Urea and sulfamide derivatives as inhibitors of TAFIa
View Patent ↗The invention relates to compounds of the formula I as defined herein, which are inhibitors of activated thrombin-activatable fibrinolysis inhibitor. The compounds of the formula I are suitable for manufacturing medicaments for the prophylaxis, secondary prevention and therapy of one or more disorders which are associated with thromboses, embolisms, hypercoagulability or fibrotic changes.
1. A compound of the formula I
where
X is —S(O) 2 —,
R1 is
1) hydrogen atom,
2) —(C 1 -C 6 )-alkyl,
3) —(C 0 -C 4 )-alkylene-(C 3 -C 12 )-cycloalkyl or
4) —(C 1 -C 6 )-alkylene-(C 6 -C 14 )-aryl,
R2 is a radical of the formula II
-(A1) m -A2 (II)
in which
m is the integer zero or 1,
A1 is
1) —(CH 2 ) n — in which n is the integer zero, 1, 2 or 3,
2) —NH—(CH 2 ) n — in which n is the integer zero, 1, 2 or 3,
3) —NH(C 1 -C 6 )-alkyl)-(CH 2 ) n — in which n is the integer zero, 1, 2 or 3,
4) —NH((C 3 -C 6 )-cycloalkyl)-(CH 2 ) n — in which n is the integer zero, 1, 2 or 3,
5) —O—(CH 2 ) n — in which n is the integer zero, 1, 2 or 3, or
6) —(CH 2 ) n —SO x — in which n is the integer zero, 1, 2 or 3 and x the integer zero, 1 or 2,
A2 is
1) Het, where Het means a 4- to 15-membered heterocyclic ring system having 4 to 15 ring atoms which are present in one, two or three ring systems connected together, and which comprise one, two, three or four identical or different heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur, and is unsubstituted or substituted independently of one another once, twice or three times by —(C 1 -C 3 )-alkyl, halogen, —NH 2 , —CF 3 or —O—CF 3 ,
2) —(C 0 -C 6 )-alkylene-NH 2 ,
3) —(C 1 -C 6 )-alkylene-NH—C(═NH)—NH 2 ,
4) —(C 1 -C 6 )-alkylene-NH—C(═NH)—(C 1 -C 4 )-alkyl,
5) —(C 0 -C 4 )-alkylene-O—NH—C(═NH)—NH 2 ,
6) —(C 0 -C 4 )-alkylene-NH—C(O)—(C 1 -C 6 )-alkyl,
7) —(C 1 -C 6 )-alkylene-NH—C(O)—O—(C 1 -C 4 )-alkylene-(C6-C14)-aryl, where aryl is unsubstituted or substituted by —NH 2 or is substituted by —NH 2 and once, twice or three times by R15,
8) —(C 3 -C 8 )-cycloalkyl-NH 2 , or
9) —(C 0 -C 4 )-alkylene-(C 6 -C 14 )-aryl, where aryl is unsubstituted or substituted by —NH 2 or is substituted by —NH 2 and once, twice or three times by R15,
R3 is
1) —(C 1 -C 6 )-alkyl,
2) —(C 0 -C 4 )-alkylene-(C 3 -C 12 )-cycloalkyl,
3) —(C 1 -C 6 )-alkylene-(C 6 -C 14 )-aryl, where aryl is substituted independently of one another once, twice or three times by R15,
4) —(C 0 -C 8 )-alkylene-N(R5)-PG1,
5) —(C 1 -C 6 )-alkylene-NH—C(O)—O—(C 1 -C 4 )-alkylene-(C6-C14)-aryl, where aryl is substituted independently of one another once, twice or three times by R15,
6) —(C 0 -C 4 )-alkylene-(C 6 -C 14 )-aryl-(C 0 -C 4 )-alkylene-N(R5)-PG1,
7) —(C 0 -C 8 )-alkylene-O-PG2,
8) —(C 0 -C 4 )-alkylene-(C 6 -C 14 )-aryl-(C 0 -C 4 )-alkylene-O-PG2,
9) —(C 0 -C 8 )-alkylene-C(O)—O-PG3,
10) —(C 0 -C 4 )-alkylene-(C 6 -C 14 )-aryl-(C 0 -C 4 )-alkylene-C(O)—O-PG3 or
11) hydrogen atom,
R4 is —N(R6) 2 ,
where R6 are identical or different and are independently of one another
1) hydrogen atom,
2) —(C 1 -C 6 )-alkyl,
3) —(C 0 -C 4 )-alkylene-(C 3 -C 12 )-cycloalkyl, where cycloalkyl is unsubstituted or substituted independently of one another once, twice, three or four times by R11, halogen, —C(O)—O—R11, —(C 1 -C 4 )-alkyl-O—R11 or —O—(C 1 -C 4 )-alkyl,
4) —(C 0 -C 6 )-alkylene-(C 6 -C 14 )-aryl, where aryl and alkylene are unsubstituted or substituted independently of one another once, twice, three or four times by R11, halogen, —C(O)—O—R11, —(C 1 -C 4 )-alkyl-O—R11, —C(O)—N(R8) 2 or —O—(C 1 -C 4 )-alkyl,
5) —(C 0 -C 8 )-alkylene-N(R5)-PG1,
6) —(C 0 -C 4 )-alkylene-(C 6 -C 14 )-aryl-(C 0 -C 4 )-alkyl-N(R5)-PG1,
7) —(C 0 -C 8 )-alkylene-O-PG2,
8) —(C 0 -C 4 )-alkylene-(C 6 -C 14 )-aryl-(C 0 -C 4 )-alkyl-O-PG2,
9) —(C 0 -C 8 )-alkylene-C(O)—O—R11,
10) —(C 0 -C 4 )-alkylene-(C 6 -C 14 )-aryl-(C 0 -C 4 )-alkyl-C(O)—O-PG3,
11) —(C 0 -C 4 )-alkylene-Het, where Het means a 4- to 15-membered heterocyclic ring system having 4 to 15 ring atoms which are present in one, two or three ring systems connected together, and which comprise one, two, three or four identical or different heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur, where Het or alkylene is unsubstituted or substituted independently of one another once, twice or three times by R11, halogen, —C(O)—O—R11, —(C 1 -C 4 )-alkyl-O—R11 or —O—(C 1 -C 4 )-alkyl,
12) —(C 1 -C 3 )-fluoroalkyl,
13) —(C 0 -C 4 )-alkylene-CH(R11)-C(O)—NH 2 ,
14) —(C 0 -C 4 )-alkylene-CH(R11)-C(O)—NH—(C 1 -C 4 )-alkyl,
15) —(C 0 -C 4 )-alkylene-CH(R11)-C(O)—NH—CH(R12)-R13, or
16) amino acid, where the linkage of the amino acid takes place by a peptide linkage, and the carboxyl radical of the amino acid is unsubstituted or substituted by PG3 or by —N(R5) 2 ,
or the two R6 radicals form together with the N atom to which they are bonded a mono- or bicyclic ring having 4 to 9 ring atoms which is saturated, partly saturated or aromatic, where the ring is unsubstituted or substituted once or twice by —(C 1 -C 4 )-alkyl, —C(O)—O—R11, halogen, —(C 1 -C 4 )-alkyl-O—R11 or phenyl,
R5 is hydrogen atom or —(C 1 -C 6 )-alkyl,
PG1 is a protective group for the amino function,
PG2 is a protective group for the hydroxy function,
PG3 is a protective group for the carboxyl function,
R7 is hydrogen atom or —(C 1 -C 6 )-alkyl,
R8 is hydrogen atom or —(C 1 -C 6 )-alkyl,
R9 is hydrogen atom or —(C 1 -C 6 )-alkyl,
R11 and R12 are identical or different and are independently of one another
1) hydrogen atom,
2) —(C 1 -C 6 )-alkyl,
3) —(C 0 -C 4 )-alkylene-phenyl, where phenyl is unsubstituted or substituted independently of one another once, twice or three times by halogen, —OH or —O—(C 1 -C 4 )-alkyl,
4) —(C 0 -C 4 )-alkylene-(C 3 -C 12 )-cycloalkyl, where cycloalkyl is unsubstituted or substituted independently of one another once, twice, three or four times by R13, halogen, —C(O)—O—R13, —(C 1 -C 4 )-alkyl-O—R13, —O—(C 1 -C 4 )-alkyl or —(C 0 -C 4 )-alkylene-phenyl,
5) —(C 0 -C 4 )-alkylene-C(O)—N(R13) 2 or
6) —(C 0 -C 4 )-alkylene-indolyl,
R13 is
1) hydrogen atom,
2) —(C 1 -C 4 )-alkyl,
3) —(C 0 -C 4 )-alkylene-C(O)—O—R14,
4) —(C 0 -C 4 )-alkylene-C(O)—R14 or
5) —(C 0 -C 4 )-alkylene-O—R14,
R14 is hydrogen atom, —(C 1 -C 4 )-alkyl, —NH 2 or —OH, and
R15 is hydrogen atom, —(C 1 -C 4 )-alkyl, —O—CF 3 , —NH 2 , —OH, —CF 3 or halogen, or
a stereoisomeric form of the compound of the formula I, or mixture of stereoisomeric forms in any ratio, or a physiologically tolerated salt of the compound of the formula I.
