US20020142969A1 - Didepsipeptide-based endoparasiticides, new didepsipeptides and process for preparing the same - Google Patents

Didepsipeptide-based endoparasiticides, new didepsipeptides and process for preparing the same Download PDF

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US20020142969A1
US20020142969A1 US09/011,599 US1159998A US2002142969A1 US 20020142969 A1 US20020142969 A1 US 20020142969A1 US 1159998 A US1159998 A US 1159998A US 2002142969 A1 US2002142969 A1 US 2002142969A1
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alkyl
optionally substituted
cycloalkyl
methyl
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Peter Jeschke
Jurgen Scherkenbeck
Andrew Plant
Achim Harder
Norbert Mencke
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Bayer AG
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/46—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylureas
    • C07C275/58—Y being a hetero atom
    • C07C275/62—Y being a nitrogen atom, e.g. biuret
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/10—Anthelmintics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/14—Ectoparasiticides, e.g. scabicides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/46—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylureas
    • C07C275/48—Y being a hydrogen or a carbon atom
    • C07C275/50—Y being a hydrogen or an acyclic carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/61—Halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/04—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D277/06—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
    • C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K11/00—Depsipeptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof

Definitions

  • the present invention relates to the use of didepsipeptides for the control of endoparasites, to new didepsipeptides and to processes for their preparation.
  • didepsipeptides are, as starting substances for endoparasiticidally active cyclic depsipeptides (cf. total synthesis of PF 1022 A: JP Pat. 05 229 997; Makoto Ohyama et al., Biosci. Biotech. Biochem. 58 (6), 1994, pp. 1193-1194; Makio Kobayshi et al., Annu. Rep. Sankyo Res. Lab. 46, 1994, pp. 67-75; Stephen J. Nelson et al., J. Antibiotics 47, (11), 1994, pp.
  • the present invention relates to:
  • R 1 represent hydrogen, straight-chain or branched alkyl, cycloalkyl, arylalkyl, aryl, heteroaryl, heteroarylalkyl, each of which is optionally substituted,
  • R 1 and R 2 together with the atoms to which they are bonded represent a 5- or 6-membered ring which can optionally be interrupted by oxygen, sulphur, sulphoxyl or sulphonyl and is optionally substituted,
  • R 2 and R 3 independently of one another represent hydrogen, straight-chain or branched alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, each of which is optionally substituted, or
  • R 2 and R 3 together represent a spirocyclic ring, which is optionally substituted
  • R 4 and R 5 independently of one another represent hydrogen, straight-chain or branched alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, each of which is optionally substituted, or
  • R 4 and R 5 together represent a spirocyclic ring, which is optionally substituted
  • A represents hydrogen, alkyl, aralkyl, fornyl, alkoxydicarbonyl or a radical of the group G 1
  • [0014] can denote carboxyl, thiocarboxyl, —CH ⁇ CH—NO 2 , —CH ⁇ CH—CN, —C ⁇ N—R 6 , sulphoxyl, sulphonyl, —P(O)—OR 7 or P(S)—OR 7 ,
  • R 6 represents hydrogen, hydroxyl, alkoxy, alkylcarbonyl, halogenoalkylcarbonyl, alkylsulphonyl, nitro or cyano, and
  • R 7 represents hydrogen or alkyl
  • Q represents straight-chain or branched alkyl, alkenyl, alkinyl, cycloalkyl, aryl, arylalkyl, hetaryl or hetarylalkyl, each of which is optionally substituted, or optionally represents a radical from the group G 2 and G 3
  • [0020] can denote carboxyl, thiocarboxyl or sulphonyl
  • Y represents oxygen, sulphur or —NR 9 ,
  • R 8 in the case where Y represents nitrogen can denote a cyclic amino group linked via a nitrogen atom
  • R 8 and R 9 independently of one another represent hydrogen, straight-chain or branched alkyl, alkenyl, alkinyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, hetaryl, hetarylalkyl, each of which is optionally substituted, or
  • R 8 and R 9 together with the adjacent N atom [lacuna] a carbocyclic 5-, 6- or 7-membered ring system or a 7 to 10-membered bicyclic ring system which can optionally also be interrupted by oxygen, sulphur, sulphoxyl, sulphonyl, carbonyl, —N—O—, —N ⁇ , —NR 11 — or by quaternized nitrogen and is optionally substituted,
  • R 10 represents hydrogen or alkyl
  • R 11 represent represents hydrogen, straight-chain or branched alkyl, alkenyl, alkinyl, cycloalkyl, cycloalkylalkyl, alkoxycarbonyl, alkylcarbonyl, cycloalkylcarbonyl, cyano, aryl, arylalkyl, hetaryl, hetarylalkyl, each of which is optionally substituted, and
  • B represents hydroxyl, alkoxy, alkenyloxy, alkinyloxy, cycloalkyloxy, cycloalkylalkyloxy, aryloxy-, arylalkyloxy, hetaryloxy, hetarylalkyloxy, each of which is optionally substituted, or
  • [0028] represents the radicals —N 12 R 13 , —NR 14 —NR 12 R 13 and —NR 15 —OR 16 ,
  • R 12 and R 13 independently of one another represent hydrogen, straight-chain or branched alkyl, alkylcarbonyl, alkylsulphonyl, alkenyl, alkinyl, cycloalkyl, cycloalkylalkyl, aryl, arylcarbonyl, arylsulphonyl, arylalkyl, hetaryl, hetarylcarbonyl, hetarylsulphonyl or hetarylalkyl, each of which is optionally substituted, or
  • R 12 and R 13 together with the adjacent N atom [lacuna] a carbocyclic 5-, 6-, 7- or 8-membered ring system or a 7 to 10-membered bicyclic ring system which can optionally also be interrupted by oxygen, sulphur, sulphoxyl, sulphonyl, carbonyl, —N—O—, —N ⁇ , —NR 11 — or by quaternized nitrogen and is optionally substituted,
  • R 14 represents hydrogen, straight-chain or branched alkyl, cycloalkyl, arylalkyl or hetarylalkyl, each of which is optionally substituted,
  • R 15 and R 16 independently of one another denote hydrogen, straight-chain or branched alkyl, alkylcarbonyl, alkenyl, alkinyl, cycloalkyl, cycloalkylalkyl, arylalkyl or hetarylalkyl, each of which is optionally substituted,
  • R 15 and R 16 together with the adjacent N—O-group represent a carbocyclic 5-, 6- or 7-membered ring
  • didepsipeptides are those of the general formula (I) and their salts
  • R 1 represent hydrogen, straight-chain or branched alkyl having up to 6 carbon atoms, C 3-6 -cycloalkyl, aryl-C 1-2 -alkyl or het-C 1-2 -alkyl, each of which is optionally substituted,
  • R 1 and R 2 together with the atoms to which they are bonded represent a 5- or 6-membered ring which can optionally be interrupted by sulphur and is optionally substituted,
  • R 2 and R 3 independently of one another represent hydrogen, straight-chain or branched alkyl having up to 6 carbon atoms, halogenoalkyl, hydroxyalkyl, C 1-4 -alkanoyloxyalkyl, C 1-2 -alkoxyalkyl, mercaptoalkyl, C 1-2 -alkylthioalkyl, C 1-2 -alkylsulphinylalkyl, C 1-2 -alkylsulphonylalkyl, carboxyalkyl, carbamoylalkyl, aminoalkyl, C 1-6 -alkylaminoalkyl, C 1-6 -dialkylaminoalkyl, guanidinoalkyl, which can optionally be substituted by one or two benzyloxycarbonyl radicals or by one, two, three or four C 1-2 -alkyl radicals, C 1-4 -alkoxycarbonylaminoalkyl, C 2-6 -alkeny
  • R 2 and R 3 together represent a spirocyclic ring
  • R 4 and R 5 independently of one another represent hydrogen, straight-chain or branched alkyl having up to 6 carbon atoms, halogenoalkyl, hydroxyalkyl, C 1-4 -alkanoyloxyalkyl, C 1-2 -alkoxyalkyl, mercaptoalkyl, C 1-2 -alkylthioalkyl, C 1-2 -alkylsulphinylalkyl, C 1-2 -alkylsulphonylalkyl, carboxyalkyl, carbamoylalkyl, aminoalkyl, C 1-6 -alkylaminoalkyl, C 1-6 -dialkylaminoalkyl, guanidinoalkyl, which can optionally be substituted by one or two benzyloxycarbonyl radicals or by one, two, three or four C 1-2 -alkyl radicals, C 1-4 -alkoxycarbonylaminoalkyl, C 2-6 -alkeny
  • R 4 and R 5 together represent a spirocyclic ring
  • A represents hydrogen, C 1-6 -alkyl, aryl-C 1-2 -alkyl, formyl, C 1-4 -alkoxydicarbonyl or a radical of the group G
  • [0047] can denote carboxyl, thiocarboxyl, —C ⁇ CH—NO 2 , —C ⁇ CH—CN, —C ⁇ N—R 6 , sulphoxyl, sulphonyl, —P(O)—OR 7 or P(S)—OR 7 ,
  • R 6 represents hydrogen, hydroxyl, C 1-4 -alkoxy, C 1-4 -alkylcarbonyl, C 1-4 -halogenoalkylcarbonyl, C 1-4 -alkylsulphonyl, nitro or cyano, and
  • R 7 represents hydrogen or C 1-4 -alkyl
  • Q represents straight-chain or branched C 1-6 -alkyl, C 1-6 -halogenoalkyl, hydroxy-C 1-6 -alkyl, C 1-4 -alkanoyloxy-C 1-6 -alkyl, C 1-2 -alkoxy-C 1-6 -alkyl, mercapto-C 1-6 -alkyl, C 1-2 -alkylthio-C 1-6 -alkyl, C 1-2 -alkylsulphinyl-C 1-6 -alkyl, C 1-2 -alkylsulphonyl-C 1-6 -alkyl, carboxy-C 1-6 -alkyl, carbamoyl-C 1-6 -alkyl, amino-C 1-6 -alkyl, C 1-6 -alkylamino-C 1-6 -alkyl, C 1-6 -dialkylaminoalkyl, C 2-6 -alkenyl, C 2-6 -alkiny
  • [0053] can denote carboxyl, thiocarboxyl or sulphonyl
  • Y represents oxygen, sulphur or —NR 9 ,
  • R 8 in the case where Y represents nitrogen can denote a cyclic amino group linked via a nitrogen atom
  • R 8 and R 9 independently of one another represent hydrogen, straight-chain or branched C 1-6 -alkyl, C 1-6 -alkenyl, C 1-6 -alkinyl, C 3-6 -cycloalkyl, C 3-6 -cycloalkyl-C 1-2 -alkyl, aryl, arylalkyl, hetaryl, hetarylalkyl, each of which is optionally substituted, or
  • R 8 and R 9 together with the adjacent N atom [lacuna] a carbocyclic 5-, 6- or 7-membered ring system or a 7 to 10-membered bicyclic ring system which can optionally also be interrupted by oxygen, sulphur, sulphoxyl, sulphonyl, carbonyl, —N—O, —N ⁇ , —NR 11 — or by quaternized nitrogen and is optionally substituted,
  • R 10 represents hydrogen or C 1-4 -alkyl
  • R 11 represents hydrogen, straight-chain or branched C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkinyl, C 3-8 -cycloalkyl, C 3-8 -cycloalkyl-C 1-2 -alkyl, C 1-4 -alkoxycarbonyl, C 1-4 -alkylcarbonyl, C 3-6 -cycloalkylcarbonyl, cyan, aryl, aryl-C 1-2 -alkyl, hetaryl, hetaryl-C 1-2 -alkyl, each of which is optionally substituted, and
  • B represents hydroxyl, C 1-6 -alkoxy, C 2-6 -alkenyloxy, C 2-6 -alkinyloxy, C 3-7 -cycloalkyloxy, C 3-7 -cycloalkylalkyloxy, aryloxy-, aryl-C 1-2 -alkyloxy, hetaryloxy, hetaryl-C 1-2 -alkyloxy, each of which is optionally substituted, or
  • [0061] represents the radicals —NR 12 R 13 —NR 14 —NR 12 R 13 and —NR 15 —OR 16 ,
  • R 12 and R 13 independently of one another represent hydrogen, straight-chain or branched C 1-6 -alkyl, C 1-6 -alkylcarbonyl, C 1-6 -alkylsulphonyl, C 2-6 -alkenyl, C 2-6 -alkinyl, C 3-8 -cycloalkyl, C 3-8 -cycloalkyl-C 1-2 -alkyl, aryl, arylcarbonyl, arylsulphonyl, aryl-C 1-2 -alkyl, hetaryl, hetarylcarbonyl, hetarylsulphonyl or hetaryl-C 1-2 -alkyl, each of which is optionally substituted, or
  • R 12 and R 13 together with the adjacent N atom [lacuna] a carbocyclic 5-, 6-, 7- or 8-membered ring system or a 7 to 10-membered bicyclic ring system, which can optionally also be interrupted by oxygen, sulphur, sulphoxyl, sulphonyl, carbonyl, —N—O—, —N ⁇ , —NR 11 — or by quaternized nitrogen and is optionally substituted,
  • R 14 represents hydrogen, straight-chain or branched C 1-6 -alkyl, C 3-6 -cycloalkyl, aryl-C 1-2 -alkyl, hetaryl-C 1-2 -alkyl, each of which is optionally substituted,
  • R 15 and R 16 independently of one another denote hydrogen, straight-chain or branched C 1-6 -alkyl, C 1-6 -alkylcarbonyl, C 2-6 -alkenyl, C 2-6 -alkinyl, C 3-6 -cycloalkyl, C 3-6 -cycloalkyl-C 1-2 -alkyl, aryl-C 1-2 -alkyl or hetaryl-C 1-2 -alkyl, each of which is optionally substituted,
  • R 15 and R 16 together with the adjacent N—O-group represent a carbocyclic 5-, 6- or 7-membered ring
  • the invention further relates to:
  • R 1 represents hydrogen, straight-chain or branched C 1-4 -alkyl, C 3-6 -cycloalkyl, aryl-C 1-2 -alkyl or hetaryl-C 1-2 -alkyl, each of which is optionally substituted, and
  • R 1 and R 2 together with the atoms to which they are bonded represent a 5- or 6-membered ring which can optionally be interrupted by oxygen, sulphur, sulphoxyl or sulphonyl and is optionally substituted,
  • R 2 represents hydrogen, straight-chain or branched alkyl having up to 6 carbon atoms, alkenyl having up to 4 carbon atoms, C 3-6 -cycloalkyl, C 3-6 -cycloalkyl-C 2 -alkyl, aryl, aryl-C 1-2 -alkyl, hetaryl, hetaryl-C 1-2 -alkyl each of which is optionally substituted,
  • R 3 and R 4 represent hydrogen
  • R 5 represents hydrogen, straight-chain or branched alkyl having up to 6 carbon atoms, alkenyl having up to 4 carbon atoms, C 3-6 -cycloalkyl, C 3-6 -cycloalkyl-C 1-2 -alkyl, aryl, aryl-C 1-2 -alkyl, hetaryl, hetaryl-C 1-2 -alkyl each of which is optionally substituted,
