EP1171435A2 - Pyrimidine-2-one derives comme ligands de recepteurs d'integrine - Google Patents

Pyrimidine-2-one derives comme ligands de recepteurs d'integrine

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Publication number
EP1171435A2
EP1171435A2 EP00920612A EP00920612A EP1171435A2 EP 1171435 A2 EP1171435 A2 EP 1171435A2 EP 00920612 A EP00920612 A EP 00920612A EP 00920612 A EP00920612 A EP 00920612A EP 1171435 A2 EP1171435 A2 EP 1171435A2
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EP
European Patent Office
Prior art keywords
optionally substituted
alkylene
aryl
radical
alkyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Application number
EP00920612A
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German (de)
English (en)
Inventor
Johann-Christian Zechel
Andreas Kling
Hervé Geneste
Udo Lange
Arnulf Lauterbach
Claudia Isabella Graef
Thomas Subkowski
Jens Sadowski
Wilfried Hornberger
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Abbott GmbH and Co KG
Original Assignee
BASF SE
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Publication date
Priority claimed from DE19916719A external-priority patent/DE19916719A1/de
Priority claimed from DE1999162998 external-priority patent/DE19962998A1/de
Application filed by BASF SE filed Critical BASF SE
Publication of EP1171435A2 publication Critical patent/EP1171435A2/fr
Withdrawn legal-status Critical Current

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Definitions

  • the invention relates to new compounds that bind to integrin receptors, their production and use.
  • Integrins are cell surface glycoprotein receptors that mediate interactions between similar and different cells as well as between cells and extracellular matrix proteins. They are involved in physiological processes such as Embryogenesis, hemostasis, wound healing, immune response and formation / maintenance of tissue architecture are involved.
  • Disorders in the gene expression of cell adhesion molecules and functional disorders of the receptors can contribute to the pathogenesis of many diseases, such as tumors, thromboembolic events, cardiovascular diseases, lung diseases, diseases of the CNS, the kidney, the gastrointestinal tract or inflammation.
  • Integrins are heterodimers each consisting of an ⁇ and a ⁇ transmembrane subunit, which are non-covalently linked. So far 16 different oc and 8 different ß subunits and 22 different combinations have been identified.
  • Integrin ⁇ v ß / also called vitronectin receptor mediates adhesion to a large number of ligands - plasma proteins, extra-cellular matrix proteins, cell surface proteins - the majority of which contain the amino acid sequence RGD (Cell, 1986, 44, 517-518; Science 1987, 238, 491-497), such as, for example, vitronectin, fibrinogen, fibronectin, from Willebrand factor, thrombospondin, osteopontin, laminin, collagen, thrombin, tenascin, MMP-2, bone sialo protein II, various viral, fungal, parasitic and bacterial Proteins, natural integrin antagonists such as disintegrins, neurotoxins - Mambin - and leech proteins - Decorsin, Ornatin - and some non-RGD ligands such as Cyr-61 and PECAM-1 (L. Piali, J. Cell Biol. 1995, 130 , 451-460; Buckley, J. Cell Science 1996, 109, 4
  • Integrin o. ⁇ I ⁇ _ß 3 also known as platelet fibrinogen receptor, recognizes fibronectin, vitronectin, thrombospondin, von Willebrand factor and fibrinogen. Integrin ⁇ v ß 3 is expressed, inter alia, on endothelial cells, platelets, monocytes / macrophages, smooth muscle cells, some B cells, fibroblasts, osteoclasts and various tumor cells, such as melanomas, glioblastomas, lung, breast, 5 prostate and bladder carcinomas , Osteosarcomas or neuroblastomas.
  • An increased expression is observed under various pathological conditions, such as in the prothrombotic state, in the case of vascular injury, tumor growth or metastasis or reperfusion, and on activated cells, in particular on endothelial cells, smooth muscle cells or macrophages.
  • Cardiovascular diseases such as atherosclerosis, restenosis after vascular injury, and angioplasty (neointima formation, smooth muscle cell migration and proliferation) (J. Vase. Surg. 1994, 19, 20 125-134; Circulation 1994, 90, 2203-2206),
  • Angiogenesis-associated microangiopathies such as diabetic retinopathy or rheumatic arthritis (Ann. Rev.
  • Cancer such as tumor metastasis or tumor growth (tumor-induced angiogenesis) (Cell 1991, 64, 327-336; Nature 1989, 339, 58-61; Science 1995, 270, 1500-1502),
  • Osteoporosis bone resorption after proliferation, chemotaxis and adhesion of osteoclasts to bone matrix
  • Pathogen protein e.g. HIV-1 tat
  • processes e.g. angiogenesis, Kaposi's sarcoma
  • Advantageous ⁇ v ß 3 integrin receptor ligands bind to the integrin ⁇ vß 3 receptor with an increased affinity.
  • Particularly advantageous O v ß 3 integrin receptor ligands have an increased selectivity compared to the integrin ot v ß 3 and are less effective with respect to the integrin ⁇ IlD ß 3 by at least a factor of 10, preferably at least by a factor of 100.
  • the object of the invention was to provide new integrin receptor ligands with advantageous properties.
