl) -eti-amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2 - [(2,2-dimethyl-propyl) -ethyl-amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -2 - [(2,2-dimethyl-propyl) -ethyl-amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) -ethyl-amino] -ethyl} -amido 5-doro-thiophene-2-carboxylic acid,. { (S) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -2 - [(2,2-dimethyl-propyl) -ethyl-amino] -ethyl} -amide of 5-cyclo-thiophene-2-carboxylic acid,. { (R) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) -ethyl-amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2 - [(2,2-dimethyl-propyl) -ethyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl } 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2 - [(2,2-dimethyl-propyl) -ethyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] - ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2 - [(2,2-dimethyl-propyl) -ethyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -eti l} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2 - [(2,2-Dimethyl-propyl) -ethyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -etiI} 5-chloro-acid amide thiophene-2-carboxylic acid,. { (S) -2- [3-difluoromethoxy-4- (3-oxo-morfoyl-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) -ethyl-amino] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [3-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) -ethyl-amino] -etl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) -ethyl-amino] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2- [2-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) -ethyl-amino] -etiI} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- (ethyl-isobutyl-amino) -2- [4- (3-oxo-morfoiin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (ethyl-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (ethyl-isobutyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Ethyl-isobutyl-amino) -2- [2-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (ethyl-isobutyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (ethyl-isobutyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-Chloro-thiophene-2-carboxylic acid amide, [(S) -2- [3-d.fluoromethyl-4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -2- (ethyl- 5-chloro-thiophene-2-carboxylic acid isobutyl-amino] -etyl] -amide, [(R) -2- [3-difluoromethyl-4- (3-oxo-morfoin-4-yl)] phenylcarbamoyl] -2- (ethyl-isobutyl-amino) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid, [(S) -2- [2-difluoromethyl-4- (3-oxo-morpholine -4-i1) -phenylcarbamoyl] -2- (ethyl-isobutyl-amino) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid, [(R) -2- [2-difluoromethyl-4- ( 3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (ethyl- -chloro-thiophene-2-carboxylic acid isobutyl-amino) -ethyl] -amide ,. { (S) -2- (ethyl- sobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -etl} - 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (ethyl-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (ethyl-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Ethyl-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, [(S) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (ethyl- 5-chloro-thiophene-2-carboxylic acid isobutyl-amino) -ethyl] -amide, [(R) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - 5- (Cyclo-thiophene-2-carboxylic acid) (2- (2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -amido] - (ethyl-isobutyl-amino) -ethyl] -amide. ) -phenylcarbamoyl] -2- (ethyl-isobutyl-amino) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid, [(R) -2- [2-difluoromethoxy-4- ( 5-Chloro-thiophene-2-carboxylic acid 3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (ethyl-isobutyl-amino) -ethyl] -amide. { (S) -2-dicyclobutylamino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-dicyclobutylamino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-d-Cyclobutylamino-2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2-dicyclobutylamino-2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-dicyclobutylamino-2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-dicyclobutylamino-2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2-dicyclobutylamino-2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-dicyclobutylamino-2- [3-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenecarbamoyl] -ethyl} -amide of 5-cyclo-thiophene-2-carboxylic acid,. { (S) -2-dicyclobutylamino-2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-dicyclobutylamino-2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-dicyclobutylamino-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2-dicyclobutylamino-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2-dicyclobutyllamno-2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-dicyclobutylamino-2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-dicyclobutyl-amino-2- [3-d-fluoro-methoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-dicyclobutylamino-2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-dicyclobutylamino-2- [2-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-dicyclobutylamino-2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-cyclopropyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclobutyl-cyclopropyl-amino) -2- [4- (3-oxo-morpholine- 4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- (cyclobutyl-cyclopropyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-cyclopropyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-cyclopropyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-cyclopropyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-cyclopropyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-cyclopropyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-cyclopropyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-cyclopropyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-cyclopropyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-cyclopropyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-cyclopropyl-amine) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclobutyl-cyclopropyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclobutyl-cyclopropylamino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-cyclopropyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclobutyl-cyclopropyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-cyclopropyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclobutyl-cyclopropylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-cyclopropylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-cyclopropylmethyl-amino) -2- [2-fIuoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-cyclopropylmethyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-cyclopropylmethyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-cyclopropylammethylamino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-cyclopropylamino-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2- (Cyclobutyl-cyclopropylmethylamino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclobutyl-cyclopropylmethyl-amino) -2- [2-d.fluoromethyl-4- (3-oxo-morpholin-4-yl) - phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclobutyl-cyclopropyl-methylamino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-cyclopropylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-cyclopropylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-cyclopropylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-cyclopropylmethyl-amino) -2- [4- (3-oxo-morfoin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-cyclopropylmethyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-cyclopropylmethyl-amino) -2- [3-difiuoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-cyclopropylmethyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-cyclopropylmethyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-cyclobutylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-cyclobutylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-cyclobutylmethyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-acidamide carboxylic, { (R) -2- (Cyclobutyl-cyclobutylmethyl-amino) -2- [2-fluoro-4- (3-oxo-morfoyl-4-yl) -phenylcarbamoyl] -etl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- (Cyclobutyl-cyclobutylmethyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclobutyl-cyclobutylmethyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -eti} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-cyclobutylmethyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-cyclobutylmethyl-amino) -2- [3-d.fluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-cyclobutylmethyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-cyclobutylmethyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-cyclobutylmethanol-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-cyclobutylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-cyclobutylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-cyclobutylmethanol-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -eti} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-cyclobutylmethyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclobutyl-cyclobutylmethyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclobutyl-cyclobutylmethyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-cyclobutylmethyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclobutyl- (2,2-dimethy1-propyl) -amino] -2- [4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclobutyl- (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclobutyl- (2,2-dimethyl-propyl) -amino] -2- [2-fIuoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclobutyl- (2,2-dimethyl-propyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclobutyl- (2,2-dimethyl-propyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2- [Cyclobutyl- (2,2-dimethyl-propyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- [Cyclobutyl- (2,2-dimethy1-propyl) -amino] -2- [3-d] -fluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclobutyl- (2,2-dimethyl-propyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclobutyl- (2,2-dimethyl-propyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclobutyl- (2,2-dimethyl-propyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) - phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclobutyl- (2,2-dimethyI-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclobutyl- (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclobutyl- (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morfoin-4-yl) -2-trifluoromethyl-1-phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclobutyl- (2,2-dimethyl-propyI) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclobutyl- (2,2-dimethyl-propyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclobutyl- (2,2-dimethyl-propyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclobutyl- (2,2-dimethyl-propyl) -amino] -2- [2-d-fluoro-methoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclobutyl- (2,2-dimethyl-propyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclobutyl-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclobutyl-isobutyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-isobutyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -eti} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclobutyl-isobutyl-amino) - 2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-isobutyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-isobutyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-isobutyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcar-bamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- (Cyclobutyl-isobutylamino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-isobutyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-isobutyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutyl-isobutyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-isobutyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclobutyl-isobutyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- dicyclopropylamino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-dicyclopropylamino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- dicyclopropylamino-2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Dicyclopropylamino-2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-Dicyclopropylamino-2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -eti} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-dicyclopropylamino-2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-dicyclo-propylamino-2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Dicyclopropylamino-2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-dicyclopropylamino-2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Dicyclopropylamino-2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-Dicyclopropylamino-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Dicyclopropylamino-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-Dicyclopropylamino-2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- dichyopropylamino-2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} - 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-Dicyclopropylamino-2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-dicyclopropylamino-2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-dicyclopropylamino-2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2-Dicyclopropylamino-2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-cyclopropylmethyl-amino) -2- [4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropyl-cyclopropylmethylamino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-cyclopropylmethyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropyl-cyclopropylmethyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-cyclopropylmethyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropyl-cyclopropylmethylamino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclopropyl-cyclopropylmethyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropyl-cyclopropylmethyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-cyclopropylmethyl-amine) -2- [2-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropyl-cyclopropylmethyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclopropyl-cyclopropylmethylamino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropyl-cyclopropylmethyl-amine) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclopropyl-cyclopropylmethyl-amino) -2- [4- (3-oxo-morfoin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropyl-cyclopropylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-cyclopropylmethyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -eti} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropyl-cyclopropylmethi-amino) -2- [3-d-fluoro-methoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylocyclopropylmethylamino) -2- [2-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropyl-cyclopropylmethyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-cyclopropyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-cyclopropyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-cyclopropyl-amino) -2- [2-fluoro-4- (3- oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-cyclopropyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclobutylmethyl-cyclopropyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-cyclopropyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-cyclopropyl-amino) -2- [3-d] -fluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-cyclopropyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclobutylmethyl-cyclopropyl-amino) -2- [2-difluoromethyl] -4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclobutylmethyl-cyclopropyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclobutylmethyl-cyclopropyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-cyclopropyl-amine) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclobutylmethyl-cyclopropyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-cyclopropyl-amino) -2- [4- (3-oxo-morfoin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-cyclopropyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) - phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethi-cyclopropyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylacarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclobutylmethyl-cyclopropyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-cyclopropyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclopropyl- (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclopropyl- (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclopropyl- (2,2-dimethyl-propyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclopropyl- (2,2-dimethyl-propyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclopropyl- (2,2-dimethyl-propyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclopropyl- (2,2-dimethyl-propyI) -amino] -2- [3-fIuoro-4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclopropyl- (2,2-dimethyl-propyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclopropyl- (2,2-dimethyl-propyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclopropyl- (2,2-dimethyl-propyI) -amino] -2- [2-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid, . { (R) -2- [Cyclopropyl- (2,2-dimethyl-propyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclopropyl- (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclopropyl- (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclopropyl- (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclopropyl- (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morfoin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclopropyl- (2,2-dimethyI-propyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclopropyl- (2,2-dimethyl-propyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclopropyl- (2,2-dimethyl-propyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclopropyl- (2,2-dimethyl-propyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropyl-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclopropyl-isobutyl-amino) -2- [2-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropyl-isobutyI-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - etii} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-isobutyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-doro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropyl-isobutyl-amino) -2- [3-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-isobutyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropyl-isobutyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-isobutyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} - 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropyl-isobutyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropyl-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropyl-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclopropyl-isobutyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropylisobutyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyl-isobutyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropyl-isobutyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Bis-cyclopropylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (bis-cyclopropylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (bis-cyclopropylmethyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (bis-cyclopropylmethyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (bis-cyclopropylmethyl-amino) -2- [3-fIuoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (bis-cyclopropylmethyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (bis-cyclopropylmethyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (bis-cyclopropylmethyl-amino) -2- [3-d.fluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (bis-cyclopropylmethyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (bis-cyclopropylmethyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} - 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- (bis-cyclopropylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (bis-cyclopropylmethyl-amino) -2- [4- (3-oxo-morpholin-4-) il) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (bis-cyclopropylmethyl-amino) -2- [4- (3-oxo-morfoin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Bis-cyclopropylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (bis-cyclopropylmethyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (bis-cyclopropylmethyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} - 