  • [0079] represents carboxyl, thiocarboxyl, —C ⁇ CH—NO 2 , —C ⁇ CH—CN, —C ⁇ N—R 6 , sulphoxyl, sulphonyl, —P(O)—OR 7 or P(S)—OR 7 ,
  • R 6 represents hydrogen, hydroxyl, C 1-4 -alkoxy, C 1-4 -alkylcarbonyl, C 1-4 -halogenoalkylcarbonyl, C 1-4 -alkylsulphonyl, nitro or cyano, and
  • R 7 represents hydrogen or C 1-4 -alkyl
  • Q represents straight-chain or branched C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkinyl, C 3-6 -cycloalkyl or hetaryl-C 1-2 -alkyl, each of which is optionally substituted, or optionally represents a radical from the group G 2 and G 3
  • [0085] can denote carboxyl, thiocarboxyl or sulphonyl
  • Y represents oxygen, sulphur or —NR 9 ,
  • R 8 in the case where Y represents nitrogen can denote a cyclic amino group linked via a nitrogen atom
  • R 8 and R 9 independently of one another represents hydrogen, straight-chain or branched C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkinyl, C 3-6 -cycloalkyl, C 3-6 -cycloalkyl-C 1-2 -alkyl, hetaryl or hetaryl-C 1-2 -alkyl, each of which is optionally substituted, or
  • R 8 and R 9 together with the adjacent N atom represent a carbocyclic 5-, 6- or 7-membered ring system or a 7 to 10-membered bicyclic ring system which can optionally also be interrupted by oxygen, sulphur, sulphoxyl, sulphonyl, carbonyl, —N—O—, —N ⁇ , —NR or by quaternized nitrogen and is optionally substituted,
  • R 10 represents hydrogen or C 1-4 -alkyl
  • R 11 represents hydrogen, straight-chain or branched C 1-6 -alkyl, C 3-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkinyl, C 3-6 -cycloalkyl, C 3-6 -cycloalkyl-C 1-2 -alkyl, C 1-4 -alkoxycarbonyl, C 1-4 -alkylcarbonyl, C 3-6 -cycloalkylcarbonyl, cyano, aryl, aryl-C 1-2 -alkyl, hetaryl or hetaryl-C 1-2 -alkyl, each of which is optionally substituted, and
  • B represents C 1-6 -alkoxy, C 2-6 -alkenyloxy, C 2-6 -alkinyloxy, C 3-7 -cycloalkyloxy, C 3-7 -cycloalkyl-C 1-2 -alkyloxy, aryloxy-, aryl-C 1-2 -alkyloxy, hetaryloxy, hetaryl-C 1-2 -alkyloxy, each of which is optionally substituted, or
  • [0093] represents the amino radicals —NR 12 R 13 , —NR 14 —NR 12 R 13 and —NR 15 —OR 16 , in which
  • R 12 and R 13 independently of one another represent hydrogen, straight-chain or branched C 1-6 -alkyl, C 1-6 -alkylcarbonyl, C 1-6 -alkylsulphonyl, C 2-6 -alkenyl, C 2-6 -alkinyl, C 3-8 -cycloalkyl, C 3-8 -cycloalkyl-C 1-2 -alkyl, aryl, arylcarbonyl, arylsulphonyl, aryl-C 1-2 -alkyl, hetaryl, hetarylcarbonyl, hetarylsulphonyl or hetaryl-C 1-2 -alkyl, each of which is optionally substituted, or
  • R 12 and R 13 together with the adjacent N atom represent a carbocyclic 5-, 6-, 7- or 8-membered ring system or a 7 to 10-membered bicyclic ring system, which can optionally also be interrupted by oxygen, sulphur, sulphoxyl, sulphonyl, carbonyl, —N—O, —N ⁇ , —NR 11 — or by quaternized nitrogen and is optionally substituted,
  • R 14 represents hydrogen, straight-chain or branched C 1-6 -alkyl, C 3-6 -cycloalkyl, each of which is optionally substituted,
  • R 15 and R 16 independently of one another denote hydrogen, straight-chain or branched C 1-6 -alkyl, C 1-6 -alkylcarbonyl, C 2-6 -alkenyl, C 2-6 -alkinyl or C 3-6 -cycloalkyl, each of which is optionally substituted, and
  • R 15 and R 16 together with the adjacent N—O-group represent a carbocyclic 5-, 6- or 7-membered ring
  • R 1 represents hydrogen and methyl
  • R 5 represents hydrogen
  • Q represents radicals other than methyl
  • B represents radicals other than —NH 2 ,
  • G 2 represents tert-butyloxy, benzyloxy and 4-nitro-benzyloxy
  • radical B represents radicals other than tert-butyloxy, benzyloxy and 4-nitrobenzyloxy
  • radicals R 1 , R 2 , R 3 , G, Q, and X have the meaning indicated under item 2, or their carboxyl-activated derivatives or their alkali metal salts, are reacted, if appropriate in the presence of a catalyst, if appropriate in the presence of an acid-binding agent and if appropriate in the presence of a diluent, with carboxylic acid derivatives of the general formula (III)
  • radicals R 4 , R 5 and B have the meaning indicated under item 2 and Z represents a suitable leaving group for example halogen such as bromine, chlorine fluorine, or hydroxyl, or
  • radicals G, Q, W and X have the meaning indicated under item 2 and W represents a suitable leaving group, for example halogen, alkoxy, alkylthio or aryloxy, or
  • radicals R 8 , G 1 , X, X 1 and Y have the meaning indicated under item 2, or for the preparation of the depsipeptides of the general formula (Ia) and their salts in which the group
  • [0131] represents carboxyl and Y represents oxygen
  • M represents a monovalent alkali metal cation, preferably lithium, sodium, potassium or caesium, in particular potassium or caesium,
  • M represents a metal cation equivalent bound like a salt, is reacted with alkylating agents of the formula (IX)
  • R 8 has the meaning indicated under item 2 and
  • Hal represents a halogen such as fluorine, chlorine, bromine or iodine
  • radicals R 8 and Y have the meaning indicated above under item 2, or
  • radicals R 1 , R 2 , R 3 , R 4 , R 5 , G, Q, X and B have the meaning indicated under item 2, or their carbokyl-activated derivatives or their alkali metal salts are reacted, if appropriate in the presence of a catalyst, if appropriate in the presence of an acid-binding agent and if appropriate in the presence of a diluent, with compounds of the general formula (XI)
  • radical B has the meaning indicated above under item 2.
  • Formula (I) provides a general definition of the substituted didepsipeptides according to the invention and their salts.
  • the substituted didepsipeptides of the formula (I) according to the invention and their acid addition salts and metal salt complexes have very good endoparasiticidal, in particular anthelmintic, action and can preferably be employed in the field of veterinary medicine.
  • Optionally substituted alkyl on its own or as a constituent of a radical in the general formulae denotes straight-chain or branched alkyl preferably having 1 to 6, in particular 1 to 4, carbon atoms.
  • Examples which may be mentioned are optionally substituted methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,2-dimethylpropyl, 1-1-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 1,1-dimethylbutyl, 2,2-dimethylbut
  • Optionally substituted alkenyl on its own or as a constituent of a radical in the general formulae denotes straight-chain or branched alkenyl preferably having 1 to 6, in particular 1 to 4, carbon atoms.
  • Examples which may be mentioned are substituted vinyl, 2-propenyl, 2-butenyl, 3-butenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-2-bute-nyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-2-pro-penyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-2-pentenyl, 2-
  • Optionally substituted alkinyl on its own or as a constituent of a radical in the general formulae denotes straight-chain or branched alkinyl preferably having 1 to 6, in particular 1 to 4, carbon atoms.
  • Examples which may be mentioned are substituted ethinyl, 2-propinyl, 2-butinyl, 3-butinyl, 1-methyl-2-pro-pinyl, 2-pentinyl, 3-pentinyl, 4-pentinyl, 1-methyl-3-butinyl, 2-methyl-3-butinyl, 1-me-thyl-2-butinyl, 1,1-dimethyl-2-propinyl, 1-ethyl-2-propinyl, 2-hexinyl, 3-hexinyl, 4-hexinyl, 5-hexinyl, 1-methyl-2-pentinyl, 1-methyl-3-pentinyl, 1-methyl-4-pentinyl, 2-methyl-3-pentinyl, 2-methyl-4-pentinyl
  • Optionally substituted cycloalkyl on its own or as a constituent of a radical in the general formulae denotes mono-, bi- and tricyclic cycloalkyl, preferably having 3 to 10, in particular having 3, 5 or 7, carbon atoms.
  • Examples which may be mentioned are substituted cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl and adamantyl.
  • Halogenoalkyl on its own or as a constituent of a radical in the general formulae contains 1 to 4, in particular 1 or 2, carbon atoms and preferably 1 to 9, in particular 1 to 5, identical or different halogen atoms preferably fluorine, chlorine and bromine, in particular fluorine and chlorine.
  • Examples which may be mentioned are trifluoromethyl, trichloromethyl, chlorodifluoromethyl, dichlorofluoromethyl, chloromethyl, bromomethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 2-chloro-2,2-difluoroethyl, pentafluoroethyl and pentafluoro-tert-butyl.
  • Optionally substituted alkoxy on its own or as a constituent of a radical in the general formulae denotes straight-chain or branched alkoxy preferably having 1 to 6, in particular 1 to 4, carbon atoms. Examples which may be mentioned are optionally substituted methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, iso-butoxy, sec-butoxy and tert-butoxy.
  • Optionally substituted halogenoalkoxy on its own or as a constituent of a radical in the general formulae denotes straight-chain or branched halogenoalkoxy preferably having 1 to 6, in particular 1 to 4, carbon atoms.
  • Examples which may be mentioned are optionally substituted difluoromethoxy, trifluoromethoxy, trichloromethoxy, chlorodifluoromethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2,2,2-trifluoroethoxy and 2-chloro-1,1,2-trifluoroethoxy.
  • Optionally substituted alkylthio on its own or as a constituent of a radical in the general formulae denotes straight-chain or branched alkylthio preferably having 1 to 6, in particular 1 to 4, carbon atoms. Examples which may be mentioned are optionally substituted methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio and tert-butylthio.
  • Optionally substituted halogenoalkylthio on its own or as a constituent of a radical in the general formulae denotes straight-chain or branched halogenoalkylthio preferably having 1 to 6, in particular 1 to 4, carbon atoms.
  • Examples which may be mentioned are optionally substituted difluoromethylthio, trifluoromethylthio, trichloromethylthio, chlorodifluoromethylthio, I-fluoroethylthio, 2-fluoroethylthio, 2,2-di-fluoroethylthio, 1,1,2,2-tetrafluoroethylthio, 2,2,2-trifluoroethylthio and 2-chloro-1,1,2-trifluoroethylthio.
  • Optionally substituted alkylcarbonyl on its own or as a constituent of a radical in the general formulae denotes straight-chain or branched alkylcarbonyl having 1 to 6, in particular 1 to 4, carbon atoms. Examples which may be mentioned are optionally substituted methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl, n-butylcarbonyl, isobutylcarbonyl, sec-butylcarbonyl and tert-bu-tyl- carbonyl.
  • Optionally substituted cycloalkylcarbonyl on its own or as a constituent of a radical in the general formulae denotes mono-, bi- and tricyclic cycloalkylcarbonyl, preferably having 3 to 10, in particular having 3, 5 or 7, carbon atoms.
  • Examples which may be mentioned are optionally substituted cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, cycloheptylcarbonyl, cyclooctylcarbonyl, bicyclo[2.2. 1]heptylcarbonyl, bicyclo[2.2.2]octylcarbonyl and adamantylcarbonyl.
  • Optionally substituted alkoxycarbonyl on its own or as a constituent of a radical in the general formulae denotes straight-chain or branched alkoxycarbonyl preferably having 1 to 6, in particular 1 to 4, carbon atoms. Examples which may be mentioned are optionally substituted methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl and tert-butoxycarbonyl.
  • Aryl is, for example, a mono-, bi- or polynuclear aromatic radical such as phenyl, naphthyl, tetrahydronaphthyl, indanyl, fluorenyl and the like, preferably phenyl or naphthyl.
  • Optionally substituted aryl in the general formulae denotes phenyl or naphthyl which is preferably optionally substituted, in particular phenyl.
  • Optionally substituted arylalkyl in the general formulae denotes arylalkyl which is preferably optionally substituted in the aryl moiety and/or alkyl, preferably having 6 or 10, in particular 8, carbon atoms in the aryl moiety (preferably phenyl or naphthyl, in particular phenyl) and preferably 1 to 4, in particular 1 or 2, carbon atoms in the alkyl moiety, where the alkyl moiety can be straight-chain or branched. Examples which may preferably be mentioned are optionally substituted benzyl and phenylethyl.
  • Optionally substituted hetaryl on its own or as a constituent of a radical in the general formulae denotes 5- to 7-membered rings preferably having 1 to 3, in particular 1 or 2, identical or different heteroatoms.
  • Heteroatoms in the heteroaromatics are oxygen, sulphur or nitrogen.
  • Examples which may preferably be mentioned are optionally substituted furyl, thienyl, pyrazolyl, imid-azolyl, 1,2,3- and 1,2,4-triazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1,2,3-, 1,3,4-, 1,2,4- and 1,2,5-oxadiazolyl, azepinyl, piperidyl, pyrrolyl, pyridyl, piperazinyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,3,5-, 1,2,4- and 1,2,3-triazinyl, 1,2,4-, 1,3,2-, 1,3,6- and 1,2,6-oxazinyl, oxepinyl, thiepinyl and 1,2,4-diazepinyl.