  • L is a structural element of the formula I L
  • R 16 L is a branched or unbranched, optionally substituted Cx-C ß alkyl, alkoxyalkyl or Ci-C ⁇ - alkylene-C 3 -C 7 cycloalkyl or a napsen- if substituted C 3 -C -cycloalkyl, aryl, arylalkyl, hetaryl or hetarylalkyl radical,
  • RG 1 'RG 2 independently of one another are hydrogen, CN, N0 2 , halogen, a branched or unbranched, optionally substituted Ci-Ce-alkyl, C 2 -C 6 alkenyl or CC 6 ⁇ alkynyl radical, a branched or unbranched, optionally substituted Rest C 1 -C 4 -alkylene-OR G 4 , C 1 -C 4 -alkylene-CO-OR G 4 , C ⁇ -C-alkylene-CO-R G 4 , C 1 -C 4 -alkylene-S0 2 -NR G 5 R G 6 , -CC 4 alkylene-CO-NR G 5 R G 6 , -C- 4 - alkylene-NR G 5 R G 6 or -C-C 4 alkylene-SR ⁇ 3 4 , an optionally substituted C 3 -C-cycloalkyl-,
  • R G 3 is hydrogen, a hydroxyl group, CN, a branched or unbranched, optionally substituted
  • B a structural element containing at least one atom which can form hydrogen bonds under physiological conditions as a hydrogen acceptor, at least one hydrogen acceptor atom being at a distance of 4 to 13 atomic bonds from structural element G along the shortest possible path along the structural element framework,
  • a halogen radical is understood to mean, for example, F, Cl, Br or I for all radicals and substituents of the present invention, unless stated otherwise.
  • Optionally substituted radicals are understood to mean the corresponding unsubstituted and substituted radicals.
  • substituents are not specified in more detail, up to 5 substituents, for example selected from the following group, are suitable independently of one another:
  • substituted hetaryl and hetarylalkyl radicals of the present invention in addition to the above list of substituents, two substituents of the hetaryl part can form an fused 5- to 7-membered, unsaturated or aromatic carbocycle.
  • R 1 has the following meaning:
  • C 1 -C 6 -alkyl such as methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1, 1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 1, 2-dimethylpropyl, 1, 1-dimethylpropyl, 2, 2-dimethylpropyl,
  • C 2 -C 6 alkenyl such as vinyl, 2-propenyl, 2-butenyl, 3-butenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 2-pentenyl, 3-pentenyl, 4- Pentenyl, l-methyl-2-butenyl, 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, l-ethyl-2-propenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, l-methyl- 2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 3-methyl-3-pentenyl, 4-pentenyl, l-methyl- 4-pentenyl
  • a phenyl radical optionally mono- or polysubstituted, for example mono- to trisubstituted by halogen, nitro, cyano, C 4 -alkyl, C 4 haloalkyl, C ⁇ -C 4 -alkoxy, C 4 -haloalkoxy or -CC 4 alkylthio such as 2-fluorophenyl, 3-chlorophenyl, 4-bromophenyl, 2-methylphenyl, 3-nitrophenyl, 4-cyanophenyl, 2-trifluoromethylphenyl,
  • Preferred radicals T are -COOH, -CO-0-C ⁇ -C 8 alkyl or -CO-O-benzyl.
  • coefficients a, c, e and g of structural element -U- independently denote 0, 1, 2 or 3, preferably 0, 1 or 2.
  • Preferred halogen radical for R L 1 , R L 2 , RL 3 / R 4 - 5 - R L 6 / RL 7 or R L 8 is F.
  • RL 5 - having a C 3 -C-cycloalkyl RL 2/3/4 RL are for R 1.
  • R L 6 , R L 7 or R L 8 in structural element L are understood independently of one another, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl.
  • Branched or unbranched C ⁇ -C 6 -alkylene-C 3 -C-cycloalkyl contact, for example, branched or unbranched Ci-C ß alkylene radicals and C 3 -C above-mentioned cycloalkyl residues together.
  • Preferred, optionally substituted arylalkyl radicals for R L 1 , R 2 'L 3 ' RL 4 - RL 5 - RL 6 - 7 or R L 8 in structural element L are, independently of one another, optionally substituted benzyl or ethylene phenyl (homobenzyl).
  • Hetaryl radicals for R L 1 , R L 2 , RL 3 - R L ⁇ R L 5 - RL 6 'RL 7 or R L 8 in structural element L are, for example, radicals such as 2-pyridyl, 3-pyridyl, 4-pyridyl, independently of one another , 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 2 -Pyrimidyl, 4-pyrimidyl, 5-pyrimidyl, 6-pyrimidyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl , 3-pyri
  • R 5 - RL 6 , R L 7 or R L 8 in structural element L are, as generally described above for terminal, substituted hetaryl radicals, also fused derivatives of the above-mentioned hetaryl radicals, such as indazole, indole, benzothiophene, benzofuran, indoline, benzimidazole , Benzthiazole, benzoxazole, quinoline, 2, 3-dihydro-l-benzofuran, furo [2, 3] pyridine, furo [3, 2] pyridine or isoquinoline.
  • substituted hetaryl radicals also fused derivatives of the above-mentioned hetaryl radicals, such as indazole, indole, benzothiophene, benzofuran, indoline, benzimidazole , Benzthiazole, benzoxazole, quinoline, 2, 3-dihydro-l-benzofuran, furo [
  • Means radicals RL R 7 or L 8 in structural element L which are composed, for example, Ci-C ß alkylene radicals, and from the above loading signed hetaryl radicals, such as the radicals -CH 2 -2-pyridyl, -CH 2 -3 Pyridyl, -CH 2 -4-pyridyl, -CH-2-thienyl, -CH 2 -3-thienyl, -CH 2 -2-thiazolyl, -CH 2 -4-thiazolyl, CH 2 -5-thiazolyl, -CH 2 -CH 2 -2-pyridyl, -CH 2 -CH 2 -3-pyridyl, -CH 2 -CH 2 -4-pyridyl, -CH 2 -CH 2 -2-thienyl,
  • two radicals R 1 and R L 2 or R 3 and R L 4 or R L 5 and R L 6 or R L 7 and R L 8 together can each independently form a 3- to 7-membered, optionally substituted, saturated or unsaturated carbo- or heterocycle, which can contain up to three heteroatoms from the group 0, N or S, represent.