2. A compound of the formula I
where
X is —S(O) 2 —,
R1 is
1) hydrogen atom or
2) —(C 1 -C 4 )-alkyl,
R2 is
1) —(C 1 -C 6 )-alkylene-NH 2 ,
2) —(C 0 -C 4 )-alkylene-pyridyl-NH 2 ,
3) —(C 0 -C 4 )-alkylene-piperidinyl-NH 2 ,
4) —(C 0 -C 4 )-alkylene-thiazolyl-NH 2 ,
5) —(C 1 -C 6 )-alkylene-NH—C(═NH)—NH 2 ,
6) —(C 0 -C 4 )-alkylene-(C 3 -C 8 )-cycloalkyl-NH 2 ,
7) —(C 1 -C 6 )-alkylene-NH—C(═NH)—(C 1 -C 4 )-alkyl,
8) —(C 0 -C 4 )-alkylene-O—NH—C(═NH)—NH 2 ,
9) —(C 1 -C 6 )-alkylene-NH—C(O)—O—(C 1 -C 4 )-alkylene-(C6-C14)-aryl, where aryl is unsubstituted or substituted by —NH 2 or is substituted by —NH 2 and once, twice or three times by R15,
10) —(C 0 -C 4 )-alkylene-NH—C(O)—(C 1 -C 4 )-alkyl,
11) —(C 0 -C 4 )-alkylene-(C 6 -C 14 )-aryl, where aryl is unsubstituted or substituted by —NH 2 or is substituted by —NH 2 and once, twice or three times by R15, or
12) —(C 1 -C 4 )-alkylene-SO x —(C 1 -C 4 )-alkylene-NH 2 in which x is the integer zero, 1 or 2,
R3 is
1) —(C 1 -C 4 )-alkyl,
2) —(C 0 -C 4 )-alkylene-(C3-C 8 )-cycloalkyl,
3) —(C 1 -C 6 )-alkylene-(C 6 -C 14 )-aryl, where aryl is substituted independently of one another once, twice or three times by R15,
4) —(C 1 -C 6 )-alkylene-NH—C(O)—O—(C 1 -C 4 )-alkylene-(C 6 -C 14 )-aryl, where aryl is substituted independently of one another once, twice or three times by R15,
5) —(C 1 -C 6 )-alkylene-NH-PG1,
6) —(C 1 -C 6 )-alkylene-O-PG2,
7) —(C 1 -C 6 )-alkyl, or
8) hydrogen atom,
where PG1 is t-butyloxycarbonyl or benzyloxycarbonyl, and PG2 is t-butyl-, t-butyloxycarbonyl or benzyloxycarbonyl,
R4 is —N(R6) 2 ,
where R6 are identical or different and are independently of one another
1) hydrogen atom,
2) —(C 1 -C 6 )-alkyl,
3) —(C 0 -C 4 )-alkylene-(C 3 -C 12 )-cycloalkyl, where cycloalkyl is unsubstituted or substituted independently of one another once, twice, three or four times by R11, halogen, —C(O)—O—R11, —(C 1 -C 4 )-alkyl-O—R11 or —O—(C 1 -C 4 )-alkyl,
4) —(C 0 -C 4 )-alkylene-C(R11)(R12)-(C 3 -C 12 )-cycloalkyl, where cycloalkyl is unsubstituted or substituted independently of one another once, twice or three times by R11, halogen, —C(O)—O—R11, —(C 1 -C 4 )-alkyl-O—R11 or —O—(C 1 -C 4 )-alkyl,
5) —(C 0 -C 4 )-alkylene-Het, where Het means a 4- to 15-membered heterocyclic ring system having 4 to 15 ring atoms which are present in one, two or three ring systems connected together, and which comprise one, two, three or four identical or different heteratoms selected from the group consisting of oxygen, nitrogen and sulfur, where Het or alkylene is unsubstituted or substituted independently of one another once, twice or three times by R11, halogen, —C(O)—O—R11, —(C 1 -C 4 )-alkyl-O—R11 or —O—(C 1 -C 4 )-alkyl,
6) —(C 0 -C 6 )-alkylene-(C6-C14)-aryl, where aryl or alkylene is unsubstituted or substituted independently of one another once, twice or three times by R11, halogen, —C(O)—O—R11, —(C 0 -C 4 )-alkyl-O—R11 or —O—(C 1 -C 4 )-alkyl,
7) —(C 0 -C 4 )-alkylene-C(R11)(R12)-aryl, where aryl or alkylene is unsubstituted or substituted independently of one another once, twice or three times by R11, halogen, —C(O)—O—R11, —(C 0 -C 4 )-alkyl-O—R11 or —O—(C 1 -C 4 )-alkyl,
8) 1,2,3,4-tetrahydronaphthalenyl, 9) —(C 0 -C 4 )-alkylene-CH(R11)-C(O)—NH 2 ,
10) —(C 0 -C 4 )-alkylene-CH(R11)-C(O)—NH—(C 1 -C 4 )-alkyl,
11) —(C 0 -C 4 )-alkylene-CH(R11)-C(O)—NH—CH(R12)-R13,
12) —(C 0 -C 6 )-alkylene-C(O)—O—R11, where alkylene is unsubstituted or substituted independently of one another once or twice by R11, halogen, —C(O)—O—R11, —(C 1 -C 4 )-alkyl-O—R11 or —O—(C 1 -C 4 )-alkyl,
13) —(C 0 -C 4 )-alkylene-C(R11)(R12)-C(O)—O—R11, or
14) —(C 1 -C 3 )-fluoroalkyl,
or the two R6 radicals form together with the N atom to which they are bonded a mono- or bicyclic ring having 4 to 9 ring atoms which is saturated, partly saturated or aromatic, where the ring is unsubstituted or substituted once or twice by —(C 1 -C 4 )-alkyl, —C(O)—O—R11, halogen, —(C 1 -C 4 )-alkyl-O—R11 or phenyl,
R7 is hydrogen atom or —(C 1 -C 4 )-alkyl,
R9 is hydrogen atom or —(C 1 -C 4 )-alkyl,
R11 and R12 are identical or different and are independently of one another
1) hydrogen atom,
2) —(C 1 -C 4 )-alkyl,
3) —(C 0 -C 4 )-alkylene-phenyl, where phenyl is unsubstituted or substituted independently of one another once, twice or three times by halogen, —OH or —O—(C 1 -C 4 )-alkyl,
4) —(C 0 -C 4 )-alkylene-(C 3 -C 12 )-cycloalkyl, where cycloalkyl is unsubstituted or substituted independently of one another once, twice, three or four times by R13, halogen, —C(O)—O—R13, —(C 1 -C 4 )-alkyl-O—R13, —O—(C 1 -C 4 )-alkyl or —(C 0 -C 4 )-alkylene-phenyl,
5) —(C 0 -C 4 )-alkylene-C(O)—N(R13) 2 or
6) —(C 0 -C 4 )-alkylene-indolyl,
R13 is
1) hydrogen atom,
2) —(C 1 -C 4 )-alkyl,
3) —(C 0 -C 4 )-alkylene-C(O)—O—R14,
4) —(C 0 -C 4 )-alkylene-C(O)—R14 or
5) —(C 0 -C 4 )-alkylene-O—R14,
R14 is hydrogen atom, —(C 1 -C 4 )-alkyl, —NH 2 or —OH, and
R15 is hydrogen atom, —(C 1 -C 4 )-alkyl, —O—CF 3 , —NH 2 , —OH, —CF 3 or halogen, or
a stereoisomeric form of the compound of the formula I, or mixture of stereoisomeric forms in any ratio, or a physiologically tolerated salt of the compound of the formula I.