  • the optionally substituted radicals of the general formulae can carry one or more, preferably 1 to 3, in particular 1 or 2, identical or different substituents. Examples of substituents which may preferably be mentioned are:
  • alkyl preferably having 1 to 4, in particular 1 to 2, carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl; alkoxy preferably having 1 to 4, in particular 1 to 2 carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy; alkylthio such as methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio and tert-butylthio; halogenoalkyl preferably having 1 to 4, in particular 1 to 2 carbon atoms and preferably 1 to 5, in particular 1 to 3, halogen atoms, where the halogen
  • Suitable cyclic amino groups are heteroaromatic or aliphatic ring systems having one or more nitrogen atoms as heteroatom, in which the heterocycles can be saturated or unsaturated, a ring system or several fused ring systems, and optionally contain further heteroatoms such as nitrogen, oxygen and sulphur etc. Additionally, cyclic amino groups can also denote a spiro ring or a bridged ring system.
  • the number of atoms which form cyclic amino groups is not restricted, for example they consist in the case of a one-ring system of 3 to 8 atoms and in the case of a three-ring system of 7 to 11 atoms.
  • Examples of cyclic amino groups having saturated and unsaturated monocyclic groups having a nitrogen atom as heteroatom which may be mentioned are 1-azetidinyl, pyr-rolidino, 2-pyrrolin-1-yl, 1-pyrrolyl, piperidino, 1,4-dihydropyridin-1-yl, 1,2,5,6-tetrahydropyridin-1-yl, homopiperidino; examples of cyclic amino groups having saturated and unsaturated monocyclic groups having two or more nitrogen atoms as heteroatoms which may be mentioned are 1-imidazolidinyl, 1-imidazolyl, 1-pyrazolyl, 1-triazolyl, 1-tetrazolyl, 1-piperazinyl, 1-homopiperazinyl, 1,2-dihydro-pyridazin-1-yl, 1,2-dihydropyrimidin-1-yl, perhydropyrimidin-1-yl and 1,4-diazacycloheptan-1-yl;
  • Preferred compounds are those of the formula (Ia) and their salts
  • R 1 represents hydrogen, straight-chain or branched C 1-6 -alkyl, in particular methyl, ethyl, propyl, isopropyl, sec-butyl, tert-butyl, C 3-6 -cycloalkyl, in particular cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aryl-C 1-2 -alkyl, in particular phenylmethyl or hetaryl-C 1-2 -alkyl, in particular pyridylmethyl and thiazolylmethyl, each of which is optionally substituted, and
  • R 1 and R 2 together with the atoms to which they are bonded represent a 5- or 6-membered ring which can optionally be interrupted by sulphur and is optionally substituted by hydroxyl,
  • R 2 represents hydrogen, straight-chain or branched alkyl having up to 6 carbon atoms, in particular methyl, ethyl, propyl, isopropyl, sec-butyl, tert-butyl, hydroxy-C 1-2 -alkyl, in particular hydroxymethyl, 1-hydroxyethyl, C 1-4 -alkanoyloxy-C 1-4 -alkyl, in particular acetoxymethyl, 1-acetoxyethyl, C 1-4 -alkoxy-C 1-4 -alkyl, in particular methoxymethyl, 1-methoxyethyl, aryl-C 1-4 -alkoxy-C 1-4 -alkyl, in particular benzyloxymethyl, 1-benzyloxymethyl, mercapto-C 1-4 -alkyl, in particular mercaptomethyl, C 1-4 -alkylthio-C 1-4 -alkyl, in particular methylsulphinylmethyl, C 1-4 -alky
  • R 3 and R 4 represent hydrogen
  • R 5 represents hydrogen, straight-chain or branched alkyl having up to 6 carbon atoms, in particular methyl, ethyl, propyl, isopropyl, sec-butyl, tert-butyl, hydroxy-C 1-2 -alkyl, in particular hydroxymethyl, 1-hydroxyethyl, C 1-4 -alkanoyloxy-C 1-4 -alkyl, in particular acetoxymethyl, 1-acetoxyethyl, C 1-4 -alkoxy-C 1-4 -alkyl, in particular methoxymethyl, 1-methoxyethyl, aryl-C 1-4 -alkoxy-C 1-4 -alkyl, in particular benzyloxymethyl, 1-benzyloxymethyl, mercapto-C 1-4 -alkyl, in particular mercaptomethyl, C 1-4 -alkylthio-C 1-4 -alkyl, in particular methylsulphinylmethyl, C 1-4 -alky
  • [0185] represents carboxyl, thiocarboxyl, —CH ⁇ CH—NO 2 , —C ⁇ CH—CN, —C ⁇ N—R 6 , sulphoxyl, sulphonyl, —P(O)—OR 7 or P(S)—OR 7 ,
  • R 6 represents hydrogen, hydroxyl, C 1-4 -alkoxy, in particular methoxy, ethoxy, sec-butyloxy, C 1-4 -alkylcarbonyl, in particular methylcarbonyl, ethylcarbonyl, C 1-4 -halogenoalkylcarbonyl, in particular trifluoromethylcarbonyl, trichloromethylcarbonyl, C 1-4 -alkylsulphonyl, in particular methylsulphonyl, ethylsulphonyl, propylsulphonyl, nitro or cyano, and
  • R 7 represents hydrogen or C 1-4 -alkyl, in particular methyl or ethyl
  • Q represents straight-chain or branched C 1-4 -alkyl, in particular methyl, ethyl, propyl, isopropyl, sec-butyl, tert-butyl, C 1-4 -halogenoalkyl, in particular trifluoromethyl, trichloromethyl, chlorodifluoromethyl, dichlorofluoromethyl, 1-fluoroethyl, chloromethyl, bromomethyl, 1-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, C 2-6 -alkenyl, in particular vinyl, 2-propenyl, 1-methyl-2-propenyl and 2-butenyl, C 2-6 -halogenoalkenyl, in particular difluorovinyl, dichlorovinyl, 2-chloro-2-propenyl, 2,3,3-trifluoro-2-propenyl, 2,3,3-trichloro-2-propen
  • [0189] optionally represents a radical from the group G 2 and G 3 R 8 —Y—(G 2 )
  • [0191] can denote carboxyl, thiocarboxyl or sulphonyl
  • Y represents oxygen, sulphur or —NR 9 ,
  • R 8 in the case where Y represents nitrogen [lacuna] a cyclic amino group linked via a nitrogen atom, in particular 1-azetidinyl, pyrrolidino, 2-pyrrolin-1-yl, 1-pyrrolyl, piperidino, 1,4-dihydropyridin-1-yl, 1-imidazolidinyl, 1-imidazolyl, 1-pyrazolyl, 1-triazolyl, 1-tetrazolyl, 1-piperazinyl, 1-homopiperazinyl, 1,2-dihydro-pyridazin- 1-yl, 1,2-dihydropyrimidin-1-yl, perhydropyrimidin-1-yl, 1,4-diazacyclo-heptan-1-yl, thiazolidin-3-yl, isothiazolin-2-yl, morpholino, thiomorpholino, dioxothiomorpholino, each of which is optionally substituted by radicals from the series
  • R 8 and R 9 independently of one another represent hydrogen, straight-chain or branched C 1-4 -alkyl, in particular methyl, ethyl, propyl, isopropyl, sec-butyl, tert-butyl, C 2-4 -alkenyl, in particular vinyl, 2-propenyl, 1-methyl-2-propenyl and 2-butenyl, C 2-4 -alkinyl, in particular ethinyl, 2-propinyl and 2-butinyl, C 3-6 -cycloalkyl, in particular cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, C 3-6 -cycloalkyl-C 1-2 -alkyl, in particular cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl and cyclohexylmethyl, hetaryl, in particular pyridyl and thiazolyl, hetaryl, in
  • R 8 and R 9 together with the adjacent N atom represent a carbocyclic 5-, 6- or 7-membered ring system or a 7 to 10-membered bicyclic ring system which can optionally also be interrupted by oxygen, sulphur, sulphoxyl, sulphonyl, carbonyl, —N—O, —N ⁇ , —NR 11 — or by quaternized nitrogen and is optionally substituted by C 1-4 -alkyl, in particular methyl, hydoxy-C 1-4 -alkyl, in particular hydroxymethyl, amino-C 1-4 -alkyl, in particular aminomethyl, aminoethyl, C 1-4 -monoalkylamino-C 1-4 -alkyl, in particular methylaminomethyl, methylaminoethyl, C 1-4 -dialkylamino-C 1-4 -alkyl, in particular dimethylaminomethyl, dimethylaminoethyl, amino, hydroxyl
  • R 10 represents hydrogen or C 1-4 -alkyl, in particular methyl, ethyl, propyl, isopropyl, sec-butyl, tert-butyl, and
  • R 11 represents hydrogen, straight-chain or branched C 1-6 -alkyl, in particular methyl, ethyl, propyl, isopropyl, sec-butyl, tert-butyl, C 2-6 -alkenyl, in particular vinyl, 2-propenyl, 1-methyl-2-propenyl and 2-butenyl, C 2-6 -alkinyl, in particular ethinyl, 2-propinyl and 2-butinyl, C 3-6 -cycloalkyl, in particular cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, C 3-6 -cycloalkyl-C 1-2 -alkyl, in particular cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl and cyclohexylmethyl, C 1-4 -alkylcarbonyl, in particular methylcarbonyl, ethylcarbonyl, n-
  • B represents straight-chain or branched C 1-6 -alkoxy, in particular methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy, C 2-6 -alkenyloxy, vinyloxy, 2-propenyloxy, 2-butenyloxy, 3 -butenyloxy, 1-methyl-2-propenyloxy, 2-methyl-2-propenyloxy, 2-pentenyloxy, 1-methyl-2-butenyloxy, 2-methyl-2-butenyloxy, 3-methyl-2-butenyloxy, 1-methyl-3-butenyloxy, 1,1-dimethyl-2-propenyloxy, 1,2-dimethyl-2-propenyloxy, 1-ethyl-2-propenyloxy, 2-hexenyloxy, 1,1 -dimethyl-2-butenyloxy, 1,2-dimethyl-2-butenyloxy, 1-ethyl-2-butenyl
  • [0199] represents the amino radicals —NR 12 R 13 , —NR 14 —NR 12 R 13 and —NR 15 —OR 16 ,
  • R 12 and R 13 independently of one another represent hydrogen, straight-chain or branched C 1-6 -alkyl, in particular methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,2-dimethylpropyl, 1,1-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1-methylpentyl, C 1-6 -alkylcarbonyl, in particular methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl, n-butylcarbonyl, isobutylcarbonyl, sec-butylcarbonyl, tert-butylcarbonyl, pentylcarbonyl, 1-methylbutyl,
  • R 12 and R 13 together with the adjacent N atom represent a carbocyclic 5-, 6-, 7- or 8-membered ring system or a 7 to 10-membered bicyclic ring system which can optionally also be interrupted by oxygen, sulphur, sulphoxyl, sulphonyl, carbonyl, —N—O—, —N ⁇ , —NR 11 — or by quaternized nitrogen and is optionally substituted by aryl, in particular phenyl, C 1-4 -alkyl, in particular methyl, hydoxy-C 1-4 -alkyl, in particular hydroxymethyl, amino-C 1-4 -alkyl, in particular aminomethyl, aminoethyl, C 1-4 -monoalkylamino-C 1-4 -alkyl, in particular methylaminomethyl, methylaminoethyl, C 1-4 -dialkylamino-C 1-4 -alkyl, in particular dimethylaminomethyl,
  • n can denote the numbers 0, 1, 2, 3 or 4,
  • R 14 represents hydrogen, straight-chain or branched C 1-6 -alkyl, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,2-dimethylpropyl, 1,1-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1-methylpentyl, C 3-6 -cycloalkyl, in particular cyclopropyl, cyclobutyl; cyclopentyl, cyclohexyl, each of which is optionally substituted,
  • R 15 and R 16 independently of one another represent hydrogen, straight-chain or branched C 1-6 -alkyl, in particular methyl, ethyl, n-propyl, iso-propyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,2-dimethylpropyl, 1,1-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1-methylpentyl, C 1-6 -alkylcarbonyl, in particular methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl, n-butylcarbonyl, isobutylcarbonyl, sec-butylcarbonyl, tert-butylcarbonyl, pentylcarbonyl, 1-methylbutyl,
  • R 15 and R 16 together with the adjacent N—O-group represent a carbocyclic 5-, 6- or 7-membered ring
  • R 1 represents hydrogen and methyl
  • R 5 represents hydrogen
  • Q represents radicals other than methyl
  • B represents radicals other than —NH 2 .