  • Ry 1 'Ry 1 * independently of one another hydrogen, a branched or unbranched, optionally substituted Ci-Ce alkyl, Ci-C ⁇ alkoxyalkyl, C 2 -C 6 alkenyl, C 3 -C ⁇ alkynyl, CO-Ci -C ⁇ alkyl, CO-0 -CC 6 alkyl or S0 2 -C 6 alkyl radical or an optionally substituted C 3 -C cycloalkyl, aryl, arylalkyl, CO-O-alkylene
  • Hydrogen a hydroxyl group, CN, halogen, a branched or unbranched, optionally substituted Ci-C ß- alkyl radical, an optionally substituted C 3 -C cycloalkyl, aryl, heteroaryl or arylalkyl radical, one optionally with C 1 -C 4 -alkyl or aryl substituted CC 6 ⁇ alkynyl or CC 6 alkenyl radical, an optionally substituted C 6 -C 2 bicycloalkyl, C 1 -C 6 alkylene-C 6 -C 2 bicycloalkyl, C 7 -C 20 - Tricycloalkyl- or -CC 6 alkylene-C 7 -C 2 o-tricycloalkyl radical, or a substituted with up to three identical or different radicals, 3- to 8-membered, saturated or unsaturated heterocycle, which up to three different or can contain the same heteroatoms 0, N, S, where two radicals together can represent an
  • R L 9 and Ry 1 or R y 1 * together can form a saturated or unsaturated C 3 -C 7 heterocycle which may optionally contain up to two further heteroatoms selected from the group 0, S or N.
  • radicals R L 9 and R y 1 or R y 1 * together form a cyclic amine as a C 3 -C 7 heterocycle, in the event that the radicals are bonded to the same nitrogen atom, for example N-pyrrolidinyl, N- Piperidinyl, N-hexahydroazepinyl, N-morpholinyl or N-piperazinyl, where the free amine protons in heterocycles, such as N-piperazinyl, carry the free amine protons by common amine protective groups, such as methyl, benzyl, Boc (tert-butoxycarbonyl), Z ( Benzyloxycarbonyl), tosyl, -S0 -CC-C-alkyl, -S0 2 -phenyl or -S0 2 -benzyl can be replaced.
  • N-pyrrolidinyl N- Piperidinyl, N-hexahydroazepinyl, N-morpholinyl or N-pipe
  • Preferred radicals - (CH 2 ) W - (Y L ) y -R L 9 for R L 1 , R L 3 , R L 5 or R L 7 in structural element L are optionally substituted side chains of the natural amino acids, preferably optionally substituted side chains of the Amino acids Ser, Thr, Tyr, Asp, Asn, Glu, Gin, Cys, Met, Lys or Orn, optionally substituted side chains of unnatural amino acids, as described for example in catalogs by the companies Bachern 1999, Novabiochem 1999, Neosystem 1997/98 and Advanced ChemTech 1999 .
  • the side chains of natural ⁇ -amino acids are the side chains of natural ⁇ -amino acids.
  • the radicals RL 1 , RL 2 . RL 3 - RL 4 - R 5 . RL 6 - RL 7 or R L 8 independently of one another are hydrogen or methyl, with the proviso that the radicals V L or X L independently of one another are a radical -CH (NR L 14 -S0 2 -RL 15 ) -, -CH (NRL 14 -C0-R L 15 ) -, -CH (NR L 14 -CO-OR L 16 ) -, -CH (NRL 14 -CO-NR L 14 ' RL 15 ) -, -CH (CO-OR L 16 ) - or -CH (CO-NR L 14 RL 15 ) - mean.
  • the radicals V L or X L independently of one another are a radical -CH (NR L 14 -S0 2 -RL 15 ) -, -CH (NRL 14 -C0-R L 15 ) -, -CH (NR L 14
  • An optionally substituted 4- to 11-membered mono- or polycyclic aliphatic or aromatic hydrocarbon, which can contain up to 6 double bonds and up to 6 heteroatoms, selected from the group N, 0, S, is preferably optionally substituted for W L Arylene, such as optionally substituted phenylene or naphthylene, optionally substituted hetarylene, such as the radicals
  • the coefficient r denotes 0, 1, 2 or 3 and Z 10 and Z 11 independently CH or nitrogen and Z 8 and Z 8 * independently oxygen, sulfur or NH.
  • W L preferably denotes an optionally substituted one
  • the coefficient r denotes 0, 1, 2 or 3 and Z 10 and Z 11 independently CH or nitrogen and Z 8 and Z 8 * independently oxygen, sulfur or NH.
  • radicals of the formula II WL or III WL for W L , Z 8 is oxygen.
  • Preferred radicals for V L and X L are independently of one another -CO-NR L 10 -, -NR L 10 -CO-, -S0 -NR L 10 -, -NR L 10 -SO 2 -, -O-, -CH (NR 14 -S0 2 -RL 15 ) -, -CH (NR L 14 -CO-RL 15 ) -, -CH (NR L 14 -C0-0RL 16 ) -, C ⁇ (NRL 1 -CO-NR L 14 'RL 15 ) -, -CH (CO-R L 15 ) -, -CH (CO-OR L 16 ) - and
  • radicals for V L and X L are independently of one another -CH (NR L 1 -S0 2 -R L 15 ) -, -CH (NR L 14 -CO-R L 15 ) -,
  • the radical R L 10 in structural element L means hydrogen
  • Ci-C ⁇ -alkyl radical for example as described above for R 1 L, preferably methyl
  • C 1 -C 6 -alkoxyalkylre ⁇ t for example methoxymethylene, ethoxy-methylene, t-butoxymethylene, methoxyethylene or ethoxyethylene, CC 6 alkenyl radical, for example as described above for R L 1 , preferably allyl,
  • C 3 -Ci 2 alkynyl radical for example 2-propynyl, 2-butynyl, 3-butynyl, l-methyl-2-propynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, l-methyl-3-butynyl , 2-methyl-3-butynyl, l-methyl-2-butynyl, 1, l-dimethyl-2-propynyl, l-ethyl-2-propynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5th -Hexinyl, 1-methyl-2-pentynyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 1-methyl-4-pentynyl, 2-methyl-3-pentynyl, 2-methyl -4-pentinyl, 3-methyl-4-pentinyl, 4-methyl-2-penty
  • CO-C 6 -alkyl CO-0-C 5 C 5 -alkyl or S0 2 -C-C 6 -alkyl radical, each of which is selected from the corresponding group CO, CO-O or S0 2 and composed, for example, of the Ci-Cg-alkyl radicals described above,
  • CO-O-alkylene-aryl CO-alkylene-aryl, CO-aryl, S0 2 -aryl, CO-hetaryl or S0 2 -alkylene-aryl radical, which is in each case from the corresponding group CO -, CO-O- or S0 2 - and composed, for example, of the corresponding arylalkyl, aryl, hetarylalkyl and hetaryl radicals described for R L 1 .