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- (bis-cyclopropylmethyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (bis-cyclopropylmethyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-cyclopropylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cidobutylmethyl-cyclopropylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-cyclopropylmethyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-cyclopropylmethyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutymethyl-cyclopropylmethyl-amino) -2- [3-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-cyclopropylmethyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, . { (S) -2- (Cyclobutylmethyl-cyclopropylmethyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-cyclopropylmethyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-cyclopropylmethyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-cyclopropylmethyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-cyclopropylmethylamino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-cyclopropylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-cyclopropylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-cyclopropylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-cyclopropyl-amino) -2- [3-d-fluoro-methoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-cyclopropylmethyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-cyclopropylmethyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-cyclopropylmethyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, . { (S) -2- [Cyclopropylmethyl- (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclopropylmethyl- (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclopropylmethyl- (2,2-dimethyl-propyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclopropylmethyl- (2,2-dimethyl-propyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclopropylmethyl- (2,2-dimethy1-propyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclopropylmethyl- (2,2-dimethyI-propyl) -amino] -2- [3-fIuoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclopropylmethyl- (2,2-dimethyl-propyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclopropylmethyl- (2,2-dimethyl-propyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclopropylmethyl- (2,2-dimethyl-propyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclopropylmethyl- (2,2-dimethyl-propyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclopropylmethyl- (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclopropylmethyl- (2,2-dimethyI-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, . { (S) -2- [Cyclopropylmethyl- (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclopropylmethyl- (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2- trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclopropylmethyl- (2,2-dimethyl-propyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclopropylmethyl- (2,2-dimethyl-propyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclopropylmethyl- (2,2-dimethyI-propyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclopropylmethyl- (2,2-dimethyl-propyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropyImethi-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-isobutyl-amino) -2- [2-fIuoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropylmethyl-isobutyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-isobutyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-butyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -eti} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-butyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) - phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropylmetyl-isobutyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-isobutyl) amino) -2- [2-d.fluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-butyl-amino) -2- [2-d-fluoro-methyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-isobutyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethoxy-isobutyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-isobutylamino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropylmethyl-isobutyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (bis-cyclobutymethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} -amide -chloro-thiophene-2-carboxylic acid,. { (R) -2- (bis-cyclobutylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (bis-cyclobutylmethyl-amino) -2- [2-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Bis-cyclobutylmethyl-amino) -2- [2-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -etl} - 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (bis-Cyclobutylmethyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (bis-cyclobutylmethyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (bis-cyclobutylmethyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (bis-cyclobutylmethyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (bis-cyclobutylmethyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (bis-cyclobutylmethyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (bis-cyclobutylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Bis-cyclobutylmethylamino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (b1s-cyclobutylmethylamino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -eti} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (bis-cyclobutylmethylamino) -2- [4- (3-oxo-morfoin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (bis-cyclobutylmethyl- amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (bis-cyclobutylmethyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5- Chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (bis-cyclobutylmethyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amido 5-doro-thiophene-2-carboxylic acid,. { (R) -2- (bis-cyclobutylmethyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclobutylmethyl- (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclobutylmethyl- (2,2-dimethyI-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclobutymethyl- (2,2-dimethyl-propyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclobutylmethyl- (2,2-dimethyl-propyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclobutylmethyl- (2,2-dimethyl-propyI) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclobutylmethyl] - (2,2-dimethyl-propyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclobutylmethyl- (2,2-dimethyl-propyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morfoyl-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclobutylmethyl- (2,2-dimethyl-propyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclobutylmethyl- (2,2-dimethyl-propyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-) il) -phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclobutylmethyl- (2,2-dimethyl-propyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclobutylmethyl- (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morfoin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] - etiI} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2- [Cyclobutylmethyl- (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclobutylmethyl- (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclobutylmethyl- (2,2-dimethy1-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclobutylmethyl- (2,2-dimethyl-propyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2- [Cyclobutylmethyl- (2,2-dimethyl-propyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- [Cyclobutylmethyl- (2,2-dimethyl-propyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Cyclobutylmethyl- (2,2-dimethyl-propyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-butyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-isobutyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-acid amide carboxylic, { (R) -2- (Cyclobutylmethyl-isobutyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclobutymethyl-isobutyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-isobutyl-amino) -2- [3-fluoro-4- (3-oxo-morfoin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethi-isobutyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-isobutyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-isobutyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-isobutylamino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclobutymethyl-isobutyl-amino) -2- [4- (3-oxo-morfoin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-isobutyl-amino) -2- [4- (3-oxo-morfoin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-isobutyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-isobutyl-amino) -2- [4- (3-oxo-morfoin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-isobutyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclobutylmethyl-isobutyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -eti} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-isobutyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-isobutyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Bis- (2,2-dimethy1-propyl) -amino] -2- [4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [bis- (2,2-Dimetii-propyI) -amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- [Bis- (2,2-dimethy1-propyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [b] - (2,2-dimethyl-propyl) -amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Bis- (2,2-dimethyI-propyI) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Bis- (2,2-dimethyl-propyl) -amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Bis- (2,2-dimethyl-propyl) -amino] -2- [3-difluoromethyl] -4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] - ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2- [Bis- (2,2-dimethyl-propyl) -amino] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Bis- (2,2-dimethy1-propyl) -amino] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl } 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- [Bis- (2,2-dimethy1-propyl) -amino] -2- [2-d-fluoro-methyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl) ] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [bis- (2,2-dimethy1-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Bis- (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Bis- (2,2-dimethyl-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl ] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- [Bis- (2,2-dimethy1-propyl) -amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Bis- (2,2-dimethyl-propyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Bis- (2,2-dimethyl-propyl) -amino] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [Bis- (2,2-dimethyl-propyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [Bis- (2,2-dimethyl-propyl) -amino] -2- [2-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2 - [(2,2-dimethyl-propyl) -isobutyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2 - [(2,2-dimethyl-propyl) -isobutyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2 - [(2,2-dimethyl-propyl) -isobutyl-amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2 - [(2,2-dimethyl-propyl) -isobutyl-amino] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2 - [(2,2-dimethyl-propyI) -isobutyl-amino] -2- [3-fluoro-4- (3-oxo- morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (R) -2 - [(2,2-dimethyl-propyl) -isobutyl-amino] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-1-propyl) -isobutyl-amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [3-D-Fluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) -isobutyl-amino] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2 - [(2,2-d-methyl-propyl) -isobuty-amino] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [2-d.fluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) -isobutyl-amino] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2 - [(2,2-dimethyl-propyl) -isobutyl-amino] -2- [4- (3-oxo-morfoin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2 - [(2,2-dimethyl-propyl) -isobutyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl ] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2 - [(2,2-dimethy-propyl) -isobutyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2 - [(2,2-dimethyl-propyl) -isobutyl-amino] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [3-D-Fluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) -isobutyl-amino] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [3-D-Fluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) -isobutyl-amino] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [2-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) - isobutyl-amino] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [2- d.fluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2 - [(2,2-dimethyl-propyl) -isobutyl-amino] -ethyl} - 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- diisobutylamino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etl} 5- Chloro-thiophene-2-carboxylic acid amide,. { (R) -2-diisobutylamino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-d¡¡-butynylamino-2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Diisobutylamino-2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-diisobutylamino-2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Diisobutylamino-2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-diisobutylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [3-difluoromethyl] -4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-diisobutylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-diisobutylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [2-d.phiuoromethyl-4- (3-oxo-morfoiin-4-yl) -phenylcarbamoyl] -2-diisobutylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-d¡¡-butynylamino-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Diisobutylamino-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenalcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-Diisobutylamino-2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-acid amide thiophene-2-carboxylic acid,. { (R) -2-Diisobutylamino-2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -2- diisobutylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-diisobutylamino-etl} - 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [2-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -2-diisobutylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [2-d.fluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -2-diisobutylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-difluoro-ethylamino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-difluoroethylamino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-difluoro-ethylamino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-d.fluoro-ethylamino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-difluoroethylamino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-difluoro-ethylamino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-difluoro-ethylamino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-difluoro-ethylamino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-difluoro-ethylamino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} - -chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-difluoroethylamino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-difluoro-ethylamino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-difiuoro-ethylamino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-difluoro-ethylamino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-difluoro-etyl) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-difluoro-ethylamino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-difluoro-ethylamino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-difluoro-ethylamino) -2- [2-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-difluoroethylamino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, [(S) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (2,2,2-trifluoro- 5-Chloro-thiophene-2-carboxylic acid ethylamino) -ethyl ([(R) -2- [4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -2- (2.2 5-Chloro-thiophene-2-carboxylic acid, 2-trifluoroethylamino) -ethyl] -amide, [(S) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) - 5-chloro-thiophene-2-carboxylic acid phenylcarbamoyl] -2- (2,2,2-trifluoro-ethylamino) -ethyl] -amide, [(R) -2- [2-fluoro-4- (3- oxo-morfoin-4-yl) -phenylcarbamoyl] -2- (2,2,2-trifluoro-ethylamino) -etiI] -amide of 5-chloro-thiophene-2-carboxylic acid, [(S) -2- [ 3-fluoro-4- (3-oxo-morpholin- -chloro-thiophene-2-carboxylic acid 4-yl) -phenylcarbamoyl] -2- (2,2,2-trifluoro-ethylamino) -ethyl] -amide, [(R) -2- [3-fluoro- 5-cyclo-thiophene-2-carboxylic acid 4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (2,2,2-trifluoro-ethylamino) -etiI] -amide, [(S) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (2,2,2-trifluoro-etyl) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid, [(R) -2- [3-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -2- (2,2,2- 5-chloro-thiophene-2-carboxylic acid trifluoro-ethylamino) -ethyl] -amide, [(S) -2- [2-difluoromethyl-4- (3-oxo-morfoin-4-ii) -phenylcarbamoyl] - 5-Chloro-thiophene-2-carboxylic acid 2- (2,2,2-trifluoro-ethylamino) -ethyl] -amide, [(R) -2- [2-difluoromethyl-4- (3-oxo-morpholine 4-yl) -phenylcarbamoyl] -2- (2,2,2-trifluoro-eti-amino) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid, [(S) -2- [4- ( 3-Oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -2- (2,2,2-trifluoro-ethylamino) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid, [( R) -2- [4- (3-Oxo-morpholin-4-yl) -3-trifluoromethyl-1-phenylcarbamoyl] -2- (2,2,2-trifluoro-ethylamino) -ethyl] - 5-chloro-thiophene-2-carboxylic acid amide, [(S) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -2- (2,2,2 -trifluoro-ethylamino) -ethyl] -am of 5-chloro-thiophene-2-carboxylic acid, [(R) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -2- (2,2,2 5-Chloro-thiophene-2-carboxylic acid, 5-cyclo-thiophene-2-carboxylic acid, [(S) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) - 5-chloro-thiophene-2-carboxylic acid phenylcarbamoyl] -2- (2,2,2-trifluoro-ethylamino) -ethyl] -amide, [(R) -2- [3-difluoromethoxy-4- (3- oxo-morfoin-4-yl) -phenylcarbamoyl] -2- (2,2,2-trifluoro-ethylamino) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid, [(S) -2- [ 2-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -2- (2,2,2-trifluoro-ethylamino) -etiI] -amide of 5-chloro-thiophene-2-carboxylic acid , [(R) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (2,2,2-trifluoro- ethylamino) -etiI] - 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-methylamino- 2- [4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-methylamino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} - 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-methylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-methylamino-ethyl-5-chloro-thiophene-2-carboxylic acid amide. { (S) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-methylamine-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-methylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-methylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [3-d.fluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-methylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [2-d.fluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-methylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-methylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-methylamino-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-methalamine-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-methylamino-2- [4- (3-oxo-morfoyl-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-methylamino-2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- methylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [3- difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-methylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-methylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-methylamino-ethyl-5-chloro-thiophene-2-carboxylic acid