  • [0216] represents carboxyl
  • G 2 represents tert-butyloxy, benzyloxy and 4-nitro-benzyloxy
  • B represents radicals other than tert-butyloxy, benzyloxy and 4-nitrobenzyloxy,
  • R 1 represents hydrogen, straight-chain or branched C 1-4 -alkyl, in particular methyl, ethyl, C 3-6 -cycloalkyl, in particular cyclopropyl,
  • R 2 represents hydrogen, straight-chain or branched C 1-4 -alkyl in particular methyl, ethyl, propyl, isopropyl, sec-butyl,
  • R 3 and R 4 represent hydrogen
  • R 5 represents hydrogen, straight-chain or branched C 1-4 -alkyl, in particular methyl, ethyl, propyl, isopropyl, sec-butyl, hetaryl-C 1-2 -alkyl, in particular pyrid-2-yl-methyl, pyrid-3-yl-methyl, pyrid-4-yl-methyl, thien-2-yl-methyl, thien-3-yl-methyl, aryl-C 1-2 -alkyl, in particular benzyl, each of which can optionally be substituted by radicals from the series consisting of halogen, in particular fluorine, chlorine, bromine or iodine, hydroxyl, C 1-4 -alkyl, in particular methyl, or tert-butyl, C 1-4 -alkoxy, in particular methoxy, ethoxy or tert-butyloxy, C 1-2 -alkylenedioxy, in particular methylenedi
  • [0226] represents carboxyl, —CH ⁇ CH—NO 2 , —C ⁇ CH—CN, —C ⁇ N—R 6 or sulphonyl,
  • R 6 represents C 1-4 -halogenoalkylcarbonyl, in particular trifluoromethylcarbonyl, trichloromethylcarbonyl, alkyl-C 1-4 -sulphonyl, in particular methylsulphonyl, ethylsulphonyl, nitro or cyano, and
  • Q represents a radical from the group G 2 and G 3
  • [0231] can denote carboxyl or sulphonyl
  • Y represents oxygen or —NR 9 ,
  • R 8 and R 9 independently of one another represent straight-chain or branched C 1-4 -alkyl, in particular methyl, ethyl, propyl, isopropyl, sec-butyl, C 2-4 -alkenyl, in particular vinyl, 2-propenyl, 1-methyl-2-propenyl, C 2-4 -alkinyl, in particular ethinyl, 2-propinyl, C 3-6 -cycloalkyl, in particular cyclopropyl, hetaryl-C 1-2 -alkyl, in particular pyridylmethyl and thiazolylmethyl, each of which can optionally be substituted by radicals from the series consisting of halogen, in particular fluorine, chlorine, bromine or iodine, C 1-4 -alkyl, in particular methyl, hydoxy-C 1-4 -alkyl, in particular hydroxymethyl, amino-C 1-4 -alkyl, in particular aminomethyl, aminoe
  • R 8 and R 9 together with the adjacent N atom represent a carbocyclic 5-, 6- or 7-membered ring system, which can optionally also be interrupted by oxygen, sulphur, sulphoxyl, carbonyl, —N ⁇ , —NR 11 or by quaternized nitrogen and is optionally substituted by C 1-4 -alkyl, in particular methyl, hydoxy-C 1-4 -alkyl, in particular hydroxymethyl, amino-C 1-4 -alkyl, in particular aminomethyl, aminoethyl, C 1-4 -monoalkylamino-C 1-4 -alkyl, in particular methylaminomethyl, methylaminoethyl, C 1-4 -dialkylamino-C 1-4 -alkyl, in particular dimethylaminomethyl, dimethylaminoethyl, amino, hydroxyl, C- 1-4 -alkoxy, in particular methoxy, C 1-4 -alkylcarbonyl,
  • R 10 represents hydrogen or C 1-4 -alkyl, in particular methyl
  • R 11 represents hydrogen, straight-chain or branched C 1-6 -alkyl, in particular methyl, ethyl, C 2-6 -alkenyl, in particular vinyl, C 3-6 -cycloalkyl, in particular cyclopropyl, C 1-4 -alkylcarbonyl, in particular methylcarbonyl, C 3-6 -cycloalkylcarbonyl, in particular cyclopropylcarbonyl, C 1-4 -alkoxycarbonyl, in particular methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, hydroxy-C 1-4 -alkyl, in particular hydroxyethyl, hydroxysulphonylethyl, C 1-4 -alkylamino, in particular ethylamino, C 1-4 -monoalkylamino-C 1-4 -alkyl, in particular methylaminoethyl, C 1-4 -dialkylamino-C
  • B represents straight-chain or branched C 1-6 -alkoxy, in particular methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy and tertbutoxy, C 2-6 -alkenyloxy, vinyloxy, 2-propenyloxy, 1,1-dimethyl-2-propenyloxy, 1,2-dimethyl-2-propenyloxy, 1-ethyl-2-propenyloxy, C 2-6 -alkinyloxy, in particular 2-propinyloxy, 1-methyl-2-propinyloxy, 1,1-dimethyl-2-propinyloxy, C 3-8 -cycloalkyloxy, in particular cyclopropyloxy, cyclohexyloxy, C 3-7 -cycloalkyl-C 1-2 -alkyloxy, in particular cyclopropylmethoxy, cyclohexylmethoxy, aryloxy-, in particular
  • R 12 and R 13 independently of one another represent hydrogen, straight-chain or branched C 1-6 -alkyl, in particular methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, 1-methylbutyl, 2,2-dimethylpropyl, C 1-6 -alkylcarbonyl, in particular methylcarbonyl, sec-butylcarbonyl, C 1-6 -alkylsulphonyl, in particular methylsulphonyl, ethylsulphonyl, C 2-6 -alkenyl, in particular vinyl, 2-propenyl, 1,2-dimethyl-2-propenyl, 2,3-dimethyl-2-butenyl, 1-ethyl-2-butenyl, C 2-6 -alkinyl, in particular 2-propinyl, 2-butinyl, C 3-8 -cycloalkyl, in particular 2-prop
  • R 12 and R 13 together with the adjacent N atom represent a carbocyclic 5-, 6-, 7- or 8-membered ring system which can optionally also be interrupted by oxygen, sulphur, sulphonyl, carbonyl, —N ⁇ , —NR 11 — or by quaternized nitrogen and is optionally substituted by C 1-4 -alkyl, in particular methyl, hydoxy-C 1-4 -alkyl, in particular hydroxymethyl, amino-C 1-4 -alkyl, in particular aminomethyl, aminoethyl, C 1-4 -monoalkylamino-C 1-4 -alkyl, in particular methylaminomethyl, methylaminoethyl, C 1-4 -dialkylamino-C 1-4 -alkyl, in particular dimethylaminoethyl, C 3-6 -cycloalkylamino, in particular pyrrolidino, piperidino or morpholino, amino, hydroxy
  • n can denote the numbers 0, 1, 2, or 3,
  • R 14 represents hydrogen, straight-chain or branched C 1-6 -alkyl, in particular methyl, ethyl, sec-butyl, C 3-6 -cycloalkyl, in particular cyclopropyl,
  • R 15 and R 16 independently of one another represent hydrogen, straight-chain or branched C 1-6 -alkyl, in particular methyl, ethyl, sec-butyl, C 1-6 -alkylcarbonyl, in particular methylcarbonyl, sec-butylcarbonyl, C 2-6 -alkenyl, in particular 2-propenyl, 1-methyl-2-propenyl, 1,1-dimethyl-2-propenyl, C 2-6 -alkinyl, in particular 2-propinyl, C 3-6 -cycloalkyl, in particular cyclopropyl,
  • R 15 and R 16 together with the adjacent N—O-group represent a carbocyclic 5-, 6- or 7-membered ring
  • R 1 represents hydrogen and methyl
  • R 5 represents hydrogen
  • [0250] represents carboxyl
  • Q represents radicals other than methyl
  • B represents radicals other than —NH 2 .
  • [0254] represents carboxyl
  • G 2 represents tert-butyloxy, benzyloxy and 4-nitro-benzyloxy
  • B represents radicals other than tert-butyloxy, benzyloxy and 4-nitrobenzyloxy,
  • R 1 represents straight-chain or branched C 1-4 -alkyl, in particular methyl
  • R 2 represents straight-chain or branched C 1-4 -alkyl, in particular methyl or ethyl,
  • R 3 and R 4 represent hydrogen
  • R 5 represents hydrogen, straight-chain or branched C 1-4 -alkyl, in particular methyl or ethyl,
  • [0264] represents carboxyl or sulfonyl
  • Q represents a radical from the group G 2 and G 3
  • [0268] can denote carboxyl or sulphonyl
  • Y represents oxygen or —NR 9 ,
  • R 8 and R 9 independently of one another represent straight-chain or branched C 4 -alkyl, in particular methyl, ethyl, propyl, isopropyl, sec-butyl, C 2-4 -alkenyl, in particular vinyl, 2-propenyl, 1-methyl-2-propenyl and C 2-4 -alkinyl, in particular ethinyl, 2-propinyl, C 3-6 -cycloalkyl, in particular cyclopropyl, hetaryl-C 1-2 -alkyl, in particular 2-chloro-pyrid-5-yl-methyl and chloro-thiazol-5-yl-methyl, or
  • R 8 and R 9 together with the adjacent N atom represent a carbocyclic 5-, 6- or 7-membered ring system which can optionally also be interrupted by oxygen, sulphur, sulphonyl, carbonyl, —N ⁇ , —NR 11 — or by quatemized nitrogen and is optionally substituted by C 1-4 -alkyl, in particular methyl, C 1-4 -dialkylamino-C 1-4 -alkyl, in particular dimethylaminoethyl, hydroxyl, C 1-4 -alkoxycarbonyl, but particularly preferably methoxycarbonyl, in particular pyrrolidino, 3-oxopyrrolidino, morpholino, 2,6-dimethylmorpholino, thiomorpholino, dioxothiomorpholino,
  • R 10 represents hydrogen or C 1-4 -alkyl, in particular methyl
  • R 11 stands straight-chain or branched C 1-6 -alkyl, in particular methyl, C 2-6 -alkenyl, in particular vinyl, C 3-6 -cycloalkyl, in particular cyclopropyl, C 1-4 -alkylcarbonyl, in particular methylcarbonyl, C 3-6 -cycloalkylcarbonyl, in particular cyclopropylcarbonyl, cyclohexylcarbonyl, C 1-4 -alkoxycarbonyl, in particular methoxycarbonyl, hydroxy-C 1-4 -alkyl, in particular hydroxyethyl, hydroxysulphonylethyl, C 1-4 -alkylamino, in particular ethylarnino, C 1-4 -dialkylamino-C 1-4 -alkyl, in particular dimethylaminoethyl, C 3-7 -cycloalkylamino-C 1-4 -alkyl, in particular N-morpholino
  • B represents straight-chain or branched C 1-6 -alkoxy, in particular methoxy, ethoxy, n-propoxy, sec-butoxy and tert-butoxy, C 2-6 -alkenyloxy, 2-propenyloxy, 1,1-dimethyl-2-propenyloxy, C 2-6 -alkinyloxy, in particular 2-propinyloxy, 1-methyl-2-propinyloxy, C 3-8 -cycloalkyloxy, in particular cyclopropyloxy, aryl-C 1-2 -alkyloxy, in particular benzyloxy, hetaryloxy, in particular pyridyloxy, hetaryl-C 1-2 -alkyloxy, in particular pyridylmethyloxy and thiazolylmehyloxy, each of which can optionally be substituted by radicals from the series consisting of halogen, in particular fluorine, chlorine, bromine or iodine, amino, hydroxy
  • R 12 and R 13 independently of one another represent hydrogen, straight-chain or branched C 1-6 -alkyl, in particular methyl, ethyl, C 1-6 -alkylcarbonyl, in particular methylcarbonyl, C 1-6 -alkylsulphonyl, in particular methylsulphonyl, C 2-6 -alkenyl, in particular 2-propenyl, 1-methyl-2-propenyl, C 2-6 -alkinyl, in particular 2-propinyl, C 3-8 -cycloalkyl, in particular cyclopropyl, cyclohexyl, C 3-8 -cycloalkyl-C 1-2 -alkyl, in particular cyclopropylmethyl, hydoxy-C 1-4 -alkyl, in particular hydroxymethyl, hydroxyethylsulphonylethyl, C 1-4 -dialkylamino-C 1-4 -alkyl, in particular dimethylaminoeth
  • R 12 and R 13 together with the adjacent N atom represent a carbocyclic 5-, 6-, 7- or 8-membered ring system which can optionally also be interrupted by oxygen, sulphur, carbonyl, —N ⁇ , —NR 11 — or by quaternized nitrogen and is optionally substituted by C 1-4 -alkyl, in particular methyl, C 1-4 -dialkylamino-C 1-4 -alkyl, in particular dimethylaminoethyl, C 3-6 -cycloalkylamino, in particular piperidino, hydroxyl, C 1-4 -alkoxy, in particular methoxy, C 1-4 -alkylcarbonyl in particular methylcarbonyl, C 1-4 -alkoxycarbonyl, in particular methoxycarbonyl, or
  • n can denote the numbers 0, 1 or 2
  • R 14 represents hydrogen, straight-chain or branched C 1-6 -alkyl, in particular methyl
  • R 15 and R 16 independently of one another represents hydrogen, straight-chain or branched C 1-6 -alkyl, in particular methyl, C 1-6 -alkylcarbonyl, in particular methylcarbonyl, sec-butylcarbonyl, C 2-6 -alkenyl, in particular 2-propenyl, C 2-6 -alkinyl, in particular 2-propinyl, C 3-6 -cycloalkyl, in particular cyclopropyl,
  • R 1 represents hydrogen and methyl
  • R 5 represents hydrogen
  • Q represents radicals other than methyl
  • B represents radicals other than —NH 2 .
  • [0291] represents carboxyl
  • G 2 represents tert-butyloxy, benzyloxy and 4-nitro-benzyloxy
  • B represents radicals other than tert-butyloxy, benzyloxy and 4-nitro-benzyloxy,
  • the compound of the general formula (I) to be used according to the invention and their salts additionally contain one or more centres of chirality and can thus be present in pure stereoisomers or in the form of various enantiomer and diastereomer mixtures which, if necessary, can be separated in a manner known per se.
  • the invention therefore relates both to the pure enantiomers and diastereomers, and to their mixtures for the control of endoparasites, particularly in the field of medicine and veterinary medicine.
  • optically active, stereoisomeric forms of the compounds of the general formula (I) and their salts are used according to the invention.
  • Suitable salts of the compounds of the general formula (I) which can be mentioned are customary non-toxic salts, i.e. salts with various bases and salts with added acids.
  • salts with inorganic, bases such as alkali metal salts, for example sodium, potassium or caesium salts, alkaline earth metal salts, for example calcium or magnesium salts, ammonium salts, salts with organic bases and also with organic amines, for example triethylammonium, pyridinium, picolinium, ethanolammonium, triethanolammonium, dicyclohexylammonium or N,N′-dibenzylethylenediammonium salts, salts with inorganic acids, for example hydrochlorides, hydrobromides, dihydrosulphates or trihydrophosphates, salts with organic carboxylic acids or organic sulpho acids, for example formates, acetates, trifluoroacetates, maleates, tartrates,
  • Table 2 contains the compounds of the general formula (Ia-1) in which represents carboxyl; Q represents —NEt 2 and B has the meanings listed in Table 1.
  • Table 3 contains the compounds of the general formula (Ia-1) in which represents carboxyl; Q represents —O—Me and B has the meanings listed in Table 1.
  • Table 4 contains the compounds of the general formula (Ia-1) in which represents carboxyl; Q represents —O—CHMe—CH 2 —Me and B has the meanings listed in Table 1.
  • Table 5 contains the compounds of the general formula (Ia-1) in which represents carboxyl; Q represents —O—CH 2 —CH ⁇ CH 2 and B has the meanings listed in Table 1.
  • Table 6 contains the compounds of the general formula (Ia-1) in which represents carboxyl; Q represents —O—CHMe—CH ⁇ CH 2 and B has the meanings listed in Table 1.
  • Table 7 contains the compounds of the general formula (Ia-1) in which represents carboxyl; Q represents —O—CH 2 —C ⁇ CH and B has the meanings listed in Table 1.