3. The compound as claimed in claim 2 ,
where
R1 is
1) hydrogen atom or
2) —(C 1 -C 4 )-alkyl,
R2 is
1) —(C 1 -C 6 )-alkylene-NH 2 ,
2) —(C 1 -C 4 )-alkylene-pyridyl-NH 2 ,
3) —(C 1 -C 4 )-alkylene-piperidinyl-NH 2 ,
4) —(C 1 -C 6 )-alkylene-NH—C(═NH)—NH 2 ,
5) —(C 0 -C 4 )-alkylene-(C 3 -C 6 )-cycloalkyl-NH 2 ,
6) —(C 1 -C 6 )-alkylene-NH—C(═NH)—(C 1 -C 4 )-alkyl,
7) —(C 1 -C 4 )-alkylene-O—NH—C(═NH)—NH 2 ,
8) —(C 1 -C 6 )-alkylene-NH—C(O)—O—(C 1 -C 4 )-alkylene-phenyl, where phenyl is unsubstituted or substituted by —NH 2 or is substituted by —NH 2 and once, twice or three times by R15,
9) —(C 1 -C 4 )-alkylene-NH—C(O)—(C 1 -C 4 )-alkyl,
10) —(C 1 -C 4 )-alkylene-phenyl, where phenyl is unsubstituted or substituted by —NH 2 or is substituted by —NH 2 and once, twice or three times by R15,
11) —(C 1 -C 4 )-alkylene-SO 2 —(C 1 -C 4 )-alkylene-NH 2 or
12) —(C 1 -C 4 )-alkylene-S—(C 1 -C 4 )-alkylene-NH 2 ,
R3 is
1) —(C 1 -C 4 )-alkyl,
2) —(C 1 -C 4 )-alkylene-(C 3 -C 6 )-cycloalkyl,
3) —(C 1 -C 4 )-alkylene-phenyl, where phenyl is substituted independently of one another once, twice or three times by R15,
4) —(C 1 -C 6 )-alkylene-NH—C(O)—O—(C 1 -C 4 )-alkylene-phenyl, where phenyl is substituted independently of one another once, twice or three times by R15,
5) hydrogen atom,
R4 is —N(R6) 2 ,
where R6 are identical or different and are independently of one another
1) hydrogen atom,
2) —(C 1 -C 4 )-alkyl,
3) —(C 0 -C 4 )-alkylene-(C 3 -C 12 )-cycloalkyl, where cycloalkyl is selected from the group consisting of cyclohexyl, cyclopentyl, cyclobutyl, cyclopropyl, adamantanyl, decahydronaphthalenyl, tetrahydronaphthalenyl, octahydro-4,7-methanoindenyl and bicyclo[2.2.1]heptanyl, and in which cycloalkyl is unsubstituted or substituted independently of one another once, twice, three or four times by —(C 1 -C 4 )-alkyl, —C(O)—O—R11 or —(C 1 -C 4 )-alkylene-phenyl, where phenyl is unsubstituted or substituted by halogen, or 1,7,7-trimethylbicyclo[3.1.1]heptanyl which is unsubstituted or substituted once by —(C 1 -C 4 )-alkyl, —C(O)—O—R11 or —(C 1 -C 4 )-alkylene-phenyl, where phenyl is unsubstituted or substituted by halogen,
4) —(C 0 -C 4 )-alkylene-C(R11)(R12)-(C 3 -C 12 )-cycloalkyl, where cycloalkyl is selected from the group consisting of cyclohexyl, cyclopentyl, cyclobutyl, cyclopropyl, adamantanyl, decahydronaphthalenyl, tetrahydronaphthalenyl, octahydro-4,7-methanoindenyl and bicyclo[2.2.1]heptanyl, and in which cycloalkyl is unsubstituted or substituted independently of one another once, twice, three or four times by —(C 1 -C 4 )-alkyl, —C(O)—O—R11 or —(C 1 -C 4 )-alkylene-phenyl, where phenyl is unsubstituted or substituted by halogen, or 1,7,7-trimethylbicyclo[3.1.1]heptanyl which is unsubstituted or substituted once by —(C 1 -C 4 )-alkyl, —C(O)—O—R11 or —(C 1 -C 4 )-alkylene-phenyl, where phenyl is unsubstituted or substituted by halogen,
5) —(C 0 -C 4 )-alkylene-Het, where Het is selected from the group consisting of acridinyl, azepinyl, azetidinyl, aziridinyl, benzimidazalinyl, benzimidazolyl, benzo[1,3]dioxolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, carbazolyl, 4aH-carbazolyl, carbolinyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, dibenzofuranyl, dibenzothiophenyl, dihydrofuran[2,3-b]-tetrahydrofuranyl, dihydrofuranyl, dioxolyl, dioxanyl, 2H, 6H-1,5,2-dithiazinyl, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl (benzimidazolyl), isothiazolidinyl, 2-isothiazolinyl, isothiazolyl, isoxazolyl, isoxazolidinyl, 2-isoxazolinyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxazolidinyl, oxothiolanyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl, purynyl, pyranyl, pyrazinyl, pyroazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pryidooxazolyl, pyridoimidazolyl, pyridothiazolyl, pyridothiophenyl, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrahydropyridinyl, 6H-1,2,5-thiadazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienoimidazolyl, thienooxazolyl, thienopyridine, thienothiazolyl, thiomorpholinyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl and xanthenyl, where Het or alkylene is unsubstituted or substituted independently of one another once or twice by —(C 1 -C 4 )-alkyl,
6) —(C 1 -C 6 )-alkylene-phenyl, where phenyl or alkylene is unsubstituted or substituted independently of one another once or twice by halogen, phenyl, —C(O)—O—R11, —(C 1 -C 4 )-alkyl-O—R11, —O—(C 1 -C 4 )-alkyl or —(C 1 -C 4 )-alkyl,
7) —(C 0 -C 4 )-alkylene-C(R11)(R12)-phenyl, where phenyl is unsubstituted or substituted independently of one another once, twice or three times by phenyl or fluorine,
8) 1,2,3,4-tetrahydronaphthalenyl,
9) —(C 0 -C 4 )-alkylene-CH(R11)-C(O)—NH 2 ,
10) —(C 0 -C 4 )-alkylene-CH(R11)-C(O)—NH—(C 1 -C 4 )-alkyl,
11) —(C 0 -C 4 )-alkylene-CH(R11)-C(O)—NH—CH(R12)-R13,
12) —(C 1 -C 6 )-alkylene-C(O)—O—R11, where alkylene is unsubstituted or substituted independently of one another once or twice by halogen, phenyl, —C(O)—O—R11, —(C 1 -C 4 )-alkyl-O—R11, —O—(C 1 -C 4 )-alkyl or —(C 1 -C 4 )-alkyl,
13) —(C 0 -C 4 )-alkylene-C(R11)(R12)-C(O)—O—R11, or
14) —(C 1 -C 3 )-fluoroalkyl,
or the two R6 radicals form together with the N atom to which they are bonded a mono- or bicyclic ring selected from the group consisting of pyrrolidine, piperidine, 2-aza-bicyclo[3.2.2]nonane and 7-aza-bicyclo[2.2.1]heptane, where the ring is unsubstituted or substituted once or twice by —(C 1 -C 4 )-alkyl, —C(O)—O—R11, —(C 1 -C 4 )-alkyl-O—R11 or phenyl,
R7 is hydrogen atom or —(C 1 -C 4 )-alkyl,
R9 is hydrogen atom or —(C 1 -C 4 )-alkyl,
R11 and R12 are identical or different and are independently of one another
1) hydrogen atom,
2) —(C 1 -C 4 )-alkyl,
3) —(C 0 -C 4 )-alkylene-phenyl, where phenyl is unsubstituted or substituted independently of one another once, twice or three times by —OH, halogen or —O—(C 1 -C 4 )-alkyl,
4) —(C 0 -C 4 )-alkylene-(C 3 -C 12 )-cycloalkyl, where cycloalkyl is selected from the group consisting of cyclohexyl, cyclopentyl, cyclobutyl, cyclopropyl, adamantanyl, decahydronaphthalenyl, tetrahydronaphthalenyl, octahydro-4,7-methanoindenyl and bicyclo[2.2.1]heptanyl, and in which cycloalkyl is unsubstituted or substituted independently of one another once, twice, three or four times by —(C 1 -C 4 )-alkyl, —C(O)—O—R13 or phenyl, or 1,7,7-trimethylbicyclo[3.1.1]heptanyl which is unsubstituted or substituted once by —(C 1 -C 4 )-alkyl, —C(O)—O—R13 or phenyl, or
5) —(C 0 -C 4 )-alkylene-indolyl,
R13 is
1) hydrogen atom,
2) —(C 1 -C 4 )-alkyl,
3) —(C 0 -C 4 )-alkylene-C(O)—O—R14,
4) —(C 0 -C 4 )-alkylene-C(O)—R14 or
5) —(C 0 -C 4 )-alkylene-O—R14, and
R14 is hydrogen atom, —(C 1 -C 4 )-alkyl, —NH 2 or —OH and
R15 is hydrogen atom, —(C 1 -C 4 )-alkyl, —O—CF 3 , —NH 2 , —OH, —CF 3 or halogen, or
a stereoisomeric form of the compound of the formula I, or mixture of stereoisomeric forms in any ratio, or a physiologically tolerated salt of the compound of the formula I.