amide; { (S) -2-ethylamino-2- [4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2-ethylamino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-ethylamino-2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-ethylamino-2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-ethylamino-2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-ethylamino-2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-ethylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-ethylamino-etii} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-ethylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [2-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -2-ethylamino-etiI} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2-ethylamino-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2-etylamino-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2-ethylamino-2- [4- (3-oxo-morfoin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-ethylamino-2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [3- difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -2-ethylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-ethylamino-ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-ethylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-ethylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-Cyclobutylamino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Cyclobutylamino-2- [4- (3-oxo-morpholin-4-yl) -phenyl-carbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-cyclobutylamino-2- [2-fIuoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Cyclobutylamino-2- [2-fIuoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-Cyclobutylamino-2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Cyclobutylamino-2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-Cyclobutylamino-2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Cyclobutylamino-2- [3-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-cyclobutylamino-2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Cyclobutylamino-2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-Cyclobutylamino-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -etiI} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2-Cyclobutylamino-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2-Cyclobutylamino-2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Cyclobutylamine-2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-Cyclobutylamino-2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} - 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2-Cyclobutylamino-2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-Cyclobutylamino-2- [2-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Cyclobutylamino-2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-cyclopropylamino-2- [4- (3-oxo-morpholin-4-yl) -phenyicarbamoyl] -etiI} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2-Cyclopropylamine-2- [4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2-cyclopropylamino-2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Cyclopropylamino-2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-cyclopropylamino-2- [3-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- cyclopropylamino-2- [3-fluoro-4- (3-oxo-morphoyl-4-yl) -phenyicarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2-Cyclopropylamine-2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-cyclopropylamino-2- [3-difluoromethyl] -4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-Cyclopropylamino-2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-cyclopropylamino-2- [2-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -etiI} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2-cyclopropylamino-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} - 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2-Cyclopropylamino-2- [4- (3-oxo-morfoin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-cyclopropyl-amino-2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2-cyclopropylamino-2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-cyclopropylamino-2- [3-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenecarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Cyclopropylamino-2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-cyclopropylammon-2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-cyclopropylamino-2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amido 5-doro-thiophene-2-carboxylic acid,. { (S) -2- (cyclopropylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethylamino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclopropymethyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-ii) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-amino) -2- [4- (3-oxo-morfoin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropylmethyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropylmethyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-amino) -2- [4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-amino) -2- [2-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-amino) -2- [3-fIuoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etií} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclobutylmethyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclobutymethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutymethyl-amino) -2- [4- (3-oxo-morfoiin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutylmethyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutylmethyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutyl-II-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} - 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutymethyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-dimethyl-propylamino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-dimethyl-propylamino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-dimethyI-propylamine) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-Dimethyl-propylamine) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-Dimethyl-propylamine) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-acid amide thiophene-2-carboxylic acid,. { (R) -2- (2,2-dimethyl-propylamino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, [(S) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (2,2- 5-chloro-thiophene-2-carboxylic acid dimethyl-propylamino) -ethyl] -amide, [(R) -2- [3- difluoromethyl] -4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -2- (2,2-dimethyl-propylamino) -ethyl] -amide of acid 5-chloro-thiophene-2-carboxylic acid, [(S) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -2- (2,2-dimethyl-propylamino) -eti) -amido of 5-chloro-thiophene-2-carboxylic acid, [(R) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -pheni-carbamoyl] -2- (5-dimethyl-propylamino) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- (2,2-Dimethyl-propylamino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-Dimethyl-propylamine) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-dimethy1-propylamino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-Dimethyl-propylamine) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} -5-Chloro-thiophene-2-carboxylic acid amide, [(S) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -2- (2,2- 5-chloro-thiophene-2-carboxylic acid dimethyl-propylamino) -ethyl] -amide, [(R) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - 5-Chloro-thiophene-2-carboxylic acid 2- (2,2-dimethyl-propylamino) -ethyl] -amide, [(S) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4 5-cyclo-thiophene-2-carboxylic acid, ((R) -2- [2-difluoromethoxy-4- (-yl) -phenylcarbamoyl] -2- (2,2-dimethyl-propylamino) -ethyl] -amide. 5-Chloro-thiophene-2-carboxylic acid 3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (2,2-dimethyl-propylamine) -ethyl] -amide; . { (S) -2-S-butylamino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-isobutylamino-2- [4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-isobutylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-isobutylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- isobutylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [3-fluoro-4- (3-oxo-morfoin-4-yl) -phenyicarbamoyl] -2-isobutyl-amino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-isobutylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-isobutylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-isobutyl amine-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-isobutylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-Isobutylamino-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Isobutylamino-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-Isobutylamino-2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Isobutylamino-2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-isobutylamino- ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [3-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -2-isobutylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-isobutylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -2- isobutylamino-ethyl-5-cyclo-thiophene-2-carboxylic acid amide. { (S) -2- acetylamino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Acetylamino-2- [4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} - 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2-Acetylamino-2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Acetylamino-2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-Acetylamine-2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Acetylamino-2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-Acetylamino-2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Acetylamino-2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-Acetylamino-2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Acetylamino-2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-Acetylamino-2- [4- (3-oxo-morfoin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-acetylamino-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl- feni Icarbamoyl] -et? 'I} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- acetylamino-2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Acetylamino-2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} -amide of 5-cyclo-thiophene-2-carboxylic acid,. { (S) -2-Acetylamino-2- [3-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Acetyl-amino-2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-Acetylamino-2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-Acetylamino-2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-difluoro-acetylamino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amido 5-doro-thiophene-2-carboxylic acid,. { (R) -2- (2,2-difluoro-acetylamino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-difluoro-acetylamino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-difluoro-acetylamino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-difiuoro-acetylamino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-difluoro-acetylamino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-difluoro-acetylamino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-difluoro-acetylamino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - etl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-difluoroacetylamino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-difluoro-acetylamino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-difluoro-acetylamino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-difluoro-acetylamino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-D-Fluoro-acetylamino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-difluoro-acetylamino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-difluoro-acetylamino) -2- [3-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-difluoro-acetylamino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-difluoro-acetylamino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-difluoro-acetylamino) -2- [2-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -pheny [carbamoyl] -ethyl} -amide of 5-chloro-thiophene-2-carboxylic acid, [(S) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (2,2,3,3- 5-Chloro-thiophene-2-carboxylic acid tetrafluoro-propionylamino) -ethyl] - [(R) -2- [4- (3-oxo-morfoin-4-yl) -phenocarbamoyl] -2- (2 5-Chloro-thiophene-2-carboxylic acid, 2,3 (3,3,3-tetrafluoro-propionylamino) -ethyl] -amide, [(S) -2- [2-fluoro-4- (3-oxo-morpholin-4 -yl) -phenylcarbamoyl] -2- (2,2,3,3-tetrafluoro- -Chloro-thiophene-2-carboxylic acid propionylamino) -ethyl] - [(R) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -2- 5-Chloro-thiophene-2-carboxylic acid (2,2,3,3-tetrafluoro-propionylamine) -ethyl] -amide, [(S) -2- [3-fluoro-4- (3-oxo-morfoin) -4-i1) -phenylcarbamoyl] -2- (2,2,3,3-tetrafluoro-propionylamino) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid, [(R) -2- [3 - fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (2,2,3,3-tetrafluoro-propionylamino) -ethyl] -amide of 5-chloro-thiophene-2-acid carboxylic acid, [(S) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (2,2,3,3-tetrafluoro-propionylamino) -ethyl] - 5-chloro-thiophene-2-carboxylic acid amide, [(R) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (2.2 5-Chloro-thiophene-2-carboxylic acid, 3,3-tetrafluoro-propionylamino) -ethyl] -amide, [(S) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl ) -phenylcarbamoyl] -2- (2,2,3,3-tetrafluoro-propionyamino) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid, [ (R) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (2,2,3,3-tetrafluoro-propionylamino) -ethyl] -amide of acid 5-Chloro-thiophene-2-carboxylic acid, [(S) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -2- (2,2,3,3- 5-chloro-thiophene-2-carboxylic acid tetrafluoro-propionylamino) -ethyl] -amide, [(R) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl) ] -2- (2,2,3,3-tetrafluoro-propionylamino) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid, [(S) -2- [4- (3-oxo-morpholine 4-yl) -2-trifluoromethyl-phenylcarbamoyl] -2- (2,2,3,3-tetrafluoro-propionylamino) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid, [(R) - 2- [4- (3-Oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -2- (2,2,3,3-tetrafluoro-propionylamino) -ethyl] -amide of 5-chloro- thiophene-2-carboxylic acid, [(S) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (2,2,3,3-tetrafluoro- -cyclo-thiophene-2-carboxylic acid propionylamino) -ethyl] - [(R) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- 5-Chloro-thiophene-2-carboxylic acid (2,2,3,3-tetrafluoro-propionylamino) -ethyl] -amide, [(S) -2- [2-difluoromethoxy-4- (3-oxo-morpholine -4-yl) -phenylcarbamoyl] -2- (25-chloro-thiophene-2-carboxylic acid, 2,3,3-tetrafluoro-propionylamino) -ethyl] -amide, [(R) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4 5-Chloro-thiophene-2-carboxylic acid (2-yl) -phenylcarbamoyl] -2- (2,2,3,3-tetrafluoro-propionylamino) -ethyl] -amide. { (S) -2- (cyclopropanecarbonyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropanecarbonyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropanecarbonyl-amino) -2- [2-fIuoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropanecarbonyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropanecarbonyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropanecarbonyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclopropanecarbonyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropanecarbonyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclopropanecarbonyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropanecarbonylamino) -2- [2-difluoromethyl-4- (3-oxo-morfoin-4-yl) - phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropanecarbonyl-amino) -2- [4- (3-oxo-morfoin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropanecarbonyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclopropanecarbonyl-amino) -2- [4- (3-oxo-morfoin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclopropanecarbonyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclopropanecarbonyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropanecarbonyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclopropanecarbonyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclopropanecarbonyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-isobutyrylamino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-isobutyrylamino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-isobutyrylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -2-isobutyrylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- -chloro-thiophene-2-carboxylic acid isobutyrylamino-ethylj-amide,. { (R) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-isobutyrylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -2-isobutyrylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [3-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -2- isobutyrylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [2- d.fluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-isobutyrylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-isobutyrylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2-Isobutyrylamino-2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-isobutyrylamino-2- [4- (3-oxo-morfoin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2-isobutyrylamino-2- [4- (3-oxo-morfoin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2-isobutyrylamino-2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-isobutyrylamino-ethyl-5-chloro-thiophene-2-carboxylic acid amide. { (R) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-isobutylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-isobutyrylamino-ethyl} -amido 5-doro-thiophene-2-carboxylic acid,. { (R) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2-isobutyrylamino-ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-dimethyl-propionylamino) -2- [4- (3-oxo-morpholin-4-yl) - phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-Dimethyl-propioni-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-dimethyl-propionylamino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-dimethyl-propioniumamino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-Dimethyl-propionylamino) -2- [3-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-dimethyI-propionylamino) -2- [3-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide, [(S) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (2,2- 5-Chloro-thiophene-2-carboxylic acid, dimethyl-propionyl-amino) -etiyl], [(R) -2- [3-d-fluoro-methyl-4- (3-oxo-morfoin-4-yl)] phenylcarbamoyl] -2- (2,2-dimethyl-propioni-amino) -ethyl] -amide of 5-cyclo-thiophene-2-carboxylic acid, [(S) -2- [2-difluoromethyl-4- (3-oxo 5-Chloro-thiophene-2-carboxylic acid, [(R) -2- [2-difluoromethyl] -morpholin-4-yl) -phenocarbamoyl] -2- (2,2-dimethyl-propionylamino) -ethyl] -amide. 5-Chloro-thiophene-2-carboxylic acid (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (2,2-dimethyI-propionylamino) -ethyl] -amide. { (S) -2- (2,2-Dimethyl-propionylamino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-Dimethyl-propionylamino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (2,2-Dimethyl-propionylamino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (2,2-dimethyl-propionylamino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl- phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, [(S) -2- [3- difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (2,2- 5-Chloro-thiophene-2-carboxylic acid dimethyl-propionylamino) -ethyl] -amide, [(R) -2- [3- difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - 5 (Chloro-thiophene-2-carboxylic acid 2- (2,2-dimethyl-propionylamino) -ethyl] -amide, [(S) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4 5-Chloro-thiophene-2-carboxylic acid, [(R) -2- [2-difluoromethoxy-4- (-yl) -phenylcarbamoyl] -2- (2,2-dimethyl-propionylamino) -ethyl] -amide. 5-Chloro-thiophene-2-carboxylic acid 3-oxo-morpholin-4-yl) -phenyicarbamoyl] -2- (2,2-dimethyl-propionylamino) -ethyl] -amide. { (S) -2- (Cyclobutanecarbonyl-amino) -2- [4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutanecarbonyl-amino) -2- [4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -etl} -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- (Cyclobutanecarbonyl-amino) -2- [2-fIuoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutanecarbonyl-amino) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutanecarbonyl-amino) -2- [3-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutanecarbonyl-amino) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutanecarbonyl-amino) -2- [3-difluoromethyl] -4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutanecarbonyl-amino) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclobutanecarbonyl-amino) -2- [2-difluoromethyl-4- (3-oxo- morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (cyclobutanecarbonyl-amino) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (cyclobutanecarbonyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutanecarbonyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutanecarbonyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutanecarbonyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutanecarbonyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutanecarbonyl-amino) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (Cyclobutanecarbonyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (Cyclobutanecarbonyl-amino) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -ethyl} -amide, ethyl ester of acid. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1 - [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid ethyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid ethyl ester. { (S) -2 - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid ethyl ester. { (R) -2 - [(5-chloro-thiophene-2-carbonyl) - amino] -1- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid ethyl ester. { (S) -2 - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} -carbamic acid ethyl ester. { (R) -2 - [(5- chloro-thiophene-2-carbonyl) -amino] -1- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylacarbamoyl] -ethyl} -carbamic, ethyl ester of acid. { (S) -2 - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} - Carbamic acid ethyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -etiI} -carbamic acid ethyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid ethyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid ethyl ester. { (S) -2 - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} -carbamic acid ethyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -etiI} -carbamic acid ethyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} -carbamic acid ethyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} -carbamic acid ethyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid ethyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid ethyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid ethyl ester . { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic, 2,2-difluoroethylic acid ester. { (S) -2 - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic, 2,2-difluoroethylic acid ester. { (R) -2 - [(5- chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -ethyl} -carbamic, 2,2-difluoroethyl acid ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-fIuoro-4- (3-oxo-morpholip-4-yl) -phenylcarbamoyl] -ethyl} -carbamic, 2,2-difluoroethyl acid ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic, 2,2-difluoroethyl acid ester. { (S) -2 - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [3-fIuoro-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} -carbamic, 2,2-difluoroethyl acid ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic, 2,2-difluoroethyl acid ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic, 2,2-difluoroethyl acid ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic, 2,2-difiuoroethyl acid ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic, 2,2-difluoroethylic acid ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic, 2,2-difluoroethyl acid ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} -carbamic, 2,2-difluoroethyl acid ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl- phenylcarbamoyl] -ethyl} -carbamic, 2,2-difluoroethyl acid ester. { (S) -2 - [(5- chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} -carbamic, 2,2-difluoroethyl acid ester. { (R) -2 - [(5- chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} -carbamic, 2,2-difluoroethyl acid ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic, 2,2-difluoroethyl acid ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic, 2,2-difluoroethyl acid ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1 - [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic, 2,2-difluoroethyl acid ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} -carbamic acid isopropyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid isopropyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid isopropyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid isopropyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid isopropyl ester. { (S) -2 - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid isopropyl ester. { (R) -2 - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid isopropyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3- difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid isopropyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} -carbamic acid isopropyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic, isopropyl ester of acid. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid isopropyl ester. { (S) -2 - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} -carbamic acid isopropyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} -carbamic acid isopropyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} -carbamic acid isopropyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} -carbamic acid isopropyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid isopropyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid isopropyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -eti} -carbamic acid isopropyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid methyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etl} -carbamic, acid methyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamate, acid methyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid methyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -etiI} -carbamic acid methyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid methyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1 - [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} -carbamic acid methyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid methyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid methyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid methyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid methyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} -carbamic acid methyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} -carbamic acid methyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} -carbamic acid methyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl] -phenylcarbamoyl] -ethyl} -carbamic acid methyl ester. { (S) -2 - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [3- difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid methyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid methyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid methyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-d-fluoro-methoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic, acid 2- hydroxyethyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -phenyicarbamoyl] -etiI} -carbamic acid 2-hydroxyethyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1 - [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid 2-hydroxyethyl ester. { (S) -2 - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid 2-hydroxyethyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid 2-hydroxyethyl ester. { (S) -2 - [(5-chloro-thiophene-2-carbonyl) -amino3-1- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic, 2-hydroxyethyl ester of (R) -2 - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [3-fluoro-4- (3-oxo-morpholin-4-yl) ester ) -phenylcarbamoyl] -ethyl} -carbamic acid 2-hydroxyethyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid 2-hydroxyethyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid 2-hydroxyethyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-difluoromethyl-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid 2-hydroxyethyl ester. { (R) -2 - [(5-chloro- thiophene-2-carbon I) -amino] -1- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid 2-hydroxyethyl ester. { (S) -2 - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -etiI} -carbamic, 2-hydroxyethyl ester of acid. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} -carbamic acid 2-hydroxyethyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -etiI} -carbamic acid 2-hydroxyethyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} -carbamic acid 2-hydroxyethyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} -carbamic acid 2-hydroxyethyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid 2-hydroxyethyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid 2-hydroxyethyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl } -carbamic, acid cyclobutyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic, acid cyclobutyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} -carbamic, acid cyclobutyl ester. { (S) -2 - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -etiI} -carbamic, acid cyclobutyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-fluoro-4- (3-oxo-morfoyl-4-yl) - phenylcarbamoyl] -ethyl} -carbamic, acid cyclobutyl ester. { (S) -2 - [(5-Cyorothiophene-2-carbonyl) -amino] -1- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethi} -carbamic, acid cyclobutyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic, acid cyclobutyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic, acid cyclobutyl ester. { (R) -2 - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} -carbamic, acid cyclobutyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic, acid cyclobutyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid cyclobutyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morfoin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} -carbamic, acid cyclobutyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} -carbamic, acid cyclobutyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] - ethyl} -carbamic, acid cyclobutyl ester. { (R) -2 - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -etiI} -carbamic, acid cyclobutyl ester. { (S) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic, acid cyclobutyl ester. { (R) -2 - [(5-Chloro-thiophene-2-carbonyl) -amino] -1- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -ethyl} -carbamic, acid cyclobutyl ester. { (S) -2 - [(5-chloro- thiophene-2-carbonyl) -amino] -1- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic acid cyclobutyl ester. { (R) -2 - [(5-Cyorothiophene-2-carbonyl) -amino] -1- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbamic, 5-chloro-thiophene-2-carboxylic acid. { (S) -2- (3-Cyclobutyl-ureido) -2- [4- (3-oxo-morfoin-4-yl) -phenylacarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (3-Cyclobutyl-ureido) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (3-Cyclobutyl-ureido) -2- [2-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (3-Cyclobutyl-ureido) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -etiI} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- (3-Cyclobutyl-ureido) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (3-Cyclobutyl) ureido) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (3-Cyclobutyl-ureido) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (3-Cyclobutyl-ureido) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (3-Cyclobutyl-ureido) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (3-Cyclobutyl-ureido) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (3-Cyclobutyl-ureido) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (3-Cyclobutyl-ureido) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide, . { (S) -2- (3-Cyclobutyl-ureido) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (3-Cyclobutyl-ureido) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (3-Cyclobutyl-ureido) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amido 5-doro-thiophene-2-carboxylic acid,. { (R) -2- (3-Cyclobutyl-ureido) -2- [3-difluoromethoxy-4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- (3-Cyclobutyl-ureido) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (3-Cyclobutyl-ureido) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (3-isopropyl-ureido) -2- [4- (3-oxo-morfoin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (3-isopropyl-ureido) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, [(S) -2- [2-fIuoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (3-isopropyl- 5-chloro-thiophene-2-carboxylic acid ureido) -ethyl], [(R) -2- [2-fluoro-4- (3-oxo-morfoin-4-yl) -phenocarbamoyl] -2- 5-Chloro-thiophene-2-carboxylic acid (3-isopropyl-ureido) -ethyl] -amide, [(S) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) - 5-Chloro-thiophene-2-carboxylic acid, phenylcarbamoyl] -2- [3-isopropyl-ureido) -etl] -amide, [(R) -2- [3-fluoro-4- (3-oxo 5-cyclo-thiophene-2-carboxylic acid, [(S) -2- [3-difluoromethyl-4-difluoromethyl] -3-difluoromethyl-4-difluoromethyl-3-difluoromethyl-3-difluoromethyl-3-difluoromethyl-3-difluoromethyl-3-difluoromethyl-5-cyclo-thiophene-2-carboxylic acid (3-difluoromethyl-4-isopropyI-ureido) -ethyl] -amide. - (3-Oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (3-isopropyl-ureido) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid, [(R) -2- [ 3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (3-isopropyl-ureido) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid, [(S ) -2- [2-difluoromethyl-4- (3-oxo- -Chloro-thiophene-2-carboxylic acid morpholin-4-yl) -phenylcarbamoyl] -2- (3-isopropyl-ureido) -ethyl] -amide, [(R) -2- [2-difluoromethyl-4-] 5-Chloro-thiophene-2-carboxylic acid (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (3-isopropyl-ureido) -etl] -amide. { (S) -2- (3-isopropyl-ureido) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (3-isopropyl-ureido) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -etl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (3-isopropyl-ureido) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -eti} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (3-isopropyl-ureido) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, [(S) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (3-isopropyl- 5-chloro-thiophene-2-carboxylic acid ureido) -ethyl], [(R) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- 5-Chloro-thiophene-2-carboxylic acid (3-isopropyl-ureido) -ethyl] -amide, [(S) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) - 5-Chloro-thiophene-2-carboxylic acid phenylcarbamoyl] -2- (3-isopropyl-ureido) -ethyl] -amide, [(R) -2- [2-difluoromethoxy-4- (3-oxo-morpholine- 5-Chloro-thiophene-2-carboxylic acid 4-yl) -phenylcarbamoyl] -2- (3-isopropyl-ureido) -ethyl] -amide. { (S) -2- (3-ethyl-ureido) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (3-Ethyl-ureido) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (3-ethyl-ureido) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (3-Ethyl-ureido) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (3-ethyl-ureido) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) - phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (3-Ethylureido) -2- [3-fIuoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -5-Chloro-thiophene-2-carboxylic acid amide, [(S) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -2- (3-ethyl- 5-chloro-thiophene-2-carboxylic acid ureido) -ethyl] - [(R) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- 5-Chloro-thiophene-2-carboxylic acid (3-ethyl-ureido) -ethyl] -amide, [(S) -2- [2-difluoromethyl-4- (3-oxo-morfo [in-4-yl] ) -phenocarbamoyl] -2- (3-ethyl-uredo) -etl] -amide of 5-cyclo-thiophene-2-carboxylic acid, [(R) -2- [2-difluoromethyl-4- ( 3-Oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (3-ethyl-ureido) -etiI] -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- (3-Ethyl-ureido) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (3-Ethyl-ureido) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (3-ethyl-ureido) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- (3-Ethyl-ureido) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} -5-Chloro-thiophene-2-carboxylic acid amide, [(S) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (3-ethyl- 5-chloro-thiophene-2-carboxylic acid ureido) -ethyl], [(R) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- 5-Chloro-thiophene-2-carboxylic acid (3-ethyl-ureido) -ethyl] -amide, [(S) -2- [2-difluoromethoxy-4- (3-oxo-morfoin-4-yl) - Phenylcarbamoyl] -2- (3-ethyl-ureido) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid, [(R) -2- [2-difluoromethoxy-4- (3-oxo-morpholine- 4-yl) -phenylcarbamoyl] -2- (3-ethyl-ureido) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid,. { (S) -2- (3-Methyl-ureido) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-acid amide thiophene-2-carboxylic,. { (R) -2- (3-Methyl-ureido) -2- [4- (3-oxo-morpholin-4-yl) -phenylacarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide, [(S) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (3-methyl- ureido) -etiI] - 5-chloro-thiophene-2-carboxylic acid amide, [(R) -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (3-methyl-ureido) -ethyl] -amide of 5-chloro- thiophene-2-carboxylic acid, [(S) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenecarbamoyl] -2- (3-methyl-ureido) -ethyl] -amide 5-Chloro-thiophene-2-carboxylic acid, [(R) -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -2- (3-methyl-ureido) - ethyl] -amido-5-chloro-thiophene-2-carboxylic acid, [(S) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (3- 5-Chloro-thiophene-2-carboxylic acid methyl-ureido) -ethyl] -amide, [(R) -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - 5-Cyclo-thiophene-2-carboxylic acid 2- (3-methyl-ureido) -ethyl] -amide, [(S) -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl)] ) -phenylcarbamoyl] -2- (3-methyl-ureido) -ethyl] -amide of 5-chloro-thiophene-2-carboxylic acid, [(R) -2- [2-difluoromethyl-4- (3-oxo- 5-chloro-thiophene-2-carboxylic acid morpholin-4-yl) -phenylcarbamoyl] -2- (3-methyl-ureido) -ethyl] -amide. { (S) -2- (3-Methyl-ureido) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (3-Methyl-uredo) -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- (3-methyI-ureido) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- (3-methyI-ureido) -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} -5-Chloro-thiophene-2-carboxylic acid amide, [(S) -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (3-methyl- 5-chloro-thiophene-2-carboxylic acid ureido) -ethyl], [(R) -2- [3- difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (3-methyl-ureido) -ethyl] -5-chloro-thiophene-2-carboxylic acid amide, [(S) - 5-Chloro-thiophene-2-carboxylic acid [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (3-methyl-ureido) -ethyl] -amide; [(R) -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -2- (3-methyl-ureido) -ethyl] -amide of 5-chloro-thiophene -2- carboxylic,. { (S) -2- [3- (2,2-d.fluoro-ethyl) -ureido] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [3- (2,2-difluoro-ethyl) -ureido] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [3- (2,2-difluoro-ethyl) -ureido] -2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amido of 5-doro-thiophene-2-carboxylic acid,. { (R) -2- [3- (2,2-difluoro-ethyl) -ureido] -2- [2-fIuoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [3- (2,2-d.fluoro-ethyl) -ureido] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [3- (2,2-difluoro-etiI) -ureido] -2- [3-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [3- (2,2-difluoro-ethyl) -ureido] -2- [3-d.fluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] - ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [3- (2,2-difluoro-ethyl) -ureido] -2- [3-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [3- (2,2-difluoro-ethyl) -ureido] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [3- (2,2-difluoro-ethyl) -ureido] -2- [2-difluoromethyl-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl } 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [3- (2,2-difluoro-ethyl) -ureido] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl- phenylcarbamoyl] -etiI} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [3- (2,2-d.fluoro-ethyl) -ureido] -2- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [3- (2,2-difluoro-ethyl) -ureido] -2- [4- (3-oxo-morpholin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (R) -2- [3- (2,2-difluoro-ethyl) -ureido] -2- [4- (3-oxo-morfoin-4-yl) -2-trifluoromethyl-phenylcarbamoyl] -eti I} 5-cyclo-thiophene-2-carboxylic acid amide,. { (S) -2- [3- (2,2-difluoro-ethyl) -ureido] -2- [3-d.fluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenocarbamoyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { (R) -2- [3- (2,2-difluoro-ethyl) -ureido] -2- [3-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { (S) -2- [3- (2,2-difluoro-ethyl) -ureido] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -Oracid 5-chloro-thiophene-2-carboxylic acid. { (R) -2- [3- (2,2-difluoro-ethyl) -uredo] -2- [2-difluoromethoxy-4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -amide.

