DE19504226A1 - New N-(carboxy-alkanoyl) derivs. of hydroxy-quinoxaline carboxamide - Google Patents

Abstract

Quinoxaline derivs. of formula (I) and their salts are new, except for N-(6,7-dichloro-3,4-dihydro-3-oxo-2- quinoxalinylcarbonyl)glycine and alpha -(6,7-dichloro-3,4-dihydro-3- oxo-2-quinoxalinylcarboxamide)phenylacetic acid. Q and X = O or S; A = 1-4C alkylene (opt. mono-substd. by a 6-12C aryloxy, 7-11C aralkyloxy, 6-12C aryl or 7-11C aralkyl (all ring-substd. by 1-5 R9), or mono substd. with the substits. of the alpha -C atom of natural L- or D- alpha -amino acid, or mono- or di-substd. (by R9, Ph, CH2Ph, OPh, OCH2Ph, NHPh, N(Me)Ph or X'Ph); B = COOH, CONHCOR''', CHNHSOR''', CONHSO2R''', NHSO2CF3, tetrazolyl, imidazolyl or 3-hydroxyisoxazolyl; R''' = aryl, heteroaryl, 3-7C cycloalkyl or R12 (opt. substd.); R1-R4 = H, OH, R9, COOH, 1-20C alkyl (opt. substd.), R16, 2-20C alkenyl, 2-20C alkynyl, 1-20C alkoxy (opt. substd.), 2-20C alkenyloxy, 2-20C alkynyloxy, retinyloxy, , O(CH2)xCfH(2f+1-g), COR14, COOR16, COOR18, COOR17, retinyloxycarbonyl, COOR11 (substd. by OR16, R18 or OR18), OCOR18, OCOR16, OCOOH (substd.), CONH2 (opt. substd.), CO(NR23CH(Rx)CO)sT, OCONH2 (opt. substd.), NH2 (opt. substd.), X'R14, X'R16, SO2NH2 (opt. substd.),etc.; or R1+R2, R2+R3, R3+R4 = satd. (CH2)o opt. with one C=C bond, opt. with one or two CH2 replaced by O, S, SO, SO2 or NR'; R' = H, 6-12C aryl, 1-8C alkyl, (opt. substd. with 1-8C alkoxy, 7-12C aralkoxy or 6-12C aryloxy), 1-10C alkanoyl, opt. substd. 7-16C aralkanoyl or opt. substd. 6-12C aroyl; Rx = the side chain of an L- or D- alpha -amino acid; s = 1-5; T = OH, OR or NR21R22; R is not defined; R21-R23 = H, 6-12C aryl, 7-11C aralkyl, R18, (+)-dehydroabietyl, 1-8C alkyl (opt. substd. by 1-8C alkoxy, 7-12C aralkoxy or 6-12C aryloxy), 1-10C alkanoyl, opt. substd. 7-16C aralkanoyl or opt. substd. 6-12C aroyl; R9 = R10, X'R11, X''R11, 1-6C hydroxyalkyl, O(CH2)xCfH(2fH+1-g)Halg, OCF2Cl, OCF2CHFCl, CONH2, mono- or di(1-4C alkyl)carbamoyl, 3-8C cycloalkyl, SO2NH2 or mono- or di(1-4C alkyl)sulphamoyl; R5 = H or a 1-20C alkyl, 6-16C aryl or 7-16C aralkyl gp. opt. substd. by one or more gps. as defined for R1; f = 1-8; g = 0 to (2f+1); x = 0-3; h = 3-6; Ph = phenyl; R10 = halo, CN, NO2 or CF3; R11 = 1-6C alkyl; R12, R13 = 1-4C alkyl; R14, R15 = 1-12C alkyl; R16 = 6-12C aryl or 7-16C aralkyl; R17 = 2-20C alkenyl or 2-20C alkynyl; R18 = 3-8C cycloalkyl; X' = S, SO or SO2; X" = bond, O, CO, OCO or COO;

Description

The invention relates to substituted quinoxalines, their preparation and their Use as inhibitors of prolyl 4-hydroxylase and their use as Medicines used to treat fibrotic diseases.

Compounds that inhibit the enzymes prolyl and lysyl hydroxylase a very selective inhibition of collagen biosynthesis by influencing the collagen-specific hydroxylation reactions. In the course of which protein-bound proline or lysine through the enzymes prolyl or Lysyl hydroxylase hydroxylated. This reaction is caused by inhibitors prevented, so a non-functional, under hydroxylated Collagen molecule that is only present in small amounts in the extracellular cells Space can be given. The under-hydroxylated collagen can also cannot be built into the collagen matrix and becomes proteolytic very easily reduced. As a result of these effects, the amount of extracellularly deposited collagen.

Inhibitors of prolyl hydroxylase are therefore suitable substances in the Therapy of diseases in which the deposition of collagens is essential contributes to the clinical picture. These include a. Fibrosis of the lungs, liver and Skin (scleroderma) and atherosclerosis.

It is known that the enzyme prolyl hydroxylase can be isolated by pyridine-2,4- and -2,5- dicarboxylic acid is effectively inhibited (K. Majamaa et al., Eur. J. Biochem. 138 (1984) 239-245). However, these compounds are only found in cell culture very high concentrations as inhibitors (Tschank, G. et al., Biochem. J. 238 (1987) 625-633).  

Prodrugs of the pyridine-2,4 (5) dicarboxylates are also known. These are in the older German applications P 42 33 124.2, P 42 38 506.7 and P 42 09 424.0.

N-oxalylglycines as inhibitors of prolyl-4-hydroxylase are known from J. Med. Chem. 1992, 35, 2652 to 2658 (Cunliffe et al.), And EP-A-0 457 163 (Baader et al.) known.

Hydroxyisoquinoline and hydroxycinnoline carboxylic acid glycylamides are made Biochem. Soc. Trans. 1991, 19, 812 to 815 (Franklin et al.). From WO 92/11245 N - ((6,7-dichloro-3,4-dihydro-3-oxo-2- quinoxalinyl) carbonyl) glycine and α - ((6,7-dichloro-3,4-dihydro-3-oxo-2- quinoxalinyl) carbonyl) amino) phenylacetic acid.

Surprisingly, it has now been found that quinoxaline-2-carboxamides with a hydroxy, a mercapto, an ether, or a thioether Substituents in the ortho position to the amide function are potent inhibitors of Prolyl 4-hydroxylase.

The compounds according to the invention correspond to the general formula I.

in which
Q O or S,
X O and S,
A (C₁-C₄) alkylene, which is optionally substituted with one or two substituents from the series halogen, cyano, nitro, trifluoromethyl, (C₁-C₆) alkyl, (C₁-C₆) hydroxyalkyl, (C₁-C₆) -Alkoxy, -O- [CH₂] _x -C _f H _{(2f + 1-g)} Hal _g , preferably (C₁-C₈) fluoroalkoxy, (C₁-C₈) fluoroalkenyloxy, (C₁-C₈) fluoroalkynyloxy, - OCF₂Cl or -O-CF₂-CHFCl, (C₁-C₆) alkyl mercapto, (C₁-C₆) alkylsulfinyl, (C₁-C₆) alkylsulfonyl, (C₁-C₆) alkylcarbonyl, (C₁-C₆) alkoxycarbonyl, carbamoyl , N- (C₁-C₄) alkylcarbamoyl, N, N-di- (C₁-C₄) alkylcarbamoyl, (C₁-C₆) alkylcarbonyloxy, (C₃-C₈) cycloalkyl, phenyl, benzyl, phenoxy, benzyloxy, anilino , N-methylanilino, phenylmercapto, phenylsulfonyl, phenylsulfinyl, sulfamoyl, N- (C₁-C₄) alkylsulfamoyl, N, N-di- (C₁-C₄) alkylsulfamoyl, or
with a substituted (C₆-C₁₂) aryloxy, (C₇-C₁₁) aralkyloxy, (C₆-C₁₂) aryl or (C₇-C₁₁) aralkyl radical which is in the aryl part 1, 2, 3, 4 or 5 identical or different substituents from the series halogen, cyano, nitro, trifluoromethyl, (C₁-C₆) alkyl, (C₁-C₆) alkoxy, -O- [CH₂] _x -C _f H _{(2f + 1-g)} Hal _g , -OCF₂Cl, -O-CF₂-CHFCl, (C₁-C₆) alkyl mercapto, (C₁-C₆) alkylsulfinyl, (C₁-C₆) alkylsulfonyl, (C₁-C₆) alkylcarbonyl, (C₁-C₆) -Alkoxycarbonyl, carbamoyl, N- (C₁-C₄) alkylcarbamoyl, N, N-di- (C₁-C₄) alkylcarbamoyl, (C₁-C₆) alkylcarbonyloxy, (C₃-C₈) cycloalkyl, sulfamoyl, N- ( C₁-C₄) - alkylsulfamoyl or N, N-di- (C₁-C₄) alkylsulfamoyl, or
with the substituents R⁵ of the α-C atom of an α-amino acid, whereby the natural L-amino acids and their D-isomers can be used;
B is an acidic group from the series -CO₂H, -CONHCOR ′ ′ ′, -CONHSOR ′ ′ ′, CONHSO₂R ′ ′ ′, -NHSO₂CF₃, tetrazolyl, imidazolyl or -3-hydroxyisoxazolyl, where R ′ ′ ′ aryl, heteroaryl, ( C₃-C₇) - cycloalkyl or (C₁-C₄) alkyl, optionally monosubstituted with (C₆-C₁₂) aryl, heteroaryl, OH, SH, (C₁-C₄) alkyl, (C₁-C₄) alkoxy, (C₁ -C₄) - thioalkyl, sulfinyl or sulfonyl, CF₃, Cl, Br, F, I, NO₂, -COOH, (C₂-C₅) - alkoxycarbonyl, NH₂, mono- or di- (C₁-C₄-alkyl) - amino or (C₁-C₄) - perfluoroalkyl means
R¹, R², R³ and R⁴ are the same or different and are hydrogen, hydroxy, halogen, cyano, trifluoromethyl, nitro, carboxy, (C₁-C₂₀) alkyl, (C₃-C₈) cycloalkyl, (C₃-C₈) cycloalkyl- (C₁-C₁₂) alkyl, (C₃-C₈) cycloalkoxy, (C₃-C₈) cycloalkyl- (C₁-C₁₂) alkoxy, (C₃-C₈) -cycloalkyloxy- (C₁-C₁₂) alkyl, (C₃ -C₈) -Cycloalkyloxy- (C₁-C₁₂) alkoxy, (C₃-C₈) cycloalkyl- (C₁ -C₈) alkyl- (C₁-C₆) alkoxy, (C₃-C₈) cycloalkyl- (C₁-C₈ ) -alkoxy- (C₁-C₆) -alkyl, (C₃-C₈) - cycloalkyloxy- (C₁-C₈) -alkoxy- (C₁-C₆) -alkyl, (C₃-C₈) -cycloalkoxy- (C₁-C₈) - alkoxy- (C₁-C₈) alkoxy, (C₆-C₁₂) aryl, (C₇-C₁₆) aralkyl, (C₂-C₂₀) alkenyl, (C₂-C₂₀) alkynyl, (C₁-C₂₀) alkoxy, (C₂-C₂₀) alkenyloxy, (C₂-C₂₀) alkynyloxy, retinyloxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxy, (C₁-C₁₂) alkoxy- (C₁-C₈) alkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy, (C -C₁₆) aralkyloxy, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxy, (C₇-C₁₆) - aralkoxy- (C₁-C₆) alkoxy, (C₁-C₈) hydroxyalkyl, (C₆-C₁₆ ) Aryloxy- (C₁-C₈) alkyl, (C₇-C₁₆) aralkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy- (C₁-C₈) alkoxy- (C₁-C₆) - alkyl, (C₇-C₁₂) aralkyloxy- (C₁-C₈) alkoxy- (C₁-C₆) alkyl, (C₂-C₂₀) - alkenyloxy- (C₁-C₆) alkyl, (C₂-C₂₀) alkynyloxy- (C₁-C₆) alkyl, retinyloxy- (C₁-C₆) alkyl, -O- [CH₂] _x C _f H _{(2f + 1-g)} F _g , -OCF₂Cl, -OCF₂-CHFCl,
(C₁-C₁₂) alkylcarbonyl, (C₃-C₈) cycloalkylcarbonyl, (C₆-C₁₂) arylcarbonyl, (C₇-C₁₆) aralkylcarbonyl, cinnamoyl, (C₂-C₁₂) alkenylcarbonyl, (C₂-C₁₂) alkynylcarbonyl,
(C₁-C₁₂) alkoxycarbonyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyl, (C₆-C₁₂) aryloxycarbonyl, (C₇-C₁₆) aralkoxycarbonyl, (C₃-C₈) - cycloalkoxycarbonyl, (C₂ -C₂₀) alkenyloxycarbonyl, retinyloxycarbonyl, (C₂-C₂₀) alkynyloxycarbonyl, (C₆-C₁₂) aryloxy (C₁-C₆) alkoxycarbonyl, (C₇-C₁₆) aralkoxy- (C₁-C₆) alkoxycarbonyl, (C₃- C₈) cycloalkyl (C₁-C₆) alkoxycarbonyl, (C₃-C₈) cycloalkoxy (C₁-C₆) alkoxycarbonyl,
(C₁-C₁₂) alkylcarbonyloxy, (C₃-C₈) cycloalkylcarbonyloxy, (C₆-C₁₂) arylcarbonyloxy, (C₇-C₁₆) aralkylcarbonyloxy, cinnamoyloxy, (C₂-C₁₂) alkenylcarbonyloxy, (C₂-C₁₂oxy) alkynylcarbonyloxy
(C₁-C₁₂) alkoxycarbonyloxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyloxy, (C₆-C₁₂) aryloxycarbonyloxy, (C₇-C₁₆) aralkyloxycarbonyloxy, (C₃-C₈) cycloalkoxycarbonyloxy, (C₂ -C₁₂) - alkenyloxycarbonyloxy, (C₂-C₁₂) alkynyloxycarbonyloxy,
Carbamoyl, N- (C₁-C₁₂) alkylcarbamoyl, N, N-di- (C₁-C₁₂) alkylcarbamoyl, N- (C₃-C₈) cycloalkylcarbamoyl, N, N-dicyclo- (C₃-C₈) alkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₃-C₈) cycloalkylcarbamoyl, N - ((C₃-C₈) cycloalkyl- (C₁-C₆) alkyl) carbamoyl, N- (C₁-C₆) alkyl -N - ((C₃-C₈) -cycloalkyl- (C₁-C₆) - alkyl) carbamoyl, N - (+) - dehydroabietylcarbamoyl, N- (C₁-C₆) alkyl-N - (+) - dehydroabietylcarbamoyl, N- (C₆-C₁₂) arylcarbamoyl, N- (C₇-C₁₆) aralkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₆) arylcarbamoyl, N- (C₁ -C₁₀) - alkyl-N- (C₇-C₁₆) aralkylcarbamoyl, N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₆-C₁₆) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆ ) aralkylo xy- (C₁-C₁₀) alkyl) carbamoyl, CON (CH₂) _h , in which a CH₂ group is represented by O, S, N- (C₁-CAl) alkylimino, N- (C₃-C -C) cycloalkylimino, N- (C₃-C₈) cycloalkyl- (C₁-C₄) alkylimino, N- (C₆-C₁₂) arylimino, N- (C₇-C₁₆) aralkylimino or N- (C₁-C₄) alkoxy- (C₁-C₆ ) alkylimino can be replaced and h is 3 to 7, or with
a carbamoyl radical of the general formula II