4. A compound of the formula I as claimed in claim 2 ,
where
R1 is
1) hydrogen atom or
2) —(C 1 -C 4 )-alkyl,
R2 is
1) —(C 1 -C 6 )-alkylene-NH 2 ,
2) —(C 1 -C 4 )-alkylene-pyridyl-NH 2 ,
3) —(C 1 -C 4 )-alkylene-piperidinyl-NH 2 ,
4) —(C 1 -C 4 )-alkylene-NH—C(═NH)—NH 2 ,
5) —(C 1 -C 6 )-alkylene-NH—C(═NH)—(C 1 -C 4 )-alkyl,
6) —(C 1 -C 4 )-alkylene-(C 3 -C 6 )-cycloalkyl-NH 2 ,
7) —(C 1 -C 4 )-alkylene-O—NH—C(═NH)—NH 2 ,
8) —(C 1 -C 6 )-alkylene-NH—C(O)—O—(C 1 -C 4 )-alkylene-phenyl,
9) —(C 1 -C 4 )-alkylene-NH—C(O)—(C 1 -C 4 )-alkyl,
10) —(C 1 -C 4 )-alkylene-phenyl-NH 2 ,
11) —(C 1 -C 4 )-alkylene-SO 2 —(C 1 -C 4 )-alkylene-NH 2 or,
12) —(C 1 -C 4 )-alkylene-S—(C 1 -C 4 )-alkylene-NH 2 ,
R3 is
1) —(C 1 -C 4 )-alkyl,
2) —(C 1 -C 4 )-alkylene-(C 3 -C 6 )-cycloalkyl,
3) —(C 1 -C 4 )-alkylene-phenyl, where phenyl is unsubstituted or substituted by —OH,
4) —(C 1 -C 6 )-alkylene-NH—C(O)—O—(C 1 -C 4 )-alkylene-phenyl,
5) hydrogen atom,
R4 is —N(R6) 2 ,
where R6 are identical or different and are independently of one another
1) hydrogen atom,
2) —(C 1 -C 6 )-alkyl,
3) —(C 0 -C 4 )-alkylene-(C 3 -C 8 )-cycloalkyl, where cycloalkyl is selected from the group consisting of cyclohexyl, cyclopentyl, cyclopropyl, adamantanyl, decahydronaphthalene, octahydro-4,7-methanoindenyl and bicyclo[2.2.1]heptanyl, and in which cycloalkyl is unsubstituted or substituted independently of one another once, twice or three times by —(C 1 -C 4 )-alkyl or phenyl, or 1,7,7-trimethylbicyclo[3.1.1]heptanyl which is unsubstituted or substituted once by —(C 1 -C 4 )-alkyl or phenyl,
4) —C(R11)(R12)-adamantanyl,
5) —CH(R11)-C(O)—NH—CH(R12)-R13,
6) —(C 0 -C 4 )-alkylene-Het, where Het is selected from the group consisting of benzimidazolyl, isoxazolyl, piperidine, pyridine, pyrrolidinyl, thiophenyl and benzo[1,3]dioxol,
7) 1,2,3,4-tetrahydronaphthalenyl,
8) —(C 0 -C 4 )-alkylene-C(R11)(R12)-phenyl, where phenyl is unsubstituted or substituted independently of one another once, twice or three times by phenyl or fluorine,
9) —CH(R11)-C(O)—NH 2 ,
10) —CH(R11)-C(O)—NH—CH(R12)-CH 2 —OH,
11) —(C 1 -C 6 )-alkylene-phenyl, where phenyl or alkylene is unsubstituted or substituted independently of one another once or twice by chlorine, fluorine, —C(O)—O—R11, —(C 1 -C 4 )-alkyl-O—R11, —O—(C 1 -C 4 )-alkyl, phenyl or —(C 1 -C 4 )-alkyl,
12) —CH(R11)-C(O)—NH—(C 1 -C 4 )-alkyl,
13) —(C 0 -C 4 )-alkylene-C(R11)(R12)-bicyclo[3.1.1]heptanyl, where bicyclo[3.1.1]heptanyl is unsubstituted or substituted once to four times by —(C 1 -C 4 )-alkyl,
14) —(C 1 -C 6 )-alkylene-C(O)—O—R11, where alkylene is unsubstituted or Substituted independently of one another once or twice by chlorine, fluorine, —C(O)—O—R11, —(C 1 -C 4 )-alkyl-O—R11, —O—(C 1 -C 4 )-alkyl, phenyl or —(C 1 -C 4 )-alkyl,
15) —(C 0 -C 4 )-alkylene-C(R11)(R12)-C(O)—O—R11, or
16) —CH 2 —CF 2 —CF 3 ,
or the two R6 radicals form together with the N atom to which they are bonded a mono- or bicyclic ring selected from the group consisting of pyrrolidines, 2-azabicyclo[3.2.2]nonane and 7-aza-bicyclo[2.2.1]heptane, where the ring is unsubstituted or substituted once or twice by —(C 1 -C 4 )-alkyl, —C(O)—O—R11, —(C 1 -C 4 )-alkyl-O—R11 or phenyl,
R7 is hydrogen atom or —(C 1 -C 4 )-alkyl,
R9 is hydrogen atom or —(C 1 -C 4 )-alkyl,
R11 and R12 are identical or different and are independently of one another
1) hydrogen atom,
2) —(C 1 -C 4 )-alkyl,
3) —(C 0 -C 4 )-alkylene-phenyl, where phenyl is unsubstituted or substituted independently of one another once, twice or three times by —OH, halogen or —O—(C 1 -C 4 )-alkyl,
4) —(C 0 -C 4 )-alkylene-(C 3 -C 12 )-cycloalkyl, where cycloalkyl is selected from the group consisting of cyclohexyl, cyclopentyl, cyclobutyl, cyclopropyl, adamantanyl, decahydronaphthalenyl, octahydro-4,7-methanoindenyl and bicyclo[2.2.1]heptanyl, and in which cycloalkyl is unsubstituted or substituted independently of one another once, twice, three or four times by —(C 1 -C 4 )-alkyl, —C(O)—O—R13 or phenyl, or 1,7,7-trimethylbicyclo[3.1.1]heptanyl which is unsubstituted or substituted once by —(C 1 -C 4 )-alkyl, —C(O)—O—R13 or phenyl, or
5) —(C 0 -C 4 )-alkylene-indolyl,
R13 is
1) hydrogen atom,
2) —(C 1 -C 4 )-alkyl,
3) —(C 0 -C 4 )-alkylene-C(O)—O—R14,
4) —(C 0 -C 4 )-alkylene-C(O)—R14 or
5) —(C 0 -C 4 )-alkylene-O—R14,
R14 is hydrogen atom, —(C 1 -C 4 )-alkyl, —NH 2 or —OH and
R15 is hydrogen atom, —(C 1 -C 4 )-alkyl, —O—CF 3 , —NH 2 , —OH, —CF 3 or halogen, or
a stereoisomeric form of the compound of the formula I, or mixture of stereoisomeric forms in any ratio, or a physiologically tolerated salt of the compound of the formula I.