Pharmacological tests The ability of the compounds of formula I to inhibit factor Xa or factor Vlla or other enzymes such as thrombin, plasmin, or trypsin can be assessed by determining the compound of formula I which inhibits 50% enzymatic activity , that is, the IC50 value, which was related to the inhibition constant Ki. Purified enzymes were used in the chromogenic assays. The inhibitory concentration causing the 50% decrease in the rate of substrate hydrolysis was determined by linear regression after plotting the relative rates of hydrolysis (compared to the uninhibited control) versus the logarithm of the concentration of the compound of formula I. To calculate the inhibition constant Ki, the IC50 value was corrected based on competition with the substrate using the formula. Ki = IC50 /. { 1 + (substrate concentration / Km)} where the Km is the constant of Michaelis-Menten (Chen and Prusoff, Biochem Pharmacol 22 (1973) 3099-3108; I. H. Segal, Enzyme Kinetics, 1975, John Wiley & Sons, New York, 100-125; which are incorporated herein by reference). a) Factor Xa Analysis In the assay to determine the inhibition of factor Xa activity, the TBS-PEG buffer [50 mM Tris-HCl, pH 7.8, 200 mM NaCl, 0.05% PEG-8000 ( p / v), NaN3 0.02% (w / v)]. Cl50 was determined by combining in the appropriate wells of a Costar semi-area microtiter plate: 25 μl of human factor Xa (Enzyme Research Laboratories, Inc., South Bend, Indiana) in TBS-PEG; 40 μl of 10% DMSO (v / v) in TBS-PEG (control uninhibited) or various concentrations of the compound to be tested diluted in 10% DMSO (v / v) in TBS-PEG; and the substrate S-2765 (N (a) -benzyloxycarbonyl-D-Arg-Gly-L-Arg-p-nitroanilide; Kabi Pharmacia, Inc.; Franklin, Ohio) in TBS-PEG. The analysis was performed preincubando the compound of the formula I plus the enzyme for 10 min. The analysis was then started by adding substrate to obtain a final volume of 100 μl. The initial velocity of the chromogenic substrate hydrolysis was measured by the change in absorbance at 405 nm by a plate kinetic reader from Bio-tek Instruments (Ceres UV900HDY) at 25 ° C during the linear part of the course of the reaction (typically 1.5 min after adding the substrate). The concentration of the enzyme was 0.5 nM and the substrate concentration was 140 μM. b) Factor Vlla analysis The inhibitory activity against factor Vlla / tissue factor activity was determined using a chromogenic assay as previously described (JA Ostrem et al., Biochemistry 37 (1998) 1053-1059 which was incorporated in the present memory by reference). Kinetic analyzes were performed at 25 ° C on a semi-section microtiter plate (Costar Corp., Cambridge, Massachusetts) using a kinetic plate reader (Molecular Devices Spectramax 250). A typical assay consists of combining 25 μl of human factor Vlla and TF (final concentration 5 nM and 10 nM, respectively) with 40 μl of inhibitory dilutions in 10% DMSO / TBS-PEG buffer (50 mM Tris, 15 mM NaCl, CaCl2 5 mM, PEG 8000 0.05%, pH 8.15). After a 15 minute preincubation period, the analysis was started by adding 35 μl of the chromogenic substrate S-2288 (D-lle-Pro-Arg-p-nitroanilide, Pharmacia Hepar Inc., final concentration 500 μM). The results (inhibition constants Ki (FXa) for the inhibition of factor Xa) are shown in table 1.

Table 1: 275 2) fluorine, chlorine, bromine, 3) wherein the alkyl is unsubstituted or is mono-, di- or trisubstituted independently of one another by R 13, 4) - (C 1 -C 4 -perfluoroalkyl, 5) phenyl, wherein the phenyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, 6) - (C0-C4) -alkylene-O-R19, wherein R19 is a) hydrogen atom b) - (C, -C4) -alkyl, wherein the alkyl is unsubstituted or is mono-, di- or trisubstituted independently of one another by R 13, or c) phenyl, wherein the phenyl is unsubstituted or is mono-, di- or trisubstituted independently of one another by R 13, d) - CF3, oe) -CHF2, 7) -NO2, 8) -CN, 9) -SOs-R, where s is 1 or 2, ) -SOt-N (R11) -R12, where t is 1 or 2, 11) - (C0-C4) -alkylene-C (O) -R11, 12) - (C0-C4) -alkylene-C (O) -O-R 1, 13) - (C0-C4) -alkylene-C (O) -N (R11) -R12. 14) - (C0-C4) -alene-N (R11) -R12, 282 R2 is a direct bond or - (Oj-C ^ -alkylene, or 1 2 R -NR -V form a cyclic group of the group 2,3 dihydroindoi or indole, wherein said cyclic group is unsubstituted or mono-, di- - or trisubstituted independently from each other by R 14, V is a cyclic moiety of the phenyl or pyridyl group, wherein said cyclic moiety is unsubstituted or is mono-, di- or trisubstituted independently of each other by R 14, R 14 is fluorine, - (C1-C3) -perfluoroaiquiio, -C (O) -O-R18, -CF3 u = O, R18 is hydrogen atom - (C, -C4) -a! Quilo, G is a direct bond, M is a heterocyclyl of the group that can be derived from 3,3-dioxo- (1,3,4) oxathiazine, midazole, morpholine, pyrazine or pyridine, wherein said heterocyclyl is unsubstituted or is mono-, di- or tri-substituted independently of others by R 14, as long as M contains or is substituted by at least one oxo- moiety, R 3 'R 4 or R 6 are independently of each other identical or different and are hydrogen atom, fluorine, - NR11-SO2-R12, - (C0-C4) -alkylene-N (R1) -C (O) -R12, - (C0-C4) -alkylene-N (R11) -R12 or - (Co-C4) -Nalkylene-N (R11) -C (O) -O-R12, R5 is fluorine, -N (R30) -SO2-R30, -N (R11) -C (O) -R30, -N (R11) - R 12 or -N (R 11) -C (O) -O-R 30, in which R 30 is hydrogen atom, - (C C 4) -alkyl or - (C C 3) -perfluoroalkyl, R 11 and R 12, are independently of each other , identical or different and are

Claims (8)

1. - A compound of the formula R ° is 1) a heterocyclyl extracted from the acridinyl group, azabenzimidoazolyl, azaspirodecanyl, azepinyl, azetidinyl, aziridinyl, benzimidazolyl, 1,3-benzodioxolyl, benzofuranyl, benzothienyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 4,5-dihydrooxa-zoliniyl, dioxazolyl, dioxazinyl, 1,3-dioxoyl anil, 1,3-dioxoleyl, 6H-1,5,2-dithiazinyl, dihydrofuro [2,3-b] -tetrahydrofuranyl, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, indanyl, 1 H-indazolyl, indolinyl, indolizinyl, indolyl, 3H-indyl, isobenzofuranyl, isochromanyl, isoindazolium, isoindolinyl, isoindolyl, isoquinolinyl , isothiazolyl, isothiazolidinyl, isothiazolinyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, 2-isoxazolinyl, cetopiperazinyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadi azolyl, 1,2,3-oxadiazoliol, 1,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,4-oxadiazolyl, 1,2-oxa-triplanyl, 1,2-oxathiolanyl, 1, 4-oxazepanyl, 1,4-oxazepinyl, 1,2-oxazinyl, 1,3-oxazinyl, 1,4-oxazinyl, oxazolidinyl, oxazolinyl, oxazolyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phenylpyridyl, fíaiazinilo, piperazinyl, piperidinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridoimidazolyl, piridooxazolilo, pyridopyrimidinyl, piridotiazolilo, pyridothienyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinolium, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, 1, 4,5,6-tetrahydropyridazinium, tetrahydropyranyl, tetrahydropyridinyl, tetrahydrothiophenyl, tetrazinyl, tetrazolyl, 6H-1, 2,5-thiadiazinyl, 1,2-thiadiazolyl, 1,4-thiadiazolyl, 1, 2,5-thiadiazolyl, 1,4-thiadiazoyl, thiantrenyl, 1,2-thiazinyl, 1,3-thiazinyl, 1,4-thiazinyl, 1,3-thiazolinyl, thiazolyl, thiazolidinyl, thiazolinyl, thienyl, thietanyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thietanyl, thiomorpholinyl, thiof enolyl, thiophenyl, thiopyranyl, 1,2,3-triazinyl, 1,4-triazinyl, 1,3,5-triazinyl, 1,2,3-triazolyl, 1,4-triazolyl, 1,2, 5-triazolyl, 1,4-triazoyl and xanthenyl, wherein said heterocyclyl is unsubstituted or is mono-, di- or trisubstituted independently of one another, by R8 or 2) an aryl of 6 to 14 members selected from the group phenyl, naphthyl, biphenylyl, 2-biphenylyl, 3-biphenylyl, 4-biphenylyl, anthryl or fluorenyl, in which aryl is mono-di- or trisubstituted independently of each other by R8, R8 is a halogen, carbamimidoyl, -NO2, - CN, -C (O) -NH2, -OH, -NH2, -O-CF3, -O- (C? -C8) -alkyl, wherein the alkyl is unsubstituted or is mono-, di- or trisubstituted independently of each other by a halogen, NH2, -OH or a methoxy, or - (C? -Cs) -alkyl residue, in which the alkyl is unsubstituted or is mono-, di- or tri-substituted independently of one another by a halogen, NH2, -OH or a methoxy moiety, or -SO2-CH3 or -SO2-CF3, provided that R8 is at least one halogen, -C (O ) -NH2 or a radical -O- (C? -C8) -alkyl, Q is a direct bond, - (Co-C2) -alkylene-C (O) - (Co-C2) -alkyl, - (C? -C6) -alkylene, - (C0-C3) -alkylene-S (O) 2- or - (C0-C2) -a! Kylene-NR10-C (O) -O- (Co-C2) -alkylene, wherein R10 is as defined below, and wherein the alkylene moieties are unsubstituted or are mono-, di- or trisubstituted independently of one another by a halogen, -NH2, -OH or - (C3-C6) - cycloalkylene, in which the cycloalkylene is unsubstituted or is mono-, di- or tri-substituted independently of one another by a halogen, -NH2 or -OH; R1 is a hydrogen atom, - (CrC) -alkyl, in which the alkyl is unsubstituted or substituted one to three times by R13; - (d-C3) -alkylene-C (O) -NH-R °, - (C? -C3) -alkylene-C (O) -O-R10, an aryl with 6 to 14 members selected from the phenyl group, naphthyl, biphenylyl, 2-biphenylyl, 3-biphenylyl, 4-biphenylyl, anthryl or fluororenyl, in which the aryl is mono-, di- or tri-substituted independently of one another by R 8, - (Co-C) -alkylene-heterocyclyl , wherein the heterocyclyl is as defined above and is unsubstituted or is mono-, di- or trisubstituted independently of one another by R 14, - (C? -C3) -perfluoroalkyl, - (C? -C3) -alkylene- S (O) - (C? -C4) -alkyl, - (C? -C3) -alkylene-S (O) 2- (C? -C3) -alkyl, - (C? -C3) -alkylene -S (O) 2-N (R4 ') - R5', - (C? -C3) -alkylene-O- (C? -C4) -alkyl or - (Co-C3) -alkylene- (C3-C8) -cyc! alkali!, R4 'and R5 are, independently of each other, identical or different and are a hydrogen atom or - (C? -C) -alkYo, R2 is a direct bond or - (C? -C4) -alkylene or R1-N-R2-V forms a cyclic group of 4 to 10 members selected from the group azepine, azetidine, dioxazole, dioxazine, 1-2. diazepine, 1,3-diazepine, 1,4-diazepine, 2,3-dihydroindo, imidazole, imidazoline, imidazolidine, indole, isothiazole, isothiazolidine, isothiazoline, isoxazoline, isoxazolidine, 2-isoxazoline, cetopiperazine, morpholine, 1, 4- oxacepan, 1,2-oxa-tiepan, 1,2-oxathiolane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazole, piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, thiazolidine, thiazoline or thiomorpholine, wherein said cyclic group is unsubstituted or is mono- or di-substituted independently of each other by R 14, V is 1) a heterocyclyl as defined for R °, and n that said heyerocyclyl is not substituted or is mono-, di- or trisubstituted independently of each other by R 14 or 2) an ary as defined for R °, wherein the aryl is independently mono-, di- or trisubstituted of others by R14, R14 is a halogen, -OH, = O, - (C? -C8) -aIlkyl, - (C? -C) -aIkoxy, -NO2, - (Co-d) -alkyl-C ( O) -O-R18, -CN, - (C0-C4) -alkyl-N (R18) -R21, - (C0-C4) -alkyl-O-R18, - (C0-dj-alkylene-heterocyclyl, in that the heterocyclyl is as defined above and that the heterocyclyl is unsubstituted or is mono-, di- or trisubstituted independently from one another by R13, - (Co-C8) -alkyl-SO2- (C -C4) -alkyl, -S-R18, - (Co-C8) -alkyl-SO2- (C? -C3) -perf ! uoroalkyl, - (Co-C8) -a! quil-S? 2-N (R18) -R21, -CF3, -C (O) -N (R18) -R21, -NR18-C (O) -NH - (C? -C8) -a! Quilo, - (C0-C3) -aIquiI- (d- C3) -perfluoroalkyl, or -NR18-C (O) -N - [(d-C8) -alkyl] 2 , in which R18 and R21 are independently of each other, hydrogen atom, - (C0-C6) -alkyl-N (R22) -R23, - (C0-C6) -alkyl-O-R22, - (C0-C6) ) -alkyl-heterocyclyl, in which the heterocyclyl is as defined above and in which the heterocyclyl is unsubstituted or is mono-, di- or trisubstituted independently of one another by R 13, - (C0-C6) -alkyl- N (R22) -C (O) -N (R22) -R23, - (C-C6) -alkyl-C (O) -O-R22, - (C? -C6) -aIlkyl, - (C0-) C6) -alkyl-C (O) -N (R22) -R23, - (C0-C6) -alkyl-SO2-R22 or - (d-C3) -perfluoroalkyl, in which R22 and R23 are independently of each other atom of hydrogen, - (C? -C3) -perfluoroalkyl, - (C3-C6) -cycloalkyl- or (C? -C6) -alkyl, 10 10 G is a direct bond, - (CH2) m-NR-SO2 -NR - (CH2) n -, - (CH2) m-CH (OH) - (CH2) n-, - (CH2) m-, - (CH2) m-O- (CH2) n-? - (CH2) m-C (O) -NR1 ° "(CH2) n-, - (CH2) -SO2- (CH2) n-, - (CH2) m NR10-C (O) -NR1 ° - (CH2) n- > - (CH ^ -NR ^ -C ^ MCH ^ -, - (CH2) m- C (O) - (CH2) p-, - (CH2) -S- (CH2) n-, - (CH2) m-SO2-NR1 ° - (CH2) n-, - (CH2) m-NR1 ° - SO2- (CH2) n-, - (CH2) m-NR1 ° -, - (CH2) mOC (O) -NR1 ° - (CH2) n- or - (CH2) m-NR1 ° -C (O) -O- (CH2) n-, n and m are independently of each other identical or different and are the integers zero, 1, 2, 3, 4, 5 or 6, M is 1) an aryl of 6 to 14 members selected from the phenyl group, naphthyl , biphenylyl, 2-biphenylyl, 3-biphenylyl, 4-biphenylyl, anthryl or fluorenyl, in which the aryl is unsubstituted or is mono-, di- or irubstituted independently of each other by R 14, or 2) a monocyclic or bicyclic heterocyclyl of 3 to 15 members selected from the group acridinyl, azaindole (1 H-pyrrolopyridinyl), azabenzimidoazolyl, azaspirodecanyl, azepinyl azetidinyl, aziridinyl, azirinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxathiolyl, benzthiazolyl, benzthiazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 1,4 diazepanyl, 1, 2-diazepinyl, 1,3-diazepinyl, 1,4-diazepinyl, diaziridinyl, diazirinyl, dihydroimidazolonyl, 4,5-dihydrooxazolinyl, dioxazolyl, dioxazinyl, dioxolyl, 1,3-dioxolanyl, 1,3-dioxoleyl, 3,3- dioxo- (1,3,4) oxathiazine, 6H-1, 5,2-dithiazinyl, dihydrofuro [2,3-b] -tetrahydrofuranyl, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolinyl, indolizinyl, indolyl, 3H-indoyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl , isoindolyl, isoquinolinyl (benzimidazolyl), isothiazolyl, isothiazolidinyl, isothiazolinyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, 2-isoxazolinyl, cetomorpholinyl, cetopiperazinyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,3-oxadiazolyl, 1, 2,4- oxadiazolyl, 1,2,5-oxadiazolyl, 1,4-oxadiazolyl, [1,4] oxathiazine 3,3-dioxidyl, 1,2-oxa-diappanil, 1,2-oxathiolanyl, 1,4- oxazepanyl, 1,4-oxazepinyl, 1,2-oxazinyl, 1,3-oxazinyl, 1,4-oxazinyl, oxazolidinyl, oxazolidinonyl, oxazolinyl, oxazolonyl, oxazolyl, oxetanyl, oxiranyl, oxocanyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxythiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperazin-2-on-yl, piperidinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazin-2-on-yl, pirazolidiniio, pyrazolinyl, pyrazolyl, pyridazinyl, piridinon-yl, piridooxazolilo, pyridoimidazolyl, piridotiazolilo, pyridyl, pyrimidinyl, pyrimidine-2,4-dion-yl, pyrrolidinyl, pyrrolidinonyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydropyridinyl, tetrahydrothiophenyl, tetrazinyl, tetrazolyl, 6H-1, 2,5-thiadiazinyl, 1,2,3-tiadiazoIilo, 1, 2,4-thiadiazolyl, 1, 2,5-thiadiazolyl, 1, 3,4-thiadiazolyl, thianthrenyl, 1, 2-thiazinyl, 1,3-tiaziniIo, 1, 4-thiazinyl, 1, 3-thiazolyl, thiazolyl, thiazolidinyl, thiazolinyl, thienyl, thietanyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thietanyl, thiomorpholinyl, thiomorpholine 1,1 -dioxidil, thiophenolyl, thio phenyl, thiopyranyl, 1, 2,3-triazinyl, 1,2,4-triazinyl, 1, 3,5-triazinyl, 1, 2,3-triazoyl, 1, 2,3-triazolyl, 1, 2,4- triazoyl, 1,2,5-triazolyl, 1,4-triazolinium and xanthenyl, in which the heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14, provided that M contains or is replace with at least one oxo moiety, R3, R4 or R6 are independent of each other and are identical or different and are 1) hydrogen atom 2) halogen 3) - (Oj-C ^ -alkyl, wherein the alkyl is unsubstituted or is mono-, di- or trisubstituted independently from each other by R 13, 4) - (C ^ CgJ-perfluoroalkyl, 5) phenyl, wherein the phenyl is EsIA sustiíuido or mono-, di- or independently írisusíituido one another by R13, 6) - (C0-C4) -alk-O-R19 ene in R19 is a) hydrogen atom b) - (dC) -alkyl, in which the alkyl is unsubstituted or is mono-, di- or trisubstituted independently of one another by R 13, or c) phenyl, in which the phenyl is unsubstituted or mono- , di- or trisubstituted independently from each other by R 13, d) -CF 3, oe) -CHF 2 7) -NO 2, 8) -CN, 11 9) -SOs-R, where s is 1 or 2, 10) -SOfN (R11) -R12. where t is 1 or 2, 11) - (C0-C4) -alkylene-C (O) -R11, 12) - (C0-C4) -alkyliene-C (O) -O-R11, 13) - (C0-C4) -alkylene-C (O) -N (R11) -R12, 14) - (C0-C4) -alkylene-N (R11) -R12, 11 12 15) -NR -SO2- R, 16) -S-R1 °, 17) - (C0-C2) alkylene-C (O) -O- (C2-C4) -alkylene-OC (O) - (C1-C4) -a -type, 18) -C (O) -OC (R15, R16) -0-C (O) -R17, igj ^ Co-C ^ alkylene-CIOJ-O-ICO-C ^ -alkylene-O-CIOJ-O - ^ - C8J -I rent, 20) -C (O) -O-C (R15, R16) -OC (O) -O-R17, 21) - (C1-C4) -alkylene- (C6-C14) -aryl, in which the aryl is mono-, di- or trisustifuido independieníemeníe each hear you by R13, 22) - (C1-C4) -alqu¡leno- (C4-C15) -heterocicl¡lo, wherein the heterocyclyl is sustiíuido or mono-, di - or trisusiiuido independent of others by R13, 23) - (C ^ C ^ -alquileno-ÍC8-C8J-cycloalkyl, in which the cycloalkyl is not substituted or is mono-, di- or iris-independent of some others by R13, 24) - (C ^ Oj--alquiieno-hel, wherein hel not EsIA susfituido or mono-, di- or trisusfiíuido independieníemeníe each hear you by R13, 25) - (C0-C4) O-CH2--alquiIeno - (C1-C3) -perfluoroa [qui [ene-CH2-O- (C0-C4) -alkyl) 26) -SOw-N (R) -R, where w is 1 or 2, 27) - (C0-C4) -alkylene-N (R11) -C (O) -R12, 28) - (C0-C4) -alkylene-N (R11) -C (O) -O-R12, 29) a resi from the following list if two resorbs -OR to adjacent atoms are linked together they can form together with the atoms with which they are linked a ring of 5 or 6 members, which is not susíiuuido or susííuido one, two, three or four times by R13, R5 is 1) halogen 2) phenyl, in which the phenyl is unsubstituted or is mono-, di- or di-irosubstituted independently of one another by R 13, 3) - (C0-C4) -alkylene-O-R29, in which R29 is phenyl , in which the phenyl is not subsituted or is mono-, di- or trisustiluido independently of each other by R13, 4) -NO2, 5) -CN, 11 6) -SOs-R, where s is 1 or 2, 7) -SOt-N (R) -R. where t is 1 or 2, 8) -C (O) -R11, 9) -C (O) -O-R11, 10) -C (O) -N (R11) -R12. 11 12 11) -N (R) -R, 12) -N (R30) -SO2-R30, in which R30 is a hydrogen atom, - (C? -C4) -alkyl, - (dd) -alkyl-OH , - (C? -C) -alkyl-O- (C? -C4) -a! Quilo or - (C? -C3) -perfluoroalkyl, 13) -C (O) -O- (C2-C4) - alkylene-OC (O) - (C 1 -C 4) -alkyl, 14) -C (O) -O- (C 2 -C 4) -acykylene-OC (O) - (C 1 -C 6) -alkyl, 15) -C (O) -OC (R15, R16) -OC (O) -R17, 16) -C (O) -OC (R15, R16) -OC (O) -O-R17, 17) - (C ^ C ^) -alkylene-C8-C ^ J-aryl, in which the aryl is mono-, di- or trisubstituted independently from each other by R13, 18) - (C ^ C ^ -alkylene- ^ - C ^ -heterocyclyl, in which Helerocyclyl is not suspended or mono-, di- or frisusified independently of one another by R 13, 19) - (C 1 -C 4) -alkylene (C 3 -C 8) -cycloalkyl, in which the cycloalkyl is not suspended or mono-cyclic. -, di- or irosusiiuid independently of each other by R13, 20) - (O, -C4) -alkylene-hei, in which hel is not susíiuuido or is mono-, di- or irrisusíiuuido independently of others by R13, 21) -SOw-N (R) -R, in which w is 1 or 2, 22) -N (R11) -C (O) -R30, 23) -N (R11) -C (O) -O-R30, or 24) a solution of the following lysis 4 3 as long as the resin -NH-CH2 (R) -R, which is part of the formula l, not 4 4 is one of the following resins of the bond -NH-CH2 (R) -N- or -N- CH2 (R) -O-, in which R4 is fal as defined above, or R3 and R4 or R5 and R6 June with the carbon atom to which they are attached form a 3 to 8 member ring selected from the azetidine group, azocan, azocan-2-one, cyclobutyl, cycloheptyl, cyclohexyl, cycloochane, cycloocinone, cyclopropyl, 1,4-diazepam, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, [1,4] diazo , [1, 2] diazocan-3-one, [1, 3] diazocan-2-one, dioxazine, [1,4] dioxocane, dioxol, ceopiperazine, morpholine, 1,2-oxa-1-ypan, 1,4- oxacepan, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, [1,4] oxazocane, [1, 3] oxazocan-2-one, oxetane, oxocane, oxocan-2-one, piperazine, piperidine, pyran, 5,6,7,8-tetrahydro-1H-azocin-2-one, iomorpholine or leirahydrofuran, in which said ring is not substituted or is mono-, di- or iridesubstituted independently of one another by R13, R11 and R12 are independently one of the other identical or different and are 1) hydrogen atom 2) - (Cj-C8J-alkyl, in which the alkyl is not solid or mono-, di- or iris-independent independently of others by R13, 3) - (C0-C6) -alkyl- (C3-C8) -cycloalkyl, 10 4) -SOt-R, in which í is 1 or 2, 5) - (C0-C8) -alkyl- (C6-C14) -aryl, in which the alkyl and the aryl independently of others is not suspended or is mono-, di- or di-substituted by R 13, 6) - (C 1 -C 4 -perfluoroalkyl, 7) -OR. or 8) - (C0-C8) -alkyl- (C4-C15) -heyerocyclylyl as defined for R °, in which the alkyl and heterocyclyl independently of one another are not substituted or are mono-, di- or di-substituted. R13, or R11 and R12 June with the nitrogen atom to which they are attached can form a 4- to 8-membered monocyclic heterocyclic ring which, in addition to the nitrogen atom, can contain one or two identical or different ring hetero rings that are chosen enire oxygen, sulfur and nitrogen; wherein said heterocyclic ring is unsubstituted or is mono-, di- or trisubstituted independently of one another by R 13, 10 10 R13 is halogen, -NO2, -CN, = O, -OH, -CF3, -C (O) -O-R, -C (O) -N (R) -R, 10 20 10 10 -N (R) -R, - (C3-C8) -cycloalkyl, - (C0-C3) -alkylene-OR, -Si- (CH3) 3, -N (R) -10 10 S (O) u- Rio, where u is 1 or 2, -SR, -SOr-R, where r is 1 or 2, -S (O) v- 10 20 10 N (R) -R, in which v is 1 or 2, -C (O) -R, - (C1-C8) -a! Quilo, - (C8) -alkoxy, phenyl, phenyloxy-, - (C ^ C ^ -perfluoroalkyl, - (C0-C4) -alkyl-C (O) -OC (R15, R16) -OC (O) -R17, -O-R15, -NH-C (O) -NH-R, -O-CF3, - (C0-C4) -alkyl-C (O) -OC (R15, R16) -OC (O) -O-R17, -NH-C (O) -OR , or a remainder of the following list R10 and R20 are independently from each other hydrogen, halogen, - (Cj-C8) -alkyl, - (C0-C4) -alkyl-OH, - (C0-C6) -alkyl-O- (C1-C4) -alkyl or - (C., -C3) -perfluoroalkyl, R15 and R16 are independently of each other hydrogen, - (C ^ CgJ-alkyl, or together with the carbon atom to which they are bound they can form a carbocyclic ring of 3 to 6 members which is not substituted or is susíiuido of a 10 times times R, and R17 is - (C Cg) -alkyl, - (C1-C6) -alkyl-OH, - (C1-C6) -alkyl-O- (C1-C6) -Alkyl, - (C3-C8) -cycloalkyl, - (C1-C6) -a! quil-O- (C1-C8) -alkyl- (C3-C8) -cycloalkyl, - (C6-C6) -Alki - (C3-C8) -cycloalkyl, in which said cycloalkyl ring is not Substituted or substituted one, two or three times by -OH, -O- (O, -C4) -alkyl or in all its stereoisomeric forms and their mixtures in any proportion, and their physiologically tolerable salts.