wherein
R ^x denotes the substituents of an α-amino acid, which include the L and D amino acids,
s 1, 2, 3, 4 or 5 and
T means OH, OR or NR * R **, where
R *, R ** and R *** are the same or different and are hydrogen (C₆-C₁₂) aryl, (C₇-C₁₁) aralkyl, (C₁-C₈) alkyl, (C₃-C₈) cycloalkyl, ( +) - Dehydroabietyl, (C₁-C₈) alkoxy- (C₁-C₈) alkyl, (C₇-C₁₂) - aralkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy- (C₁-C₈) -alkyl, (C₁-C₁₀) alkanoyl, optionally substituted (C₇-C₁₆) aralkanoyl, optionally substituted (C₆-C₁₂) aryl, or
R * and R ** together represent - [CH₂] _h , in which a CH₂ group is represented by O, S, SO, SO₂, N-acylamino, N- (C₁-C₁₀) alkoxycarbonylimino, N- (C₁-C₈) - Alkylimino, N- (C₃-C₈) -cycloalkylimino, N- (C₃-C₈) - cycloalkyl- (C₁-C₄) alkylimino, N- (C₆-C₁₂) arylimino, N- (C₇-C₁₆) aralkylimino or N- (C₁-C₄) alkoxy- (C₁-C₆) alkylimino can be replaced and h is 3 to 7, or with
Carbamoyloxy, N- (C₁-C₁₂) alkylcarbamoyloxy, N, N-Di- (C₁-C₁₂) alkylcarbamoyloxy, N- (C₃-C₈) cycloalkylcarbamoyloxy, N- (C₆-C₁₂) arylcarbamoyloxy, N- (C₇ -C₁₆) aralkylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₂) arylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylcarbamoyloxy, N - (( C₁-C₁₀) alkyl) carbamoyloxy, N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy , N- (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) -aryloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy, - amino, (C₁- C₁₂) alkylamino, di- (C₁-C₁₂) alkylamino, (C₃-C₈) - cycloalkylamino, (C₃-C₁₂) alkenylamino, (C₃-C₁₂) alkynylamino, N- (C₆-C₁₂) arylamino, N. - (C₇-C₁ ₁) aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C₁- C₁₂) alkoxyamino, (C₁-C₁₂) alkoxy-N- (C₁-C₁₀) alkylamino,
(C₁-C₁₂) alkanoylamino, (C₃-C₈) cycloalkanoylamino, (C₆-C₁₂) aroylamino, (C₇-C₁₆) aralkanoylamino, (C₁-C₁₂) alkanoyl-N- (C₁-C₁₀) alkylamino, (C₃-C₈) cycloalkanoyl-N- (C₁-C₁₀) alkylamino, (C₆-C₁₂) aroyl- N- (C₁-C₁₀) alkylamino, (C₇-C₁₁) aralkanoyl-N- (C₁-C₁₀ ) alkylamino,
(C₁-C₁₂) alkanoylamino- (C₁-C₈) alkyl, (C₃-C₈) cycloalkanoylamino- (C₁-C₈) alkyl, (C₆-C₁₂) aroylamino- (C₁-C₈) alkyl, (C₇ -C₁₆) - aralkanoylamino- (C₁-C₈) alkyl, amino- (C₁-C₁₀) alkyl, N- (C₁-C₁₀) alkylamino- (C₁-C₁₀) alkyl, N, N-di (C₁- C₁₀) alkylamino- (C₁-C₁₀) alkyl, (C₃-C₈) cycloalkylamino- (C₁-C₁₀) alkyl, (C₁-C₁₂) alkylmercapto, (C₁-C₁₂) alkylsulfinyl, (C₁-C₁₂) -Alkylsulfonyl, (C₆-C₁₂) arylmercapto, (C₆-C₁₂) - arylsulfinyl, (C₆-C₁₂) arylsulfonyl, (C₇-C₁₆) aralkylmercapto, (C₇-C₁₆) - aralkylsulfinyl, (C₇-C₁onyl) aralkylsulfinyl ,
Sulfamoyl, N- (C₁-C₁₀) alkylsulfamoyl, N, N-di- (C₁-C₁₀) alkylsulfamoyl, (C₃-C₈) cycloalkylsulfamoyl, N- (C₆-C₁₂) arylsulfamoyl, N- (C₇-C₁₆ ) Aralkylsulfamoyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₂) arylsulfamoyl, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylsulfamoyl, (C₁-C₁₀) - Alkyl sulfonamido, N - ((C₁-C₁₀) alkyl) - (C₁-C₁₀) alkylsulfonamido, (C₇-C₁₆) aralkylsulfonamido, N - ((C₁-C₁₀) alkyl- (C₇-C₁₆) aralkylsulfonamido , where the radicals which contain an aryl radical in turn can be substituted on the aryl by 1 to 5 identical or different radicals from the series:
Hydroxy, halogen, cyano, trifluoromethyl, nitro, carboxy, (C₁-C₁₂) alkyl, (C₃-C₈) cycloalkyl, (C₃-C₈) cycloalkyl- (C₁-C₁₂) alkyl, (C₃-C₈) - Cycloalkoxy, (C₃-C₈) cycloalkyl- (C₁-C₁₂) alkoxy, (C₃-C₈) cycloalkyloxy- (C₁-C₁₂) alkyl, (C₃-C₈) cycloalkyloxy- (C₁-C₁₂) alkoxy, (C₃-C₈) cycloalkyl- (C₁-C₈) alkyl- (C₁-C₆) alkoxy, (C₃-C₈) cycloalkyl- (C₁-C₈) alkoxy- (C₁-C₆) - alkyl, (C₃ -C₈) -Cycloalkyloxy- (C₁-C₈) alkoxy- (C₁-C₆) alkyl, (C₃-C₈) - cycloalkoxy- (C₁-C₈) alkoxy- (C₁-C₈) alkoxy, (C₆-C₁₂ ) Aryl, (C₇-C₁₆) aralkyl, (C₂-C₁₂) alkenyl, (C₂-C₁₂) alkynyl, (C₁-C₁₂) alkoxy, (C₁-C₁₂) - alkoxy- (C₁-C₁₂) - alkyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxy, (C₁-C₁₂) alkoxy- (C₁-C₈) alkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy, (C₇-C₁₆) aralkyloxy, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxy, (C₇-C₁₆) aralkoxy- (C₁-C₆) alkoxy, (C₁-C₈) hydroxyalkyl , (C₆-C₁₆) aryloxy- (C₁-C₈) alkyl, (C₇-C₁₆) aralkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy- (C₁-C₈) alkoxy- ( C₁-C₆) alkyl, (C₇-C₁₂) aralkyloxy- (C₁-C₈) alkoxy- (C₁-C₆) alkyl, -O- [CH _2- ] _x C _f H _{(2f + 1-g)} F _g , -OCF₂Cl, -OCF₂-CHFCl,
(C₁-C₁₂) alkylcarbonyl, (C₃-C₈) cycloalkylcarbonyl, (C₆-C₁₂) arylcarbonyl, (C₇-C₁₆) aralkylcarbonyl,
(C₁-C₁₂) alkoxycarbonyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyl, (C₆-C₁₂) aryloxycarbonyl, (C₇-C₁₆) aralkoxycarbonyl, (C₃-C₈) - cycloalkoxycarbonyl, (C₂ -C₁₂) alkenyloxycarbonyl, (C₂-C₁₂) alkynyloxycarbonyl, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxycarbonyl, (C₇-C₁₆) - aralkoxy- (C₁-C₆) alkoxycarbonyl, (C₃-C₈ ) -Cycloalkyl- (C₁-C₆) alkoxycarbonyl, (C₃-C₈) -cycloalkoxy- (C₁-C₆) alkoxycarbonyl,
(C₁-C₁₂) alkylcarbonyloxy, (C₃-C₈) cycloalkylcarbonyloxy, (C₆-C₁₂) arylcarbonyloxy, (C₇-C₁₆) aralkylcarbonyloxy, cinnamoyloxy, (C₂-C₁₂) alkenylcarbonyloxy, (C₂-C₁₂), alkynylcarbonyloxy
(C₁-C₁₂) alkoxycarbonyloxy, (C₁-C₁₂) alkoxy (C₁-C₁₂) alkoxycarbonyloxy, (C₆-C₁₂) aryloxycarbonyloxy, (C₇-C₁₆) aralkyloxycarbonyloxy, (C₃-C₈) cycloalkoxycarbonyloxy, (C₂- C₁₂) - alkenyloxycarbonyloxy, (C₂-C₁₂) alkynyloxycarbonyloxy,
Carbamoyl, N- (C₁-C₁₂) alkylcarbamoyl, N, N-di- (C₁-C₁₂) alkylcarbamoyl, N- (C₃-C₈) cycloalkylcarbamoyl, N, N-dicyclo- (C₃-C₈) alkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₃-C₈) cycloalkylcarbamoyl, N - ((C₃-C₈) cycloalkyl- (C₁-C₆) alkyl) carbamoyl, N- (C₁-C₆) alkyl -N - ((C₃-C₈) -cycloalkyl- (C₁-C₆) - alkyl) carbamoyl, N - (+) - dehydroabietylcarbamoyl, N- (C₁-C₆) alkyl-N - (+) - dehydroabietylcarbamoyl, N- (C₆-C₁₂) arylcarbamoyl, N- (C₇-C₁₆) aralkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₆) arylcarbamoyl, N- (C₁-C₁₀) - alkyl-N- (C₇-C₁₆) aralkylcarbamoyl, N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₆-C₁₆) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆ ) aralkylox y- (C₁-C₁₀) alkyl) carbamoyl, CON (CH₂) _h , in which a CH₂ group is represented by O, S, N- (C₁-C₈) alkylimino, N- (C₃-C₈) cycloalkylimino, N- (C₃-C₈) cycloalkyl- (C₁-C₄) alkylimino, N- (C₆-C₁₂) arylimino, N- (C₇-C₁₆) aralkylimino or N- (C₁-C₄) alkoxy- (C₁-C₆ ) alkylimino can be replaced and h is 3 to 7,
Carbamoyloxy, N- (C₁-C₁₂) alkylcarbamoyloxy, N, N-Di- (C₁-C₁₂) alkylcarbamoyloxy, N- (C₃-C₈) cycloalkylcarbamoyloxy, N- (C₆-C₁₆) arylcarbamoyloxy, N- (C₇ -C₁₆) aralkylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₂) arylcarbamoyloxy, N- (C₁-C₁₀) alkyl N- (C₇-C₁₆) aralkylcarbamoyloxy, N - ((C₁- C₁₀) alkyl) carbamoyloxy, N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N ((C₇-C₁₆) aralkyloxy- (C₁-C ₁₀) alkyl) carbamoyloxy, N - (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) aryloxy - (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy, - amino, (C₁-C₁₂) Alkylamino, di- (C₁-C₁₂) alkylamino, (C₃-C₈) cycloalkylamino, (C₃-C₁₂) alkenylamino, (C₃-C₁₂) alkynylamino, N- (C₆-C₁₂) arylamino, N- ( C₇-C₁₁) aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C₁- C₁₂) alkoxyamino, (C₁-C₁₂) alkoxy-N- (C₁-C₁₀) alkylamino,
(C₁-C₁₂) alkanoylamino, (C₃-C₈) cycloalkanoylamino, (C₆-C₁₂) aroylamino, (C₇-C₁₆) aralkanoylamino, (C₁-C₁₂) alkanoyl-N- (C₁-C₁₀) alkylamino, (C₃-C₈) cycloalkanoyl-N- (C₁-C₁₀) alkylamino, (C₆-C₁₂) aroyl- N- (C₁-C₁₀) alkylamino, (C₇-C₁₁) aralkanoyl-N- (C₁-C₁₀ ) alkylamino,
(C₁-C₁₂) alkanoylamino- (C₁-C₈) alkyl, (C₃-C₈) cycloalkanoylamino- (C₁-C₈) alkyl, (C₆-C₁₂) aroylamino- (C₁-C₈) alkyl, (C₇ -C₁₆) - aralkanoylamino- (C₁-C₈) alkyl, amino- (C₁-C₁₀) alkyl, N- (C₁-C₁₀) alkylamino- (C₁-C₁₀) alkyl, N, N-di- (C₁ -C₁₀) alkylamino- (C₁-C₁₀) alkyl, (C₃-C₈) cycloalkylamino- (C₁-C₁₀) alkyl,
(C₁-C₁₂) alkylmercapto, (C₁-C₁₂) alkylsulfinyl, (C₁-C₁₂) alkylsulfonyl, (C₆-C₁₆) arylmercapto, (C₆-C₁₆) arylsulfinyl, (C₆-C₁₆) arylsulfonyl, (C₆ -C₁₆) aralkylmercapto, (C₇-C₁₆) aralkylsulfinyl, (C₇-C₁₆) aralkylsulfonyl,
R¹ and R², R² and R³ or R³ and R⁴ can form a chain [CH₂] _o , in which one or two CH₂ groups of the saturated or unsaturated chain with a C = C double bond optionally by O, S, SO, SO₂ or NR 'are replaced, o = 3, 4 or 5 means and
R ′ is hydrogen, (C₆-C₁₂) aryl, (C₁-C₈) alkyl, (C₁-C₈) alkoxy- (C₁-C₈) alkyl, (C₇-C₁₂) aralkoxy- (C₁-C₈) - alkyl, (C₆-C₁₂) aryloxy- (C₁-C₈) alkyl, (C₁-C₁₀) alkanoyl, optionally substituted (C₇-C₁₆) aralkanoyl, optionally substituted (C₆-C₁₂) aryl,
R⁵ is hydrogen or a branched or unbranched (C₁-C₂₀) alkyl radical, a (C₆-C₁₆) aryl radical or a (C₇-C₁₆) aralkyl radical,
these radicals being substituted by one or more radicals from the series
Hydroxy, halogen, cyano, trifluoromethyl, nitro, carboxy, (C₁-C₁₂) alkyl, (C₃-C₈) cycloalkyl, (C₃-C₈) cycloalkyl- (C₁-C₁₂) alkyl, (C₃-C₈) - Cycloalkoxy, (C₃-C₈) cycloalkyl- (C₁-C₁₂) alkoxy, (C₃-C₈) cycloalkyloxy- (C₁-C₁₂) alkyl, (C₃-C₈) cycloalkyloxy- (C₁-C₁₂) alkoxy, (C₃-C₈) -cycloalkyl- (C₁-C₈) -alkyl- (C₁-C₆) - alkoxy, (C₃-C₈) -cycloalkyl- (C₁-C₈) alkoxy- (C₁-C₆) alkyl, (C₃ -C₈) -Cycloalkyloxy- (C₁-C₈) alkoxy- (C₁-C₆) alkyl, (C₃-C₈) -cycloalkoxy- (C₁-C₈) alkoxy- (C₁-C₈) alkoxy, (C₆-C₁₂ ) Aryl, (C₇-C₁₆) aralkyl, (C₂-C₁₂) alkenyl, (C₂-C₁₂) alkynyl, (C₁-C₁₂) alkoxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) - alkyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxy, (C₁-C₁₂) alkoxy- (C₁-C₈) alkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy, (C₇-C₁₆) aralkyloxy, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxy, (C₇-C₁₆) aralkoxy- (C₁-C₆) alkoxy, (C₁-C₈) hydroxyalkyl, ( C₆-C₁₆) aryloxy- (C₁-C₈) alkyl, (C₇-C₁₆) aralkoxy- (C₁-C₈) - alkyl, (C₆-C₁₂) aryloxy- (C₁-C₈) alkoxy- (C₁- C₆) alkyl, (C₇-C₁₂) aralkyloxy- (C₁-C₈) alkoxy- (C₁-C₆) alkyl, -O- [CH _2- ] _x C _f H _{(2f + 1-g)} F _g , -OCF₂Cl, -OCF₂-CHFCl,
(C₁-C₁₂) alkylcarbonyl, (C₃-C₈) cycloalkylcarbonyl, (C₆-C₁₂) arylcarbonyl, (C₇-C₁₆) aralkylcarbonyl, cinnamoyl, (C₂-C₁₂) alkenylcarbonyl, (C₂-C₁₂) alkynylcarbonyl,
(C₁-C₁₂) alkoxycarbonyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyl, (C₆-C₁₂) aryloxycarbonyl, (C₇-C₁₆) aralkoxycarbonyl, (C₃-C₈) cycloalkoxycarbonyl, (C₂ -C₁₂) alkenyloxycarbonyl, (C₂-C₁₂) alkynyloxycarbonyl, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxycarbonyl, (C₇-C₁₆) aralkoxy- (C₁-C₆) alkoxycarbonyl, (C₃-C₈ ) - Cycloalkyl- (C₁-C₆) -alkoxycarbonyl, (C₃-C₈) -cycloalkoxy- (C₁-C₆) -alkoxycarbonyl, (C₁-C₁₂) -alkylcarbonyloxy, (C₃-C₈) -cycloalkylcarbonyloxy, (C₆-C₁₂) - Arylcarbonyloxy, (C₇-C₁₆) aralkylcarbonyloxy, cinnamoyloxy, (C₂-C₁₂) alkenylcarbonyloxy, (C₂-C₁₂) alkynylcarbonyloxy,
(C₁-C₁₂) alkoxycarbonyloxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyloxy, (C₆-C₁₂) aryloxycarbonyloxy, (C₇-C₁₆) aralkyloxycarbonyloxy, (C₃-C₈) - cycloalkoxycarbonyloxy, (C₂ -C₁₂) alkenyloxycarbonyloxy, (C₂-C₁₂) alkynyloxycarbonyloxy,
Carbamoyl, N- (C₁-C₁₂) alkylcarbamoyl, N, N-di- (C₁-C₁₂) alkylcarbamoyl, N- (C₃-C₈) cycloalkylcarbamoyl, N, N-dicyclo- (C₃-C₈) alkylcarbamoyl, N- (C₁-C₁₀) - alkyl-N- (C₃-C₈) -cycloalkylcarbamoyl, N - ((C₃-C₈) -cycloalkyl- (C₁-C₆) - alkyl) carbamoyl, N- (C₁-C₆) alkyl -N - ((C₃-C₈) cycloalkyl- (C₁-C₆) alkyl) carbamoyl, N - (+) - dehydroabietylcarbamoyl, N- (C₁-C₆) alkyl-N - (+) - dehydroabietylcarbamoyl, N- (C₆-C₁₂) arylcarbamoyl, N- (C₇-C₁₆) aralkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₆) arylcarbamoyl, N- (C₁-C₁₀) alkyl- N- (C₇-C₁₆) aralkylcarbamoyl, N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₆-C₁₆) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆ ) aralkylo xy- (C₁-C₁₀) alkyl) carbamoyl, CON (CH₂) _h , in which a CH₂ group through O, S, N- (C₁-C₈) alkylimino, N- (C₃-C₈) - cycloalkylimino, N- (C₃-C₈) cycloalkyl- (C₁-C₄) alkylimino, N- (C₆-C₁₂) arylimino, N- (C₇-C₁₆) aralkylimino or N- (C₁-C₄) alkoxy (C₁-C₆) -alkylimino can be replaced and h is 3 to 7, or with
a carbamoyl radical of the general formula II