5. A compound which is (S)-6-amino-2-(3-{(S)-1-[(S)-1-((S)-1-methoxycarbonyl-2-methyl-propylcarbamoyl)-2-methyl-propylcarbamoyl]-2-phenyl-ethyl}-sulfamidyl)-hexanoic acid, (S)-6-amino-2-{3-[(R)-1-(bicyclo[2.2.1]hept-2-ylcarbamoyl)-2-cyclohexyl-ethyl]-sulamidyl}-hexanoic acid, (S)-6-amino-2-[3-((S)-1-cyclohexylcarbamoyl-2-phenyl-ethyl)-sulfamidyl]-hexanoic acid, (S)-6-acetimidoylamino-2-{[(S)-2-cyclohexyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethylsulfamidyl]}-hexanoic acid, ethyl 3-(6-amino-pyridin-3-yl)-2-[(S)-2-cyclohexyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethylsulfamidyl]-propionate, (S)-6-amino-2-{[(S)-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-propylsulfamidyl]-}-hexanoic acid, (S)-2-{[(S)-2-cyclohexyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethylsulfamidyl]-}-5-guanidino-pentanoic acid, (S)-6-amino-2-{[(S)-2-cyclobutyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethylsulfamidyl]}-hexanoic acid, (S)-5-amino-2-({2-cyclohexyl-1-[(R)-(1,2,3,4-tetrahydro-naphthalen-2-yl)carbamoyl]-ethylsulfamidyl})-pentanoic acid, ethyl(S)-2-{[(S)-2-cyclohexyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethylsulfamidyl]}-6-hexanoylaminohexanoate, (S)-6-amino-2-{[(S)-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-butylsulfamidyl]}-hexanoic acid, (S)-6-amino-2-{[(S)-3-cyclohexyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-propylsulfamidyl]-methyl}-hexanoic acid, (S)-6-amino-2-{[(S)-2-cyclohexyl-1-(decahydro-naphthalen-2-ylcarbamoyl)-ethylsulfamidyl]}-hexanoic acid, (S)-2-{[(S)-1-(adamantan-1-ylcarbamoyl)-2-cyclohexyl-ethylsulfamidyl]}-6-amino-hexanoic acid, (S)-2-[(S)-2-cyclohexyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]-hept-2-ylcarbamoyl)-ethylsulfamidyl]-3-pyridin-3-yl-propionic acid, (S)-2-[(S)-2-cyclohexyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethylsulfamidyl]-3-pyridin-4-yl-propionic acid, (S)-6-amino-2-{[(S)-2-cyclohexyl-1-((1S,2S,3S,5R)-2,6,6-trimethyl-bicyclo[3.1.1]hept-3-ylcarbamoyl)-ethylsulfamidyl]}-hexanoic acid, (S)-6-amino-2-{[(S)-2-cyclohexyl-1-(3,3,5-trimethyl-cyclohexylcarbamoyl)-ethylsulfamidyl]}-hexanoic acid, (S)-6-amino-2-{[(S)-1-(4-tert-butyl-cyclohexylcarbamoyl)-2-cyclohexyl-ethylsulfamidyl]}-hexanoic acid, (S)-6-amino-2-{[(S)-2-cyclohexyl-1-(3-methyl-cyclohexylcarbamoyl)-ethylsulfamidyl]}-hexanoic acid, (S)-6-amino-2-{[(S)-2-cyclohexyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethylsulfamidyl]}-hexanoic acid, 3-(6-amino-pyridin-3-ylmethyl)-2-[(S)-2-cyclohexyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-yl-carbamoyl)-ethylsulfamidyl]-propionic acid, 2-[(S)-2-cyclohexyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethylsulfamidyl]-3-piperidin-4-yl-propionic acid, (S)-3-(4-amino-phenyl)-2-[(S)-2-cyclohexyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethylsulfamidyl]-propionic acid, (S)-6-amino-2-[((S)-1-cyclohexylmethyl-2-oxo-2-piperidin-1-yl-ethylsulfamidyl)]-hexanoic acid, (S)-5-amino-2-{[(S)-2-cyclohexyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethylsulfamidyl]}-pentanoic acid, (S)-6-amino-2-{[(S)-2-cyclohexyl-1-((S)-1-isobutylcarbamoyl-2-methyl-propylcarbamoyl)-ethylsulfamidyl]}-hexanoic acid, (S)-6-amino-2-{[(S)-1-((S)-1-isobutylcarbamoyl-2-methyl-propylcarbamoyl)-2-phenyl-ethylsulfamidyl]}-hexanoic acid, (S)-6-amino-2-[((S)-2-cyclohexyl-1-isobutylcarbamoyl-ethylsulfamidyl)]-hexanoic acid, (S)-6-amino-2-{[(S)-1-((1R,2R,4S)-bicyclo[2.2.1]hept-2-ylcarbamoyl)-2-cyclohexyl-ethylsulfamidyl]}-hexanoic acid, (S)-6-amino-2-{[(S)-2-cyclohexyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethylsulfamidyl]}-hexanoic acid, (S)-6-amino-2-{[(S)-1-((1S,4R)-bicyclo[2.2.1]hept-2-ylcarbamoyl)-2-cyclohexyl-ethylsulfamidyl]}-hexanoic acid, (S)-6-amino-2-{[(S)-2-cyclohexyl-1-(octahydro-4,7-methano-inden-5-ylcarbamoyl)-ethylsulfamidyl]}-hexanoic acid, (S)-6-amino-2-[((S)-1-tert-butylcarbamoyl-2-cyclohexyl-ethylsulfamidyl)]-hexanoic acid, (S)-2-{[(S)-1-(adamantan-1-ylcarbamoyl)-2-phenyl-ethylsulfamidyl]}-6-amino-hexanoic acid, (S)-6-amino-2-{[(S)-1-((1S,4R)-bicyclo[2.2.1]hept-2-ylcarbamoyl)-2-phenyl-ethylsulfamidyl]}-hexanoic acid, (S)-2-{[(S)-1-(adamantan-1-ylcarbamoyl)-2-(4-hydroxy-phenyl)-ethylsulfamidyl]}-6-amino-hexanoic acid, (S)-6-amino-2-{[(S)-2-phenyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethylsulfamidyl]}-hexanoic acid, (S)-6-amino-2-({[(S)-cyclohexyl-(1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-methyl]-sulfamidyl})-hexanoic acid, (S)-6-amino-2-{[(S)-2-cyclohexyl-1-((1R,2R,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethylsulfamidyl]}-hexanoic acid, (S)-6-amino-2-{[(S)-2-cyclopropyl-1-((1R,2R,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethylsulfamidyl]}-hexanoic acid, (S)-6-amino-2-{[(S)-2-cyclohexyl-1-(3,5-dimethyl-adamantan-1-ylcarbamoyl)-ethylsulfamidyl]}-hexanoic acid, (S)-6-amino-2-{[(S)-2-cyclohexyl-1-(3-isopropyl-adamantan-1-ylcarbamoyl)-ethylsulfamidyl]}-hexanoic acid, tert-butyl (S)-6-amino-2-{[(S)-2-cyclohexyl-1-((1R,2R,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethylsulfamidyl]}-hexanoate or (S)-2-{[(S)-1-(adamantan-1-ylcarbamoyl)-3-methyl-butylsulfamidyl]}-6-amino-hexanoic acid or
a stereoisomeric form of the compound of the formula I, or mixture of stereoisomeric forms in any ratio, or a physiologically tolerated salt of the compound of the formula I.