2. - A compound of the formula I according to claim 1, wherein R ° is 1) phenyl, in which phenyl is unsubstituted or is mono-, di- or tri-substituted independently one of the other, by R8, 2) a heterocyclyl extracted from the benzimidazolyl group, 1,3-benzodioxolyl, benzofuranyl, benzoxazolyl, benzyaliazolyl , benzthiophenyl, cinnolinyl, chromanyl, furyl, imidazolyl, indanyl, indazolyl, indolyl, isochromanyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, phenylpyridyl, phthalazinyl, pyridinyl, purinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyridoimidazolyl, pyridopyridinyl, pyridopimidinyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolyl, quinoxalinyl, iorahydropyranyl, 1,4,5,6-iorahydro-pyridazinyl, thiazolyl, thiadiazolyl, thienyl, triazolyl or teryrazolyl, wherein said heterocyclyl is not mono- or di-, or independently of one another, for R8, R8 is an F, Cl, Br, carbamimidoyl, -C (O) -NH2, - (C? -C4) -alkyl, in which the alkyl is not susíit It is either mono-, di- or tri-unsubstituted independently of one another by a halogen, -OH or a methoxy, or - (C1-C4) - alkyl, in which the alkyl is not susiiluido or mono-, di- or irosusliuido independently of others by a halogen or a methoxy resin, provided that R8 is at least one F, Cl, Br, -C (O) - NH2 or a resin -O- (d- d) -acyl, Q is - (Co-C2) -alkylene-C (O) - (C0-C2) -alkylene or -S (O) 2-, R1 is a hydrogen atom, - (C? -C2) -alkylene, - (C? -C3) -acylene-C (O) -NH-R °, - (C? -C3) -perfluoroalkyl, - (C? -C2) -alkylene-C (O) -O-R10, - (d-C3) -alkylene-S (O) 2- (C? -C3) -alkyl or - (C? -C3) -alkylen -S (O) 2-N (R4 ') - R5', in which R4 'and R5' are, independently of one another, identical or different and are a hydrogen atom or - (dd) -alkyl, R2 is a direct bond or - (C? -C2) -alkylene or R1-N-R2-V forms a cyclic group of 4 to 10 members selected from the group azetidinone, 2,3-dihydroindole, indole, piperidine, piperazine, pyridine, pyrrole, pyrazole, pyrimidine, pyrrolidine, pyrrolidinone, 1, 2,3-Iriazine, 2,4-Iriazine, 1,3,5-triazine, 1, 2,3-Iriazole, 1,2,4-friazole, eryrazine, idrazole, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, azepipal, ceopiperazine, 1,4-oxazepam, oxazole, isoxazole, isoxazolidine, 2-isoxazoine, morfoiin, Iiazol, isoliazol, diadiazole or liomorpholine, in which said cyclic group is unsubstituted or is mono- or dihydrosulfide independently of one another by R 14, V is 1) a cyclic residue of the group containing compounds derived from azaindole (1). H-pyrroIopyridine), aziridine, azirine, azetidine, azetidinone, 1,4-diazepine, pyrrole, pyrrolidine, pyridonyl, imidazole, pyrazole, 1,2,3-triazole, 1,2,4-triazole, teyrazol, pyridine, pyrimidine , pyridazine, pyrazine, 1,2,3-Iriazine, 1,2,4- Iriazine, 1,3,5-Iriazine, Iephrazine, Iefrazol, Azepine, Diazirine, 1,2-Diazepine, 1,3-Diazepine, 1,4-Diazepine, Pyridine, Pyrazine, Pyrimidine, Pyridazine, Piperidine, Piperazine, Pyrrolidinone, cetopiperazine, furan, pyran, dioxol, 1,4-oxazepane, oxazole, soxazole, 2-isoxazoline, isoxazolidine, morpholine, oxirane, oxaziridine, 1,3-dioxolene, 1,3-dioxolane, 1,2-oxazine, 1 , 3-oxazine, 1, 4-oxazine, oxaziridine, thiophene, thiopyran, tieiane, iazole, isoiazole, isoiazoin, isoiazolidine, 1,2-oxaiolane, diazodiazole, iopirane, 1,2-diazine, 1,3-thiazole, 1.3 - Iiazine, 1,4-iiazine, Idiadiazine or Iomorpholine, wherein said cyclic moiety is unsubstituted or is mono- or di-irosituituted independently from each other by R 14, or 2) phenyl, in which phenyl is unsubstituted or mono- -, di- or frisusfituido independently of each other by R14, 18 R14 is fluorine, chlorine, -OH, = O, - (C8) -acyl, -C (O) -OR, -NH2, -C (O) - N (R18) -R21, -CF3, -CN, - (Co-C-ii-alkyKCi-CaJ-perfluoroalkyl or -N (R18) -R21, wherein R18 and R21 are independently one of the other hydrogen atoms, 22 - (C0-C6) -alkyl-N (R) -R, - (C0-C4) -alkyl-OR, - (C0-C4) -alkyl-heterocyclyl, in which the heterocyclyl is azetidinyl, and in which the heterocyclic is not suspended or is mono-, di- or frisusified independently from each other by R13, - (C0-C4) -alkyl-N (R22) -C (O) -N (R22) -R23, - (C C4) - 22 23 22 alkyl, - (C0-C4) -alkyl-C (O) -N (R) -R, - (C0-C4) -alkyl-SO2-R or - (C C3) -perfluoroalkyl, in which R and R are independently from each other a hydrogen atom, - (C ^ C ^ -perfluoroalkyl, - (C3-C6) -cycloalkyl or - (O, -C4) -alkyl, 10 G is a direct bond, - (CH2) m-, - (CH2) mC (0) -NR - (CH2) n-, - (CH2) mC (0) - (CH2) n- or - (CH2) m-NR °, p and m are independently one of different or different and are the integers zero, 1, 2, 3 or 4, M is heterocyclyl, in which helerocyclyl is a compound the group may be derived from azepane, azepine, 1, 4-diazepane, 1, 2-diazepine, 1, 3-diazepine, 1,4-diazepine, dihydropyrimidinone, dihidroimidazolona, 3,3-dioxo- (1,3, 4) oxaíiazina, imidazole, imidazolidinone, isoliazol, isoxazole, isoxazolidine, 2-isoxazoIina, ceíomorfolina, ketopiperazine, morpholine, morpholinone, oxazole, oxazolone, oxazolidinone, [1, 4] -oxacepan, piperazine, piperazinone, piperidine, piperidinone, pyrazine, pyridazine, piridazipona, pyridine, pyridone, pyrimidine-2,4-dione, pyrimidine, pyrimidinone, pyrimidinedione, pyrrolidine, pyrrolidinone, íeírahidropiran, 1,4,5,6-íeírahidro-pyridazinyl, fetrahidro-pyrimidinone, íeírazina, íeírazol, íiadiazol, thiazole, thiophene, thiomorpholine, 1, 1-thiomorpholine dioxide, pyrazinone, 1, 2,3-triazine, 1, 2,4-Iriazine, 1, 3,5-Iriazin a, 1, 2,3-iriazole or 1,2,4-friazole, in which said heyerocyclyl is unsubstituted or is mono-, di- or trisusliuide independently of others by R 14, provided that M contains or is substituted with at least one oxo resi, R3, R4, or R6 are independently of identical or different vectors and are 1) hydrogen atom, 10 10 15) -NR-SO2-R, 10 16) -SR, 17) - (C0-C2) alkylene-C (O) -O- (C2-C4) -alkylene-OC (O) - (C C4) ) -alway, 18) -C (O) -OC (R15, R16) -OC (O) -R17, 19) - (C0-C2) alkylene-C (O) -O- (C2-C4) -alkylene-OC (O ) -O- (C C6) -alkyl, 20) -C (O) -OC (R15, R16) -OC (O) -O-R17, 21) - (C0-C4) -alkylene-N (R11) -C (O) -R12, 22) - (C ^ -alkylene-O ^ O ^ -heíerociclilo Ic, in which no EsIA heferociclilo I susíiíuido or ESLA spherical mono-, di- or independently írisusíituido one another by R13, 23) - (C ^ C ^ ^ -alkylene- -C8J-cycloalkyl, where the cycloalkyl is not spherical sustiíuido or mono-, di- or independently frisustítuido one another by R13 24) -. (C, -. C4) -alqu¡leno-het, where Hei not EsIA susíiúuido or eslá mono-, di- or Irisusfluido independently from each other by R13. 25) - (C0-C4) -alkinene-N (R 1) -C (O) -R12 or 26) a remainder of the following list R5 is 1) fluorine, chlorine or bromine, 2) phenyl, in which the phenyl is unsubstituted or is mono-, di- or trisubstituted independently of one another by R13, 3) - (C ° -C4) -alkylien-O -R29, in which R29 is phenyl, in which the phenyl is not subsituted or is mono-, di- or trisusituituted independently of one another by R13, 4) -NO2, 5) -CN, 6) -SOs-Rn, in that s is 1 or 2, 7) -SOfN (R) -R «in which t is 1 or 2, 8) -C (O) -R11, 9) -C (O) -O-R11, 11 12 10) -C (0) -N (R) -R, 11 12 11) -N (R) -R, 12) -N (R30) -SO2 -R30, in which R30 is hydrogen atom, - (C? -C4) -aIqui!, - (C? -C4) -alkyl-OH, - (C? -C) -alkyl-0- (C? -C4) -alkyl or - (C1-C3) -perfluoroalkyl, 13) -C (O ) -O- (C2-C4) -alkylene-OC (O) - (C1-C4) -alkyl, 14) -C (O) -O- (C2-C4) -alkylene-OC (O) - (C1 -C6) -alkyl, 15) -C (O) -OC (R15, R16) -OC (O) -R17, 16) -C (O) -OC (R15, R16) -OC (O) -O- R17, 17) - (C ^ C ^ alkylene-C ^ icj--heíerociclilo in the heíerociclilo EsIA unsubstituted or mono-, di- or independently trisusíituido one another by R13, 18) -. (C -C4) -alkylene (C3-C8) -cycloalkyl, in which the cycloalkyl is unsubstituted or is mono-, di- or di-substituted independently of each other by R13, 20) -N (R1) -C (O) -R30, 21) -N (R11) -C (O) -O-R30, or 22) a remainder of the following list in which M & It is methyl. if two -OR19 moieties are bound to adjacent atoms, they can form, together with the atoms to which they are bound, a 1,3-dioxoyl ring or a 2,3-dihydro [1,4] dioxin ring, which is substituted one, two, three or four times with R13, 4 3 as long as the rest -NH-CH2 (R) -R, which is part of the formula I, not 4 4 is one of the following remains of the -NH- link CH2 (R) -N- or -N-CH2 (R) -O-, wherein R4 is as defined above, or R11 and R12 are independently of each other identical or different and are 1) hydrogen atom 2) - (C., - C8) -alkyl, in which the alkyl is not substituted or is mono-, di- or trisusituituted independently from each other by R 13, 3) - (C ^ CgJ-perfluoroalkyl) , 4) - (C0-C3) -a (C3-C6) alkyl-cycloalkyl, 5) - (C0-C6) -alkyl-phenyl, wherein the phenyl is as defined above and in which alkyl and phenyl independently of each other are unsubstituted or are mono-, di- or trisubstituted by R13, or 6) - (C0-C6) -alkyl (C4-C15) -heterocyclyl as defined for R °, wherein alkyl and the heterocyclyl are as defined above, and independently of one another, they are not substituted or mono-, di- or iridescent by R13, or R11 and R12 together with the nitrogen atom to which they are bound can form a ring selected from the group azepine, azetidine, 1,4-diazepam, dioxazole, dioxazine, 1,2-diazepine, 1,3- diazepine, 1,4-diazepine, imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, cetopiperazine, morpholine, [1,4] oxacepan, 1,4-oxazepine, oxazole, piperazine , piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tetrazine, terazosin, thiazole, thiazole, thiazolidine, thiazoline, thiomorpholine, thiophene, 