  • Table 8 contains the compounds of the general formula (Ia-1) in which represents carboxyl; Q represents —O—CMe ⁇ CH 2 and B has the meanings listed in Table 1.
  • Table 9 contains the compounds of the general formula (Ia-1) in which represents carboxyl; Q represents —NMe—CO—NMe 2 and B has the meanings listed in Table 1.
  • Table 10 contains the compounds of the general formula (Ia-1) in which represents carboxyl; Q represents —NMe—CO—NEt 2 and B has the meanings listed in Table 1.
  • Table 11 contains the compounds of the general formula (Ia-1) in which represents carboxyl; Q represents and B has the meanings listed in Table 1.
  • Table 12 contains the compounds of the general formula (Ia-1) in which represents sulphonyl; Q represents —NMe 2 and B has the meanings listed in Table 1.
  • Table 13 contains the compounds of the general formula (Ia-1) in which represents sulphonyl; Q represents —NEt 2 and B has the meanings listed in Table 1.
  • Table 14 contains the compounds of the general formula (Ia-1) in which represents sulphonyl; Q represents and B has the meanings listed in Table 1.
  • Table 16 contains the compounds of the general formula (Ia-2) in which represents carboxyl; Q represents —NEt 2 and B has the meanings listed in Table 1.
  • Table 17 contains the compounds of the general formula (Ia-2) in which represents carboxyl; Q represents —O—Me and B has the meanings listed in Table 1.
  • Table 18 contains the compounds of the general formula (Ia-2) in which represents carboxyl; Q represents —O—CHMe—CH 2 —Me and B has the meanings listed in Table 1.
  • Table 19 contains the compounds of the general formula (Ia-2) in which represents carboxyl; Q represents —O—CH 2 —CH ⁇ CH 2 and B has the meanings listed in Table 1.
  • Table 20 contains the compounds of the general formula (Ia-2) in which represents carboxyl; Q represents —O—CHMe—CH ⁇ CH 2 and B has the meanings listed in Table 1.
  • Table 21 contains the compounds of the general formula (Ia-2) in which represents carboxyl; Q represents —O—CH 2 —C ⁇ CH and B has the meanings listed in Table 1.
  • Table 22 contains the compounds of the general formula (Ia-2) in which represents carboxyl; Q represents —O—CMe ⁇ CH 2 and B has the meanings listed in Table 1.
  • Table 23 contains the compounds of the general formula (Ia-2) in which represents carboxyl; Q represents —NMe—CO—NMe 2 and B has the meanings listed in Table 1.
  • Table 24 contains the compounds of the general formula (Ia-2) in which represents carboxyl; Q represents —NMe—CO—NEt 2 and B has the meanings listed in Table 1.
  • Table 25 contains the compounds of the general formula (Ia-2) in which represents carboxyl; Q represents and B has the meanings listed in Table 1.
  • Table 26 contains the compounds of the general formula (Ia-2) in which represents sulphonyl; Q represents —NMe 2 and B has the meanings listed in Table 1.
  • Table 27 contains the compounds of the general formula (Ia-2) in which represents sulphonyl; Q represents —NEt 2 and B has the meanings listed in Table 1.
  • Table 28 contains the compounds of the general formula (Ia-2) in which represents sulphonyl; Q represents and B has the meanings listed in Table 1.
  • Table 30 contains the compounds of the general formula (Ia-3) in which represents carboxyl; Q represents —NEt 2 and B has the meanings listed in Table 1.
  • Table 31 contains the compounds of the general formula (Ia-3) in which represents carboxyl; Q represents —O—Me and B has the meanings listed in Table 1.
  • Table 32 contains the compounds of the general formula (Ia-3) in which represents carboxyl; Q represents —O—CHMe—CH 2 —Me and B has the meanings listed in Table 1.
  • Table 33 contains the compounds of the general formula (Ia-3) in which represents carboxyl; Q represents —O—CH 2 —CH ⁇ CH 2 and B has the meanings listed in Table 1.
  • Table 34 contains the compounds of the general formula (Ia-3) in which represents carboxyl; Q represents —O—CHMe—CH ⁇ CH 2 and B has the meanings listed in Table 1.
  • Table 35 contains the compounds of the general formula (Ia-3) in which represents carboxyl; Q represents —O—CH 2 —C ⁇ CH and B has the meanings listed in Table 1.
  • Table 36 contains the compounds of the general formula (Ia-3) in which represents carboxyl; Q represents —O—CMe ⁇ CH 2 and B has the meanings listed in Table 1.
  • Table 37 contains the compounds of the general formula (Ia-3) in which represents carboxyl; Q represents —NMe—CO—NMe 2 and B has the meanings listed in Table 1.
  • Table 38 contains the compounds of the general formula (Ia-3) in which represents carboxyl; Q represents —NMe—CO—NEt 2 and B has the meanings listed in Table 1.
  • Table 39 contains the compounds of the general formula (Ia-3) in which represents carboxyl; Q represents and B has the meanings listed in Table 1.
  • Table 40 contains the compounds of the general formula (Ia-3) in which represents sulphonyl; Q represents —NMe 2 and B has the meanings listed in Table 1.
  • Table 41 contains the compounds of the general formula (Ia-3) in which represents sulphonyl; Q represents —NEt 2 and B has the meanings listed in Table 1.
  • Table 42 contains the compounds of the general formula (Ia-3) in which represents sulphonyl; Q represents and B has the meanings listed in Table 1.
  • Table 44 contains the compounds of the general formula (Ia-4) in which represents carboxyl; Q represents —NEt 2 and B has the meanings listed in Table 1.
  • Table 45 contains the compounds of the general formula (Ia-4) in which represents carboxyl; Q represents —O—Me and B has the meanings listed in Table 1.
  • Table 46 contains the compounds of the general formula (Ia-4) in which represents carboxyl; Q represents —O—CHMe—CH 2 —Me and B has the meanings listed in Table 1.
  • Table 47 contains the compounds of the general formula (Ia-4) in which represents carboxyl; Q represents —O—CH 2 —CH ⁇ CH 2 and B has the meanings listed in Table 1.
  • Table 48 contains the compounds of the general formula (Ia-4) in which represents carboxyl; Q represents —O—CHMe—CH ⁇ CH 2 and B has the meanings listed in Table 1.
  • Table 49 contains the compounds of the general formula (Ia-4) in which represents carboxyl; Q represents —O—CH 2 —C ⁇ CH and B has the meanings listed in Table 1.
  • Table 50 contains the compounds of the general formula (Ia-4) in which represents carboxyl; Q represents —O—CMe ⁇ CH 2 and B has the meanings listed in Table 1.
  • Table 51 contains the compounds of the general formula (Ia-4) in which represents carboxyl; Q represents —NMe—CO—NMe 2 and B has the meanings listed in Table 1.
  • Table 52 contains the compounds of the general formula (Ia-4) in which represents carboxyl; Q represents —NMe—CO—NEt 2 and B has the meanings listed in Table 1.
  • Table 53 contains the compounds of the general formula (Ia-4) in which represents carboxyl; Q represents and B has the meanings listed in Table 1.
  • Table 54 contains the compounds of the general formula (Ia-4) in which represents sulphonyl; Q represents —NMe 2 and B has the meanings listed in Table 1.
  • Table 55 contains the compounds of the general formula (Ia-4) in which represents sulphonyl; Q represents —NEt 2 and B has the meanings listed in Table 1.
  • Table 56 contains the compounds of the general formula (Ia-4) in which represents sulphonyl; Q represents and B has the meanings listed in Table 1.
  • Table 58 contains the compounds of the general formula (Ia-5) in which represents carboxyl; Q represents —NEt 2 and B has the meanings listed in Table 1.
  • Table 59 contains the compounds of the general formula (Ia-5) in which represents carboxyl; Q represents —O—Me and B has the meanings listed in Table 1.
  • Table 60 contains the compounds of the general formula (Ia-5) in which represents carboxyl; Q represents —O—CHMe—CH 2 —Me and B has the meanings listed in Table 1.
  • Table 61 contains the compounds of the general formula (Ia-5) in which represents carboxyl; Q represents —O—CH 2 —CH ⁇ CH 2 and B has the meanings listed in Table 1.
  • Table 62 contains the compounds of the general formula (Ia-5) in which represents carboxyl; Q represents —O—CHMe—CH ⁇ CH 2 and B has the meanings listed in Table 1.
  • Table 63 contains the compounds of the general formula (Ia-5) in which represents carboxyl; Q represents —O—CH 2 —C ⁇ CH and B has the meanings listed in Table 1.
  • Table 64 contains the compounds of the general formula (Ia-5) in which represents carboxyl; Q represents —O—CMe ⁇ CH 2 and B has the meanings listed in Table 1.
  • Table 65 contains the compounds of the general formula (Ia-5) in which represents carboxyl; Q represents —NMe—CO—NMe 2 and B has the meanings listed in Table 1.
  • Table 66 contains the compounds of the general formula (Ia-5) in which represents carboxyl; Q represents —NMe—CO—NEt 2 and B has the meanings listed in Table 1.
  • Table 67 contains the compounds of the general formula (Ia-5) in which represents carboxyl; Q represents and B has the meanings listed in Table 1.
  • Table 68 contains the compounds of the general formula (Ia-5) in which represents sulphonyl; Q represents —NMe 2 and B has the meanings listed in Table 1.
  • Table 69 contains the compounds of the general formula (Ia-5) in which represents sulphonyl; Q represents —NEt 2 and B has the meanings listed in Table 1.
  • Table 70 contains the compounds of the general formula (Ia-5) in which represents sulphonyl; Q represents and B [lacuna] the [lacuna] in Table 1 listed.
  • Table 72 contains the compounds of the general formula (Ia-6) in which represents carboxyl; Q represents —NEt 2 and B has the meanings listed in Table 1.
  • Table 73 contains the compounds of the general formula (Ia-6) in which represents carboxyl; Q represents —O—Me and B has the meanings listed in Table 1.
  • Table 74 contains the compounds of the general formula (Ia-6) in which represents carboxyl; Q represents —O—CHMe—CH 2 —Me and B has the meanings listed in Table 1.
  • Table 75 contains the compounds of the general formula (Ia-6) in which represents carboxyl; Q represents —O—CH 2 —CH ⁇ CH 2 and B has the meanings listed in Table 1.
  • Table 76 contains the compounds of the general formula (Ia-6) in which represents carboxyl; Q represents —O—CHMe—CH ⁇ CH 2 and B has the meanings listed in Table 1.
  • Table 77 contains the compounds of the general formula (Ia-6) in which represents carboxyl; Q represents —O—CH 2 —C ⁇ CH and B has the meanings listed in Table 1.
  • Table 78 contains the compounds of the general formula (Ia-6) in which represents carboxyl; Q represents —O—CMe ⁇ CH 2 and B has the meanings listed in Table 1.
  • Table 79 contains the compounds of the general formula (Ia-6) in which represents carboxyl; Q represents —NMe—CO—NMe 2 and B has the meanings listed in Table 1.
  • Table 80 contains the compounds of the general formula (Ia-6) in which represents carboxyl; Q represents —NMe—CO—NEt 2 and B has the meanings listed in Table 1.
  • Table 81 contains the compounds of the general formula (Ia-6) in which represents carboxyl; Q represents and B has the meanings listed in Table 1.
  • Table 82 contains the compounds of the general formula (Ia-6) in which represents sulphonyl; Q represents —NMe 2 and B has the meanings listed in Table 1.
  • Table 83 contains the compounds of the general formula (Ia-6) in which represents sulphonyl; Q represents —NEt 2 and B has the meanings listed in Table 1.
  • Table 84 contains the compounds of the general formula (Ia-6) in which represents sulphonyl; Q represents and B has the meanings listed in Table 1.
  • Formula (II) provides a general definition of the N-terminal-acylated N-alkyl-amino acids needed as starting substances for carrying out process 3a according to the invention.
  • R 1 , R 2 , R 3 , G, Q and X preferably represent those radicals which have already been mentioned as preferred for these substituents in connection with the description of the substances of the general formula (II) according to the invention.
  • N-acylated N-alkyl-amino acids of the general formula (II) used as starting materials are known in some cases (cf. for example: N-methylamino acids: R. Bowmann et al. J. Chem. Soc. (1950) p. 1346, J. R. McDermott et al. Can. J. Chem. 51 (1973) p. 1915, H. Wurziger et al. Mixe (Merck, Darmstadt) 3 (1987) p. 8) or can be obtained by the processes described there.
  • Formula (III) provides a general definition of the carboxylic acid derivatives additionally to be used as starting substances for carrying out process 3a according to the invention.
  • R 4 , R 5 , B and Z have the meaning which have already been mentioned as preferred for these substituents in connection with the description of the substances of the general formula (Ia) according to the invention.
  • the compounds of the formula (III) are generally known compounds of organic chemistry or can be obtained by methods known from the literature (e.g.: 2-hydroxycarboxylic acid derivatives: cf. Houben-Weyl, Methoden der organischen Chemie, Volume VIII; 2-halogenocarboxylic acid derivatives: S. M. Birnbaum et al. J. Amer. Chem. Soc. 76 (1954) p. 6054, C. S. Rondestvedt, Jr. et al. Org. Reactions 11 (1960) p. 189 [Review]) or can be obtained by the processes described there.
  • 2-hydroxycarboxylic acid derivatives cf. Houben-Weyl, Methoden der organischen Chemie, Volume VIII
  • 2-halogenocarboxylic acid derivatives S. M. Birnbaum et al. J. Amer. Chem. Soc. 76 (1954) p. 6054, C. S. Rondestvedt, Jr. et al
  • N-acylated N-alkylamino acids (II) with 2-hydroxycarboxylic acid derivatives (III) is preferably carried out using diluents in the presence of coupling reagents and in the presence of a basic reaction auxiliary.
  • the coupling reagents used for carrying out process 3a are all those which are suitable for the preparation of an amide bond (cf. for example: Houben-Weyl, Methoden der organischen Chemie [Methods of Organic Chemistry], Volume 15/2; Bodanszky et al., Peptide Synthesis 2nd ed. (Wiley & Sons, New York 1976) or Gross, Meienhofer, The Peptides: Analysis Synthesis, Biology (Academic Press, New York 1979).