  • R L 10 and a residue can be selected from the group R L 1 , R L 2 , R L 3 .
  • R L 4 , R L 5 - R 6 - R L 7 or R L 8 together form an optionally substituted 4- to 8-membered heterocycle which can contain up to five identical or different heteroatoms 0, N or S.
  • radicals for R L 10 are hydrogen, methyl, cyclopropyl, allyl and propargyl.
  • Ci-Ce alkyl Under a branched or unbranched Ci-Ce alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or -C-C 6 alkylene-C 3 -C 7 cycloalkyl radical or an optionally substituted C3-C-cycloalkyl, aryl, arylalkyl, hetaryl or hetarylalkyl radicals are used for RL 11 or R L 12 independently of one another, for example, understood the corresponding radicals mentioned above for R L 1 .
  • R L 11 or R L 12 independently of one another, for example, the radicals methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy or 1, 1st -Dimethylethoxy understood.
  • a branched or unbranched C ⁇ -C 6 alkyl, C 2 -C 6 -alkenyl, C-Ce-alkynyl or C ⁇ -C 6 -alkylene-C 3 -C rest-cycloalkyl or an optionally substituted C 3 -C-cycloalkyl, aryl, arylalkyl, hetaryl or hetarylalkyl radical, for R L 13 are understood, for example, the corresponding radicals mentioned above for R L 1 .
  • R L 14 and R L 14 ' are independently hydrogen, a branched or unbranched, optionally substituted Ci-Cg-alkyl or C 3 -C 2 -alkynyl radical or an optionally substituted C 3 -C -cycloalkyl-, aryl -, Hetaryl or arylalkyl.
  • radicals for R L 14 and R L 1 ' are, independently of one another, hydrogen, methyl, cyclopropyl, allyl or propargyl.
  • R L 15 denotes a branched or unbranched, optionally substituted
  • Ci-C ß- alkyl radical as described above for L 1 , preferably a branched or unbranched, optionally substituted C 1 -C 4 -alkyl radical, particularly preferably n-butyl, 2-methylpropyl, 1-methylethyl,
  • C 6 -C 2 bicycloalkyl or CC 2 o-tricycloalkyl such as, for example, bicyclo [4.4.0] decanyl, bicyclo [2.2.2] octanyl, bicyclo-
  • C 1 -C 6 -alkylene-C 6 -C 2 -bicycloalkyl- or -C-C 6 alkylene-C 7 -C 2 o -tri- cycloalkyl radical such as -CH 2 bicyclo [4.4.0] ecanyl, -CH -Bicyclo [2.2.2] octanyl, -CH 2 -Bicyclo [3.2.1] octanyl, -CH 2 - Indanyl, -CH 2 -Adaman yl, -CH 2 -norbornyl, -CH -Noradamantyl or
  • R L 15 and R L 14 or R L 14 * together can form a saturated or unsaturated C 3 -C heterocycle which may optionally contain up to two further heteroatoms selected from the group 0, S or N.
  • the radicals R L 15 and R L 14 or R L 14 * together form a cyclic amine radical as a C 3 -C 7 heterocycle, in the event that the radicals are bonded to the same nitrogen atom, such as N-pyrrolidinyl, N- Piperidinyl, N-hexahydroazepinyl, N-morpholinyl or N-piperazinyl, where the free amine protons in heterocycles such as N-piperazinyl carry the free amine protons by common amine protecting groups, such as methyl, benzyl, Boc (tert-butoxycarbonyl), Z ( Benzyloxycarbonyl), tosyl, -S0 2 -C ⁇ -C-alkyl, -S0 2 -phenyl or -S0 2 -benzyl can be replaced.
  • nitrogen atom such as N-pyrrolidinyl, N- Piperidinyl, N-hexahydroazepinyl, N-morpholin
  • the cyclic amine residue NR L 15 R L 14 or NR L 15 R L 14 * can also be part of an amide, sulfonamide, urethane or other possible composite structural element.
  • Preferred radicals for R L 15 are a branched or unbranched, optionally substituted C 1 -C 4 alkyl or -CH 2 -C5-C 7 cycloalkyl radical, an optionally substituted C 5 -C 7 cycloalkyl, phenyl, 1-naphthyl-, 2-naphthyl-, -CH 2 -naphthyl-, pyridyl, -CH 2 - pyridyl-, ethylenephenyl-, thienyl-, -CH 2 -thienyl-, oxazolyl-, -CH-oxazolyl-, isoxazolyl- , -CH 2 -isoxazolyl-, quinolinyl-, iso-quinolinyl-, -CH 2 -quinolinyl-, -CH 2 -isoquinolinyl-, adamantyl-, -
  • Ci-C ⁇ alkyl, alkoxyalkyl or Ci-Cg alkylene C 3 -C 7 cycloalkyl radical or an optionally substituted C 3 -C7 cycloalkyl, aryl, arylalkyl , Hetaryl or hetarylalkyl radicals for R L 16 are, for example, the corresponding radicals mentioned above for R L 15 , preferably hydrogen, a branched or unbranched, optionally substituted C ⁇ -C 4 -alkyl- or -CH -C 5 -C 7 Cycloalkyl residue, an optionally substituted C 5 -C 7 cycloalkyl, phenyl, 1-naphthyl, 2-naphthyl, -CH 2 -naphthyl, benzyl, pyridyl, -CH 2 -pyridyl, ethylene-phenyl - understood
  • Particularly preferred radicals for R L 16 are a branched or unbranched, optionally substituted C 1 -C 4 -alkyl radical and optionally substituted benzyl.