6. A compound of the Formula (I),
and/or a stereoisomeric form of the compound of Formula I, and/or a mixture of stereoisomeric forms in any ratio, and/or a physiologically tolerated salt of the compound of the formula I, wherein:
X is —C(O)—
R1 is
1) hydrogen atom or
2) —(C 1 -C 4 )-alkyl,
R2 is
1) —(C 1 -C 6 )-alkylene-NH 2 ,
2) —(C 1 -C 4 )-alkylene-pyridyl-NH 2 ,
3) —(C 1 -C 4 )-alkylene-piperidinyl-NH 2 ,
4) —(C 1 -C 4 )-alkylene-NH—C(═NH)—NH 2 ,
5) —(C 1 -C 6 )-alkylene-NH—C(═NH)—(C 1 -C 4 )-alkyl,
6) —(C 1 -C 4 )-alkylene-(C 3 -C 6 )-cycloalkyl-NH 2 ,
7) —(C 1 -C 4 )-alkylene-O—NH—C(═NH)—NH 2 ,
8) —(C 1 -C 6 )-alkylene-NH—C(O)—O—(C 1 -C 4 )-alkylene-phenyl,
9) —(C 1 -C 4 )-alkylene-NH—C(O)—(C 1 -C 4 )-alkyl,
10) —(C 1 -C 4 )-alkylene-phenyl-NH 2 ,
11) —(C 1 -C 2 )-alkylene-SO 2 —(C 1 -C 4 )-alkylene-NH 2 or
12) —(C 1 -C 2 )-alkylene-S—(C 1 -C 4 )-alkylene-NH 2
R3 is 1) —(C 1 -C 4 )-alkyl,
2) —(C 1 -C 4 )-alkylene-(C 3 -C 6 )-cycloalkyl,
3) —(C 1 -C 4 )-alkylene-phenyl, where phenyl is unsubstituted or substituted by —OH,
4) —(C 1 -C 6 )-alkylene-NH—C(O)—O—(C 1 -C 4 )-alkylene-phenyl,
5) hydrogen atom,
R4 is —N(R6) 2 ,
where R6 are identical or different and are independently of one another
1) hydrogen atom,
2) —(C 1 -C 6 )-alkyl,
3) —(C 0 -C 4 )-alkylene-(C 3 -C 8 )-cycloalkyl, where cycloalkyl is selected from the group consisting of cyclohexyl, cyclopentyl, cyclopropyl, adamantyl, 1,7,7-trimethylbicyclo[3.1.1]heptanyl, decahydronaphthalenyl, octahydro-4,7-methanoindenyl and bicyclo[2.2.1]heptanyl, and in which cycloalkyl is unsubstituted or substituted independently of one another once, twice or three times by —(C 1 -C 4 )-alkyl or phenyl, or 1,7,7-trimethylbicyclo[3.1.1]heptanyl is unsubstituted,
4) —C(R11)(R12)-adamantanyl,
5) —CH(R11)-C(O)—NH—CH(R12)-R13,
6) —(C 0 -C 4 )-alkylene-Het, where Het is selected from the group consisting of benzimidazolyl, isoxazolyl, piperidinyl, pyridyl, pyrrolidinyl, thiophenyl and benzo[1,3]dioxolyl,
7) 1,2,3,4-tetrahydronaphthalenyl,
8) —(C 0 -C 4 )-alkylene-C(R11)(R12)-phenyl, where phenyl is unsubstituted or substituted independently of one another once, twice or three times by phenyl or fluorine,
9) —CH(R11)-C(O)—NH 2 ,
10) —CH(R11)-C(O)—NH—CH(R12)-CH 2 —OH,
11) —(C 1 -C 6 )-alkylene-phenyl, where phenyl is unsubstituted or substituted independently of one another once or twice by chlorine, fluorine, —C(O)—O—R11, —(C 1 -C 4 )-alkyl-O—R11, —O—(C 1 -C 4 )-alkyl, phenyl or —(C 1 -C 4 )-alkyl, and alkylene is unsubstituted or substituted independently of one another once or twice by chlorine, fluorine, —(C 1 -C 4 )-alkyl-O—R11, —O—(C 1 -C 4 )-alkyl, phenyl or —(C 1 -C 4 )-alkyl,
12) —CH(R11)-C(O)—NH—(C 1 -C 4 )-alkyl,
13) —(C 0 -C 4 )-alkylene-C(R11)(R12)-bicyclo[3.1.1]heptanyl, where bicyclo[3.1.1]heptanyl is unsubstituted or substituted once to four times by —(C 1 -C 4 )-alkyl,
14) —CH 2 —CF 2 —CF 3 ,
or the two R6 radicals form together with the N atom to which they are bonded a mono- or bicyclic ring selected from the group consisting of pyrrolidines, 2-azabicyclo[3.2.2]nonane and 7-aza-bicyclo[2.2.1]heptane, where the ring is unsubstituted or substituted once or twice by —(C 1 -C 4 )-alkyl, —C(O)—O—R11, —(C 1 -C 4 )-alkyl-O—R11 or phenyl,
R7 is hydrogen atom or —(C 1 -C 4 )-alkyl,
R9 is hydrogen atom or —(C 1 -C 4 )-alkyl,
R11 and R12 are identical or different and are independently of one another
1) hydrogen atom,
2) —(C 1 -C 4 )-alkyl,
3) —(C 0 -C 4 )-alkylene-phenyl, where phenyl is unsubstituted or substituted independently of one another once, twice or three times by —OH, halogen or —O—(C 1 -C 4 )-alkyl,
4) —(C 0 -C 4 )-alkylene-(C 3 -C 12 )-cycloalkyl, where cycloalkyl is selected from the group consisting of cyclohexyl, cyclopentyl, cyclobutyl, cyclopropyl, adamantanyl, decahydronaphthalenyl, octahydro-4,7-methanoindenyl and bicyclo[2.2.1]heptanyl, and in which cycloalkyl is unsubstituted or substituted independently of one another once, twice, three or four times by —(C 1 -C 4 )-alkyl, —C(O)—O—R13 or phenyl, or 1,7,7-trimethylbicyclo[3.1.1]heptanyl is unsubstituted or substituted once by -(—(C 1 -C 4 )-alkyl, —C(O)—O—R13 or phenyl, or
5) —(C 0 -C 4 )-alkylene-indolyl,
R13 is
1) hydrogen atom,
2) —(C 1 -C 4 )-alkyl,
3) —(C 0 -C 4 )-alkylene-C(O)—O—R14,
4) —(C 0 -C 4 )-alkylene-C(O)—R14 or
5) —(C 0 -C 4 )-alkylene-O—R14,
R14 is hydrogen atom, —(C 1 -C 4 )-alkyl, —NH 2 or —OH and
R15 is hydrogen atom, —(C 1 -C 4 )-alkyl, —O—CF 3 , —NH 2 , —OH, —CF 3 or halogen, or
a stereoisomeric form of the compound of the formula I, or mixture of stereoisomeric forms in any ratio, or a physiologically tolerated salt of the compound of the formula I.