  • the following methods are preferably used: active ester method using pentachlorophenol (Pcp) and pentafluorophenol (Pfp), N-hydroxysuccinimide, N-hydroxy-5-norbornene-2,3-dicarbox-amide (HONB), 1-hydroxy-benzotriazole (HOBt) or 3-hydroxy-4-oxo-3,4-dihydrol,2,3-benzotriazine as the alcohol component, coupling using carbodiimides such as dicyclohexyl-carbodiimide (DCC) according to the DCC additive process, or using n-propanephos-phonic anhydride (PPA) and mixed anhydride method using pivaloyl chloride, ethyl chloroformate (EEDQ) and isobutyl chloroformate (IIDQ) or coupling using phosphonium reagents, such as benzotriazol-1-yl-oxy-tris(dimethylamino-phosphonium)
  • the preferred coupling is using phosphonium reagents such as bis(2-oxo-3-oxazolidinyl)-phosphonium acid chloride (BOP-Cl), benzotriazol-1-yl-oxy-tris(dimethylamino-phosphonium) hexafluorophosphate (BOP) and phosphonic acid ester reagents, such as diethyl cyanophosphonate (DEPC) or diphenylphosphoryl azide (DPPA).
  • BOP-Cl bis(2-oxo-3-oxazolidinyl)-phosphonium acid chloride
  • BOP benzotriazol-1-yl-oxy-tris(dimethylamino-phosphonium) hexafluorophosphate
  • phosphonic acid ester reagents such as diethyl cyanophosphonate (DEPC) or diphenylphosphoryl azide (DPPA).
  • Basic reaction auxiliaries which can be employed for carrying out process 3a according to the invention are all suitable acid-binding agents, such as amines, in particular tertiary amines, and alkali metal and alkaline earth metal compounds.
  • Examples which may therefore be mentioned are the hydroxides, oxides and carbonates of lithium, sodium, potassium, magnesium, calcium and barium, and further other basic compounds such as amidine bases or guanidine bases such as 7-methyl-1,5,7-triazabi-cyclo(4.4.0)dec-5-ene (MTBD); diazabicyclo(4.3 .0)nonene (DBN), diazabicyclo(2.2.2)-octane (DABCO), 1,8-diaza-bicyclo(5.4.0)undecene (DBU) cyclohexyl-tetrabutylguanidine (CyTGB), cyclohexyltetramethylguanidine (CyTMG), N,N,N,N-tetramethyl-1,8-naphthalenediamine, pentamethylpiperidine, tertiary amines such as triethylamine, trimethylamine, tribenzylamine, triisopropylamine, tribu
  • tertiary amrines in particular trialkylamines such as triethylamine, N,N-diisopropylethylamine, N-propyl-diisopropylamine, N,N′-dimethyl-cyclohexylamine or N-methylmorpholine.
  • diluents are advantageously employed in an amount such that the reaction mixture remains readily stirrable during the whole process.
  • Suitable diluents for carrying out process 3a according to the invention are all inert organic solvents.
  • halogenohydrocarbons in particular chlorohydrocarbons, such as tetrachloroethylene, tetrachloroethane, dichloropropane, methylene chloride, dichlorobutane, chloroform, carbon tetrachloride, trichloroethane, trichloroethylene, pentachloroethane, difluorobenzene, 1,2-dichloroethane, chlorobenzene, dichlorobenzene, chlorotoluene, trichlorobenzene; alcohols such as methanol, ethanol, isopropanol, butanol; ethers such as ethyl propyl ether, methyl tert-butyl ether, n-butyl ether, anisole, phenetole, cyclohexyl methyl ether, dimethyl ether, diethyl ether, dipropyl est
  • esters such as methyl acetate, ethyl acetate, butyl acetate, isobutyl acetate, and also dimethyl carbonate, dibutyl carbonate, ethylene carbonate; amides such as hexamethylenephosphoramide, formamide, N-methylformamide, N,N-di-methylformamide, N,N-dipropylformamide, N,N-dibutylformamide, N-methyl-pyrrolidone, N-methyl-caprolactam, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidine, octylpyrrolidone, octylcaprolactam, 1,3-dimethyl-2-imidazolinedione, N
  • Preferred diluents are halogenohydrocarbons, in particular chlorohydrocarbons, such as methylene chloride or 1,2-dichloroethane and mixtures of these with other diluents mentioned.
  • Process 3a is in general carried out by reacting compounds of the formula (II) with compounds of the general formula (III) in one of the given diluents in the presence of one of the given coupling reagents and in the presence of one of the given basic auxiliaries.
  • the reaction time is 4 to 72 hours.
  • the reaction is carried out at temperatures between ⁇ 10° C. and +120° C., preferably between ⁇ 5° C. and +50° C., particularly preferably at 0° C. to room temperature. It is carried out under normal pressure.
  • reaction solution is washed, and the organic phase is separated off, dried and concentrated in vacuo.
  • the products formed can be purified in a customary manner by recrystallization, vacuum distillation or column chromatography (cf. also the Preparation Examples).
  • the didepsipeptides according to the invention can also be prepared according to classical processes, for example that as is described by H.-G. Lerchen and H. Kunz (Tetrahedron Lett. 26 (43) (1985) p. 5257-5260; 28 (17) (1987) p. 1873-1876) utilizing the esterification method according to B. F. Gisin (Helv. Chim. Acta 56 (1973) p. 1476).
  • Formula (Ib) provides a general definition of the N-terminal-deblocked didepsipeptides needed as starting substances for carrying out process 3b according to the invention.
  • R 1 , R 2 , R 3 , R 4 , R 5 and B preferably represent those radicals which have already been mentioned as preferred for these substituents in connection with the description of the substances of the general formula (Ia) according to the invention.
  • N-terminal-deblocked didepsipeptides of the general formula (Ib) used as starting materials are known in some cases (cf. DE-OS [German Published Specification] 4 341 991, DE-OS [German Published Specification] 4 341 992, DE-OS [German Published Specification] 4 341 992) or can be obtained from N-terminal-protected didepsipeptides by the processes described there.
  • Formula (IV) provides a general definition of the compounds additionally to be used as starting substances for carrying out process 3b according to the invention.
  • G, X, Y, and W have the meaning which have already been mentioned as preferred for these substituents in connection with the description of the substances of the general formula (Ia) according to the invention.
  • the compounds of the formula (IV) are generally known compounds of organic chemistry or can be obtained by methods known from the literature (e.g.: per-substituted allophanoyl halides: DE-OS [German Published Specification] 2 008 116; carbamoyl chlorides: Liebigs Ann. 299, p. 85; carbamates: Houben-Weyl, Methoden der organischen Chemie, Volume E 4).
  • reaction of the compounds (Ib) with (IV) is preferably carried out using diluents in the presence of a basic reaction auxiliary.
  • Diluents used for carrying out process 3b according to the invention are the inert, aprotic solvents mentioned in process 3a, e.g. dioxane, acetonitrile or tetrahydrofuran but also halogenohydrocarbons, in particular chlorohydrocarbons, such as methylene chloride.
  • Basic reaction auxiliaries which can be used for carrying out process 3b according to the invention are all acid-binding agents mentioned in process 3a, but preferably tertiary amines, in particular trialkylamines such as triethylamine, N,N-diisopropyl-ethylamine, N-propyl-diisopropylamine, N,N′-dimethyl-cyclohexylamine or N-methylmorpholine.
  • Process 3b is carried out by reacting compounds of the general formula (Ib) in the presence of a basic reaction auxiliary with compounds of thegeneral formula (IV) in one of the given diluents.
  • the reaction time is 4 to 72 hours.
  • the reaction is carried out at temperatures between ⁇ 10° C. and +150° C., preferably between ⁇ 5° C. and +80° C., particularly preferably at 0° C. to room temperature. It is carried out under normal pressure.
  • process 3b in general 1.0 to 3.0 mol, preferably 1.0 to 1.5 mol, of acylating agent are employed per mole of N-alkylamino acid of the formula (Ib).
  • reaction solution is washed, and the organic phase is separated off, dried and concentrated in vacuo.
  • the products formed can be purified in a customary manner by recrystallization, vacuum distillation or column chromatography (cf. also the Preparation Examples).
  • Formula (Ib) provides a general definition of the N-terminal-deblocked didepsipeptides needed as starting substances for carrying out process 3c according to the invention.
  • R 1 , R 2 , R 3 , R 4 , R 5 and B preferably represent those radicals which have already been mentioned as preferred for these substituents in connection with the description of the substances of the general formula (Ia) according to the invention.
  • N-terminal-deblocked didepsipeptides of the general formula (Ib) used as starting materials are known in some cases (cf. DE-OS [German Published Specification] 4 341 991, DE-OS [German Published Specification] 4 341 992, DE-OS [German Published Specification] 4 341 992) or can be obtained from N-terminal-protected didepsipeptides by the processes described there.
  • Formulae (V) and (VI) provide a general definition of the compounds additionally to be used as starting substances for carrying out process 3c according to the invention.
  • R 8 , Y, G 1 , X 1 and X have the meaning which has already been mentioned as preferred for these substituents in connection with the description of the substances of the general formula (Ia) according to the invention.
  • the compounds of the formula (VI) are generally known compounds of organic chemistry and can be obtained commercially in some cases or by methods known from the literature (Houben-Weyl, Methoden der organischen Chemie, [Methods of organic chemistry] Volume E4).
  • reaction of the compounds (Ib) with (VI) by process 3c according to the invention is preferably carried out in the presence of diluents, if appropriate in the presence of a basic reaction auxiliary.
  • Diluents used for carrying out process 3c according to the invention are the solvents mentioned in process 3a, e.g. nitriles such as acetonitrile, propionitrile, butyronitrile, in particular acetonitrile, and ethers such as ethyl propyl ether, n-butyl ether, diethyl ether, dipropyl esther, diisopropyl ether, di-n-butyl ether, diusobutyl ether, diisoamyl ether, tetrahydrofuran, dioxane, in particular terahydrofuran and dioxane.
  • nitriles such as acetonitrile, propionitrile, butyronitrile, in particular acetonitrile
  • ethers such as ethyl propyl ether, n-butyl ether, diethyl ether, dipropyl esther, diisopropy
  • Process 3c can also be carried out in the presence of basic reaction auxiliaries.
  • basic reaction auxiliaries which can use for carrying out process 3c according to the invention are all acid-binding agents mentioned in process 3a, but preferably tertiary amines, in particular trialkylamines such as triethylamine, N,N-diisopropylethylamine or N-methylmorpholine, and amidine bases or guanidine bases such as diazabicyclo-(4.3.0)nonene (DBN), diazabicyclo (2.2.2)-octane (DABCO), 1,8-diazabicyclo(5.4.0)-undecene (DBU), in particular 1,8-diazabicyclo(5.4.0)-undecene (DBU), use.
  • tertiary amines in particular trialkylamines such as triethylamine, N,N-diisopropylethylamine or N-methylmorpholine
  • Process 3c is carried out by combining compounds of the general formula (Ib) with equimolar amounts of a compound of the formula (VI) in one of the diluents given above, if appropriate in the presence of a basic reaction auxiliary.
  • the reaction time is 1 to 72 hours.
  • the reaction is carried out at temperatures between ⁇ 50° C. to +200° C., preferably in a temperature range between ⁇ 20° C. and +150° C., in particular in a temperature range between ⁇ 10° C. and +120° C.
  • reaction mixture is worked up by generally customary methods (cf. also the Preparation Examples).
  • the didepsipeptides of the formula (Ib) are employed in which the radicals R 1 , R 2 , R 3 , R 4 , R 5 and B have the preferred and particularly preferred meanings in the case of the compounds of the general formula (Ia).
  • N-terminal-deblocked didepsipeptides of the general formula (Ib) used as starting materials are known in some cases (cf. DE-OS [German Published Specification] 4 341 991, DE-OS [German Published Specification] 4 341 992, DE-OS [German Published Specification] 4 341 992) or can be obtained from N-terminal-protected didepsipeptides by the processes described there.
  • alkylating agents of the formula (IX) additionally to be used as starting substances for carrying out process 3d according to the invention are generally known compounds of organic chemistry.
  • R 8 has the meaning which has already been mentioned as preferred for these substituents in connection with the description of the substances of the general formula (Ia) according to the invention and Hal has the meaning of an electron-withdrawing leaving group.
  • Suitable leaving groups are, for example, halogen, such as fluorine, chlorine, bromine and iodine, sulphonate such as aryl- and perfluoroalkylsulphonate, monosubstituted diazo and monosubstituted nitrato, and those additionally mentioned in J. March, Advanced Organic Chemistry, 3rd ed., John Wiley & Sons, New York 1985, pp. 310-316.
  • Compounds having a basic reaction which can be used in the present invention are one or more basic compounds of the elements lithium, sodium, magnesium, potassium, calcium, rubidium, strontium, caesium, barium, and/or of the ammonium ion.
  • Suitable basic compounds are, for example, salts, oxides, hydrides and hydroxides which have a basic reaction.
  • Alkali metal carbonates and/or hydrogencarbonates are preferred, very particularly preferably caesium carbonate or potassium carbonate.
  • the compounds having a basic reaction can be employed in anhydrous form, or if they are salts which crystallize with water of hydration, also in hydrated form. Preferably, however, anhydrous compounds are used.
  • Diluents used for carrying out process 3d according to the invention are the solvents mentioned in process 3a, e.g. amides such as hexamethylenephosphoramide, N,N-di-methylformamide, N,N-dipropylformamide, N,N-dibutylformamide, N-methyl-pyrrolidone or N-methyl-caprolactam, in particular N,N-dialkylformamides, such as N,N-dimethylformamide, and sulphoxides such as dimethyl sulphoxide, tetramethylene sulphoxide, dipropyl sulphoxide, benzyl methyl sulphoxide, diisobutyl sulphoxide, dibutyl sulphoxide, diisoamyl sulphoxide, in particular dimethyl sulphoxide.
  • amides such as hexamethylenephosphoramide, N,N-di-methylformamide, N,N-dipropy
  • process 3d can also be carried out in the presence of basic reaction auxiliaries, i.e. in the presence of other bases, for example in an amount of less than 0.5 mol, based on the base employed.
  • Those basic reaction auxiliaries which can use for carrying out process 3d according to the invention are all acid-binding agents mentioned in process 3a, but preferably tertiary amines, in particular trialkylamines such as triethylamine, N,N-diisopropylethylamine or N-methylmorpholine, and amidine bases or guanidine bases such as 7-methyl-1,5,7-triazabi-cyclo(4.4.0)dec-5-ene (MTBD); diazabicyclo-(4.3.0)nonene (DBN), diazabicyclo(2.2.2)-octane (DABCO), 1,8-diazabicyclo(5.4.0)-undecene (DBU) cyclohexyltetrabutylguanidine (CyTBG), cyclohexyltetramethylguani-dine (CyTMG), cyclohexyltetrabutylguanidine, N,N
  • Process 3d is carried out by combining compounds of the general formula (Ib) at room temperature in the presence of carbon dioxide, a 2- to 3-fold excess of alkali metal carbonate of the formula (VII) and an alkylating agent of the formula (IX) in one of the diluents given above, if appropriate in the presence of a basic reaction auxiliary.