  • Preferred structural elements L are composed of at least one preferred radical of the radicals belonging to structural element L, while the remaining radicals are widely variable.
  • Particularly preferred structural elements L are composed of the preferred residues of structural element L.
  • G represents a structural element of the formula I G ,
  • structural element G can be installed in both orientations.
  • Z G means oxygen, sulfur or NR G 3 , preferably
  • the substitution pattern is as defined in formula I G B, here, too, the structural element G can be installed in both orientations.
  • the substitution pattern is defined as in formula I GB and the structural element G is installed in such a way that the structural element E is connected to the 4-carbon position and that the structural element L is connected to the 1-nitrogen position.
  • R G 1 and R G 2 in structural element G independently of one another denote hydrogen, CN, N0, halogen, a branched or unbranched, optionally substituted
  • Ci-C ⁇ alkyl such as optionally substituted methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1, 1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 1, 2 -Dimethylpropyl, 1, 1-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1-methylpentyl, 1, 2-dimethylbutyl, 1, 3-dimethylbutyl, 2, 3-dimethylbutyl, 1, 1 -Dimethylbutyl, 2, 2-dimethylbutyl, 3, 3-dimethylbutyl, 1, 1, 2-trimethylpropyl,
  • C 2 -C 6 alkenyl such as optionally substituted vinyl, 2-propenyl, 2-butenyl, 3-butenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, l-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-1-2-butenyl, l-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3- butenyl, 1, l-dimethyl-2-propenyl, 1, 2-dimethyl-1-propenyl, 1-ethyl-2-propenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, l-methyl 2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, l
  • C 3 -C 7 cycloalkyl such as optionally substituted cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl,
  • C 3 -C 7 heterocycloalkyl such as optionally substituted aziridinyl, diaziridinyl, oxiranyl, oxaziridinyl, oxetanyl, thiiranyl, thietanyl, pyrrolidinyl, piperazinyl, morpholinyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, 1, 4, 1, 4, 1, 1, 4, 1 2-oxathiolanyl or oxazolidinyl,
  • C 3 -C 7 heterocycloalkenyl such as optionally substituted azirinyl, diazirinyl, thiirenyl, thietyl, pyrrolinyls, oxazolinyls, azepinyl, oxepinyl, ⁇ -pyranyl, ⁇ -pyranyl, ⁇ -pyranyl, dihydropyranyle, 2, 5-dihydro-pyrrolinyl or 4, 5-dihydro-oxazolyl,
  • C 1 -C 4 -alkylene-C 3 -C 7 cycloalkyl radical which is, for example, from branched or unbranched C 1 -C 4 -alkylene radicals such as methylene, ethylene, propylene, n-butylene, iso -Butylene or t-butylene and, for example, those mentioned above
  • a branched or unbranched optionally substituted C 1 -C 4 alkylene C 3 -C 7 heterocycloalkyl or C 4 -C 4 alkylene C 3 -C 7 heterocycloalkenyl radical which is composed of optionally substituted C 1 -C 4 alkylene Residues such as, for example, methylene, ethylene, propylene, n-butylene, isobutylene or t-butylene and, for example, the above-mentioned C 3 -C heterocycloalkyl or C 3 -C heterocycloalkenyl residues, the residues being preferred, which contain one or two heteroatoms selected from the group N, 0 or S and contain up to two double bonds in the cyclic part,
  • Aryl radical preferably optionally substituted phenyl, 1-naphthyl or 2-naphthyl,
  • Arylalkyl radical preferably optionally substituted benzyl or ethylenephenyl (homobenzyl),
  • Hetaryl radical preferably optionally substituted 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-thienyl, 3-thienyl, 2-thiazolyl, 4 -Thiazolyl, 5-thiazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 2-pyrimidyl, 4-pyrimidyl, 5-pyrimidyl, 6-pyrimidyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 3-isothiazolyl , 4-isothiazolyl, 5-isothiazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3-pyridazinyl, 4-pyridazinyl, 5-pyridazinyl, 6-pyridazinyl, 3-isoxazolyl, 4-isoxazolyl, 5-is
  • Hetarylalkyl radical preferably optionally substituted -CH 2 -2-pyridyl, -CH 2 -3-pyridyl, -CH 2 -4-pyridyl, -CH 2 -2-thienyl, -CH-3-thienyl, -CH 2 -2- Thiazolyl, -CH-4-thiazolyl, CH 2 -5-thiazol-yl, -CH 2 -CH 2 -2-pyridyl, -CH 2 -CH 2 -3-pyridyl, -CH 2 -CH 2 -4-pyridyl , -CH 2 -CH 2 -2-thienyl, -CH 2 -CH 2 -3-thienyl, -CH 2 -CH 2 -2-thiazolyl, -CH 2 -CH 2 -4-thiazolyl or -CH 2 -CH 2 -5-thiazolyl or
  • radicals R G 1 and R G 2 can together form an optionally substituted, saturated, unsaturated or aromatic 3- to 9-membered carbocycle, carbopolycycle, heterocycle or heteropolycycle which has up to 4 heteroatoms selected from group 0, N, S can contain.