wherein
R ^x denotes the substituents of an α-amino acid, which include the L and D amino acids,
s 1, 2, 3, 4 or 5 and
T means OH, OR or NR * R **, where
R *, R ** and R *** are the same or different and are hydrogen, (C₆-C₁₂) aryl, (C₇-C₁₁) aralkyl, (C₁-C₈) alkyl, (C₃-C₈) cycloalkyl, (+) - Dehydroabietyl, (C₁-C₈) alkoxy- (C₁-C₈) alkyl, (C₇-C₁₂) - aralkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy- (C₁-C₈ ) alkyl, (C₁-C₁₀) alkanoyl, optionally substituted (C₇-C₁₆) aralkanoyl, optionally substituted (C₆-C₁₂) aroyl, or
R * and R ** together represent - [CH₂] _h , in which a CH₂ group is represented by O, S, SO, SO₂, N-acylamino, N- (C₁-C₁₀) alkoxycarbonylimino, N- (C₁-C₈) - Alkylimino, N- (C₃-C₈) -cycloalkylimino, N- (C₃-C₈) - cycloalkyl- (C₁-C₄) alkylimino, N- (C₆-C₁₂) arylimino, N- (C₇-C₁₆) aralkylimino or N- (C₁-C₄) alkoxy- (C₁-C₆) alkylimino can be replaced and h is 3 to 7, or with
Carbamoyloxy, N- (C₁-C₁₂) alkylcarbamoyloxy, N, N-Di- (C₁-C₁₂) alkylcarbamoyloxy, N- (C₃-C₈) cycloalkylcarbamoyloxy, N- (C₆-C₁₂) arylcarbamoyloxy, N- (C₇ -C₁₆) aralkylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₂) arylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylcarbamoyloxy, N - (( C₁-C₁₀) alkyl) carbamoyloxy, N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy , N- (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) -aryloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy, - amino, (C₁- C₁₂) alkylamino, di- (C₁-C₁₂) alkylamino, (C₃-C₈) - cycloalkylamino, (C₃-C₁₂) alkenylamino, (C₃-C₁₂) alkynylamino, N- (C₆-C₁₂) arylamino, N. - (C₇-C₁₁) aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C₁-C ₁₂) alkoxyamino, (C₁-C₁₂) alkoxy-N- (C₁-C₁₀) alkylamino,
(C₁-C₁₂) alkanoylamino, (C₃-C₈) cycloalkanoylamino, (C₆-C₁₂) aroylamino, (C₇-C₁₆) aralkanoylamino, (C₁-C₁₂) alkanoyl-N- (C₁-C₁₀) alkylamino, (C₃-C₈) cycloalkanoyl-N- (C₁-C₁₀) alkylamino, (C₆-C₁₂) aroyl- N- (C₁-C₁₀) alkylamino, (C₇-C₁₁) aralkanoyl-N- (C₁-C₁₀ ) alkylamino,
(C₁-C₁₂) alkanoylamino- (C₁-C₈) alkyl, (C₃-C₈) cycloalkanoylamino- (C₁-C₈) alkyl, (C₆-C₁₂) aroylamino- (C₁-C₈) alkyl, (C₇ -C₁₆) - aralkanoylamino- (C₁-C₈) alkyl, amino- (C₁-C₁₀) alkyl, N- (C₁-C₁₀) alkylamino- (C₁-C₁₀) alkyl, N, N-di (C₁- C₁₀) alkylamino- (C₁-C₁₀) alkyl, (C₃-C₈) cycloalkylamino- (C₁-C₁₀) alkyl,
(C₁-C₁₂) alkylmercapto, (C₁-C₁₂) alkylsulfinyl, (C₁-C₁₂) alkylsulfonyl, (C₆-C₁₂) arylmercapto, (C₆-C₂) arylsulfinyl, (C₆-C₁₂) arylsulfonyl, (C₇ -C₁₆) aralkylmercapto, (C₇-C₁₆) aralkylsulfinyl, (C₇-C₁₆) aralkylsulfonyl,
Sulfamoyl, N- (C₁-C₁₀) alkylsulfamoyl, N, N-di- (C₁-C₁₀) alkylsulfamoyl, (C₃-C₈) cycloalkylsulfamoyl, N- (C₆-C₁₂) arylsulfamoyl, N- (C₇-C₁₆ ) Aralkylsulfamoyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₂) arylsulfamoyl, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylsulfamoyl, (C₁-C₁₀) - Alkylsulfonamido, N - ((C₁-C₁₀) alkyl) - (C₁-C₁₀) alkylsulfonamido, (C₇-C₁₆) aralkylsulfonamido, N - ((C₁-C₁₀) alkyl (C₇-C₁₆) aralkylsulfonamido, where the radicals which contain an aryl radical in turn can be substituted on the aryl by 1 to 5 identical or different radicals from the series:
Hydroxy, halogen, cyano, trifluoromethyl, nitro, carboxy, (C₁-C₁₂) alkyl, (C₃-C₈) cycloalkyl, (C₃-C₈) cycloalkyl- (C₁-C₁₂) alkyl, (C₃-C₈) - Cycloalkoxy, (C₃-C₈) cycloalkyl- (C₁-C₁₂) alkoxy, (C₃-C₈) cycloalkyloxy- (C₁-C₁₂) alkyl, (C₃-C₈) cycloalkyloxy- (C₁-C₁₂) alkoxy, (C₃-C₈) cycloalkyl- (C₁-C₈) alkyl- (C₁-C₆) alkoxy, (C₃-C₈) cycloalkyl- (C₁-C₈) alkoxy- (C₁-C₆) - alkyl, (C₃ -C₈) -Cycloalkyloxy- (C₁-C₈) alkoxy- (C₁-C₆) alkyl, (C₃-C₈) - cycloalkoxy- (C₁-C₈) alkoxy- (C₁-C₈) alkoxy, (C₆-C₁₂ ) Aryl, (C₇-C₁₆) aralkyl, (C₂-C₁₂) alkenyl, (C₂-C₁₂) alkynyl, (C₁-C₁₂) alkoxy, (C₁-C₁₂) - alkoxy- (C₁-C₁₂) - alkyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxy, (C₁-C₁₂) alkoxy- (C₁-C₈) alkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy, (C₇-C₁₆) aralkyloxy, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxy, (C₇-C₁₆) aralkoxy- (C₁-C₆) alkoxy, (C₁-C₈) hydroxyalkyl , (C₆-C₁₆) aryloxy- (C₁-C₈) alkyl, (C₇-C₁₆) aralkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy- (C₁-C₈) alkoxy- ( C₁-C₆) alkyl, (C₇-C₁₂) aralkyloxy- (C₁-C₈) alkoxy- (C₁-C₆) alkyl, -O- [CH _2- ] _x C _f H _{(2f + 1-g)} F _g , -OCF₂Cl, -OCF₂-CHFCl,
(C₁-C₁₂) alkylcarbonyl, (C₃-C₈) cycloalkylcarbonyl, (C₆-C₁₂) arylcarbonyl, (C₇-C₁₆) aralkylcarbonyl,
(C₁-C₁₂) alkoxycarbonyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyl, (C₆-C₁₂) aryloxycarbonyl, (C₇-C₁₆) aralkoxycarbonyl, (C₃-C₈) - cycloalkoxycarbonyl, (C₂ -C₁₂) alkenyloxycarbonyl, (C₂-C₁₂) - alkynyloxycarbonyl, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxycarbonyl, (C₇-C₁₆) - aralkoxy- (C₁-C₆) alkoxycarbonyl, (C₃- C₈ ) -Cycloalkyl- (C₁-C₆) alkoxycarbonyl, (C₃-C₈) -cycloalkoxy- (C₁-C₆) alkoxycarbonyl,
(C₁-C₁₂) alkylcarbonyloxy, (C₃-C₈) cycloalkylcarbonyloxy, (C₆-C₁₂) arylcarbonyloxy, (C₇-C₁₆) aralkylcarbonyloxy, cinnamoyloxy, (C₂-C₁₂) alkenylcarbonyloxy, (C₂-C₁₂), alkynylcarbonyloxy (C₁-C₁₂) alkoxycarbonyloxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyloxy, (C₆-C₁₂) aryloxycarbonyloxy, (C₇-C₁₆) aralkyloxycarbonyloxy, (C₃-C₈) cycloalkoxycarbonyloxy, (C₂ -C₁₂) - alkenyloxycarbonyloxy, (C₂-C₁₂) alkynyloxycarbonyloxy,
Carbamoyl, N- (C₁-C₁₂) alkylcarbamoyl, N, N-di- (C₁-C₁₂) alkylcarbamoyl, N- (C₃-C₈) cycloalkylcarbamoyl, N, N-dicyclo- (C₃-C₈) alkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₃-C₈) cycloalkylcarbamoyl, N - ((C₃-C₈) cycloalkyl- (C₁-C₆) alkyl) carbamoyl, N- (C₁-C₆) alkyl -N - ((C₃-C₈) -cycloalkyl- (C₁-C₆) - alkyl) carbamoyl, N - (+) - dehydroabietylcarbamoyl, N- (C₁-C₆) alkyl-N - (+) - dehydroabietylcarbamoyl, N- (C₆-C₁₂) arylcarbamoyl, N- (C₇-C₁₆) aralkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₆) arylcarbamoyl, N- (C₁-C₁₀) - alkyl-N- (C₇-C₁₆) aralkylcarbamoyl, N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₆-C₁₆) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆ ) aralkyl oxy- (C₁-C₁₀) alkyl) carbamoyl, CON (CH₂) _h , in which a CH₂ group is represented by O, S, N- (C₁-C₈) alkylimino, N- (C₃-C₈) cycloalkylimino, N- (C₃-C₈) cycloalkyl- (C₁-C₄) alkylimino, N- (C₆-C₁₂) arylimino, N- (C₇-C₁₆) aralkylimino or N- (C₁-C₄) alkoxy- (C₁-C₆ ) alkylimino can be replaced and h is 3 to 7,
Carbamoyloxy, N- (C₁-C₁₂) alkylcarbamoyloxy, N, N-Di- (C₁-C₁₂) alkylcarbamoyloxy, N- (C₃-C₈) cycloalkylcarbamoyloxy, N- (C₆-C₁₆) arylcarbamoyloxy, N- (C₇ -C₁₆) aralkylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N-
(C₆-C₁₂) arylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylcarbamoyloxy, N - ((C₁-C₁₀) alkyl) carbamoyloxy,
N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀ ) -Alkyl-N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀ ) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁ ₀) alkyl) carbamoyloxy,
Amino, (C₁-C₁₂) alkylamino, di- (C₁-C₁₂) alkylamino, (C₃-C₈) - cycloalkylamino, (C₃-C₁₂) alkenylamino, (C₃-C₁₂) alkynylamino, N- (C₆- C₁₂ ) Arylamino, N- (C₇-C₁₁) aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C₁-C₁₂) alkoxyamino, (C₁-C₁₂) alkoxy-N- (C₁-C₁₀) - alkylamino,
(C₁-C₁₂) alkanoylamino, (C₃-C₈) cycloalkanoylamino, (C₆-C₁₂) aroylamino, (C₇-C₁₆) aralkanoylamino, (C₁-C₁₂) alkanoyl-N- (C₁-C₁₀) alkylamino, (C₃-C₈) cycloalkanoyl-N- (C₁-C₁₀) alkylamino, (C₆-C₁₂) aroyl-N- (C₁-C₁₀) alkylamino, (C₇-C₁₁) aralkanoyl-N- (C₁-C₁₀ ) - alkylamino,
(C₁-C₁₂) alkanoylamino- (C₁-C₈) alkyl, (C₃-C₈) cycloalkanoylamino- (C₁-C₈) alkyl, (C₆-C₁₂) aroylamino- (C₁-C₈) alkyl, (C₇ -C₁₆) - aralkanoylamino- (C₁-C₈) alkyl, amino- (C₁-C₁₀) alkyl, N- (C₁-C₁₀) alkylamino- (C₁-C₁₀) alkyl, N, N-di- (C₁ -C₁₀) alkylamino- (C₁-C₁₀) alkyl, (C₃-C₈) cycloalkylamino- (C₁-C₁₀) alkyl,
(C₁-C₁₂) alkylmercapto, (C₁-C₁₂) alkylsulfinyl, (C₁-C₁₂) alkylsulfonyl, (C₆-C₁₆) arylmercapto, (C₆-C₁₆) arylsulfinyl, (C₆-C₁₆) arylsulfonyl, (C₆ -C₁₆) aralkylmercapto, (C₇-C₁₆) aralkylsulfinyl, (C₇-C₁₆) aralkylsulfonyl,
and
f = 1 to 8,
g = 0.1 to (2f + 1),
x = 0 to 3,
h = 3 to 6 mean
including the physiologically active salts,
where N - ((6,7-dichloro-3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine and α- ((6,7-dichloro-3,4-dihydro-3-oxo-2 -chinoxalinyl) carbonyl) amino) phenyl-acetic acid are excluded.

Aryl is generally carbocyclic and heterocyclic understood aromatic ring systems. This is understood in particular Phenyl, biphenyl or naphthyl or unsubstituted 5- and 6-membered heteroaromatic rings with 1, 2 or 3 nitrogen and / or oxygen and / or sulfur atoms, such as pyridyl, pyridazyl, pyrimidyl, pyrazyl, Imidazolyl, triazolyl, thienyl, oxazolyl, and thiazolyl derivatives, and their benzo-fused derivatives. Phenyl, pyridyl and thienyl are preferred.

The invention further encompasses salts of the compounds of the general Formula I.

Salt formation with basic reagents can be done once, twice or three times at the Acid groups of the compounds of formula I take place, in particular on the Residues B and R⁵.

Reagents used are, for example, alcoholates, hydroxides, carbonates, hydrogen carbonates, hydrogen phosphates, metal organyls of the alkali and alkaline earth elements, the elements of the 3rd and 4th main group of the periodic table and the elements of the transition metals,
Amines, optionally 1 to 3 times substituted with (C₁-C₈) hydroxyalkyl, (C₁-C₄) alkoxy- (C₁-C₈) alkyl, phenyl, benzyl or (C₁-C₈) alkyl, which 1 - Can be substituted up to 3 times with hydroxy or (C₁-C₄) alkoxy, for example tromethane (Tris buffer), 2-aminoethanol, 3-aminopropanol, hydroxylamine, dimethylhydroxylamine, 2-methoxyethylamine, 3-ethoxypropylamine, and basic amino acids and derivatives, such as amino acid esters, histidine, arginine and lysine and their derivatives, and
Medicines containing a basic group, such as ®Amilorid, ®Verapamil and beta blockers.

The invention further relates to the compounds according to formula I, plus N - ((6,7-dichloro-3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine and α - ((6,7- Dichloro-3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) amino) phenylacetic acid for Use of medicines.