7. A compound of claim 6 selected from:
(S)-6-amino-2-{3-[(R)-1-(3-methyl-butylcarbamoyl)-2-phenyl-ethyl]-ureido}-hexanoic acid hydrochloride, (S)-6-amino-2-{3-[(R)-5-benzyloxycarbonylamino-1-(3-methyl-butylcarbamoyl)-pentyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-1-(3-methyl-butylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-3-methyl- 1-(3-methyl-butylcarbamoyl)-butyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-1-(3-methyl-butylcarbamoyl)-butyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-1-(3-methyl-butylcarbamoyl)-pentyl]-ureidol-hexanoic acid, (S)-6-amino-2-{3-[(R)-1-(3-methyl-butylcarbamoyl)-2-phenyl-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-[3-((R)-1-isobutylcarbamoyl-2-phenyl-ethyl)-ureido]-hexanoic acid, (S)-6-amino-2-{3-[(R)-5-benzyloxy-carbonylamino-1-((S)-1-ethylcarbamoyl-2-methyl-propylcarbamoyl)-pentyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-((S)-1-ethylcarbamoyl-2-methyl-propylcarb-amoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-(2,4-difluoro-benzylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-(2-phenyl-propylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-(2-o-tolyl-ethylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-1-(4-chloro-benzylcarbamoyl)-2-cyclohexyl-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-((R)-1-phenyl-ethylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-1-(bicyclo[2.2.1]hept-2-ylcarbamoyl)-2-cyclohexyl-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-(3-phenyl-propylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-(2-methyl-cyclohexylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-(3-{(R)-1-[(S)-1-(4-chloro-phenyl)-ethylcarbamoyl]-2-cyclohexyl-ethyl}-ureido)-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-(4-methoxy-benzylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-(3-{(R)-2-cyclohexyl-1-[(3-methyl-isoxazol-5-ylmethyl)-carbamoyl]-ethyl}-ureido)-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-((R)-1-phenyl-ethylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[2-(7-aza-bicyclo[2.2.1]hept-7-yl)-1-cyclohexylmethyl-2-oxo-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-(2,3 -dimethyl-benzylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-(1,2-dimethyl-butylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-(2,2-diphenyl-ethylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-(2,2-dimethyl-propylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-1-(2-benzo[1,3]dioxol-5 -yl-ethylcarb-amoyl)-2-cyclohexyl-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-(4-methyl-cyclohexylcarbamoyl)-ethyl]-ureido}-hexanoic acid, ethyl (1R,2S)-2-{(R)-2-[3-((S)-5-amino-1-carboxy-pentyl)-ureido]-6-benzyloxycarbonylamino-hexanoylamino}-cyclohexane-carboxylate, (S)-6-amino-2-{3-[(R)-5-benzyloxycarbonylamino-1-(2-phenyl-propylcarbamoyl)-pentyl]-ureido}-hexanoic acid, (S)-6-amino-2-(3-{(R)-5-benzyloxycarbonylamino-1-[(biphenyl-2-ylmethyl)-carbamoyl]-pentyl}-ureido)-hexanoic acid, (S)-6-amino-2-{3-[(R)-5-benzyloxycarbonyl-amino-1-((1S,2S)-1-methoxycarbonyl-2-methyl-butylcarbamoyl)-pentyl]-ureido}-hexanoic acid, (S)-2-(3-{(R)-1-[(S)-1-((S)-1-benzyl-2-hydroxy-ethylcarbamoyl)-2-methyl-propylcarbamoyl]-2-cyclohexyl-ethyl}-ureido)-5-benzyloxycarbonylamino-pentanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-(3-methyl-cyclohexylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-5-benzyloxycarbonylamino-1-(2-methyl-cyclohexylcarbamoyl)-pentyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-5-benzyloxycarbonylamino-1-((1S,4R)-bicyclo[2.2.1]hept-2-ylcarbamoyl)-pentyl]-ureido}-hexanoic acid, (S)-6-amino-2-(3-{(R)-5-benzyloxycarbonyl-amino-1-[(S)-1-(4-chloro-phenyl)-ethylcarbamoyl]-pentyl}-ureido)-hexanoic acid, (S)-6-amino-2-(3-(R)-5-benzyloxycarbonylamino-1-[(3-methyl-isoxazol-5-ylmethyl)-carbamoyl]-pentyl}-ureido)-hexanoic acid, (S)-6-amino-2-{3-[(R)-5-benzyloxycarbonylamino-1-((R)-1-phenyl-ethylcarbamoyl)-pentyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-5-benzyloxycarbonylamino-1-(3-phenyl-propylcarbamoyl)-pentyl]-ureido}-hexanoic acid, (S)-6-amino-2-(3-{(R)-2-cyclohexyl-1-[(thiophen-2-ylmethyl)-carbamoyl]-ethyl}-ureido)-hexanoic acid, (S)-6-amino-2-[3-((R)-2-cyclohexyl-1-cyclopropylcarbamoyl-ethyl)-ureido]-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-((R)-1,2-dimethyl-propylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-(1-ethyl-propylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-1-cyclohexylmethyl-2-(2-methyl-pyrrolidin-1-yl)-2-oxo-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-((S)-1-cyclohexyl-ethylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-5-benzyloxycarbonylamino-1-(4-chloro-benzylcarbamoyl)-pentyl]-ureido}-hexanoic acid, (S)-6-amino-2-(3-{(R)-2-cyclohexyl-1-[(thiophen-3-ylmethyl)-carbamoyl]-ethyl}-ureido)-hexanoic acid, (S)-6-amino-2-(3-{(R)-2-cyclohexyl-1-[(R)-1-(4-fluoro-phenyl)-ethylcarbamoyl]-ethyl}-ureido)-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-(1,2,3,4-tetrahydro-naphthalen-1-ylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-[3-((R)-2-cyclohexyl-1-propylcarbamoyl-ethyl)-ureido]-hexanoic acid, (S)-6-amino-2-{3-(R)-1-[(biphenyl-2-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-ureido)-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-((R)-2-phenyl-cyclopropylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-(3-{(R)-2-cyclohexyl-1-[(pyridin-3-ylmethyl)-carbamoyl]-ethyl}-ureido)-hexanoic acid, (S)-6-amino-2-(3-{(R)-2-cyclohexyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-ethyl}-ureido)-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-(1-methyl-piperidin-4-ylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-(3,3,3-trifluoro-propylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-(2-methyl-butyl-carbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-(cyclopropylmethyl-carbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-(3,5-difluoro-benzylcarbamoyl-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-(2,3-dimethyl-cyclohexylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-(1,2,3,4-tetrahydro-naphthalen-2-ylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-2-{3-[(R)-1-(adamantan-2-ylcarbamoyl)-2-cyclohexyl-ethyl]-ureido}-6-amino-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-(1,3-dimethyl-butylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-[3-((R)-2-cyclohexyl-1-isobutylcarbamoyl-ethyl)-ureido]-hexanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-((S)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-2-(3-{(R)-1-[(adamantan-1-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-ureido)-6-amino-hexanoic acid, (S)-2-{3-[(R)-1-(adamantan-1-ylcarbamoyl)-2-cyclohexyl-ethyl]-ureido}-6-amino-hexanoic acid, (S)-6-amino-2-[3-((R)-2-cyclohexyl-1-cyclohexylcarbamoyl-ethyl)-ureido]-hexanoic acid, (S)-6-amino-2-(3-{(R)-2-cyclohexyl-1-[(pyridin-4-ylmethyl)-carbamoyl]-ethyl}-ureido)-hexanoic acid, (S)-6-amino-2-(3-{(R)-2-cyclohexyl-1-[((1S,2S)-2,6,6-trimethyl-bicyclo[3.1.1]hept-3-ylmethyl)-carbamoyl]-ethyl}-ureido)-hexanoic