  • Preferred radicals for R G 1 in the structural element G are hydrogen, a branched or unbranched, optionally substituted Ci-Cg-alkyl radical, preferably CF 3 , C 2 -C 6 ⁇ alkenyl, C-Cg-alkynyl radical, C 1 -C 4 -alkylene -OR G 4 , optionally substituted aryl, arylalkyl, hetaryl or hetarylalkyl or a radical -0-R G 4 .
  • R G 2 in the structural element G are hydrogen, CN, halogen, a branched or unbranched, optionally substituted Ci-Cg-alkyl radical, preferably CF 3 , an optionally substituted C 3 -C 7 cycloalkyl, aryl, arylalkyl , Hetaryl or hetarylalkyl radical, a radical -SO-RQ 4 , -S0 -RQ 4 , -CO-OR G 4 , -S0 2 -NR G 5 R G 6 , -CO-NR G 5 R G 6 , -NR G 5 R G 6 , CO-RQ 4 , Cx-j-alkylene-CO-ORQ 4 , C ⁇ -C4-alkylene-S ⁇ 2-N G 5 RG 6 , C ⁇ -C-alkylene-CO-NR G 5 RG 6 or C 1 -C 4 -alkylene-NR G 5 R G 6 or an optionally substituted C
  • RQ 2 in structural element G is a branched or unbranched, optionally substituted Ci-Cg-alkyl radical, an optionally substituted C 3 -C 7 cycloalkyl, aryl, arylalkyl, hetaryl or hetarylalkyl radical, a radical - CO-OR G 4 , -CO-NRG R G 6 .
  • R G 3 represents hydrogen, a hydroxyl group, CN, a branched or unbranched, optionally substituted
  • Ci-Cg-alkyl radical as described, for example, above for RQ 1 , -C-C 4 alkoxy, as described above for R L 1: L ,
  • Ci-Cg-alkyl radical for R G 4 , R G 4 * , G 5 and RQ 6, independently of one another means for example the Ci-Cg-alkyl radicals mentioned above for RQI plus the radicals heptyl and Octyl.
  • Preferred substituents of the branched or unbranched, optionally substituted Ci-Cg-alkyl radicals for RQ 4 , R G 4 ', R G 5 and R G 6 are, independently of one another, the radicals halogen, hydroxy, C 1 -C 4 -alkoxy, -CN, - COOH and -CO-0-C ⁇ -C-alkyl.
  • C 3 -C 7 cycloalkyl, aryl, arylalkyl, hetaryl or hetarylalkyl are, for R G 4 , R G 4 * , R G 5 and R G 6, independently of one another, for example, the corresponding radicals mentioned above for R G 1 Roger that.
  • Preferred, branched or unbranched, optionally substituted -CC 5 alkylene -CC 4 alkoxy radicals for R G 4 , RQ 4 * , R G 5 and R G 6 are, independently of one another, methoxymethylene, ethoxymethylene, t-butoxymethylene , Methoxyethylene or ethoxyethylene.
  • RQ 4 , R G 4 * , R G 5 and R G 6 are independently branched or unbranched, optionally substituted radicals -C 1 -C 4 -Alkylene-NH (-C-alkyl), -C ⁇ -C 4 -alkylene-N (-C-C-alkyl) 2 or -C ⁇ -C-alkylene-NH-CO-C ⁇ -C 4 alkyl.
  • RG 5 and R G 6 are independently of one another the C 3 -C 7 heterocycloalkyl, C 3 -C 7 heterocycloalkenyl, C 1 -C 4 -Al y- described above for RQ 1 len-C 3 -C7 heterocycloalkyl or -CC 4 alkylene-C 3 -C heterocyclo alkenyl radicals.
  • R G 5 and RQ 6 are independently of one another the C 3 -C 7 heterocycloalkyl, C 3 -C 7 heterocycloalkenyl, C ⁇ C 4 alkylene, C 3 -C 7 heterocycloalkyl or C 1 described above for RQ 1 -C 4 alkylene-C 3 -C 7 heterocycloalkenyl radicals, the cyclic part containing one or two heteroatoms selected from the group N, 0 or S and up to two double bonds.
  • R G 5 and RQ 6 can independently of one another represent a radical -S0 2 -R G 4 , -CO-O-RQ 4 , -CO-NR G 4 R G 4 * or -CO-R G 4 , where RQ 4 * represents a radical R G 4 which is independent of RQ 4 .
  • Preferred structural elements G are composed of at least one preferred radical of the radicals belonging to structural element G or the preferred substitution pattern of structural element G, while the remaining radicals are widely variable.
  • Particularly preferred structural elements G are composed of the preferred residues of structural element G.
  • Very particularly preferred structural elements G are composed of the preferred residues of structural element G and the preferred substitution pattern of structural element G.
  • Structural element B is understood to mean a structural element containing at least one atom which can form hydrogen bonds under physiological conditions as a hydrogen acceptor, with at least one hydrogen acceptor atom being at a distance of 4 to 13 atomic bonds to the structural element along the shortest possible path along the structural element framework G.
  • the design of the structural framework of structural element B is widely variable.
  • Atoms which can form hydrogen bonds under physiological conditions as hydrogen acceptors are, for example, atoms with Lewis base properties, such as, for example, the heteroatoms nitrogen, oxygen or sulfur.
  • Physiological conditions are understood to mean a pH value that prevails at the location in an organism at which the ligands interact with the receptors.
  • the physiological conditions have a pH of, for example, 5 to 9.