Preferred compounds of the formula I are those in which
QO or S,
XO,
A (C₁-C₃) alkylene, which is optionally monosubstituted with halogen, cyano, trifluoromethyl, (C₁-C₆) alkyl, (C₁-C₆) hydroxyalkyl, (C₁ -C₆) alkoxy, -O- [CH₂ ] _x -C _f H _{(2f + 1-g)} F _g or
A means -CHR⁶-, where R⁶ means one of the substituents of the α-C atom of an α-amino acid, in particular a natural L-amino acid and its D isomer,
B CO₂H
R¹, R², R³ and R⁴ are the same or different and are hydrogen, (C₁-C₂₀) alkyl, (C₂-C₂₀) alkenyloxy, (C₂-C₂₀) alkynyloxy, retinyloxy, (C₂-C₂₀) - alkenyloxy- (C₁ -C₃) alkyl, retinyloxy- (C₁-C₃) alkyl, (C₂-C₂₀) alkynyloxy- (C₁-C₃) alkyl, (C₁-C₂₀) alkoxy, halogen, cyano, trifluoromethyl, (C₁-C₈ ) - Hydroxyalkyl, (C₁-C₁₀) alkanoyl, (C₇-C₁₂) aralkanoyl, (C₆-C₁₂) aroyl, -O- [CH₂] _x C _f H _{(2f + 1-g)} F _g , (C₁ -C₁₀) alkylmercapto, (C₁-C₁₀) alkylsulfinyl, (C₁-C₁₀) alkylsulfonyl, (C₆-C₁₂) arylmercapto, (C₆-C₁₂) arylsulfinyl, (C₆-C₁₂) arylsulfonyl, (C₇-C₁ ) Aralkylmercapto, (C₇-C₁₂) aralkylsulfinyl, (C₇-C₁₂) aralkylsulfonyl, (C₆-C₁₂) aryloxy, (C₇-C₁₆) aralkyloxy, carboxy, (C₁-C₂₀) alkoxycarbonyl, (C₁-C₁₂ ) Alkoxy- (C₁-C₁₂) alkoxycarbonyl, (C₆-C₁₂) aryloxycarbonyl, (C₇-C₁₆) aralkoxycarbonyl, (C₃-C₈) - cycloalkoxycarbonyl, (C₂-C₂₀) - Alkenyloxycarbonyl, retinyloxycarbonyl, (C₂-C₂₀) alkynyloxycarbonyl, (C₃-C₈) cycloalkyl- (C₁-C₆) alkoxycarbonyl, (C₃-C₈) -cycloalkoxy- (C₁-C₆) alkoxycarbonyl, (C₆-C₁₂) - Aryloxy- (C₁-C₆) alkoxycarbonyl, (C₇-C₁₆) aralkoxy- (C₁-C₆) alkoxycarbonyl,
(C₁-C₁₂) alkoxy- (C₁-C₁₂) alkyl, (C₁-C₈) alkoxy- (C₁-C₁₂) alkoxy, (C₁-C₁₂) alkoxy- (C₁-C₈) alkoxy- (C₂ -C₆) alkyl, (C₇-C₁₁) aralkyloxy, (C₃-C₈) - cycloalkyl, (C₃-C₈) cycloalkyl- (C₁-C₈) alkyl, (C₃-C₈) cycloalkyloxy, (C₃-C₈ ) -Cycloalkyl- (C₁-C₈) -alkoxy, (C₃-C₈) -cycloalkyloxy- (C₁-C₈) -alkyl, (C₃-C₈) -cycloalkyloxy- (C₁-C₈) -alkoxy, (C₃-C₈) - Cycloalkyl- (C₁-C₆) -alkyl- (C₁-C₆) -alkoxy, (C₃-C₈) -cycloalkyl- (C₁-C₆) -alkoxy- (C₁-C₆) -alkyl, (C₃-C₈) -cycloalkoxy- (C₁-C₆) alkoxy- (C₁-C₆) alkyl, NR ^Y R ^Z , substituted (C₆-C₁₂) aryloxy- (C₁-C₆) alkyl, (C₇-C₁₁) aralkoxy- (C₁-C₆ ) alkyl, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxy- (C₁-C₁) alkyl, (C₇-C₁₁) aralkyloxy- (C₁-C₆) alkoxy- (C₁-C₆) - are alkyl, (C₆-C₁₂) aryloxy, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxy or (C₇-C₁₁) - aralkoxy- (C₁-C₆) alkoxy, an aromatic radical having 1, 2, 3, 4 or 5 identical or different substituents from the series hydrogen, halogen, cyano, nitro, trifluoromethyl, (C₁-C₆) alkyl, (C₁-C₆) hydroxyalkyl, (C₁-C₆) alkoxy, -O- [CH₂] _x C _f H _{(2f + 1-g)} F _g , -OCF₂Cl, -O-CF₂-CHFCl, (C₁-C₆) alkyl mercapto, (C₁-C₆) alkylsulfinyl, (C₁-C₆) alkylsulfonyl, (C₁-C₆ ) -Alkylcarbonyl, (C₁-C₆) -alkoxycarbonyl, carbamoyl, N- (C₁-C₄) -alkylcarbamoyl, N, N-di- (C₁-C₄) -alkylcarbamoyl, (C₁-C₆) - alkylcarbonyloxy, (C₃-C₈ ) -Cycloalkylcarbamoyl, phenyl, benzyl, phenoxy, benzyloxy, NR ^Y R ^Z , phenylmercapto, phenylsulfonyl, phenylsulfinyl, sulfamoyl, N- (C₁-C₄) alkylsulfamoyl or N, N-di- (C₁-C₄) -alkylsulfamoyl, or optionally carries up to 3 of the same or different substituents mentioned above and two adjacent C atoms of the aralkyloxy radical together bear a chain - [CH₂-] and / or -CH = CH-CH = CH-, one CH₂ group of the chain optionally replaced by O, S, SO, SO₂ or NR ' is
Carbamoyl, N- (C₁-C₁₂) alkylcarbamoyl, N, N-di- (C₁-C₁₂) alkylcarbamoyl, N- (C₃-C₈) cycloalkylcarbamoyl, N, N-dicyclo (C₃-C₈) alkylcarbamoyl, N - (C₁-C₁₀) alkyl-N- (C₃-C₈) cycloalkylcarbamoyl, N- (C₃-C₈) cycloalkyl- (C₁-C₆) alkyl) carbamoyl, N- (C₁-C₆) alkyl-N - ((C₃-C₈) -cycloalkyl- (C₁-C₆) - alkyl) carbamoyl, N - (+) - dehydroabietylcarbamoyl, N- (C₁-C₆) alkyl-N - (+) - dehydroabietylcarbamoyl, N- (C₆ -C₁₂) arylcarbamoyl, N- (C₇-C₁₆) aralkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₆) arylcarbamoyl, N- (C₁ -C₁₀) - alkyl-N- (C₇ -C₁₆) aralkylcarbamoyl, N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₆-C₁₆) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N- ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N- ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆) - aralkylox y- (C₁-C₁₀) alkyl) carbamoyl, CON (CH₂) _h , in which a CH₂ group is represented by O, S, N- (C₁-C₈) alkylimino, N- (C₃-C₈) cycloalkylimino, N- (C₃-C₈) cycloalkyl- (C₁-C₄) alkylimino, N- (C₆-C₁₂) arylimino, N- (C₇-C₁₆) aralkylimino or N- (C₁-C₄) alkoxy- (C₁-C₆ ) alkylimino can be replaced and h is 3 to 7,
R¹ and R² or R² and R³ or R³ and R⁴ can form a chain [CH₂] _o , where o = 3, 4 or 5,
R⁵ is hydrogen or a branched or unbranched (C₁-C₁₂) alkyl radical which can contain up to 3 CC multiple bonds, a (C₆- C₁₆) aryl radical or a (C₇-C₁₆) aralkyl radical which contains up to 2 CC multiple compounds can contain means, where these radicals are substituted with one or more radicals from the series hydroxy, fluorine, chlorine, cyano, trifluoromethyl, carboxy, (C₁-C₁₂) alkyl, (C₃-C₈) - cycloalkyl, (C₃-C₈ ) -Cycloalkoxy, (C₃-C₈) -cycloalkyl- (C₁-C₁₂) -alkoxy, (C₃-C₈) -cycloalkyloxy- (C₁-C₁₂) -alkoxy, (C₆-C₁₂) -aryl, (C₇-C₁₆) - Aralkyl, (C₂-C₁₂) alkenyl, (C₂-C₁₂) alkynyl, (C₁-C₁₂) alkoxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxy, (C₆-C₁₂) aryloxy, (C₇-C₁₆) aralkyloxy, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxy, (C₇-C₁₆) aralkoxy- (C₁-C₆) alkoxy, (C₁-C₈) hydroxyalkyl, - O - [CH _2- ] _x C _f H _{(2f + 1-g)} F _g ,
Carbamoyl, N- (C₁-C₁₂) alkylcarbamoyl, N, N-di- (C₁-C₁₂) alkylcarbamoyl, N- (C₃-C₈) cycloalkylcarbamoyl, N, N-dicyclo- (C₃-C₈) alkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₃-C₈) cycloalkylcarbamoyl, N - ((C₃-C₈) cycloalkyl- (C₁-C₆) alkyl) carbamoyl, N- (C₆-C₁₂) arylcarbamoyl , N- (C₇-C₁₆) aralkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₆) arylcarbamoyl, N- (C₁-C₁₀) - alkyl-N- (C₇-C₁₆) aralkylcarbamoyl , N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₆-C₁₆) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₇-C₁₆ ) Aralkyloxy- (C₁-C₁₀) alkyl) carbamoyl, CON (CH₂) _h , in which a CH₂ group is substituted by O, N- (C₁-C₈) alkylimino, N- (C₃-C₈) cycloalkylimino, N- (C₃-C₈) cycloalkyl- (C₁-C₄) alkylimino, N- (C₆-C₁₂) arylimino or N- (C₇-C₁₆) aralkylimino can be replaced and h is 3 to 6, or with
(C₁-C₁₂) alkanoylamino, (C₃-C₈) cycloalkanoylamino, (C₆-C₁₂) aroylamino, (C₇-C₁₆) aralkanoylamino, (C₁-C₁₂) alkanoyl-N- (C₁-C₁₀) alkylamino, (C₃-C₈) cycloalkanoyl-N- (C₁-C₁₀) alkylamino,
where the residues containing an aryl residue are 25664 00070 552 001000280000000200012000285912555300040 0002019504226 00004 25545ts on the aryl may be substituted by 1 to 5 identical or different residues from the series:
Hydroxy, fluorine, chlorine, cyano, trifluoromethyl, carboxy, (C₁-C₁₂) alkyl, (C₃-C₈) cycloalkyl, (C₂-C₁₂) alkenyl, (C₁-C₁₂) alkoxy,
Carbamoyl, N- (C₁-C₁₂) alkylcarbamoyl, N, N-di- (C₁-C₁₂) alkylcarbamoyl, N- (C₃-C₈) cycloalkylcarbamoyl, or (C₁-C₁₂) alkylmercapto, (C₁-C₁₂) - alkylsulfinyl, (C₁-C₁₂) alkylsulfonyl,
in which
R ^Y and R ^{Z are the} same or different and are hydrogen, (C₆-C₁₂) aryl, (C₁-C₁₀) alkyl, (C₃-C₁₀) cycloalkyl, (C₁-C₈) alkoxy- (C₁-C₈) - alkyl, (C₇-C₁₂) aralkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy- (C₁-C₈) alkyl, (C₁-C₁₀) alkanoyl, optionally substituted (C₇-C₁₆) Aralkanoyl, optionally substituted (C₆-C₁₂) aroyl or
R ^Y and R ^Z together represent - [CH₂] _h -, in which a CH₂ group can be replaced by O, S, N- (C₁-C₄) alkanoylimino or N- (C₁-C₄) alkoxycarbonylimino, and
f 1 to 8,
g 0.1 to (2f + 1),
h 3 to 6,
x 0 to 3, and
n is 3 or 4,
including the physiologically active salts where N - ((6,7-dichloro-3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine and α - ((6,7-dichloro-3,4-dihydro- 3-oxo-2-quinoxalinyl) carbonyl) amino) are excluded.

Compounds of the formula I in which
QO or S,
XO,
A -CHR⁶-, where R⁶ is the substituent of the α-C atom of an α-amino acid, in particular a natural L-amino acid or its D isomer,
B CO₂H,
R¹, R², R³ and R⁴ are the same or different and are hydrogen, (C₁-C₁₂) alkyl, (C₃-C₇) cycloalkyl, (C₁-C₁₂) alkoxy, (C₃-C₇) cycloalkyloxy, (C₃-C₇ ) - Cycloalkyl- (C₁-C₂) alkoxy, -O- [CH₂] _x -C _f H _{(2f + 1-g)} F _g , (C₁-C₄) alkoxy- (C₁-C₄) alkoxy, substituted (C₆-C₁₂) phenoxy, (C₇-C₁₁) phenylalkyloxy, (C₆-C₁₂) phenoxy- (C₁-C₄) alkoxy, (C₇-C₁₁) phenylalkoxy- (C₁-C₄) alkoxy, fluorine, Trifluoromethyl, chlorine, N- (C₁-C₁₀) alkylcarbamoyl, N, N-di- (C₁-C₈) alkylcarbamoyl, N- (C₃-C₇) cycloalkylcarbamoyl, N-phenylcarbamoyl, N-phenyl- (C₁-C₄ ) -alkylcarbamoyl, carboxy, (C₁-C₁₆) alkoxycarbonyl, (C₂-C₁₆) alkenyloxycarbonyl, retinyloxycarbonyl, (C₃-C₇) - cycloalkoxycarbonyl, where an aromatic radical having 1, 2 or 3 identical or different substituents from the Series fluorine, chlorine, cyano, trifluoromethyl, (C₁-C₆) alkyl, (C₁-C₆) alkoxy is substituted
R⁵ is hydrogen or a branched or unbranched (C₁-C₁₂) alkyl radical, which can contain one or two CC multiple bonds, and
f 1 to 4
g 0.1 to (2f + 1)
x means 0 and 1,
including the physiologically active salts, where N - ((6,7-dichloro-3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine and α - ((6,7-dichloro-3,4-dihydro -3-oxo-2-quinoxalinyl) carbonyl) amino) phenylacetic acid are excluded.

Compounds of the formula I in which
QO,
XO,
A represents a -CH₂ group which can be substituted by a methyl group,
B CO₂H,
R¹, R², R³ and R⁴ are the same or different and are hydrogen, (C₁-C₁₂) alkyl, (C₃-C₇) cycloalkyl, (C₁-C₁₂) alkoxy, (C₃-C₇) cycloalkyloxy, (C₃-C₇ ) - Cycloalkyl- (C₁-C₂) alkoxy, -O- [CH₂] _x -C _f H _{(2f + 1-g)} F _g , (C₁-C₄) alkoxy- (C₁-C₄) alkoxy, substituted (C₆-C₁₂) phenoxy, (C₇-C₁₁) phenylalkyloxy, (C₆-C₁₂) phenoxy- (C₁-C₄) alkoxy, (C₇-C₁₁) phenylalkoxy- (C₁-C₄) alkoxy, fluorine, Trifluoromethyl, chlorine, N- (C₁-C₁₀) alkylcarbamoyl, N, N-di- (C₁-C₈) alkylcarbamoyl, N- (C₃-C₇) cycloalkylcarbamoyl, N-phenylcarbamoyl, N-phenyl- (C₁-C₄ ) -alkylcarbamoyl, carboxy, (C₁-C₁₆) alkoxycarbonyl, (C₂-C₁₆) alkenyloxycarbonyl, retinyloxycarbonyl, (C₃-C₇) - cycloalkoxycarbonyl, where an aromatic radical having 1, 2 or 3 identical or different substituents from the Series fluorine, chlorine, cyano, trifluoromethyl, (C₁-C₆) alkyl, (C₁-C₆) alkoxy is substituted and
R⁵ is hydrogen or a branched or unbranched (C₁-C₆) alkyl radical and
f 1 to 4,
g 0.1 to (2f + 1) and
x means 0 and 1,
including the physiologically active salts, where N - ((6,7-dichloro-3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine and α - ((6,7-dichloro-3,4-dihydro -3-oxo-2-quinoxalinyl) carbonyl) amino) phenylacetic acid are excluded.

Compounds of the formula I in which
QO,
XO,
A is a -CH₂ group and,
B means CO₂H, and
R¹ and R⁴ are identical or different and are hydrogen, fluorine, chlorine and (C₁-C₄) alkyl,
R² and R³ are the same or different and are hydrogen, fluorine, chlorine, (C₁-C₁₂) alkoxy, (C₃-C₇) cycloalkoxy, -O- [CH₂] _x -C _f H _{(2f + 1-g)} F _g , (C₁-C₄) alkyl, benzyloxy, optionally substituted with up to 3 substituents from the series fluorine, chlorine, trifluoromethyl, (C₁-C₆) alkoxy, (C₁-C₆) alkyl, O [CH₂) _x -C _f H _{(2f + 1-g)} F _g mean
R⁵ is hydrogen or (C₁-C₆) alkyl and
f 1 to 4,
g 0.1 to (2f + 1),
x mean 0 and 1 and
their physiologically active salts, where N - ((6,7-dichloro-3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine and α - ((6,7-dichloro-3,4-dihydro- 3-oxo-2-quinoxalinyl) carbonyl) amino) phenylacetic acid are excluded.

The invention further comprises prodrugs for the compounds of the formula (I) which inhibit collagen biosynthesis in vivo by releasing Effect compounds of formula I or their salts.

Finally, the invention also encompasses prodrugs released in vivo of compounds of formula I or their salts have an inhibitory effect on the prolyl 4-hydroxylase.

Prodrug groupings are chemical groups that are in vivo

• - Converted to the carboxylate group of the compounds of formula I. be and / or
• - Can be split off from the amide N atom and / or
• - Can be converted to a pyridine ring.

The prodrug groups in question are known to the person skilled in the art.

The following prodrug groups are mentioned in particular:
for the carboxylate group ester, amide, hydroxymethyl and aldehyde groups and their derivatives for the pyridine N atom, N-oxides and N-alkyl derivatives and for the pyridine ring 1,4-dihydropyridine derivatives.

The invention relates to the use of compounds of the general formula I and the physiologically tolerable salts for inhibiting the Collagen biosynthesis.

The invention relates to the use of compounds of the general formula I and the physiologically tolerable salts for inhibiting prolyl-4 hydroxylase.

The invention further relates to the use of compounds of general formula I and the physiologically tolerable salts for the preparation a medicine for fibrotic diseases.

The invention further relates to the use of compounds of general formula I and the physiologically tolerable salts for the preparation a medicine for fibrotic diseases of the liver, lungs and Skin.

Finally, the invention relates to the compounds of general formula I for Use as a medicine.

In particular, the invention relates to the compounds of formula I for Use as a fibrosuppressant.

The invention further relates to a method for producing compounds of the general formula I.

The compounds of the formula I in which A is an alkylene part, B = CO₂H and X = 0 are prepared as illustrated in Scheme I:
3,4-Dihydro-3-oxo-quinoxaline-2-carboxylic acid esters of the formula 5 are obtained by

• i1) substituted o-phenylenediamines of the formula 4 with mesoxalic acid esters of Formula 2 or
• i2) substituted 2-nitroanilines of formula 1 with mesoxalic acid esters of Formula 2 are implemented to the imines of formula 3, which in the subsequent reduction of the nitro group among the Ring reaction conditions to the compounds of formula 5; and
• ii1) the compounds of the formula 5 are saponified to give the compounds Formula 7, where R⁵ = H, or
• ii2) the compounds of formula 5 are halogenated z. B. with SOCl₂ or (COCl) ₂ and then reacted to compounds of the formula 7, wherein R⁵ has the meaning according to the claims except H, and
• iii) the compounds of formula 7 with the amino esters of formula 8 Compounds of formula 9 are reacted, with subsequent
• iv1) saponification to give compounds of the formula I and / or
• iv2) the salt formation in the physiologically active salts with N - ((6,7- Dichloro-3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine and α - ((6,7- Dichloro-3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) amino) phenylacetic acid he follows.

The substituted 2-nitroanilines of the formula 1 are, for example, from EP-A-0 166 287 known.  

Scheme 1

Suitable methods for amide formation are the methods of carboxy activation (iii) and the condensation reactions known from peptide chemistry.

The person skilled in the art can use reagents for carboxylic acid activation known substances, such as thionyl chloride, oxalyl chloride, pivaloyl chloride, Chloroformic acid ester derivatives or N, N'-carbonyldimidazole use Find. The activated derivatives of the compounds of formula II are after Production implemented in situ with the amide derivatives of the formula III.

A suitable condensing agent is, for example, the combination of N, N'-dicyclohexylcarbodiimide / N-hydroxy-1H-benzotriazole, N-ethylmorpholine and N-Cyclohexyl-N '- (2-morpholinoethyl) carbodiimide-methyl-p-toluenesulfonate (CMC).

Suitable solvents are dichloromethane, carbon tetrachloride, butyl acetate, Ethyl acetate, toluene, tetrahydrofuran, dimethoxyethane, 1,4-dioxane, acetonitrile, N, N-dimethylformamide, N, N-dimethylacetamide, dimethyl sulfoxide, nitromethane and / or pyridine.

The compounds of formula I are inhibitors of prolyl 4-hydroxylase. The Inhibition of this enzyme has been described by Kaule and Günzler in Annal. Biochem. 184, 291 to 297 (1990).

The compounds of formula I according to the invention have valuable pharmacological properties and in particular show antifibrotic Effectiveness.

The antifibrotic effect can be induced in the carbon tetrachloride model Liver fibrosis can be determined. For this, rats are dissolved with CCl₄ (1 ml / kg) in olive oil - treated twice a week. The test substance is possibly even twice a day by os or intraperitoneally - dissolved in a suitable compatible solvent. The extent of Liver fibrosis is determined histologically and the percentage of collagen in the liver per  Hydroxyproline determination - as in Kivirikko et al. (Anal. Biochem. 19, 249 f. (1967)) - analyzed. The activity of fibrogenesis can be caused by radioimmunological determination of collagen fragments and Procollagen peptides can be determined in serum. The invention Compounds are in this model in concentrations of 1 to 100 mg / kg effective.

The activity of fibrogenesis can be determined by radioimmunological determination of the N-terminal propeptide of type III collagen or the N- or C-terminal Cross-linking domain of collagen type IV (7s collagen or type IV collagen NC₁) can be determined in the serum.

For this purpose the hydroxyproline, procollagen III peptide, 7s collagen and type IV collagen NC concentrations in the liver of

• a) untreated rats (control)
• b) rats to which carbon tetrachloride was administered (CCl₄ control)
• c) rats, which first CCl₄ and then an inventive Compound was administered

measured (this test method is described by Rouiller, C., experimental toxic injury of the liver; in The Liver, C. Rouiller, Vol. 2, 5, 335 to 476, New York, Academic Press, 1964).

Furthermore, the compounds according to the invention can be effective in following systems can be demonstrated.