1,2,3-triazine , 1, 2,4-Iriazine, 1,3,5-Iriazine, 1, 2,3-Iriazole or 1, 2,4-triazoI, in which said heterocyclic ring is unsubstituted or is mono-, di- or iris-lauded independently of others by R13, R13 is fluorine, chlorine, -NO2, -CN, = O, -OH, -CF3, -C (O) -O-R1 °, -C (O) -N (R1 °) -R2 °, -N (R10) -R2 °, - (C0-C3) -alkylene-O-R1 °, -Si- (CH3) 3, -N (R1 °) -S (O) 2 -R1 °, -S ( O) 2-10 20 10 N (R) -R, -C (O) -R, - (C 8) -alkyl, - (C 1 -C 8) -alkoxy, phenyl, phenyloxy-, -O-CF 3, - (C1-C3) -perfluoroalkyl, -NH-C (O) -NH-R1 °, - (CQ-C4) -alkyl-C (O) -OC (R15, R16) -OC (O) -R17, - (C1-C4) -alkoxy-phenyl, - (C0-C4) -alkyl-C (O) -OC (R15, R16) - 15 10 OC (O) -O-R17, -OR, -NH-C (O) -OR, or a resio of the following lisia , in qm Me is methyl, R10 and R20 are independently one of ore, hydrogen, - (Cj-C ^ -alkyl, - (C0-C4) -alkyl-OH, fluorine, - (C0-C4) -alkyl-O- (C1-C4) -alkyl or - (C3) - perfiuoroalkyl, R15 and R16 are independently of each other, hydrogen , - (C ^ CgJ-alkyl, or together they form a ring of the cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group, in which each ring is unsubstituted or is substituted one to three times by R10, and R17 is - (C1-C6) ) -alkyl, - (C ^ CgJ-alkyl-OH, - (C1-C6) -alkyl-O- (C C6) -Alkium, - (C3-C8) -cycloaikyl, - (C1-C6) -alkyl-O- (C1-C8) -alkyl- (C3-C8) -cycloalkyl, - (O, -C6) -alkyl- (C3-C8) ) -cycloalkyl, in which said cycloalkyl ring is not substituted or is substituted one, two or three times by -OH, -O - ^ - C ^ -alkyl or R10, in all its stereoisomeric forms and their mixtures in any proportion and their physiologically tolerable salts.

3. - A compound of the formula I according to claim 1 or 2, wherein R ° is a residue of the phenyl, pyridyl or thienyl group, wherein said heterocyclyl is unsubstituted or is mono-, di- or irrisuccinate independently of others by R8, R8 is F, Cl or carbamimidoyl, provided that R8 is at least one F or Ci, Q is a -C (O) - or -SO2-, R1 is a hydrogen atom, -CH "-C (O) -OR or CH2CF, 1) hydrogen atom, 2) - (C ^ CgJ-alkyl, in which the alkyl is not solid or mono-, di- or iridesuccessed independently of one another by R13, 3) indanyl, piperidinyl, teirahydropyranyl or 4) - (C0-C3) -alkyl- (C3-C6) -cycloalkyl, 5) - (Oj-C ^ -perfluoroalkyl, 6) - (C0-C6) -alkyl-phenyl, wherein the phenyl is as defined above and wherein the alkyl and the phenyl independently of each other are unsubstituted or mono-, di- or tri-substituted by R13, R13 is fluorine, chlorine, -S-R10, - (C1-C4) -aIqui, or u = O , R10 is hydrogen, fluorine or - (C, - C4) alkyl, in all its stereoisomeric forms and their mixtures in any proportion, and its physiologically tolerable salts.

4. A compound of formula I according to claims 1 to 3, wherein said compound of formula I is. { (R) -2- (2,2-difluoro-etlylamino) -. { 2- [4- (3-oxo-morpholin-4-yl) -3-ylfluoromethyl-phenylcarbamoyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { 2,2-difluoro-2- [4- (2-oxo-2H-pyrazin-1-yl) -phenylcarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { 2,2-difluoro-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ilel} 5-chloro-phofen-2-carboxylic acid amide, benzyl ester of acid. { (R) -2- (5-Chloro-thiophene-2-carbonii) -amino] -1- [4- (3-oxo-morpholin-4-yl) -3-trifluoromethyl-phenylcarbaminyl] -ile} -carbamic, ester-urea-bufillic acid. { 2- (2S) - [(5-chloro-iiophen-2-carbonyl) -amino] -1- [4- (3-oxo-morpholin-4-yl) -phenylcarbamoyl] -ethyl} -carbámico,. { 2- (2S) -amino-2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ilel} 5-chloro-iiophene-2-carboxylic acid amide,. { 2- (2S) -dicyclopropylamino-2- [4- (3-oxo-morpholip-4-yl) -phenylcarbamyl] -i'I} -5-Chloro-1-phenophene-2-carboxylic acid amide, [2- [4- (3-oxo-4-morpholin-4-yl) -phenylcarbamini] -2- (2S) - (yiirahydropyran-4-ylamino) -ethyl} 5-chloro-iiophene-2-carboxylic acid amide,. { 2- (2S) - (1-isopropyl-piperidin-4-ylamino) -2- [4- (3-oxo-morfoin-4-yl) -phenylcarbaminyl] -ethyl} 5-chloro-iiophene-2-carboxylic acid amide,. { 2- (2S) - (indap-2-ylamino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ile} 5-chloro-iiophene-2-carboxylic acid amide,. { 2- (2,2-Dimethyl-propylamino) -2- (2S) - (4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl} -amide of 5-chloro- Fiophene-2-carboxylic acid,. {2- (2S) -cyclobutylamino-2- (4- (3-oxo-morfoin-4-yl) -phenylcarbaminyl] -ethyl} -amide of 5-chloro-liofepo-acid -2-carboxylic acid,. {2- (2S) -cyclohexylamine-2- (4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl} -amide of 5-chloro- Fiophene-2-carboxylic acid,. {2- (2S) - (2,2-difluoro-eyl-amino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ethyl}. .-5-chloro-thiophene-2-carboxylic acid amide,. {2- (2S) - (2,2-difluoro-acetylamino) -2- [4- (3-oxo-morpholin-4- il) -phenylcarbaminyl] -ethyl.} - 5-chloro-thiophene-2-carboxylic acid amide, [2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -2- (2S) - (2,2,3,3-tetrafluoro-propionylamino) -y-yl} -amide of 5-chloro-thiophene-2-carboxylic acid, [2- [4- (3-oxo-morfoin-4-yl) -phenylcarbaminyl] -2- (2S) - (2,2,2-fluoride) ethylene sulfonylamino) -ile} 5-chloro-iiophene-2-carboxylic acid amide,. { 2- (2R) - (2,2-difluoro-ethylamino) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ilel} - 5-cyclo-phofen-2-carboxylic acid amide,. { 2- [Cyclopropylmethyl- (2,2-d-fluoro-eyl) amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ilel} 5-chloro-phofen-2-carboxylic acid amide,. { 2- (2R) - [Cyclobuyl- (2,2-difluoro-ethyl) amino] -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ilel} 5-chloro-thiophene-2-carboxylic acid amide, acidic acid ester. { 2- (2S) - [(5-chloro-thiophene-2-carbonyl) -amino] -1- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -efil} -carbámico,. { 2- (2S) -amino-2- [2-fiuoro-4- (3-oxo-morfoin-4-yl) -phenylcarbaminyl] -ethyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { 2- [2-fluoro-4- (3-oxo-morpholin-4-yl) -phepylcarbamyl] -2- (2S) -isopropylamine-eyl} 5-cyclo-thiophene-2-carboxylic acid amide,. { 2- (2S) -ephilamino-2- [2-fIuoro-4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ile} 5-chloro-iiophene-2-carboxylic acid amide,. { 2-Cyclobutylamino-2- [2-fluoro-4- (3-oxo-morfoin-4-yl) -phenylcarbaminyl] -ethyl} 5-chloro-thiophene-2-carboxylic acid amide,. { 2- (2S) - (4-penfafluorothio-benzoylamine) -2- [4- (3-oxo-morpholin-4-yl) -phenylcarbaminyl] -ile} 5-chloro-iiophene-2-carboxylic acid amide or. { 2- (2R) -yrylamino- (2,2-difluoro-acetylamino) -2- [4- (3-oxo-morpholin-4-yl) - phenylcarbaminyl] -ethyl} 5-chloro-iiophene-2-carboxylic acid amide.

5. - A process for the preparation of a compound of the formula I according to claims 1 to 4, which comprises condensing a compound of the formula 2 with a compound of the formula HR8 to give a compound of the formula 3 and optionally to convert the compound of the formula 3 to a compound of the formula I, 3 formula I wherein the residue R has the donation of -N (R) -R-VGM as indicated in claims 1 to 4, but where in the functional groups of R8 'they may also be present in the form of groups that are transformed later in the final functional groups present in -N (R) -R-VGM, and where the rest R50 denotes the group -QR ° or can denote a group that is later transformed into the -QR ° group, and where the group - C (O) -R49 can be a carboxylic acid group or derivatives thereof, and wherein the 1a 1b 1c 1d groups R, R, R and R in formulas 2 and 3 have the corresponding definitions of R3, R4, R5 and R6 in formula I as defined in claims 1 to 4 or the functional groups in them can present in a protected way or in the form of precursor groups.

6. A pharmaceutical preparation, comprising at least one compound of formula I as claimed in one or more of claims 1 to 4 in all its stereoisomeric forms and mixtures thereof in any proportion and / or its physiologically tolerable salts and a pharmaceutically excipient acceptable.

7. The use of a compound of formula I as claimed in one or more of claims 1 to 4 in all its stereoisomeric forms and mixtures thereof in any proportion and / or their physiologically tolerable salts for the production of drugs to inhibit the factor Xa and / or factor Vlla or to influence blood coagulation or fibrinolysis.

8. The use according to claim 7 against the formation of abnormal thrombi, acute myocardial infarction, cardiovascular disorders, unstable angina, thromboembolism, acute vessel obliteration associated with thrombolytic therapy or percutaneous transluminal coronary angioplasty (PTCA), transient ischemic attacks, stroke, intermittent claudication, coronary or peripheral artery bypass, narrowing of vessel lumen, postcoronary restenosis or venous angioplasty, maintenance of vascular permeability in patients on hemodialysis for a long time, training of pathological debris that occur in the veins of the lower extremities after abdominal, rhodiila or hip surgery, risk of pulmonary thromboembolism or dissemination of seizure-induced invasive coagulopathy that occurs in vascular systems during a septic shock, viral infections or cancer, or reduce an inflammatory response, fibrinolysis, or treatment of ischemic heart disease, myocardial infarction, angina pectoris, vascular restenosis, for example restenosis after angioplasty such as PTCA, acute adult respiratory syndrome, multi-organ failure and dissemination of the disorder. intravascular coagulation, deep vein thrombosis or thrombosis of the nearest vein, which may occur after surgery.