  • the structural element B means a structural element of the formula IB
  • a 4- to 8-membered monocyclic saturated, unsaturated or aromatic hydrocarbon which can contain up to 4 heteroatoms selected from the group 0, N or S, where the ring nitrogen or the carbons which may be present can be substituted independently of one another with the proviso that at least one heteroatom selected from the group 0, N or S is contained in the structural element A,
  • a 9- to 14-membered polycyclic saturated, unsaturated or aromatic hydrocarbon which can contain up to 6 heteroatoms selected from the group N, 0 or S, where the ring nitrogen or the carbons which may be present can be substituted independently of one another with the proviso that at least one heteroatom selected from the group 0, N or S is contained in the structural element A,
  • Z A 1 oxygen, sulfur or optionally substituted nitrogen, preferably oxygen or nitrogen and Z A 2 optionally substituted nitrogen, oxygen or sulfur, preferably nitrogen
  • RA 19 is independently hydrogen, a branched or unbranched, optionally substituted Ci-Cg-alkyl, C 2 -Cg alkenyl, C 2 -Cg alkynyl, -C-C 5 alkylene -CC-C 4 alkoxy- , Mono- and bis-alkylaminoalkylene or acylaminoalkylene or an optionally substituted aryl, heterocycloalkyl, heterocycloalkenyl, hetaryl, C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene C 3 -C 7 -cycloalkyl, arylalkyl, -CC 4 alkylene heterocycloalkyl, -C 4 -alkylene heterocycloalkenyl or hetarylalkyl radical, or a radical -S0 2 -RQ 4 , -CO-ORQ 4 , -CO-NR G R G 4 * or
  • E is a spacer structural element which connects structural element A covalently to structural element G, the number of atomic bonds along the shortest possible path along the structural element framework E being 3 to 12.
  • the structural element A means a structural element selected from the group of structural elements of the formulas IA 1 to IA 19 ,
  • RA 1 , RA 2 independently of one another are hydrogen, CN, halogen, a branched or unbranched, optionally substituted Ci-Cg-alkyl or CO-Ci-Cg-alkyl radical or an optionally substituted aryl, arylalkyl, Hetaryl, hetarylalkyl or C 3 -C 7 cycloalkyl radical or a radical CO-0-R A 14 , 0-R A 14 , SR A 14 , NR A 15 R A 16 , CO-NR A 15 R A 16 or S0 2 NR A 15 R A 16 or both radicals R A 1 and R A 2 together form a fused, optionally substituted, 5- or 6-membered, unsaturated or aromatic carbocycle or heterocycle of up to three heteroatoms, selected from group 0, Can contain N or S
  • RA 13 , RA 13 * independently of one another are hydrogen, CN, halogen, a branched or unbranched, optionally substituted Ci-Cg-alkyl radical or an optionally substituted aryl, arylalkyl, hetaryl, C 3 -C 7 cycloalkyl radical or one Balance CO-0-R A 14 , 0-R A 14 , SR A 14 , NR A 15 R A 16 , S0 2 -NR A 15 RA 16 or CO-NR A 15 RA 16 , whereby
  • R A 14 is hydrogen, a branched or unbranched, optionally substituted Ci-Cg-alkyl, alkylene
  • Ci- j-alkoxy C 2 -Cg-alkenyl, C 2 -Cg-alkynyl or -C-Cg-alkylene-C 3 -C 7 cycloalkyl or an optionally substituted C 3 -C 7 cycloalkyl, aryl -, arylalkyl, hetaryl or hetarylalkyl radical,
  • R A 15 , R A 16 independently of one another, hydrogen, a branched or unbranched, optionally substituted Ci-Cg-alkyl, CO-C ⁇ -C 6 alkyl-, S0 2 -C ⁇ -Cg-alkyl, COO-Ci- Cg-alkyl, CO-NH-Ci-Cg-alkyl, arylalkyl,
  • RA 3 'RA 4 independently of one another hydrogen, - (CH 2 ) n - (X A ) -R A 12 . or both radicals together form a 3- to 8-membered, saturated, unsaturated or aromatic N-heterocycle which can additionally contain two further, identical or different heteroatoms 0, N, or S, the cycle optionally being substituted or a further one on this cycle, optionally substituted, saturated, unsaturated or aromatic cycle can be fused on, in which
  • n 0, 1, 2 or 3
  • R A 12 is hydrogen, a branched or unbranched, optionally substituted C 1 -C 6 -alkyl radical, a C 2 -C 6 -alkynyl or C 6 -alkenyl radical which is optionally substituted by C 1 -C 4 -alkyl or aryl, or one with up to three identical or different radicals substituted, 3- to 6-membered, saturated or unsaturated heterocycle, which may contain up to three different or identical heteroatoms 0, N, S, C 3 -C 7 cycloalkyl, aryl or heteroaryl radical, where two radicals together can form an fused, saturated, unsaturated or aromatic carbocycle or heterocycle, which can contain up to three different or identical heteroatoms 0, N, S, and the cycle optionally substituted or on this cycle another, optionally substituted, saturated, unsaturated or aromatic cycle can be condensed, or the radical R A 12 forms together with Rx 1 or Rx 1 * a saturated or unsaturated
  • C 3 -C heterocycle which may optionally contain up to two further heteroatoms selected from the group 0, S or N,
  • Rx 1 - 1 * Rx is independently hydrogen, a branched or unbranched, optionally substituted C ⁇ -C6 alkyl, Ci-Cg alkoxyalkyl, C 2 -C 6 alkenyl, C 2 -C ⁇ 2 alkynyl, CO -Ci-Cg-alkyl, CO-0-C ⁇ -C-alkyl or S0 2 -C ⁇ ⁇ Cg-alkyl radical or an optionally substituted C 3 -C 7 cycloalkyl, aryl, arylalkyl, CO-O-alkylene Aryl, CO alkylene aryl, CO aryl, S0 2 aryl, hetaryl, CO hetaryl or S0 2 alkylene aryl radical, R A 5 is a branched or unbranched, optionally substituted Ci-Cg-alkyl, arylalkyl, C 3 -C 7 cycloalkyl or -CC 4 alkylene-C 3