Inhibition of hepatic prolyl 4-hydroxylase in vivo:
This model serves to demonstrate the acute inhibition of prolyl 4-hydroxylase in vivo. For this purpose, rats of both sexes (healthy or with induced liver fibrosis) are administered the test substance or the corresponding vehicle (intraperitoneally, intravenously, per os) and administered intraperitoneally after administration of substance ¹⁴C-L-proline (250 µCi / kg body weight). Then an intraperitoneal application of ¹⁴C-L-proline (250 µCi / kg body weight) again. Finally, the animals are bled under pentobarbital anesthesia and the liver removed. The hepatic collagen was purified by pepsin digestion and fractionated ammonium sulfate precipitation in accordance with published protocols (Ref. 1, 2). The purified liver collagen was hydrolyzed and the content of ¹⁴C-hydroxyproline and ¹⁴C-proline was determined by amino acid analysis using ion exchange chromatography. An inhibition of prolyl-4-hydroxylase results from a lowering of the quotient ¹⁴C-hydroxyproline / [¹⁴C-hydroxyproline + ¹⁴C-proline]. 2,2'-Dipyridyl is used as the reference substance. (1: Chojkier, M. 1986. Hepatocyte collagen production in vivo in normal rats. J. Clin. Invest. 78: 333-339 and 2: Ogata I., et al. 1991. Minor contribution of hepatocytes of hepatocytes to collagen production in normal and early fibrotic livers. Hepatology 14: 361-367).

Inhibition of Prnlyl-4-hydroxylase in cell cultures:
The following cell types are used for testing prolyl-4-hydroxylase inhibitors in cell cultures:
Normal human skin fibrolasts (NHDF), rat liver epithelial cells (ref. 1) and primary fat storage cells from the rat liver (fat storing cells, ref. 2). For this purpose, the cells are cultivated in the presence of inhibitors. At the same time, the collagen newly synthesized during this time is metabolically marked by 4-³H-L-proline and ¹⁴C-proline. The influence of the test substances on the degree of hydroxylation of the collagen is then determined according to the method of Chojkier et al (Ref. 3). 2,2'-Dipyridyl is used as the reference substance. (1 .: Schrode, W., Mecke, D., Gebhard, R. 1990. Induction of glutamine synthetase in periportal hepatocytes by co-cultivation with a liver epithelial cell line. Eur. J. Cell. Biol. 53: 35- 41, 2. Blomhoff, R., Berg T. 1990. Isolation and cultivation of rat liver stellate cells. Methods Enzymol. 190: 59-71 and 3 .: Chojkier, M. Peterkofsky, B. Bateman, J. 1980. A new method for determining the extent of proline hydroxylation by measuring changes in the ration of [4-³H]: [¹⁴C] proline in collagenase digests. Anal. Biochem. 108: 385-393).

The compounds of formula I can be used as drugs in the form of pharmaceutical preparations are used, which they may be used with compatible pharmaceutical carriers. The connections can be made as Remedies, e.g. B. find use in the form of pharmaceutical preparations these compounds mixed with one for enteral, percutaneous or parenteral application of suitable pharmaceutical, organic or inorganic carriers, such as. B. water, gum arabic, gelatin, Milk sugar, starch, magnesium stearate, talc, vegetable oils, Contain polyalkylene glycols, petroleum jelly, etc.

For this purpose you can take orally in doses of 0.1 to 25 mg / kg / day, preferably 1 to 5 mg / kg / day or parenterally in doses of 0.01 to 5 mg / kg / day, preferably 0.01 to 2.5 mg / kg / day, in particular 0.5 to 1.0 mg / kg / day. The dosage can also be severe increase. In many cases, however, lower doses are sufficient. These Figures refer to an adult weighing approximately 75 kg.

Compounds of the formula I are substituted N- (quinoxalinyl-2- classified carbonyl) glycine.

Substituted quinoxaline-2-carboxylic acid Understand N- (carboxymethyl) amides.

example 1 N - ((3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine

• a) N - ((3,4-Dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine ethyl ester
  4.8 g (25 mmol) of 3-hydroxyquinoxaline-2-carboxylic acid were suspended in 500 ml of anhydrous dichloromethane and successively at 20 ° C. with 3.5 g (25 mmol) of glycine ethyl ester hydrochloride, 7.2 ml (55 mmol ) N-ethylmorpholine, 3.6 g (27 mmol) of 1-hydroxy-1-H-benzotriazole and 11.4 g (27 mmol) of N-cyclohexyl-N ′ - (2-morpholinoethyl) carbodiimide-methyl-p- toluenesulfonate (abbreviation CMC) and stirred for 20 h at room temperature. The undissolved material was then filtered off, the organic phase was shaken out in each case with 1 mol of saturated aqueous HCl and with water, dried over magnesium sulfate, in vacuo. concentrated and the residue brought to crystallization with diethyl ether. 1.4 g of product were obtained, mp. 224-227 ° C.
• b) The title compound was obtained by adding 0.69 g (25 mmol) of the the above compound at 20 ° C with stirring in a mixture of 0.12 g (5 mmol) LiOH in 40 ml methanol / water (3: 1) were added. After 1 h became i.Vak. concentrated, the residue dissolved in 60 ml of water, 1 × with Extracted dichloromethane, the aqueous phase with conc. aqueous HCl to pH 1 brought. The precipitated product was filtered off, washed with water and dried. 0.5 g, mp. 283-285 ° C. was obtained.

Example 2 N - ((3-methoxy-2-quinoxalinyl) carbonyl) glycine

• a) 3-chloroquinoxaline-2-carboxylic acid chloride was obtained from 3-hydroxyquinoxaline-2 carboxylic acid with SOCl₂ / catalytic amount of DMF obtained, mp. 125 ° C. Diethyl ether.  
• b) 3-methoxyquinoxaline-2-carboxylic acid by reaction with Na methylate in Methanol and saponification with 1.5 N methanolic NaOH. Mp 128-130 ° C aqueous hydrochloric acid).
• c) N - ((3-methoxy-2-quinoxalinyl) carbonyl) glycine ethyl ester
  2.0 g (10 mmol) of 3-methoxyquinoxaline-2-carboxylic acid were condensed with glycine ethyl ester analogously to Example 1a). 1.9 g of product were obtained, mp 113-115 ° C. (from diisopropyl ether).
• d) The title compound was obtained by 0.8 g of the above ester were saponified with 1.5 N methanolic NaOH. One obtained after acidification aqueous hydrochloric acid and concentration 0.27 g of product, mp. 199-201 ° C.

Example 3 N - ((3-ethoxy-2-quinoxalinyl) carbonyl) glycine

• a) 3-ethoxy-2-quinoxaline-2-carboxylic acid was obtained from 3-chloroquinoxaline-2- carboxylic acid ethyl ester and ethanolic Na ethanolate solution and subsequent ester hydrolysis obtained, mp. 119-120 ° C (from aqueous Hydrochloric acid).
• b) N - ((3-Ethoxy-2-quinoxalinyl) carbonyl) glycine ethyl ester 2.2 g (10 mmol) of the above carboxylic acid were added as in Example 1a) Glycine ethyl ester hydrochloride condensed. 1.9 g of product, mp. 126-127 ° C (from diisopropyl ether).
• c) The title compound was obtained from 0.5 g of the above ester Saponification obtained with 1.5 N ethanolic sodium hydroxide solution. 0.37 g was isolated from aqueous hydrochloric acid (pH 2-3), mp. 198-200 ° C.

Example 4 N - ((6-methoxy-3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine

• a) 6-Methoxy-3,4-dihydro-3-oxo-quinoxaline-2-carboxylic acid ethyl ester
  12 g (71.4 mmol) of 4-methoxy-2-nitroaniline were dissolved in 250 toluene, 12.5 g (11 ml, 72 mmol) of diethyl mesoxalate and a spatula tip of p-TosOH were added and the mixture was heated for 2 hours on a water separator. After cooling, the mixture was extracted with saturated aqueous Na bicarbonate, dried, concentrated in vacuo, the residue was dissolved in ethanol and hydrogenated with Raney nickel in the shaking duck (H₂ uptake: 4.9 l). The catalyst was then filtered off with suction, the filtrate was concentrated to 100 ml in vacuo and 2.6 g of product were obtained, mp. 220-222 ° C. A further 4 g of product, mp 218-220 ° C., were obtained from the filtrate by treating the residue with ethyl acetate.
• b) 6-methoxy-3,4-dihydro-3-oxo-quinaxoline-2-carboxylic acid
  2.6 g of the above ester were saponified with 150 ml of 1.5 N methanolic sodium hydroxide solution (100 ml of tetrahydrofuran and water were added until a clear solution formed). 2.66 g of product were obtained from aqueous hydrochloric acid, mp. 239-241 ° C. (with evolution of gas).
• c) N - ((6-methoxy-3,4-dihydro-3-oxo-quinoxalinyl) carbonyl) glycinoctyl ester
  2.2 g (10 mmol) of the above carboxylic acid were analogous to Example 1a) using 3.75 ml (30 mmol) of N-ethylmorpholine, 1.8 g (12 mmol) of 1-hydroxy-1H-benzotriazole and 4.2 g (10 mmol) CMC condensed with 3.6 g (10 mmol) glycine octyl ester tosylate. After working up (Example 1a)), 2.2 g of product, mp 203-206 ° C. (sintering at 190 ° C.) was obtained by crystallization with diethyl ether.
• d) The title compound was obtained by adding 0.58 g (15 mmol) of the above Ester with 1.5 N methanolic sodium hydroxide solution (water until clear Solution) were saponified. After concentration, the residue was in water  solved and with conc. aqueous HCl brought to pH 1. 0.35 g of the was isolated Title compound, mp. 310 ° C (with decomposition).

Example 5 N - ((7-methoxy-3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine

• a) ethyl 7-methoxy-3,4-dihydro-3-oxo-quinoxaline-2-carboxylate, Mp 167-168 ° C (from diisopropyl ether).
• b) 7-methoxy-3,4-dihydro-3-oxo-quinoxaline-2-carboxylic acid, Mp 222-223 ° C (with decomposition, from aqueous hydrochloric acid).
• c) N - ((7-methoxy-3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine ethyl ester, Mp 233-234 ° C (from diisopropyl ether).
• d) The title compound was obtained after alkaline saponification of the above Ester (350 mg) obtained from aqueous hydrochloric acid, yield 340 mg, mp. 292 ° C. (with decomposition).

Example 6 N - ((7-methoxy-3-ethoxy-2-quinoxalinyl) carbonyl) glycine

• a) Ethyl 3-chloro-7-methoxyquinoxaline-2-carboxylate
• b) 3-ethoxy-7-methoxyquinoxaline-2-carboxylic acid, Mp 156-158 ° C (from aqueous hydrochloric acid)
• c) N - ((3-ethoxy-7-methoxy-2-quinoxalinyl) carbonyl) glycine ethyl ester, Mp 131-132 ° C (from diisopropyl ether)  
• d) 0.8 g of the above ester was treated with 1.5 N ethanolic NaOH saponified. 0.7 g of the title compound, mp. 203-204 ° C. (from aqueous Hydrochloric acid, then treated with dichloromethane).

The following compounds were prepared analogously to Example 4:

Example 7 N - ((6- (1-propyloxy) -3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine - Example 8 N - ((6- (1-butyloxy) -3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine Example 9 N - ((6- (1-Hexyloxy) -3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine Example 10 N - ((6- (1-octyloxy) -3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine Example 11 N - ((6- (1-decyloxy) -3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine Example 12 N - ((6- (1-dodecyloxy) -3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glyci-n Example 13 N - ((6- (3-Methyl-1-butyloxy) -3,4-dihydro-3-oxo-2-quinoxalinyl) carbony-1) glycine Example 14 N - ((6- (2,2,2-trifluoroethyloxy) -3,4-dihydro-3-oxo-2-quinoxalinyl) carb-onyl) glycine Example 15 N - ((6-trifluoromethoxy-3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine Example 16 N - ((6- (2,2,3,3,3-pentafluoropropyloxy) -3,4-dihydro-3-oxo-2- quinoxalinyl) carbonyl) glycine Example 17 N - ((6- (1,1,2,2-tetrafluoroethyloxy) -3,4-dihydro-3-oxo-2- quinoxalinyl) carbonyl) glycine Example 18 N - ((6- (2,2,3,3,4,4,4-heptafluorobutyloxy) -3,4-dihydro-3-oxo-2- quinoxalinyl) carbonyl) glycine Example 19 N - ((6-Benzyloxy-3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine Example 20 N - ((6- (4-fluorobenzyloxy) -3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) g-lycine

Claims (16)