acid, (S)-6-amino-2-(3-{(R)-2-cyclohexyl-1-[(S)-(1,2,3,4-tetrahydro-naphthalen-2-yl)carbamoyl]-ethyl}-ureido)-hexanoic acid, S)-6-amino-2-{3-[(R)-1-(4-tert-butyl-cyclohexylcarbamoyl)-2-cyclohexyl-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-[3-((R)-1-cyclohexylmethyl-2-oxo-2-pyrrolidin-1-yl-ethyl)-ureido]-hexanoic acid, 3-(6-amino-pyridin-3-yl)-2-{3-[(R)-1-(bicyclo[2.2.1]hept-2-ylcarbamoyl)-2-cyclohexyl-ethyl]-ureido}-propanoic acid, (S)-6-amino-2-(3-{(R)-2-cyclohexyl-1-[(1-methyl-1H-benzoimidazol-2-ylmethyl)-carbamoyl]-ethyl}-ureido)-hexanoic acid, 3-(3-amino-cyclobutyl)-2-{3-[(R)-1-(bicyclo[2.2.1]hept-2-ylcarbamoyl)-2-cyclohexyl-ethyl]-ureido}-propanoic acid, (S)-6-amino-2-{3-[(R)-1-((1S,2R)-1-carbamoyl-2-methyl-butylcarbamoyl)-2-cyclohexyl-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(R)-5-benzyloxycarbonylamino-1-((1S,2R)-1-carbamoyl-2-methyl-butylcarbamoyl)-pentyl]-ureido}-hexanoic acid, (S)-6-amino-2-(3-{(R)-1-[1-((S)-1-benzyl-2-hydroxy-ethylcarbamoyl)-2-methyl-propylcarbamoyl]-2-cyclohexyl-ethyl}-ureido)-hexanoic acid, (S)-6-amino-2-(3-{(R)-1-[(S)-1-((S)-1-carbamoyl-2-methyl-propylcarbamoyl)-2-methyl-propylcarbamoyl]-2-cyclohexyl-ethyl}-ureido)-hexanoic acid, (S)-2-{3-[(R)-5-benzyloxycarbonylamino-1-((1S,2R)-1-carbamoyl-2-methyl-butylcarbamoyl)-pentyl]-ureido}-5-guanidino-pentanoic acid, (S)-2-(3-{(R)-5-benzyloxycarbonylamino-1-[1-(1-carbamoyl-2-methyl-propylcarbamoyl)-2-methyl-propylcarbamoyl]-pentyl}-ureido)-5-guanidino-pentanoic acid, (S)-6-amino-2-(3-{(R)-5-benzyloxycarbonylamino-1-[(S)-1-((S)-1-carbamoyl-2-methyl-propylcarbamoyl)-2-methyl-propylcarbamoyl]-pentyl}-ureido)-hexanoic acid, S)-6-amino-2-{3-[(R)-5-benzyloxy-carbonylamino-1-((R)-1-carbamoyl-2-methyl-butylcarbamoyl)-pentyl]-ureido}-hexanoic acid, 2-{(S)-3-[(R)-2-cyclohexyl-1-((1R,2S ,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethyl]-ureido}-5-guanidino-pentanoic acid, (S)-6-amino-2-{3-[(R)-2-cyclohexyl-1-(decahydro-naphthalen-2-ylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-3-(6-amino-pyridin-3-yl)-2-{3-[(R)-2-cyclohexyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethyl]-ureido }-propionic acid, (R)-3-(6-amino-pyridin-3-yl)-2-{3-[(R)-2-cyclohexyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethyl]-ureido}-propionic acid, (S)-5-amino-2-(3-{2-cyclohexyl-1-[((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-methyl]-ethyl}-ureido)-pentanoic acid, 6-amino-2-{3-[(R)-2-phenyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethyl]-ureido}-hexanoic acid, 6-amino-2-{3-[2-methyl-1-((R)-(1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-propyl]-ureido}-hexanoic acid, 6-amino-2-{3-[(R)-cyclohexyl-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-methyl]-ureido}-hexanoic acid, 6-amino-2-{3-[3-methyl-1-((R)-(1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-butyl]-ureido}-hexanoic acid, 3-(3-amino-cyclobutyl)-2-{3-[(R)-1-(bicyclo[2.2.1]-hept-2-ylcarbamoyl)-2-cyclohexyl-ethyl]-ureido }-propionic acid trifluoroacetate, 6-amino-2-{3-[((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-methyl]-ureido}-hexanoic acid, 6-amino-2-{3-[1-methyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethyl]-ureido}-hexanoic acid, 6-amino-2-{3-[1-((R)-(1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]-hept-2-ylcarbamoyl)-butyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(S)-2-cyclohexyl-1-(3-methyl-cyclohexylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(S)-1-(4-tert-butyl-cyclohexylcarbamoyl)-2-cyclohexyl-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-{3-[(S)-2-cyclohexyl-1-(3,3,5-trimethyl-cyclohexylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-4-guanidino-oxy-2-{3-[(R)-2-cyclohexyl-1-((1R,2S)-1,7,7-trimethyl-bicyclo[2.2.1 ]hept-2-ylcarbamoyl)-ethyl]-ureido}-butanoic acid, 6-amino-2-{3-[(R)-2-cyclopropyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethyl]-ureido}-hexanoic acid, 6-amino-2-{3-[(R)-2-cyclobutyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethyl]-ureido}-hexanoic acid, 3-(6-amino-pyridin-3-yl)-2-{3-[(R)-2-cyclohexyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethyl]-ureido}-propionic acid, 6-amino-2-{3-[2-cyclopentyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethyl]-ureido}-hexanoic acid, (S)-6-amino-2-(3-{(R)-5-benzyloxycarbonylamino-1-[(S)-2-methyl-1-(3-phenyl-propylcarbamoyl)-propylcarbamoyl]-pentyl}-ureido)-hexanoic acid, (S)-6-amino-2-(3-{(R)-5-benzyloxycarbonylamino-1-[(S)-1-((1R,2R,4S)-bicyclo[2.2.1]hept-2-ylcarbamoyl)-2-methyl-propylcarbamoyl]-pentyl}-ureido)-hexanoic acid, (S)-6-amino-2-(3-{(R)-5-benzyloxycarbonyl-amino-1-[(S)-1-((1S,4R)-bicyclo[2.2.1]hept-2-ylcarbamoyl)-2-methyl-propylcarbamoyl]-pentyl}-ureido)-hexanoic acid, (S)-6 -amino-2-{3-[(R)-5-benzyloxycarbonylamino-1-((S)-1-cyclopropylcarbamoyl-2-methyl-propylcarbamoyl)-pentyl]-ureido}-hexanoic acid, (S)-6-amino-2-[3-((R)-5-benzyloxycarbonylamino-1-{(S)-1-[(S)-1-(4-chloro-phenyl)-ethylcarbamoyl]-2-methyl-propylcarbamoyl}-pentyl)-ureido]-hexanoic acid, (S)-6-amino-2-(3-{(R)-5-benzyloxycarbonylamino-1-[(S)-2-methyl-1-(3-methyl-cyclohexylcarbamoyl)-propylcarbamoyl]-pentyl}-ureido)-hexanoic acid, (S)-6-amino-2-(3-{(R)-5-benzyloxycarbonylamino-1-[(S)-1-(2,2-dimethyl-propylcarbamoyl)-2-methyl-propylcarbamoyl]-pentyl}-ureido)-hexanoic acid, (S)-6-amino-2-(3-(R)-5-benzyloxycarbonylamino-1-[(S)-2-methyl-1-{(R)-1-phenyl-ethylcarbamoyl)-propylcarbamoyl]-pentyl}-ureido)-hexanoic acid, (S)-5-amino-2-{3-[(R)-2-cyclohexyl-1-(3-methyl-butylcarbamoyl)-ethyl]-ureido}-pentanoic acid hydrochloride, (S)-5-amino-2-{3-[(R)-2-cyclohexyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoye-ethyl]-ureido }-pentanoic acid, (S)-6-amino-2-(3-{(R)-5-benzyloxycarbonylamino-1-[(S)-1-((S)-1-cyclohexyl-ethylcarbamoyl)-2-methyl-propylcarbamoyl]-pentyl}-ureido)-hexanoic acid, (S)-6-amino-2-(3-{(R)-5-benzyloxycarbonylamino-1-[(S)-2-methyl-1-(1,2,2-trimethyl-propylcarbamoyl)-propylcarbamoyl]-pentyl}-ureido)-hexanoic acid, (S)-6-amino-2-(3-{(R)-5-benzyloxycarbonylamino-1-[(S)-2-methyl-1-((1R,2S)-2-phenyl-cyclopropylcarbamoyl-propylcarbamoyl]-pentyl}-ureido)-hexanoic acid, (S)-6-amino-2-(3-{(R)-5-benzyloxycarbonylamino-1-[(S)-2-methyl-1-(2-methyl-cyclohexylcarbamoyl)-propylcarbamoyl]-pentyl}-ureido)-hexanoic acid, (S)-6-amino-2-(3-{(R)-5-benzyloxycarbonylamino-1-[(S)-1-(4-chloro-benzylcarbamoyl)-2-methyl-propylcarbamoyl]-pentyl}-ureido)-hexanoid acid, (S)-6-amino-2-{3-[(R)-5 -benzyloxycarbonylamino-1-((S)-1-carbamoyl-2-methyl-propylcarbamoyl)-pentyl]-ureido}-hexanoic acid, (R)-3-(2-amino-ethanesulfonyl)-2-{3-[(R)-2-cyclohexyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethyl]-ureido}propionic acid or (R)-3-(2-amino-ethylsulfanyl)-2-{3-[(R)-2-cyclohexyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethyl]-ureido}propionic acid, or
a stereoisomeric form of the compound of the formula I, or mixture of stereoisomeric forms in any ratio, or a physiologically tolerated salt of the compound of the formula I.