  • the alkylation of the alkali metal salts of the formula (VIII) formed in situ with compounds of the formula (IX) takes place during a reaction time of 1 to 72 hours and a reaction temperature between ⁇ 50 and +180° C.; temperatures in the range between ⁇ 30 and +150° C. are preferred, in particular those in the range ⁇ 10 to +100° C.
  • Formula (Ie) provides a general definition of the N-terminal-acylated didepsipeptides needed as starting substances for carrying out process 3e according to the invention.
  • R 1 , R 2 , R 3 , R 4 , R 5 , G, W, X and B preferably represent those radicals which have already been mentioned as preferred for these substituents in connection with the description of the substances of the general formula (Ia) according to the invention.
  • N-terminal-acylated didepsipeptides of the general formula (Ib) used as starting materials are known in some cases (cf. DE-OS [German Published Specification] 4 341 991, DE-OS [German Published Specification] 4 341 992, DE-OS [German Published Specification] 4 341 992), can be obtained by the processes described there or can be prepared by process 3b according to the invention shown above.
  • nucleophilic agents of the formula (X) additionally to be used as starting substances for carrying out process 3e according to the invention are generally known compounds of organic chemistry.
  • R 8 and Y have the meaning which has already been mentioned as preferred in connection with the description of the substances of the general formula (Ia) according to the invention.
  • Process 3e is carried out by reacting compounds of the general formula (le) in the presence of a nucleophilic agent of the formula (X) in one of the diluents given above.
  • the reaction time is 4 to 72 hours.
  • the reaction is carried out at temperatures between +10° C. and +200° C., preferably between +20° C. and +150° C., particularly preferably at boiling temperature of the diluent.
  • reaction solution is washed, and the organic phase is separated off, dried and concentrated in vacuo.
  • the products which are formed can be purified in a customary manner by recrystallization, vacuum distillation or column chromatography (cf. also the Preparation Examples).
  • Formula (Id) provides a general definition of the C-terminal-deblocked didepsipeptides needed as starting substances for carrying out process 3e according to the invention.
  • R 1 , R 2 , R 3 , R 4 , R 5 , G, X and Q preferably represent those radicals which have already been mentioned as preferred for these substituents in connection with the description of the substances of the general formula (Ia) according to the invention.
  • the C-terminal-deblocked didepsipeptides of the general formula ( Id ) used as starting materials are known in some cases (cf. DE-OS [German Published Specification] 4 341 991, DE-OS [German Published Specification] 4 341 992, DE-OS [German Published Specification] 4 341 992) or can be obtained by the processes described there.
  • the C-terminal-deblocked didepsipeptides (Id) used as starting materials can be prepared by means of customary methods of a C-terminal deblocking such as acidolysis, for example in the case of a tert-butyl ester, or catalytic hydrogenation, for example in the case of a benzyl ester.
  • a C-terminal deblocking such as acidolysis, for example in the case of a tert-butyl ester, or catalytic hydrogenation, for example in the case of a benzyl ester.
  • Formula (XI) provides a general definition of the nucleophiles additionally to be used as starting substances for carrying out process 3e according to the invention.
  • the compounds of the formula (XI) are generally known compounds of organic chemistry and can be obtained commercially in some cases or by methods known from the literature.
  • reaction of the C-terminal-deblocked didepsipeptides of the formula (Id) with compounds of the formula (M) is preferably carried out using diluents in the presence of coupling reagents and in the presence of a basic reaction auxiliary.
  • Coupling reagents used for carrying out process 3f are all coupling reagents suitable for the preparation of an amide bond and already employed in process 3a mentioned above.
  • the preferred coupling is with phosphonium reagents such as bis(2-oxo-3-oxazolidinyl)-phosphonium acid chloride (BOP-Cl), benzotriazol-1-yl-oxy-tris(dimethylamino-phosphonium) hexafluorophosphate (BOP) and phosphonic acid ester reagents, such as diethyl cyanophosphonate (DEPC) or diphenylphosphoryl azide (DPPA).
  • BOP-Cl bis(2-oxo-3-oxazolidinyl)-phosphonium acid chloride
  • BOP benzotriazol-1-yl-oxy-tris(dimethylamino-phosphonium) hexafluorophosphate
  • phosphonic acid ester reagents such as diethyl cyanophosphonate (DEPC) or diphenylphosphoryl azide (DPPA).
  • Basic reaction auxiliaries which can be employed for carrying out process 3f according to the invention are also all acid-binding agents suitable for process 3a.
  • tertiary amines in particular trialkylamines such as triethylamine N,N-diisopropylethylamine, N-propyl-diisopropylamine, N,N′-dimethyl-cyclohexylamine or N-methylmorpholine are suitable.
  • Diluents used for carrying out process 3f according to the invention are the solvents mentioned in process 3e, e.g. halogenohydrocarbons, in particular chlorohydrocarbons, such as methylene chloride of 1,2-dichloroethane and mixtures of these with other diluents mentioned.
  • halogenohydrocarbons in particular chlorohydrocarbons, such as methylene chloride of 1,2-dichloroethane and mixtures of these with other diluents mentioned.
  • Process 3j is in general carried out by reacting compounds of the formula (Id) with compounds of the general formula (XI) in one of the given diluents in the presence of one of the given coupling reagents and in the presence of one of the given basic reaction auxiliaries.
  • the reaction time is 4 to 72 hours.
  • the reaction is carried out at temperatures between ⁇ 10° C. and +120° C., preferably between ⁇ 5° C. and +50° C., particularly preferably at 0° C. to room temperature. It is carried out under normal pressure.
  • reaction solution is washed, and the organic phase is separated off, dried and concentrated in vacuo.
  • the products which are formed can be purified in a customary manner by recrystallization, vacuum distillation or column chromatography (cf. also the Preparation Examples).
  • solvents which are inert under the respective reaction conditions, but do not have to be inert under any reaction conditions.
  • the active compounds have favourable toxicity for warm-blooded mammals and are suitable for controlling pathogenic endoparasites which occur in humans and in productive, breeding, zoo, laboratory, experimental animals and pets in animal keeping and animal breeding. In this connection, they are resistant to all or individual stages of development of the pests and to resistant and normally sensitive strains.
  • pathogenic endoparasites include cestodes, trematodes, nematodes, Acantocephalae, in particular:
  • Cyclophyllidea e.g.: Mesocestoides spp., Anoplocephala spp., Paranoplocephala spp., Moniezia spp., Thysanosomsa spp., Thysaniezia spp., Avitellina spp., Stilesia spp., Cittotaenia spp., Andyra spp., Bertiella spp., Taenia spp., Echinococcus spp., Hydatigera spp., Davainea spp., Raillietina spp., Hymenolepis spp., Echinolepis spp., Echinocotyle spp., Diorchis spp., Dipylidium spp., Joyeuxiella spp., Diplopylidium spp.
  • Oxyurida e.g.: Oxyuris spp., Enterobius spp., Passalurus spp., Syphacia spp., Aspiculuris spp., Heterakis spp.
  • Ascaridia spp. From the order of the Ascaridia e.g.: Ascaris spp., Toxascaris spp., Toxocara spp., Parascaris spp., Anisakis spp., Ascaridia spp.
  • Filariida e.g.: Stephanofilaria spp., Parafilaria spp., Setaria spp., Loa spp., Dirofilaria spp., Litomosoides spp., Brugia spp., Wuchereria spp., Onchocerca spp..
  • the productive and breeding animals include mammals such as cattle, horses, sheep, pigs, goats, camels, water buffalo, donkeys, rabbits, fallow deer, reindeer, fur-bearing animals such as mink, chinchilla, raccoon, birds such as hens, geese, turkeys, ducks, fresh- and salt-water fish such as trout, carp, eels, reptiles, insects such as honey bees and silkworms.
  • mammals such as cattle, horses, sheep, pigs, goats, camels, water buffalo, donkeys, rabbits, fallow deer, reindeer, fur-bearing animals such as mink, chinchilla, raccoon, birds such as hens, geese, turkeys, ducks, fresh- and salt-water fish such as trout, carp, eels, reptiles, insects such as honey bees and silkworms.
  • Laboratory and experimental animals include mice, rats, guinea-pigs, golden hamsters, dogs and cats.
  • the pets include dogs and cats.
  • Administration can be carried out both prophylactically and therapeutically.
  • Administration of the active compounds is carried out, directly or in the form of suitable preparations, enterally, parenterally, dermally, nasally, by treatment of the surroundings or with the aid of active compound-containing shaped articles such as strips, disks, tapes, collars, ear tags, limb bands, marking devices.
  • Enteral administration of the active compounds is carried out, for example, orally in the form of powders, tablets, capsules, pastes, drinks, granules, orally administrable solutions, suspensions and emulsions, boli, medicated feed or drinking water.
  • Dermal administration is carried out, for example, in the form of dipping, spraying or pouring-on and spotting-on.
  • Parental administration is carried out, for example, in the form of injection (intramuscular, subcutaneous, intravenous, intraperitoneal) or by implants.
  • Suitable preparations are:
  • solutions such as injection solutions, oral solutions, concentrates for oral administration after dilution, solutions for use on the skin or in body cavities, pouring-on formulations, gels;
  • formulations in which the active compound is processed in an ointment base or in an oil-in-water or water-in-oil emulsion base are also included.
  • Solid preparations such as powders, premixes or concentrates, granules, pellets, tablets, boli, capsules; aerosols and inhalants, active compound-containing shaped articles.
  • Injection solutions are administered intravenously, intramuscularly and subcutaneously.
  • Injection solutions are prepared by dissolving the active compound in a suitable solvent and possibly adding additives such as solubilizers, acids, bases, buffer salts, antioxidants, preservatives.
  • the solutions are sterile-filtered and bottled.
  • Solvents which may be mentioned are: physiologically tolerable solvents such as water, alcohols such as ethanol, butanol, benzyl alcohol, glycerol, propylene glycol, polyethylene glycols, N-methyl-pyrrolidone, and mixtures thereof.
  • the active compounds can optionally also be dissolved in physiologically tolerable vegetable or synthetic oils which are suitable for injection.
  • Solubilizers which may be mentioned are: solvents which promote the dissolution of the active compound in the main solvent or prevent its precipitation. Examples are polyvinylpyrrolidone, polyoxyethylated castor oil, polyoxyethylated sorbitan ester.
  • Preservatives are: benzyl alcohol, trichlorobutanol, p-hydroxybenzoic acid esters, n-butanol.
  • Oral solutions are administered directly. Concentrates are administered orally after prior dilution to the use concentration. Oral solutions and concentrates are prepared as described above in the case of the injection solutions, where sterile working can be dispensed with.
  • Solutions for use on the skin are trickled on, spread on, rubbed in, sprinkled on or sprayed on. These solutions are prepared as described above in the case of the injection solutions.
  • Thickeners are: inorganic thickeners such as bentonites, colloidal silicic acid, aluminium monostearate, organic thickeners such as cellulose derivatives, polyvinyl alcohols and their copolymers, acrylates and methacrylates.
  • Gels are applied to or spread on the skin or introduced into body cavities. Gels are prepared by treating solutions which have been prepared as described in the case of the injection solutions with sufficient thickener that a clear material having an ointment-like consistency results.
  • the thickeners employed are the thickeners given above.
  • pouring-on formulations are prepared by dissolving, suspending or emulsifying the active compound in suitable skin-compatible solvents or solvent mixtures. If appropriate, other auxiliaries such as colourants, absorption-promoting substances, antioxidants, sunscreens, adhesives are added.
  • Solvents which may be mentioned are: water, alkanols, glycols, polyethylene glycols, polypropylene glycols, glycerol, aromatic alcohols such as benzyl alcohol, phenylethanol, phenoxyethanol, esters such as ethyl acetate, butyl acetate, benzyl benzoate, ethers such as alkylene glycol alkyl ethers such as dipropylene glycol monomethyl ether, diethylene glycol mono-butyl ether, ketones such as acetone, methyl ethyl ketone, aromatic and/or aliphatic hydrocarbons, vegetable or synthetic oils, DMF, dimethylacetamide, N-methylpyrrolidone, 2,2-dimethyl-4-oxy-methylene-1,3-dioxolane.
  • Colourants are all colourants permitted for use on animals and which can be dissolved or suspended.
  • Absorption-promoting substances are, for example, DMSO, spreading oils such as isopropyl myristate, dipropylene glycol pelargonate, silicone oils, fatty acid esters, triglycerides, fatty alcohols.
  • Antioxidants are sulphites or metabisulphites such as potassium metabisulphite, ascorbic acid, butylhydroxytoluene, butylhydroxyanisole, tocopherol.
  • Sunscreens are, for example, novantisolic acid.
  • Adhesives are, for example, cellulose derivatives, starch derivatives, polyacrylates, natural polymers such as alginates, gelatin.
  • Emulsions can be administered orally, dermally or as injections.
  • Emulsions are either of the water-in-oil type or of the oil-in-water type.
  • Hydrophobic phases which may be mentioned are: liquid paraffins, silicone oils, natural vegetable oils such as sesame oil, almond oil, castor oil, synthetic triglycerides such as caprylic/capric biglyceride, triglyceride mixture with vegetable fatty acids of the chain length C 8-12 or other specially selected natural fatty acids, partial glyceride mixtures of saturated or unsaturated fatty acids possibly also containing hydroxyl groups, mono- and diglycerides of the C 8 /C 10 fatty acids.
  • Fatty acid esters such as ethyl stearate, di-n-butyryl adipate, hexyl laurate, dipropylene glycol perlargonate, esters of a branched fatty acid of medium chain length with saturated fatty alcohols of chain length C 16 -C 18 , isopropyl myristate, isopropyl palmitate, caprylic/capric acid esters of saturated fatty alcohols of chain length C 12 -C 18 , isopropyl stearate, oleyl oleate, decyl oleate, ethyl oleate, ethyl lactate, waxy fatty acid esters such as synthetic duck coccygeal gland fat, dibutyl phthalate, diisopropyl adipate, ester mixtures related to the latter, inter alia.