1. Compounds of the general formula I in which
Q O or S,
X O and S,
A (C₁-C₄) alkylene, which is optionally substituted with one or two substituents from the series halogen, cyano, nitro, trifluoromethyl, (C₁-C₆) alkyl, (C₁-C₆) hydroxyalkyl, (C₁-C₆) -Alkoxy, -O- [CH₂] _x -C _f H _{(2f + 1-g)} Hal _g , preferably (C₁-C₈) fluoroalkoxy, (C₁-C₈) fluoroalkenyloxy, (C₁-C₈) fluoroalkynyloxy, - OCF₂Cl or -O-CF₂-CHFCl, (C₁-C₆) alkyl mercapto, (C₁-C₆) alkylsulfinyl, (C₁-C₆) alkylsulfonyl, (C₁-C₆) alkylcarbonyl, (C₁-C₆) alkoxycarbonyl, carbamoyl , N- (C₁-C₄) alkylcarbamoyl, N, N-di- (C₁-C₄) alkylcarbamoyl, (C₁-C₆) alkylcarbonyloxy, (C₃-C₈) cycloalkyl, phenyl, benzyl, phenoxy, benzyloxy, anilino , N-methylanilino, phenylmercapto, phenylsulfonyl, phenylsulfinyl, sulfamoyl, N- (C₁-C₄) alkylsulfamoyl, N, N-di- (C₁-C₄) alkylsulfamoyl, or
with a substituted (C₆-C₁₂) aryloxy, (C₇-C₁₁) aralkyloxy, (C₆-C₁₂) aryl or (C₇-C₁₁) aralkyl radical which is in the aryl part 1, 2, 3, 4 or 5 identical or different substituents from the series halogen, cyano, nitro, trifluoromethyl, (C₁-C₆) alkyl, (C₁-C₆) alkoxy, -O- [CH₂] _x -C _f H _{(2f + 1-g)} Hal _g , -OCF₂Cl, -O-CF₂-CHFCl, (C₁-C₆) alkyl mercapto, (C₁-C₆) alkylsulfinyl, (C₁-C₆) alkylsulfonyl, (C₁-C₆) alkylcarbonyl, (C₁-C₆) -Alkoxycarbonyl, carbamoyl, N- (C₁-C₄) alkylcarbamoyl, N, N-di- (C₁-C₄) alkylcarbamoyl, (C₁-C₆) alkylcarbonyloxy, (C₃-C₈) cycloalkyl, sulfamoyl, N- ( C₁-C₄) - alkylsulfamoyl or N, N-di- (C₁-C₄) alkylsulfamoyl, or
with the substituents R⁵ of the α-C atom of an α-amino acid, whereby the natural L-amino acids and their D-isomers can be used;
B is an acidic group from the series -CO₂H, -CONHCOR ′ ′ ′,
-CONHSOR ''',CONHSO₂R''', -NHSO₂CF₃, tetrazolyl, imidazolyl or 3-hydroxyisoxazolyl, where R '''aryl, heteroaryl, (C₃-C₇) - cycloalkyl or (C₁-C₄) -alkyl, optionally monosubstituted with (C₆-C₁₂) aryl, heteroaryl, OH, SH, (C₁-C₄) alkyl, (C₁-C₄) alkoxy, (C₁-C₄) thioalkyl, sulfinyl or sulfonyl, CF₃, Cl, Br , F, I, NO₂, -COOH, (C₂-C₅) - alkoxycarbonyl, NH₂, mono- or di- (C₁-C₄-alkyl) -amino or (C₁-C₄) - perfluoroalkyl,
R¹, R², R³ and R⁴ are the same or different and are hydrogen, hydroxy, halogen, cyano, trifluoromethyl, nitro, carboxy, (C₁-C₂₀) alkyl, (C₃-C₈) cycloalkyl, (C₃-C₈) cycloalkyl- (C₁-C₁₂) alkyl, (C₃-C₈) cycloalkoxy, (C₃-C₈) cycloalkyl- (C₁-C₁₂) alkoxy, (C₃-C₈) -cycloalkyloxy- (C₁-C₁₂) alkyl, (C₃ -C₈) -Cycloalkyloxy- (C₁-C₁₂) alkoxy, (C₃-C₈) cycloalkyl- (C₁ -C₈) alkyl- (C₁-C₆) alkoxy, (C₃-C₈) cycloalkyl- (C₁-C₈ ) -alkoxy- (C₁-C₆) -alkyl, (C₃-C₈) - cycloalkyloxy- (C₁-C₈) -alkoxy- (C₁-C₆) -alkyl, (C₃-C₈) -cycloalkoxy- (C₁-C₈) - alkoxy- (C₁-C₈) alkoxy, (C₆-C₁₂) aryl, (C₇-C₁₆) aralkyl, (C₂-C₂₀) alkenyl, (C₂-C₂₀) alkynyl, (C₁-C₂₀) alkoxy, (C₂-C₂₀) alkenyloxy, (C₂-C₂₀) alkynyloxy, retinyloxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxy, (C₁-C₁₂) alkoxy- (C₁-C₈) alkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy, (C -C₁₆) aralkyloxy, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxy, (C₇-C₁₆) - aralkoxy- (C₁-C₆) alkoxy, (C₁-C₈) hydroxyalkyl, (C₆-C₁₆ ) Aryloxy- (C₁-C₈) alkyl, (C₇-C₁₆) aralkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy- (C₁-C₈) alkoxy- (C₁-C₆) - alkyl, (C₇-C₁₂) aralkyloxy- (C₁-C₈) alkoxy- (C₁-C₆) alkyl, (C₂-C₂₀) - alkenyloxy- (C₁-C₆) alkyl, (C₂-C₂₀) alkynyloxy ( C₁-C₆) alkyl, retinyloxy- (C₁-C₆) alkyl, -O- [CH _2- ] _x C _f H _{(2f + 1-g)} F _g , -OCF₂Cl, -OCF₂-CHFCl,
(C₁-C₁₂) alkylcarbonyl, (C₃-C₈) cycloalkylcarbonyl, (C₆-C₁₂) arylcarbonyl, (C₇-C₁₆) aralkylcarbonyl, cinnamoyl, (C₂-C₁₂) alkenylcarbonyl, (C₂-C₁₂) alkynylcarbonyl,
(C₁-C₁₂) alkoxycarbonyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyl, (C₆-C₁₂) aryloxycarbonyl, (C₇-C₁₆) aralkoxycarbonyl, (C₃-C₈) - cycloalkoxycarbonyl, (C₂ -C₂₀) alkenyloxycarbonyl, retinyloxycarbonyl, (C₂-C₂₀) alkynyloxycarbonyl, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxycarbonyl, (C₇-C₁₆) aralkoxy- (C₁-C₆) alkoxycarbonyl, (C₃ -C₈) cycloalkyl- (C₁-C₆) alkoxycarbonyl, (C₃-C₈) cycloalkoxy- (C₁-C₆) alkoxycarbonyl,
(C₁-C₁₂) alkylcarbonyloxy, (C₃-C₈) cycloalkylcarbonyloxy, (C₆-C₁₂) arylcarbonyloxy, (C₇-C₁₆) aralkylcarbonyloxy, cinnamoyloxy, (C₂-C₁₂) alkenylcarbonyloxy, (C₂-C₁₂oxy) alkynylcarbonyloxy
(C₁-C₁₂) alkoxycarbonyloxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyloxy, (C₆-C₁₂) aryloxycarbonyloxy, (C₇-C₁₆) aralkyloxycarbonyloxy, (C₃-C₈) cycloalkoxycarbonyloxy, (C₂ -C₁₂) - alkenyloxycarbonyloxy, (C₂-C₁₂) alkynyloxycarbonyloxy,
Carbamoyl, N- (C₁-C₁₂) alkylcarbamoyl, N, N-di- (C₁-C₁₂) alkylcarbamoyl, N- (C₃-C₈) cycloalkylcarbamoyl, N, N-dicyclo- (C₃-C₈) alkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₃-C₈) cycloalkylcarbamoyl, N - ((C₃-C₈) cycloalkyl- (C₁-C₆) alkyl) carbamoyl, N- (C₁-C₆) alkyl -N - ((C₃-C₈) -cycloalkyl- (C₁-C₆) - alkyl) carbamoyl, N - (+) - dehydroabietylcarbamoyl, N- (C₁-C₆) alkyl-N - (+) - dehydroabietylcarbamoyl, N- (C₆-C₁₂) arylcarbamoyl, N- (C₇-C₁₆) aralkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₆) arylcarbamoyl, N- (C₁-C₁₀) - alkyl-N- ( C₇-C₁₆) aralkylcarbamoyl, N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₆-C₁₆) aryloxy (C₁-C₁₀) alkyl) carbamoyl, N- ((C₇-C₁₆) aralkyloxy (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆) aralkyloxy - (C₁-C₁₀) alkyl) carbamoyl, CON (CH₂) _h , in which a CH₂ group by O, S, N- (C₁-C₈) alkylimino, N- (C₃-C₈) -cycloalkylimino, N- ( C₃-C₈) cycloalkyl- (C₁-C₄) alkylimino, N- (C₆-C₁₂) arylimino, N- (C₇-C₁₆) aralkylimino or N- (C₁-C₄) alkoxy- (C₁-C₆) -alkylimino can be replaced and h is 3 to 7, or with
a carbamoyl radical of the general formula II wherein
R ^x denotes the substituents of an α-amino acid, which include the L and D amino acids,
s 1, 2, 3, 4 or 5 and
T means OH, OR or NR * R **, where
R *, R ** and R *** are the same or different and are hydrogen (C₆-C₁₂) aryl, (C₇-C₁₁) aralkyl, (C₁-C₈) alkyl, (C₃-C₈) cycloalkyl, ( +) - Dehydroabietyl, (C₁-C₈) alkoxy- (C₁-C₈) alkyl, (C₇-C₁₂) - aralkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy- (C₁-C₈) -alkyl, (C₁-C₁₀) alkanoyl, optionally substituted (C₇-C₁₆) aralkanoyl, optionally substituted (C₆-C₁₂) aryl, or
R * and R ** together represent - [CH₂] _h , in which a CH₂ group is represented by O, S, SO, SO₂, N-acylamino, N- (C₁-C₁₀) alkoxycarbonylimino, N- (C₁-C₈) - Alkylimino, N- (C₃-C₈) -cycloalkylimino, N- (C₃-C₈) - cycloalkyl- (C₁-C₄) alkylimino, N- (C₆-C₁₂) arylimino, N- (C₇-C₁₆) aralkylimino or N- (C₁-C₄) alkoxy- (C₁-C₆) alkylimino can be replaced and h is 3 to 7, or with
Carbamoyloxy, N- (C₁-C₁₂) alkylcarbamoyloxy, N, N-Di- (C₁-C₁₂) alkylcarbamoyloxy, N- (C₃-C₈) cycloalkylcarbamoyloxy, N- (C₆-C₁₂) arylcarbamoyloxy, N- (C₇ -C₁₆) aralkylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₂) arylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylcarbamoyloxy, N - (( C₁-C₁₀) alkyl) carbamoyloxy, N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy , N- (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) -aryloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy, -
Amino, (C₁-C₁₂) alkylamino, di- (C₁-C₁₂) alkylamino, (C₃-C₈) - cycloalkylamino, (C₃-C₁₂) alkenylamino, (C₃-C₁₂) alkynylamino, N- (C₆-C₁₂ ) Arylamino, N- (C₇-C₁₁) aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C₁-C₁₂) alkoxyamino, (C₁-C₁₂) alkoxy-N- (C₁-C₁₀) - alkylamino,
(C₁-C₁₂) alkanoylamino, (C₃-C₈) cycloalkanoylamino, (C₆-C₁₂) aroylamino, (C₇-C₁₆) aralkanoylamino, (C₁-C₁₂) alkanoyl-N- (C₁-C₁₀) alkylamino, (C₃-C₈) cycloalkanoyl-N- (C₁-C₁₀) alkylamino, (C₆-C₁ ₂) aroyl- N- (C₁-C₁₀) alkylamino, (C₇-C₁₁) aralkanoyl-N- (C₁- C₁₀) alkylamino,
(C₁-C₁₂) alkanoylamino- (C₁-C₈) alkyl, (C₃-C₈) cycloalkanoylamino- (C₁-C₈) alkyl, (C₆-C₁₂) aroylamino- (C₁-C₈) alkyl, (C₇ -C₁₆) - aralkanoylamino- (C₁-C₈) alkyl, amino- (C₁-C₁₀) alkyl, N- (C₁-C₁₀) alkylamino- (C₁-C₁₀) alkyl, N, N-di- (C₁ -C₁₀) alkylamino- (C₁-C₁₀) alkyl, (C₃-C₈) -cycloalkylamino- (C₁-C₁₀) alkyl, (C₁-C₁₂) alkylmercapto, (C₁-C₁₂) alkylsulfinyl, (C₁-C₁₂ ) Alkylsulfonyl, (C₆-C₁₂) arylmercapto, (C₆-C₁₂) arylsulfinyl, (C₆-C₁₂) arylsulfonyl, (C₇-C₁₆) aralkylmercapto, (C₇-C₁₆) aralkylsulfinyl, (C₇-C₁₆) - Aralkylsulfonyl,
Sulfamoyl, N- (C₁-C₁₀) alkylsulfamoyl, N, N-di- (C₁-C₁₀) alkylsulfamoyl, (C₃-C₈) cycloalkylsulfamoyl, N- (C₆-C₁₂) arylsulfamoyl, N- (C₇-C₁₆ ) Aralkylsulfamoyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₂) arylsulfamoyl, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylsulfamoyl, (C₁-C₁₀) - Alkyl sulfonamido, N - ((C₁-C₁₀) alkyl) - (C₁-C₁₀) alkylsulfonamido, (C₇-C₁₆) aralkylsulfonamido, N - ((C₁-C₁₀) alkyl) - (C₇-C₁₆) - aralkylsulfonamido,
where the radicals which contain an aryl radical in turn can be substituted on the aryl by 1 to 5 identical or different radicals from the series:
Hydroxy, halogen, cyano, trifluoromethyl, nitro, carboxy, (C₁-C₁₂) alkyl, (C₃-C₈) cycloalkyl, (C₃-C₈) cycloalkyl- (C₁-C₁₂) alkyl, (C₃-C₈) - Cycloalkoxy, (C₃-C₈) cycloalkyl- (C₁-C₁₂) alkoxy, (C₃-C₈) cycloalkyloxy- (C₁-C₁₂) alkyl, (C₃-C₈) cycloalkyloxy- (C₁-C₁₂) alkoxy, (C₃-C₈) cycloalkyl- (C₁-C₈) alkyl- (C₁-C₆) alkoxy, (C₃-C₈) cycloalkyl- (C₁-C₈) alkoxy- (C₁-C₆) - alkyl, (C₃ -C₈) -Cycloalkyloxy- (C₁-C₈) alkoxy- (C₁-C₆) alkyl, (C₃-C₈) - cycloalkoxy- (C₁-C₈) alkoxy- (C₁-C₈) alkoxy, (C₆-C₁₂ ) Aryl, (C₇-C₁₆) aralkyl, (C₂-C₁₂) alkenyl, (C₂-C₁₂) alkynyl, (C₁-C₁₂) alkoxy, (C₁-C₁₂) - alkoxy- (C₁-C₁₂) - alkyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxy, (C₁-C₁₂) alkoxy- (C₁-C₈) alkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy, (C₇-C₁₆) aralkyloxy, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxy, (C₇-C₁₆) aralkoxy- (C₁-C₆) alkoxy, (C₁-C₈) hydroxyalkyl , (C₆-C₁₆) aryloxy- (C₁-C₈) alkyl, (C₇-C₁₆) aralkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy- (C₁-C₈) alkoxy- ( C₁-C₆) alkyl, (C₇-C₁₂) aralkyloxy- (C₁-C₈) alkoxy- (C₁-C₆) alkyl, -O- [CH _2- ] _x C₂H _{(2f + 1-g)} F _g , -OCF₂Cl, -OCF₂-CHFCl,
(C₁-C₁₂) alkylcarbonyl, (C₃-C₈) cycloalkylcarbonyl, (C₆-C₁₂) arylcarbonyl, (C₇-C₁₆) aralkylcarbonyl,
(C₁-C₁₂) alkoxycarbonyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyl, (C₆-C₁₂) aryloxycarbonyl, (C₇-C₁₆) aralkoxycarbonyl, (C₃-C₈) - cycloalkoxycarbonyl, (C₂ -C₁₂) alkenyloxycarbonyl, (C₂-C₁₂) alkynyloxycarbonyl, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxycarbonyl, (C₇-C₁₆) - aralkoxy- (C₁-C₆) alkoxycarbonyl, (C₃-C₈ ) -Cycloalkyl- (C₁-C₆) alkoxycarbonyl, (C₃-C₈) -cycloalkoxy- (C₁-C₆) alkoxycarbonyl,
(C₁-C₁₂) alkylcarbonyloxy, (C₃-C₈) cycloalkylcarbonyloxy, (C₆-C₁₂) arylcarbonyloxy, (C₇-C₁₆) aralkylcarbonyloxy, cinnamoyloxy, (C₂-C₁₂) alkenylcarbonyloxy, (C₂-C₁₂), alkynylcarbonyloxy
(C₁-C₁₂) alkoxycarbonyloxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyloxy, (C₆-C₁₂) aryloxycarbonyloxy, (C₇-C₁₆) aralkyloxycarbonyloxy, (C₃-C₈) cycloalkoxycarbonyloxy, (C₂ -C₁₂) - alkenyloxycarbonyloxy, (C₂-C₁₂) alkynyloxycarbonyloxy,
Carbamoyl, N- (C₁-C₁₂) alkylcarbamoyl, N, N-di- (C₁-C₁₂) alkylcarbamoyl, N- (C₃-C₈) cycloalkylcarbamoyl, N, N-dicyclo- (C₃-C₈) alkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₃-C₈) cycloalkylcarbamoyl, N - ((C₃-C₈) cycloalkyl- (C₁-C₆) alkyl) carbamoyl, N- (C₁-C₆) alkyl -N - ((C₃-C₈) -cycloalkyl- (C₁-C₆) - alkyl) carbamoyl, N - (+) - dehydroabietylcarbamoyl, N- (C₁-C₆) alkyl-N - (+) - dehydroabietylcarbamoyl, N- (C₆-C₁₂) arylcarbamoyl, N- (C₇-C₁₆) aralkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₆) arylcarbamoyl, N- (C₁ -C₁₀) - alkyl-N- (C₇-C₁₆) aralkylcarbamoyl, N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₆-C₁₆) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₇- C₁₆) aralky loxy- (C₁-C₁₀) alkyl) carbamoyl, CON (CH₂) _h , wherein a CH₂ group through O, S, N- (C₁-C₈) alkylimino, N- (C₃-C₈) cycloalkylimino, N- (C₃ -C₈) cycloalkyl- (C₁-C₄) alkylimino, N- (C₆-C₁₂) arylimino, N- (C₇-C₁₆) aralkylimino or N- (C₁-C₄) alkoxy- (C₁-C₆) - alkylimino can be replaced and h represents 3 to 7,
Carbamoyloxy, N- (C₁-C₁₂) alkylcarbamoyloxy, N, N-Di- (C₁-C₁₂) alkylcarbamoyloxy, N- (C₃-C₈) cycloalkylcarbamoyloxy, N- (C₆-C₁₆) arylcarbamoyloxy, N- (C₇ -C₁₆) aralkylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₂) arylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylcarbamoyloxy, N - (( C₁-C₁₀) alkyl) carbamoyloxy, N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy , N- (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) -aryloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy, -
Amino, (C₁-C₁₂) alkylamino, di- (C₁-C₁₂) alkylamino, (C₃-C₈) - cycloalkylamino, (C₃-C₁₂) alkenylamino, (C₃-C₁₂) alkynylamino, N- (C₆-C₁₂ ) Arylamino, N- (C₇-C₁₁) aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C₁-C₁₂) alkoxyamino, (C₁-C₁₂) alkoxy-N- (C₁-C₁₀) - alkylamino,
(C₁-C₁₂) alkanoylamino, (C₃-C₈) cycloalkanoylamino, (C₆-C₁₂) aroylamino, (C₇-C₁₆) aralkanoylamino, (C₁-C₁₂) alkanoyl-N- (C₁-C₁₀) alkylamino, (C₃-C₈) cycloalkanoyl-N- (C₁-C₁₀) alkylamino, (C₆-C₁₂) aroyl- N- (C₁-C₁₀) alkylamino, (C₇-C₁₁) aralkanoyl-N- (C₁-C₁₀ ) alkylamino,
(C₁-C₁₂) alkanoylamino- (C₁-C₈) alkyl, (C₃-C₈) cycloalkanoylamino- (C₁-C₈) alkyl, (C₆-C₁₂) aroylamino- (C₁-C₈) alkyl, (C₇ -C₁₆) - aralkanoylamino- (C₁-C₈) alkyl, amino- (C₁-C₁₀) alkyl, N- (C₁-C₁₀) alkylamino- (C₁-C₁₀) alkyl, N, N-di- (C₁ -C₁₀) alkylamino- (C₁-C₁₀) alkyl, (C₃-C₈) cycloalkylamino- (C₁-C₁₀) alkyl,
(C₁-C₁₂) alkylmercapto, (C₁-C₁₂) alkylsulfinyl, (C₁-C₁₂) alkylsulfonyl, (C₆-C₁₆) arylmercapto, (C₆-C₁₆) arylsulfinyl, (C₆-C₁₆) arylsulfonyl, (C₆ -C₁₆) aralkylmercapto, (C₇-C₁₆) aralkylsulfinyl, (C₇-C₁₆) aralkylsulfonyl,
R¹ and R², R² and R³ or R³ and R⁴ can form a chain [CH₂] _o , in which one or two CH₂ groups of the saturated or unsaturated chain with a C = C double bond optionally by O, S, SO, SO₂ or NR 'are replaced, o = 3, 4 or 5 means and
R ′ is hydrogen, (C₆-C₁₂) aryl, (C₁-C₈) alkyl, (C₁-C₈) alkoxy- (C₁-C₈) alkyl, (C₇-C₁₂) aralkoxy- (C₁-C₈) - alkyl, (C₆-C₁₂) aryloxy- (C₁-C₈) alkyl, (C₁-C₁₀) alkanoyl, optionally substituted (C₇-C₁₆) aralkanoyl, optionally substituted (C₆-C₁₂) aryl,
R⁵ is hydrogen or a branched or unbranched (C₁-C₂₀) alkyl radical, a (C₆-C₁₆) aryl radical or a (C₇-C₁₆) aralkyl radical,
these radicals being substituted by one or more radicals from the series
Hydroxy, halogen, cyano, trifluoromethyl, nitro, carboxy, (C₁-C₁₂) alkyl, (C₃-C₈) cycloalkyl, (C₃-C₈) cycloalkyl- (C₁-C₁₂) alkyl, (C₃-C₈) - Cycloalkoxy, (C₃-C₈) cycloalkyl- (C₁-C₁₂) alkoxy, (C₃-C₈) cycloalkyloxy- (C₁-C₁₂) alkyl, (C₃-C₈) cycloalkyloxy- (C₁-C₁₂) alkoxy, (C₃-C₈) -cycloalkyl- (C₁-C₈) -alkyl- (C₁-C₆) - alkoxy, (C₃-C₈) -cycloalkyl- (C₁-C₈) alkoxy- (C₁-C₆) alkyl, (C₃ -C₈) -Cycloalkyloxy- (C₁-C₈) alkoxy- (C₁-C₆) alkyl, (C₃-C₈) -cycloalkoxy- (C₁-C₈) alkoxy- (C₁-C₈) alkoxy, (C₆-C₁₂ ) Aryl, (C₇-C₁₆) aralkyl, (C₂-C₁₂) alkenyl, (C₂-C₁₂) alkynyl, (C₁-C₁₂) alkoxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) - alkyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxy, (C₁-C₁₂) alkoxy- (C₁-C₈) alkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy, (C₇-C₁₆) aralkyloxy, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxy, (C₇-C₁₆) aralkoxy- (C₁-C₆) alkoxy, (C₁-C₈) hydroxyalkyl, ( C₆-C₁₆) aryloxy- (C₁-C₈) alkyl, (C₇-C₁₆) aralkoxy- (C₁-C₈) - alkyl, (C₆-C₁₂) aryloxy- (C₁-C₈) alkoxy- (C₁- C₆) alkyl, (C₇-C₁₂) aralkyloxy- (C₁-C₈) alkoxy- (C₁-C₆) alkyl, -O- [CH _2- ] _x C _f H _{(2f + 1-g)} F _g , -OCF₂Cl, -OCF₂-CHFCl,
(C₁-C₁₂) alkylcarbonyl, (C₃-C₈) cycloalkylcarbonyl, (C₆-C₁₂) arylcarbonyl, (C₇-C₁₆) aralkylcarbonyl, cinnamoyl, (C₂-C₁₂) alkenylcarbonyl, (C₂-C₁₂) alkynylcarbonyl,
(C₁-C₁₂) alkoxycarbonyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyl, (C₆-C₁₂) aryloxycarbonyl, (C₇-C₁₆) aralkoxycarbonyl, (C₃-C₈) cycloalkoxycarbonyl, (C₂ -C₁₂) alkenyloxycarbonyl, (C₂-C₁₂) alkynyloxycarbonyl, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxycarbonyl, (C₇-C₁₆) aralkoxy- (C₁-C₆) alkoxycarbonyl, (C₃-C₈ ) - cycloalkyl- (C₁-C₆) alkoxycarbonyl, (C₃-C₈) cycloalkoxy- (C₁-C₆) alkoxycarbonyl,
(C₁-C₁₂) alkylcarbonyloxy, (C₃-C₈) cycloalkylcarbonyloxy, (C₆-C₁₂) arylcarbonyloxy, (C₇-C₁₆) aralkylcarbonyloxy, cinnamoyloxy, (C₂-C₁₂) alkenylcarbonyloxy, (C₂-C₁₂oxy) alkynylcarbonyloxy
(C₁-C₁₂) alkoxycarbonyloxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyloxy, (C₆-C₁₂) aryloxycarbonyloxy, (C₇-C₁₆) aralkyloxycarbonyloxy, (C₃-C₈) - cycloalkoxycarbonyloxy, (C₂ -C₁₂) alkenyloxycarbonyloxy, (C₂-C₁₂) alkynyloxycarbonyloxy,
Carbamoyl, N- (C₁-C₁₂) alkylcarbamoyl, N, N-di- (C₁-C₁₂) alkylcarbamoyl, N- (C₃-C₈) cycloalkylcarbamoyl, N, N-dicyclo- (C₃-C₈) alkylcarbamoyl, N- (C₁-C₁₀) - alkyl-N- (C₃-C₈) -cycloalkylcarbamoyl, N - ((C₃-C₈) -cycloalkyl- (C₁-C₆) - alkyl) carbamoyl, N- (C₁-C₆) alkyl -N - ((C₃-C₈) -cycloalkyl- (C₁-C₆) alkyl) carbamoyl, N - (+) - dehydroabietylcarbamoyl, N- (C₁-C₆) alkyl-N - (+) - dehydroabietylcarbamoyl, N- ( C₆-C₁₂) arylcarbamoyl, N- (C₇-C₁₆) aralkylcarbamcyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₆) arylcarbamoyl, N- (C₁-C₁₀) alkyl- N- ( C₇-C₁₆) aralkylcarbamoyl, N - ((C₁-C₁₀) alkoxy (C₁-C₁₀) alkyl) carbamoyl, N - ((C₆-C₁₆) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N- ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆) - aralkylox y- (C₁-C₁₀) alkyl) carbamoyl, CON (CH₂) _h , in which a CH₂ group by O, S, N- (C₁-C₈) alkylimino, N- (C₃-C₈) - cycloalkylimino, N- (C₃-C₈) cycloalkyl- (C₁-C₄) alkylimino, N- (C₆-C₁₂) arylimino, N- (C₇-C₁₆) aralkylimino or N- (C₁-C₄) alkoxy- (C₁-C₆ ) alkylimino can be replaced and h is 3 to 7, or with
a carbamoyl radical of the general formula II wherein
R ^x denotes the substituents of an α-amino acid, which include the L and D amino acids,
s 1, 2, 3, 4 or 5 and
T means OH, OR or NR * R **, where
R *, R ** and R *** are the same or different and are hydrogen, (C₆-C₁₂) aryl, (C₇-C₁₁) aralkyl, (C₁-C₈) alkyl, (C₃-C₈) cycloalkyl, (+) - Dehydroabietyl, (C₁-C₈) alkoxy- (C₁-C₈) alkyl, (C₇-C₁₂) - aralkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy- (C₁-C₈ ) alkyl, (C₁-C₁₀) alkanoyl, optionally substituted (C₇-C₁₆) aralkanoyl, optionally substituted (C₆-C₁₂) aroyl, or
R * and R ** together represent - [CH₂] _h , in which a CH₂ group is represented by O, S, SO, SO₂, N-acylamino, N- (C₁-C₁₀) alkoxycarbonylimino, N- (C₁-C₈) - Alkylimino, N- (C₃-C₈) -cycloalkylimino, N- (C₃-C₈) - cycloalkyl- (C₁-C₄) alkylimino, N- (C₆-C₁₂) arylimino, N- (C₇-C₁₆) aralkylimino or N- (C₁-C₄) alkoxy- (C₁-C₆) alkylimino can be replaced and h is 3 to 7, or with
Carbamoyloxy, N- (C₁-C₁₂) alkylcarbamoyloxy, N, N-Di- (C₁-C₁₂) alkylcarbamoyloxy, N- (C₃-C₈) cycloalkylcarbamoyloxy, N- (C₆-C₁₂) arylcarbamoyloxy, N- (C₇ -C₁₆) aralkylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₂) arylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylcarbamoyloxy, N - (( C₁-C₁₀) alkyl) carbamoyloxy, N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy , N- (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) -aryloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy, -
Amino, (C₁-C₁₂) alkylamino, di- (C₁-C₁₂) alkylamino, (C₃-C₈) - cycloalkylamino, (C₃-C₁₂) alkenylamino, (C₃-C₁₂) alkynylamino, N- (C₆-C₁₂ ) Arylamino, N- (C₇-C₁₁) aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C₁-C₁₂) alkoxyamino, (C₁-C₁₂) alkoxy-N- (C₁-C₁₀) - alkylamino,
(C₁-C₁₂) alkanoylamino, (C₃-C₈) cycloalkanoylamino, (C₆-C₁₂) aroylamino, (C₇-C₁₆) aralkanoylamino, (C₁-C₁₂) alkanoyl-N- (C₁-C₁₀) alkylamino, (C₃-C₈) cycloalkanoyl-N- (C₁-C₁₀) alkylamino, (C₆-C₁₂) aroyl- N- (C₁-C₁₀) alkylamino, (C₇-C₁₁) aralkanoyl-N- (C₁-C₁₀ ) alkylamino,
(C₁-C₁₂) alkanoylamino- (C₁-C₈) alkyl, (C₃-C₈) cycloalkanoylamino- (C₁-C₈) alkyl, (C₆-C₁₂) aroylamino- (C₁-C₈) alkyl, (C₇ -C₁₆) - aralkanoylamino- (C₁-C₈) alkyl, amino- (C₁-C₁₀) alkyl, N- (C₁-C₁₀) alkylamino- (C₁-C₁₀) alkyl, N, N-di- (C₁ -C₁₀) alkylamino- (C₁-C₁₀) alkyl, (C₃-C₈) cycloalkylamino- (C₁-C₁₀) alkyl,
(C₁-C₁₂) alkylmercapto, (C₁-C₁₂) alkylsulfinyl, (C₁-C₁₂) alkylsulfonyl, (C₆-C₁₂) arylmercapto, (C₆-C₁₂) arylsulfinyl, (C₆-C₁₂) arylsulfonyl, (C₆ -C₁₆) aralkylmercapto, (C₇-C₁₆) aralkylsulfinyl, (C₇-C₁₆) aralkylsulfonyl,
Sulfamoyl, N- (C₁-C₁₀) alkylsulfamoyl, N, N-di- (C₁-C₁₀) alkylsulfamoyl, (C₃-C₈) cycloalkylsulfamoyl, N- (C₆-C₁₂) arylsulfamoyl, N- (C₇-C₁₆ ) Aralkylsulfamoyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₂) arylsulfamoyl, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylsulfamoyl, (C₁-C₁₀) - Alkyl sulfonamido, N - ((C₁-C₁₀) alkyl) - (C₁-C₁₀) alkylsulfonamido, (C₇-C₁₆) aralkylsulfonamido, N - ((C₁-C₁₀) alkyl- (C₇-C₁₆) aralkylsulfonamido ,
where the radicals which contain an aryl radical in turn can be substituted on the aryl by 1 to 5 identical or different radicals from the series:
Hydroxy, halogen, cyano, trifluoromethyl, nitro, carboxy, (C₁-C₁₂) alkyl, (C₃-C₈) cycloalkyl, (C₃-C₈) cycloalkyl- (C₁-C₁₂) alkyl, (C₃-C₈) - Cycloalkoxy, (C₃-C₈) cycloalkyl- (C₁-C₁₂) alkoxy, (C₃-C₈) cycloalkyloxy- (C₁-C₁₂) alkyl, (C₃-C₈) cycloalkyloxy- (C₁-C₁₂) alkoxy, (C₃-C₈) cycloalkyl- (C₁-C₈) alkyl- (C₁-C₆) alkoxy, (C₃-C₈) cycloalkyl- (C₁-C₈) alkoxy- (C₁-C₆) - alkyl, (C₃ -C₈) -Cycloalkyloxy- (C₁-C₈) alkoxy- (C₁-C₆) alkyl, (C₃-C₈) - cycloalkoxy- (C₁-C₈) alkoxy- (C₁-C₈) alkoxy, (C₆-C₁₂ ) Aryl, (C₇-C₁₆) aralkyl, (C₂-C₁₂) alkenyl, (C₂-C₁₂) alkynyl, (C₁-C₁₂) alkoxy, (C₁-C₁₂) - alkoxy- (C₁-C₁₂) - alkyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxy, (C₁-C₁₂) alkoxy- (C₁-C₈) alkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy, (C₇-C₁₆) aralkyloxy, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxy, (C₇-C₁₆) aralkoxy- (C₁-C₆) alkoxy, (C₁-C₈) hydroxyalkyl , (C₆-C₁₆) aryloxy- (C₁-C₈) alkyl, (C₇-C₁₆) aralkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy- (C₁-C₈) alkoxy- ( C₁-C₆) alkyl, (C₇-C₁₂) aralkyloxy- (C₁-C₈) alkoxy- (C₁-C₆) alkyl, -O- [CH _2- ] _x C _f H _{(2f + 1-g)} F _g , -OCF₂Cl, -OCF₂-CHFCl,
(C₁-C₁₂) alkylcarbonyl, (C₃-C₈) cycloalkylcarbonyl, (C₆-C₁₂) arylcarbonyl, (C₇-C₁₆) aralkylcarbonyl,
(C₁-C₁₂) alkoxycarbonyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyl,
(C₆-C₁₂) aryloxycarbonyl, (C₇-C₁₆) aralkoxycarbonyl, (C₃-C₈) - cycloalkoxycarbonyl, (C₂-C₁₂) alkenyloxycarbonyl, (C₂-C₁₂) alkynyloxycarbonyl, (C₆-C₁₂) aryloxy- (C₁ -C₆) -alkoxycarbonyl, (C₇-C₁₆) - aralkoxy- (C₁-C₆) -alkoxycarbonyl, (C₃-C -C) -cycloalkyl- (C₁-C₆) - alkoxycarbonyl, (C₃-C₈) -cycloalkoxy- (C₁-C₆ ) alkoxycarbonyl,
(C₁-C₁₂) alkylcarbonyloxy, (C₃-C₈) cycloalkylcarbonyloxy, (C₆-C₁₂) arylcarbonyloxy, (C₇-C₁₆) aralkylcarbonyloxy, cinnamoyloxy, (C₂-C₁₂) alkenylcarbonyloxy, (C₂-C₁₂), alkynylcarbonyloxy
(C₁-C₁₂) alkoxycarbonyloxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyloxy, (C₆-C₁₂) aryloxycarbonyloxy, (C₇-C₁₆) aralkyloxycarbonyloxy, (C₃-C₈) cycloalkoxycarbonyloxy, (C₂ -C₁₂) - alkenyloxycarbonyloxy, (C₂-C₁₂) alkynyloxycarbonyloxy,
Carbamoyl, N- (C₁-C₁₂) alkylcarbamoyl, N, N-di- (C₁-C₁₂) alkylcarbamoyl, N- (C₃-C₈) cycloalkylcarbamoyl, N, N-dicyclo- (C₃-C₈) alkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₃-C₈) cycloalkylcarbamoyl, N - ((C₃-C₈) cycloalkyl- (C₁-C₆) alkyl) carbamoyl, N- (C₁-C₆) alkyl -N - ((C₃-C₈) -cycloalkyl- (C₁-C₆) - alkyl) carbamoyl, N - (+) - dehydroabietylcarbamoyl, N- (C₁-C₆) alkyl-N - (+) - dehydroabietylcarbamoyl, N- (C₆-C₁₂) arylcarbamoyl, N- (C₇-C₁₆) aralkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₆) arylcarbamoyl, N- (C₁-C₁₀) - alkyl-N- (C₇-C₁₆) aralkylcarbamoyl, N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₆-C₁₆) aryloxy- (C₁-C₁₀) alkyl) - carbamoyl, N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) - alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₇ -C₁₆) aralkyl oxy- (C₁-C₁₀) alkyl) carbamoyl, CON (CH₂) _h , in which a CH₂ group is represented by O, S, N- (C₁-C₈) alkylimino, N- (C₃-C₈) cycloalkylimino, N- (C₃-C₈) cycloalkyl- (C₁-C₄) alkylimino, N- (C₆-C₁₂) arylimino, N- (C₇-C₁₆) aralkylimino or N- (C₁-C₄) alkoxy- (C₁-C₆ ) alkylimino can be replaced and h is 3 to 7,
Carbamoyloxy, N- (C₁-C₁₂) alkylcarbamoyloxy, N, N-Di- (C₁-C₁₂) alkylcarbamoyloxy, N- (C₃-C₈) cycloalkylcarbamoyloxy, N- (C₆-C₁₆) arylcarbamoyloxy, N- (C₇ -C₁₆) aralkylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₂) arylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylcarbamoyloxy, N - (( C₁-C₁₀) alkyl) carbamoyloxy, N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy , N- (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) -aryloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy, -
Amino, (C₁-C₁₂) alkylamino, di- (C₁-C₁₂) alkylamino, (C₃-C₈) cycloalkylamino, (C₃-C₁₂) alkenylamino, (C₃-C₁₂) alkynylamino, N- (C₆- C₁₂ ) Arylamino, N- (C₇-C₁₁) aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C₁-C₁₂) alkoxyamino, (C₁-C₁₂) alkoxy-N- (C₁-C₁₀) - alkylamino,
(C₁-C₁₂) alkanoylamino, (C₃-C₈) cycloalkanoylamino, (C₆-C₁₂) aroylamino, (C₇-C₁₆) aralkanoylamino, (C₁-C₁₂) alkanoyl-N- (C₁-C₁₀) alkylamino, (C₃-C₈) cycloalkanoyl-N- (C₁-C₁₀) alkylamino, (C₆-C₁₂) aroyl-N- (C₁-C₁₀) alkylamino, (C₇-C₁₁) aralkanoyl-N- (C₁-C₁₀ ) - alkylamino,
(C₁-C₁₂) alkanoylamino- (C₁-C₈) alkyl, (C₃-C₈) cycloalkanoylamino- (C₁-C₈) alkyl, (C₆-C₁₂) aroylamino- (C₁-C₈) alkyl, (C₇ -C₁₆) - aralkanoylamino- (C₁-C₈) alkyl, amino- (C₁-C₁₀) alkyl, N- (C₁-C₁₀) alkylamino- (C₁-C₁₀) alkyl, N, N-di- (C₁ -C₁₀) alkylamino- (C₁-C₁₀) alkyl, (C₃-C₈) cycloalkylamino- (C₁-C₁₀) alkyl,
(C₁-C₁₂) alkylmercapto, (C₁-C₁₂) alkylsulfinyl, (C₁-C₁₂) alkylsulfonyl, (C₆-C₁₆) arylmercapto, (C₆-C₁₆) arylsulfinyl, (C₆-C₁₆) arylsulfonyl, (C₆ -C₁₆) aralkylmercapto, (C₇-C₁₆) aralkylsulfinyl, (C₇-C₁₆) aralkylsulfonyl,
and
f = 1 to 8,
g = 0.1 to (2f + 1),
x = 0 to 3,
h = 3 to 6 mean
including the physiologically active salts, where N - ((6,7-dichloro-3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine and α- ((6,7-dichloro-3,4-dihydro -3-oxo-2-quinoxalinyl) carbonyl) amino) phenyl-acetic acid are excluded. 2. Compounds of formula I according to claim 1, in which
QO or S,
XO,
A (C₁-C₃) alkylene, which is optionally monosubstituted with halogen, cyano, trifluoromethyl, (C₁-C₆) alkyl, (C₁-C₆) hydroxyalkyl, (C₁-C₆) alkoxy, -O- [CH₂ ] _x -C _f H _{(2f + 1-g)} F _g or
A means -CHR⁶-, where R⁶ means one of the substituents of the α-C atom of an α-amino acid, in particular a natural L-amino acid and its D isomer,
B CO₂H