  • Fatty acid esters such as ethyl stearate, di-n-butyryl adipate
  • Fatty alcohols such as isotridecyl alcohol, 2-octyldodecanol, cetylstearyl alcohol, oleyl alcohol.
  • Fatty acids such as oleic acid and its mixtures.
  • Hydrophilic phases which may be mentioned are: water, alcohols such as propylene glycol, glycerol, sorbitol and its mixtures.
  • Emulsifiers which may be mentioned are: non-ionic surfactants, e.g. polyethoxylated castor oil, polyethoxylated sorbitan monooleate, sorbitan monostearate, glycerol monostearate, polyoxyethyl stearate, alkylphenol polyglycol ether;
  • non-ionic surfactants e.g. polyethoxylated castor oil, polyethoxylated sorbitan monooleate, sorbitan monostearate, glycerol monostearate, polyoxyethyl stearate, alkylphenol polyglycol ether;
  • ampholytic surfactants such as di-Na N-lauryl-o-iminodipropionate or lecithin;
  • anionic surfactants such as Na lauryl sulphate, fatty alcohol ether sulphates, mono/dialkyl polyglycol ether orthophosphoric acid ester monoethynolamine salt.
  • auxiliaries which may be mentioned are: substances which enhance the viscosity and stabilize the emulsion, such as carboxymethylcellulose, methylcellulose and other cellulose and starch derivatives, polyacrylates, alginates, gelatin, gum arabic, polyvinylpyrrolidone, polyvinyl alcohol, copolymers of methyl vinyl ether and maleic anhydride, polyethylene glycols, waxes, colloidal silicic acid or mixtures of the substances mentioned.
  • substances which enhance the viscosity and stabilize the emulsion such as carboxymethylcellulose, methylcellulose and other cellulose and starch derivatives, polyacrylates, alginates, gelatin, gum arabic, polyvinylpyrrolidone, polyvinyl alcohol, copolymers of methyl vinyl ether and maleic anhydride, polyethylene glycols, waxes, colloidal silicic acid or mixtures of the substances mentioned.
  • Suspensions can be administered orally, dermally or as an injection. They are prepared by suspending the active compound in a suspending agent, if appropriate with addition of other auxiliaries such as wetting agents, colourants, absorption-promoting substances, preservatives, antioxidants light screens.
  • Suspending agents which may be mentioned are all homogeneous solvents and solvent mixtures.
  • wetting agents which may be mentioned are the surfactants given above.
  • Semi-solid preparations can be administered orally or dermally. They differ from the suspensions and emulsions described above only by their higher viscosity.
  • the active compound is mixed with suitable excipients, if appropriate with addition of auxiliaries, and brought into the desired form.
  • Excipients which may be mentioned are all physiologically tolerable solid inert substances. Those used are inorganic and organic substances. Inorganic substances are, for example, sodium chloride, carbonates such as calcium carbonate, hydrogencarbonates, aluminium oxides, silicic acids, argillaceous earths, precipitated or colloidal silica, phosphates.
  • Organic substances are, for example, sugar, cellulose, foodstuffs and feeds such as milk powder, animal meal, grain meals and shreds, starches.
  • Auxiliaries are preservatives, antioxidants, colourants which have already been mentioned above.
  • auxiliaries are lubricants and glidants such as magnesium stearate, stearic acid, talc, bentonites, disintegration-promoting substances such as starch or crosslinked polyvinylpyrrolidone, binders such as starch, gelatin or linear polyvinylpyrrolidone, and dry binders such as microcrystalline cellulose.
  • lubricants and glidants such as magnesium stearate, stearic acid, talc, bentonites, disintegration-promoting substances such as starch or crosslinked polyvinylpyrrolidone, binders such as starch, gelatin or linear polyvinylpyrrolidone, and dry binders such as microcrystalline cellulose.
  • the active compounds can also be present in the preparations as a mixture with synergists or with other active compounds which act against pathogenic endoparasites.
  • active compounds are, for example, L-2,3,5,6-tetrahydro-6-phenylimidazolthiazole, benzimidazole carbamates, praziquantel, pyrantel, febantel.
  • Ready-to-use preparations contain the active compound in concentrations of 10 ppm—20 per cent by weight, preferably from 0.1-10 per cent by weight.
  • Preparations which are diluted before use contain the active compound in concentrations of 0.5-90% by weight, preferably of 5-50% by weight.
  • the degree of effectiveness is determined by quantitatively counting the worm eggs excreted with the faeces before and after treatment.
  • Complete cessation of oviposition after treatment means that the worms have been expelled or are so damaged that they no longer produce eggs (effective dose).
  • Active compounds tested and effective doses can be seen from the following table. Active compound Effective dose Example No. in [mg/kg] 2 5 9 5 11 5 12 5 13 5 18 5 I-7 5 46 5 68 5
  • the degree of effectiveness is determined by quantitatively counting the worm eggs excreted with the faeces before and after treatment.
  • Complete cessation of oviposition after treatment means that the worms have been expelled or are so damaged that they no longer produce eggs (effective dose).
  • Active compounds tested and effective doses can be seen from the following tables. Active Effective Active compound Effective dose compound dose in Example No. in [mg/kg] Example No. [mg/kg] 2 5 34 5 8 5 35 5 9 5 36 5 10 5 38 5 11 5 47 5 12 5 49 5 19 5 50 5 20 5 68 5 30 5 61 5 31 5 I-4 5 I-5 5 I-7 5
  • the reaction solution is shaken twice with water, and the organic phase is separated off and concentrated in vacuo after drying over sodium sulphate.
  • the residual crude product is chromatographed on a silica gel column (silica gel 60—Merck, particle size: 0.04 to 0.063 mm) using the eluent cyclohexane: acetone (4:1). 1.6 g (57.2 % of theory) of isobutyl N-methyl-N-trimethylallophanoyl-L-alanyl-D-lactate are obtained.
  • the residual crude product is chromatographed on a silica gel column (silica gel 60—Merck, particle size: 0.04 to 0.063 mm) using the eluent cyclohexane:ethyl acetate (3:1). 1.35 g (40.2 % of theory) of methyl N-methyl-N-trimethylallophanoyl-L-alanyl-D-lactate are obtained.
  • the residual crude product is chromatographed on a silica gel column (silica gel 60—Merck, particle size: 0.04 to 0.063 mm) using the eluent cyclohexane:acetone (4:1). 4.2 g (77.2 % of theory) of tert-butyl N-methyl-N-trichloro-acetyl-L-alanyl-D-lactate are obtained.
  • the residual crude product is chromatographed on a silica gel column (silica gel 60—Merck, particle size: 0.04 to 0.063 mm) using the eluent cyclohexane:ethyl acetate (1:1).
  • Dry hydrogen chloride gas is passed into a solution, cooled to 0° C., of 11.8 g (32.8 mmol) of tert-butyl N-methyl-N-trimethylallophanoyl-L-alanyl-D-lactate in 250 ml of absolute methylene chloride for 20 minutes. The mixture is then stirred at room temperature for about 16 hours and the entire reaction mixture is concentrated in vacuo.
  • the residual crude product is chroma-tographed on a LiChroprep RP-18 column (LiChroprep RP-18—Merck, particle size: 0.04 to 0.063 mm) using the eluent acetonitrile-water (3:7). 0.32 g (11.3% of theory) is obtained.
  • the residual crude product is chromatographed on a silica gel column (silica gel 60—Merck, particle size: 0.04 to 0.063 mm) using the eluent cyclohexane:ethyl acetate (3: 1). 3.5 g (55.8 % of theory) of N-benzyl-N-methyl-L-alanyl-D-lactic acid piperidide are obtained.

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  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
US09/011,599 1995-08-11 1996-07-30 Didepsipeptide-based endoparasiticides, new didepsipeptides and process for preparing the same Abandoned US20020142969A1 (en)

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6974802B2 (en) 1998-02-13 2005-12-13 Medivir Ab Treatment of viral infections using prodrugs of 2′,3-dideoxy,3′-fluoroguanosine
WO2009070631A3 (en) * 2007-11-28 2009-07-30 Univ Virginia Ethoid compounds for use as food additives
US7625946B2 (en) 2006-02-24 2009-12-01 Yissum Research Development Company Of The Hebrew University Of Jerusalem Propargylated aminoindans, processes for preparation, and uses thereof
WO2010146083A1 (en) * 2009-06-18 2010-12-23 Intervet International B.V. Anthelmintic agents and their use
US20110021506A1 (en) * 2007-12-17 2011-01-27 Intervet International B.V. Anthelmintic agents and their use

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DE19962145A1 (de) 1999-12-22 2001-06-28 Bayer Ag Schädlingsbekämpfungsmittel/Depsipeptide
DE19962147A1 (de) 1999-12-22 2001-06-28 Bayer Ag Schädlingsbekämpfungsmittel / PF 1022-221
JP2009518433A (ja) 2005-12-09 2009-05-07 イッサム リサーチ ディベロップメント カンパニー オブ ザ ヘブライ ユニバーシティー オブ エルサレム 神経保護用の低用量ラドスチギルの使用
EP4284804A1 (en) 2021-01-26 2023-12-06 Schrödinger, Inc. Tricyclic compounds useful in the treatment of cancer, autoimmune and inflammatory disorders

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FR2365341A1 (fr) * 1976-09-28 1978-04-21 Synthelabo Derives de l'acide l-(phenyl-3 amino-2 propionyloxy)-2 acetique
HU181008B (en) * 1980-01-18 1983-05-30 Richter Gedeon Vegyeszet Process for producing angiotenzin-ii analogues of antagonistic activity containing sarcosyl-group at the 1-positon,and an alpha-hydroxy-carboxylic acid at the 8-position
JPS606649A (ja) * 1983-06-24 1985-01-14 Daicel Chem Ind Ltd モノマ−
DK406686D0 (da) * 1986-08-26 1986-08-26 Hans Bundgaard Carboxylsyrederivater
DK0634408T3 (da) * 1992-03-17 2002-04-22 Fujisawa Pharmaceutical Co Depsipeptidderivater, fremstilling og anvendelse deraf
DE4317458A1 (de) * 1992-06-11 1993-12-16 Bayer Ag Verwendung von cyclischen Depsipeptiden mit 18 Ringatomen zur Bekämpfung von Endoparasiten, neue cyclische Depsipeptide mit 18 Ringatomen und Verfahren zu ihrer Herstellung
CN1073560C (zh) * 1993-02-19 2001-10-24 明治制果株式会社 环缩酚酸肽pf1022衍生物
DE4317457A1 (de) * 1993-05-26 1994-12-01 Bayer Ag Octacyclodepsipeptide mit endoparasitizider Wirkung
DE4341992A1 (de) * 1993-12-09 1995-06-14 Bayer Ag Endoparasitizide Mittel auf Basis von offenkettigen Tetradepsipeptiden
DE4341991A1 (de) * 1993-12-09 1995-06-14 Bayer Ag Endoparasitizide Mittel auf Basis von offenkettigen Hexadepsipeptiden

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6974802B2 (en) 1998-02-13 2005-12-13 Medivir Ab Treatment of viral infections using prodrugs of 2′,3-dideoxy,3′-fluoroguanosine
US7071173B2 (en) 1998-02-13 2006-07-04 Medivir Ab Antiviral methods employing double esters of 2′, 3′-dideoxy-3′-fluoroguanosine
US7825238B2 (en) 1998-02-13 2010-11-02 Medivir Ab Antiviral methods employing double esters of 2′, 3′-dideoxy-3′-fluoroguanosine
US7625946B2 (en) 2006-02-24 2009-12-01 Yissum Research Development Company Of The Hebrew University Of Jerusalem Propargylated aminoindans, processes for preparation, and uses thereof
US20100093848A1 (en) * 2006-02-24 2010-04-15 Victor Piryatinsky Propargylated aminoindans, processes for preparation, and uses thereof
US8609719B2 (en) 2006-02-24 2013-12-17 Yissum Research Development Company Of The Hebrew University Of Jerusalem Propargylated aminoindans, processes for preparation, and uses thereof
WO2009070631A3 (en) * 2007-11-28 2009-07-30 Univ Virginia Ethoid compounds for use as food additives
US20110021506A1 (en) * 2007-12-17 2011-01-27 Intervet International B.V. Anthelmintic agents and their use
WO2010146083A1 (en) * 2009-06-18 2010-12-23 Intervet International B.V. Anthelmintic agents and their use
US8507474B2 (en) 2009-06-18 2013-08-13 Intervet International B.V. Anthelmintic agents and their use

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CN1053657C (zh) 2000-06-21
CN1254596A (zh) 2000-05-31
WO1997007093A1 (de) 1997-02-27
BRPI9610049B1 (pt) 2017-05-02
PL324893A1 (en) 1998-06-22
HUP9802316A3 (en) 2001-04-28
US20040034048A1 (en) 2004-02-19
HK1017340A1 (en) 1999-11-19
CN1199394A (zh) 1998-11-18
AU6739496A (en) 1997-03-12
SK15598A3 (en) 1998-09-09
TW492976B (en) 2002-07-01
NO980324D0 (no) 1998-01-26
BG102213A (en) 1998-08-31
US7772190B2 (en) 2010-08-10
CA2228939C (en) 2007-01-30
EP0843658A1 (de) 1998-05-27
ES2190476T3 (es) 2003-08-01
EP0843658B1 (de) 2002-12-18
CZ41698A3 (cs) 1998-06-17
DE19529604A1 (de) 1997-02-13
HUP9802316A2 (hu) 1999-02-01
ATE229933T1 (de) 2003-01-15
BG64091B1 (bg) 2003-12-31
KR19990036304A (ko) 1999-05-25
AU707123B2 (en) 1999-07-01
BR9610049A (pt) 1999-07-06
DK0843658T3 (da) 2003-04-14
ZA966749B (en) 1997-02-18
TR199800210T2 (xx) 1998-08-21
DE59610011D1 (de) 2003-01-30
CA2228939A1 (en) 1997-02-27
JPH11511142A (ja) 1999-09-28
NZ315642A (en) 2000-01-28
MX9801133A (es) 1998-05-31
NO311566B1 (no) 2001-12-10
PL187412B1 (pl) 2004-07-30
AR003977A1 (es) 1998-09-30
NO980324L (no) 1998-03-05
JP2010222361A (ja) 2010-10-07
JP2014159449A (ja) 2014-09-04

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