R¹, R², R³ and R⁴ are the same or different and are hydrogen, (C₁-C₂₀) alkyl, (C₂-C₂₀) alkenyloxy, (C₂-C₂₀) alkynyloxy, retinyloxy, (C₂-C₂₀) - alkenyloxy- (C₁ -C₃) alkyl, retinyloxy- (C₁-C₃) alkyl, (C₂-C₂₀) alkynyloxy- (C₁-C₃) alkyl, (C₁-C₂₀) alkoxy, halogen, cyano, trifluoromethyl, (C₁-C₈ ) - Hydroxyalkyl, (C₁-C₁₀) alkanoyl, (C₇-C₁₂) aralkanoyl, (C₆-C₁₂) aroyl, -O- [CH₂] _x C _f H _{(2f + 1-g)} F _g , (C₁ -C₁₀) alkylmercapto, (C₁-C₁₀) alkylsulfinyl, (C₁-C₁₀) alkylsulfonyl, (C₆-C₁₂) arylmercapto, (C₆-C₁₂) arylsulfinyl, (C₆-C₁₂) arylsulfonyl, (C₇-C₁ ) Aralkylmercapto, (C₇-C₁₂) aralkylsulfinyl, (C₇-C₁₂) aralkylsulfonyl, (C₆-C₁₂) aryloxy, (C₇-C₁₆) aralkyloxy, carboxy, (C₁-C₂₀) alkoxycarbonyl, (C₁-C₁₂ ) -Alkoxy- (C₁-C₁₂) alkoxycarbonyl, (C₆-C₁₂) aryloxycarbonyl, (C₇-C₁₆) aralkoxycarbonyl, (C₃-C₈) - cycloalkoxycarbonyl, (C₂-C₂₀) -A lkenyloxycarbonyl, retinyloxycarbonyl, (C₂-C₂₀) alkynyloxycarbonyl, (C₃-C₈) cycloalkyl- (C₁-C₆) alkoxycarbonyl, (C₃-C₈) -cycloalkoxy- (C₁-C₆) alkoxycarbonyl, (C₆-C₁₂) - Aryloxy- (C₁-C₆) alkoxycarbonyl, (C₇-C₁₆) aralkoxy- (C₁-C₆) alkoxycarbonyl,
(C₁-C₁₂) alkoxy- (C₁-C₁₂) alkyl, (C₁-C₈) alkoxy- (C₁-C₁₂) alkoxy, (C₁-C₁₂) alkoxy- (C₁-C₈) alkoxy- (C₂ -C₆) alkyl, (C₇-C₁₁) aralkyloxy, (C₃-C₈) - cycloalkyl, (C₃-C₈) cycloalkyl- (C₁-C₈) alkyl, (C₃-C₈) cycloalkyloxy, (C₃-C₈ ) -Cycloalkyl- (C₁-C₈) -alkoxy, (C₃-C₈) -cycloalkyloxy- (C₁-C₈) -alkyl, (C₃-C₈) -cycloalkyloxy- (C₁-C₈) -alkoxy, (C₃-C₈) - Cycloalkyl- (C₁-C₆) -alkyl- (C₁-C₆) -alkoxy, (C₃-C -C) -cycloalkyl- (C₁-C₆) -alkoxy- (C₁-C₆) -alkyl, (C₃-C₈) -cycloalkoxy- (C₁-C₆) alkoxy- (C₁-C₆) alkyl, NR ^Y R ^Z , substituted (C₆-C₁₂) aryloxy- (C₁-C₆) alkyl, (C₇-C₁₁) aralkoxy- (C₁-C₆ ) alkyl, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxy- (C₁-C₆) alkyl, (C₇-C₁₁) aralkyloxy- (C₁-C₆) alkoxy (C₁-C₆) - alkyl , (C₆-C₁₂) aryloxy, (C₆-C₁₂) aryloxy (C₁-C₆) alkoxy or (C₇-C₁₁) aralkoxy- (C₁-C₆) alkoxy, an aromatic radical having 1, 2, 3, 4 or 5 identical or different substituents from the series hydrogen, halogen, cyano, nitro, trifluoromethyl, (C₁-C₆) alkyl, (C₁-C₆) hydroxyalkyl, (C₁-C₆) alkoxy, -O- [CH₂] _x C _f H _{(2f + 1-g)} F _g , -OCF₂Cl, -O-CF₂-CHFCl, (C₁-C₆) alkylmercapto, (C₁-C₆) alkylsulfinyl, (C₁ -C₆) alkylsulfonyl, (C₁-C₆ ) -Alkylcarbonyl, (C₁-C₆) -alkoxycarbonyl, carbamoyl, N- (C₁-C₄) -alkylcarbamoyl, N, N-di- (C₁-C₄) -alkylcarbamoyl, (C₁-C₆) - alkylcarbonyloxy, (C₃-C₈ ) -Cycloalkylcarbamoyl, phenyl, benzyl, phenoxy, benzyloxy, NR ^Y R ^Z , phenylmercapto, phenylsulfonyl, phenylsulfinyl, sulfamoyl, N- (C₁-C₄) alkylsulfamoyl or N, N-di- (C₁-C₄) -alkylsulfamoyl, or optionally carries up to 3 of the same or different substituents mentioned above and two adjacent C atoms of the aralkyloxy radical together bear a chain - [CH₂-] and / or -CH = CH-CH = CH-, one CH₂ group of the chain optionally replaced by O, S, SO, SO₂ or NR ' is
Carbamoyl, N- (C₁-C₁₂) alkylcarbamoyl, N, N-di- (C₁-C₁₂) alkylcarbamoyl, N- (C₃-C₈) cycloalkylcarbamoyl, N, N-dicyclo (C₃-C₈) alkylcarbamoyl, N - (C₁-C₁₀) alkyl-N- (C₃-C₈) cycloalkylcarbamoyl, N- (C₃-C₈) cycloalkyl- (C₁-C₆) alkyl) carbamoyl, N- (C₁-C₆) alkyl-N - ((C₃-C₈) -cycloalkyl- (C₁-C₆) - alkyl) carbamoyl, N - (+) - dehydroabietylcarbamoyl, N- (C₁-C₆) alkyl-N - (+) - dehydroabietylcarbamoyl, N- (C₆ -C₁₂) arylcarbamoyl, N- (C₇-C₁₆) aralkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₆) arylcarbamoyl, N- (C₁-C₁₀) - alkyl-N- (C₇ -C₁₆) aralkylcarbamoyl, N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₆-C₁₆) aryloxy- (C₁-C₁ ₀) alkyl) carbamoyl, N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N- ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl , N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆) -aralkylox y- (C₁-C₁₀) alkyl) carbamoyl, CON (CH₂) _h , in which a CH₂ group is represented by O, S, N- (C₁-C₈) alkylimino, N- (C₃-C₈) cycloalkylimino, N- (C₃-C₈) cycloalkyl- (C₁-C₄) alkylimino, N- (C₆-C₁₂) arylimino, N- (C₇-C₁₆) aralkylimino or N- (C₁-C₄) alkoxy- (C₁-C₆ ) alkylimino can be replaced and h is 3 to 7,
R¹ and R² or R² and R³ or R³ and R⁴ can form a chain [CH₂] _o , where o = 3, 4 or 5,
R⁵ is hydrogen or a branched or unbranched (C₁-C₁₂) alkyl radical which can contain up to 3 CC multiple bonds, a (C₆- C₁₆) aryl radical or a (C₇-C₁₆) aralkyl radical which contains up to 2 CC multiple compounds can contain means, where these radicals are substituted with one or more radicals from the series hydroxy, fluorine, chlorine, cyano, trifluoromethyl, carboxy, (C₁-C₁₂) alkyl, (C₃-C₈) - cycloalkyl, (C₃-C₈ ) -Cycloalkoxy, (C₃-C₈) -cycloalkyl- (C₁-C₁₂) -alkoxy, (C₃-C₈) -cycloalkyloxy- (C₁-C₁₂) alkoxy, (C₆-C₁₂) aryl, (C₇-C₁ ₆) -Aralkyl, (C₂-C₁₂) alkenyl, (C₂-C₁₂) alkynyl, (C₁-C₁₂) alkoxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxy, (C₆-C₁₂) aryloxy , (C₇-C₁₆) aralkyloxy, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxy, (C₇-C₁₆) aralkoxy- (C₁-C₆) alkoxy, (C₁-C₈) hydroxyalkyl, - O- [CH _2- ] _x C _f H _{(2f + 1-g)} F _g ,
Carbamoyl, N- (C₁-C₁₂) alkylcarbamoyl, N, N-di- (C₁-C₁₂) alkylcarbamoyl, N- (C₃-C₈) cycloalkylcarbamoyl, N, N-dicyclo- (C₃-C₈) alkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₃-C₈) cycloalkylcarbamoyl, N - ((C₃-C₈) cycloalkyl- (C₁-C₆) alkyl) carbamoyl, N- (C₆-C₁₂) arylcarbamoyl , N- (C₇-C₁₆) aralkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₆) arylcarbamoyl, N- (C₁-C₁₀) - alkyl-N- (C₇-C₁₆) aralkylcarbamoyl , N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₆-C₁₆) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₇-C₁₆ ) Aralkyloxy- (C₁-C₁₀) alkyl) carbamoyl, CON (CH₂) _h , in which a CH₂ group is substituted by O, N- (C₁-C₈) alkylimino, N- (C₃-C₈) cycloalkylimino, N- (C₃-C₈) cycloalkyl- (C₁-C₄) alkylimino, N- (C₆-C₁₂) arylimino or N- (C₇-C₁₆) aralkylimino can be replaced and h is 3 to 6, or with
(C₁-C₁₂) alkanoylamino, (C₃-C₈) cycloalkanoylamino, (C₆-C₁₂) aroylamino, (C₇-C₁₆) aralkanoylamino, (C₁-C₁₂) alkanoyl-N- (C₁-C₁₀) alkylamino, (C₃-C₈) cycloalkanoyl-N- (C₁-C₁₀) alkylamino,
where the radicals which contain an aryl radical in turn can be substituted on the aryl by 1 to 5 identical or different radicals from the series:
Hydroxy, fluorine, chlorine, cyano, trifluoromethyl, carboxy, (C₁-C₁₂) alkyl, (C₃-C₈) cycloalkyl, (C₂-C₁₂) alkenyl, (C₁-C₁₂) alkoxy,
Carbamoyl, N- (C₁-C₁₂) alkylcarbamoyl, N, N-di- (C₁-C₁₂) alkylcarbamoyl, N- (C₃-C₈) cycloalkylcarbamoyl, or (C₁-C₁₂) alkylmercapto, (C₁-C₁₂) - alkylsulfinyl, (C₁-C₁₂) alkylsulfonyl,
in which
R ^Y and R ^{Z are the} same or different and are hydrogen, (C₆-C₁₂) aryl, (C₁-C₁₀) alkyl, (C₃-C₁₀) cycloalkyl, (C₁-C₈) alkoxy- (C₁-C₈) - alkyl, (C₇-C₁₂) aralkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy- (C₁-C₈) alkyl, (C₁-C₁₀) alkanoyl, optionally substituted (C₇-C₁₆) Aralkanoyl, optionally substituted (C₆-C₁₂) aroyl or
R ^Y and R ^Z together represent - [CH₂] _h -, in which a CH₂ group can be replaced by O, S, N- (C₁-C₄) alkanoylimino or N- (C₁-C₄) alkoxycarbonylimino, and
f 1 to 8,
g 0.1 to (2f + 1),
h 3 to 6,
x 0 to 3, and
n is 3 or 4,
including the physiologically active salts where N - ((6,7-dichloro-3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine and α - ((6,7-dichloro-3,4-dihydro- 3-oxo-2-quinoxalinyl) carbonyl) amino) are excluded. 3. Compounds of formula I according to claims 1 or 2, in which
QO or S,
XO,
A -CHR⁶-, where R⁶ is the substituent of the α-C atom of an α-amino acid, in particular a natural L-amino acid or its D isomer,
B CO₂H,
R¹, R², R³ and R⁴ are the same or different and are hydrogen, (C₁-C₁₂) alkyl, (C₃-C₇) cycloalkyl, (C₁-C₁₂) alkoxy, (C₃-C₇) cycloalkyloxy, (C₃-C₇ ) - Cycloalkyl- (C₁-C₂) alkoxy, -O- [CH₂] _x -C _f H _{(2f + 1-g)} F _g , (C₁-C₄) alkoxy- (C₁-C₄) alkoxy, substituted (C₆-C₁₂) phenoxy, (C₇-C₁₁) phenylalkyloxy, (C₆-C₁₂) phenoxy- (C₁-C₄) alkoxy, (C₇-C₁₁) phenylalkoxy- (C₁-C₄) alkoxy, fluorine, Trifluoromethyl, chlorine, N- (C₁-C₁₀) alkylcarbamoyl, N, N-di- (C₁-C₈) alkylcarbamoyl, N- (C₃-C₇) cycloalkylcarbamoyl, N-phenylcarbamoyl, N-phenyl- (C₁-C₄ ) -alkylcarbamoyl, carboxy, (C₁-C₁₆) alkoxycarbonyl, (C₂-C₁₆) alkenyloxycarbonyl, retinyloxycarbonyl, (C₃-C₇) - cycloalkoxycarbonyl, where an aromatic radical having 1, 2 or 3 identical or different substituents from the Series fluorine, chlorine, cyano, trifluoromethyl, (C₁-C₆) alkyl, (C₁-C₆) alkoxy is substituted
R⁵ is hydrogen or a branched or unbranched (C₁-C₁₂) alkyl radical, which can contain one or two CC multiple bonds, and
f 1 to 4
g 0.1 to (2f + 1)
x means 0 and 1,
including the physiologically active salts, where N - ((6,7-dichloro-3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine and α - ((6,7-dichloro-3,4-dihydro -3-oxo-2-quinoxalinyl) carbonyl) amino) phenylacetic acid are excluded. 4. Compounds of formula I according to one or more of claims 1 to 3, in which
QO,
XO,
A represents a -CH₂ group which can be substituted by a methyl group,
B CO₂H,
R¹, R², R³ and R⁴ are the same or different and are hydrogen, (C₁-C₁₂) alkyl, (C₃-C₇) cycloalkyl, (C₁-C₁₂) alkoxy, (C₃-C₇) cycloalkyloxy, (C₃-C₇ ) - Cycloalkyl- (C₁-C₂) alkoxy, -O- [CH₂] _x -C _f H _{(2f + 1-g)} F _g , (C₁-C₄) alkoxy- (C₁-C₄) alkoxy, substituted (C₆-C₁₂) phenoxy, (C₇-C₁₁) phenylalkyloxy, (C₆-C₁₂) phenoxy- (C₁-C₄) alkoxy, (C₇-C₁₁) phenylalkoxy- (C₁-C₄) alkoxy, fluorine, Trifluoromethyl, chlorine, N- (C₁-C₁₀) alkylcarbamoyl, N, N-di- (C₁-C₈) alkylcarbamoyl, N- (C₃-C₇) cycloalkylcarbamoyl, N-phenylcarbamoyl, N-phenyl- (C₁-C₄ ) -alkylcarbamoyl, carboxy, (C₁-C₁₆) alkoxycarbonyl, (C₂-C₁₆) alkenyloxycarbonyl, retinyloxycarbonyl, (C₃-C₇) - cycloalkoxycarbonyl, where an aromatic radical having 1, 2 or 3 identical or different substituents from the Series fluorine, chlorine, cyano, trifluoromethyl, (C₁-C₆) alkyl, (C₁-C₆) alkoxy is substituted and
R⁵ is hydrogen or a branched or unbranched (C₁-C₆) alkyl radical and
f 1 to 4,
g 0.1 to (2f + 1) and
x means 0 and 1,
including the physiologically active salts, where N - ((6,7-dichloro-3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine and α - ((6,7-dichloro-3,4-dihydro -3-oxo-2-quinoxalinyl) carbonyl) amino) phenylacetic acid are excluded. 5. Compounds of formula I according to one or more of claims 1 to 4, in which
QO,
XO,
A is a -CH₂ group and,
B means CO₂H, and
R¹ and R⁴ are identical or different and are hydrogen, fluorine, chlorine and (C₁-C₄) alkyl,
R² and R³ are the same or different and are hydrogen, fluorine, chlorine, (C₁-C₁₂) alkoxy, (C₃-C₇) cycloalkoxy, -O- [CH₂] _x -C _f H _{(2f + 1-g)} F _g , (C₁-C₄) alkyl, benzyloxy, optionally substituted with up to 3 substituents from the series fluorine, chlorine, trifluoromethyl, (C₁-C₆) alkoxy, (C₁-C₆) alkyl, O [CH₂) _x -C _f H _{(2f + 1-g)} F _g mean
R⁵ is hydrogen or (C₁-C₆) alkyl and
f 1 to 4,
g 0.1 to (2f + 1),
x mean 0 and 1 and
their physiologically active salts, where N - ((6,7-dichloro-3,4-dihydro-3-oxo-2-quinoxalinyl) carbonyl) glycine and α - ((6,7-dichloro-3,4-dihydro- 3-oxo-2-quinoxalinyl) carbonyl) amino) phenylacetic acid are excluded. 6. Compounds according to formula I according to one or more of the claims 1 to 5, plus N - ((6,7-dichloro-3,4-dihydro-3-oxo-2- quinoxalinyl) carbonyl) glycine and α - ((6,7-dichloro-3,4-dihydro-3-oxo-2- quinoxalinyl) carbonyl) amino) phenylacetic acid for use as a medicament. 7. Prodrugs to the compounds of formula I according to one or more of claims 1 to 6. 8. prodrugs according to claim 7, characterized in that these instead one or more carboxylate groups in the compounds of formula I according to one or more of claims 1 to 6, ester, amide and / or Contain hydroxymethyl groups.   9. Compounds of formula I according to claims 1 to 6 for the Use to inhibit collagen biosynthesis. 10. Compounds of formula I according to claims 1 to 6 for Use as inhibitors of prolyl hydroxylase. 11. Compounds of formula I according to claims 1 to 6 for Use as a fibrosuppressant. 12. Compounds of formula I according to claims 1 to 6 for the preparation a medicine for fibrotic diseases. 13. Compounds of formula I according to claims 1 to 6 and 12 for Production of a drug for fibrotic diseases of the liver. 14. Compounds of formula I according to claims 1 to 6 and 12 for Production of a drug for fibrotic diseases of the lungs. 15. Compounds of formula I according to claims 1 to 6 and 12 for Manufacture of a drug for fibrotic diseases of the skin. 16. A process for the preparation of compounds of formula I according to claims 1 to 8, in which A is an alkylene radical, B = CO₂H and X = O, in which

• i1) substituted o-phenylenediamines of the formula 4 with mesoxalic acid esters of the formula 2 to give compounds of the formula 5 or
• i2) substituted 2-nitroanilines of the formula 1 are reacted with mesoxalic acid esters of the formula 2 to give the imines of the formula 3 and then, after reduction of the nitro group, the ring for the compound of the formula 5 is closed and
• ii1) the compounds of formula 5 are saponified to give compounds of formula 7 (R⁵ = H) or
• ii2) the compounds of formula 5 are halogenated to compounds of formula 6 and these are subsequently converted to compounds of formula 7 and
• iii) reacting the compounds of the formula 7 with compounds of the formula 8 to give compounds of the formula 9 and optionally
• iv1) saponification to give compounds of the formula I and / or
• iv2) salt formation occurs.