  • radicals R A 6 and R A 6 * together form an optionally substituted, saturated, unsaturated or aromatic heterocycle which, in addition to the ring nitrogen, can contain up to two further different or identical heteroatoms 0, N, S,
  • R A 7 is hydrogen, -OH, -CN, -CONH _ a branched or unbranched, optionally substituted C ⁇ -C4 alkyl, C ⁇ -C 4 alkoxy, C 3 -C 7 cycloalkyl, or -0-CO -C ⁇ ⁇ C 4 alkyl radical, or an optionally substituted arylalkyl, -O-alkylene-aryl, -O-CO-aryl, -O-CO-alkylene-aryl or -O-CO-allyl radical, or both R A 6 and R A 7 together form an optionally substituted, unsaturated or aromatic heterocycle which, in addition to the ring nitrogen, can contain up to two further different or identical heteroatoms 0, N, S,
  • R A 8 is hydrogen, a branched or unbranched, optionally substituted C 1 -C 4 -alkyl, CO-C 1 -C 4 -alkyl-, S0 2 -C-C-alkyl or CO-0-C ⁇ ⁇ C 4 - Alkyl radical or an optionally substituted aryl, CO-aryl, S0 2 aryl, CO-O-aryl, CO-alkylene-aryl, S0 2 -alkylene-aryl, CO-O-alkylene-aryl or alkylene Aryl residue,
  • RA 9 , RA 10 independently of one another are hydrogen, -CN, halogen, a branched or unbranched, optionally substituted Ci-Cg-alkyl radical or an optionally substituted aryl, arylalkyl, hetaryl, C 3 -C 7 cycloalkyl radical or one Remainder CO-0-R A 14 , 0-R A 14 , SR A 14 , NR A 15 R A 16 , S0 2 -NR A 15 RA 16 or CO-NR A 15 RA 16 , or both residues R A 9 and R A 10 together in structural element I A 14 is a 5- to 7-membered saturated, unsaturated or aromatic carbocycle or heterocycle which contains up to three different can contain different or identical heteroatoms 0, N, S and is optionally substituted with up to three identical or different radicals,
  • R A n is hydrogen, -CN, halogen, a branched or unbranched, optionally substituted Ci-Cg-alkyl radical or an optionally substituted aryl, arylalkyl, hetaryl, C 3 -C 7 cycloalkyl radical or a radical CO-O-RA 14 , 0-R A 14 , SR A 14 , NR A 15 RA 16 , S0 2 -NR A 15 RA 16 or CO-NR A 15 RA 16 .
  • R A 17 is hydrogen or, in structural element I A 16, both R A 9 and R A 17 together form a 5- to 7-membered saturated, unsaturated or aromatic heterocycle which, in addition to the ring nitrogen, has up to three different or identical heteroatoms 0, N Can contain S and is optionally substituted with up to three identical or different radicals,
  • RA 18 , RA 19 independently of one another hydrogen, a branched or unbranched, optionally substituted Ci-Cg-alkyl, C 2 -Cg-alkenyl, C 2 -Cg-alkynyl, -C-C 5 -alkylene- -CC 4 Alkoxy, mono- and bis-alkylaminoalkylene or acylaminoalkylene or an optionally substituted aryl, heterocycloalkyl, heterocycloalkenyl, hetaryl, C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene C 3 -C 7 -Cycloalkyl, arylalkyl, -C-C 4 alkylene heterocycloalkyl, -C -C alkylene heterocycloalkenyl or hetarylalkyl radical, or a radical -S0 2 -RQ 4 , -CO-OR G 4 , -CO- NR G
  • Z 1 - Z 2 ' Z 3 - Z 4 independently of one another nitrogen, CH, C-halogen or a branched or unbranched, optionally substituted C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy radical,
  • the structural element A is a structural element of the formulas IA 1 , IA 4 , IA 7 , IA 8 , IA 9 , IA 14 or I A 15 .
  • a branched or unbranched, optionally substituted C 1 -C 6 -alkyl radical for R A 1 or R A 2, independently of one another, is understood to mean, for example, the corresponding radicals described above for RQ 1 , preferably methyl or trifluoromethyl.
  • Optionally substituted hetaryl, hetarylalkyl, aryl, arylalkyl or CC 7 cycloalkyl radicals for R 1 or R A 2, independently of one another, are understood to mean, for example, the corresponding radicals described above for RQ 1 .
  • CO-NRA 15 R A 16 or S0 2 NR A 15 RA 16 are for RA 1 or R A 2, for example, from the groups CO-O, 0, S, N, CO-N or S0-N and the following in more detail described radicals R A 14 , R A 15 and R A 16 together.
  • both radicals R A 1 and R A 2 together can contain an fused, optionally substituted, 5- or 6-membered, unsaturated or aromatic carbocycle or heterocycle which can contain up to three heteroatoms selected from the group 0, N, or S, form.
  • R A 13 and R A 13 * independently of one another denote hydrogen, CN,
  • Halogen such as fluorine, chlorine, bromine or iodine
  • Ci-Cg-alkyl radical preferably methyl or trifluoromethyl or
  • Ci-Cg-alkyl, C 3 -C 7 cycloalkyl, alkylene-cycloalkyl, alkylene -CC 4 alkoxy, C 2 -Cg alkenyl or C 2 -Cg-alkynyl radical for R A 14 in structural element A are understood, for example, to be the corresponding radicals described above for RQ 1 .
  • Optionally substituted aryl, arylalkyl, hetaryl or alkylhetaryl radicals for R A 14 in structural element A are understood to mean, for example, the corresponding radicals described above for RG 1 .
  • Preferred radicals for R A 14 are hydrogen, a branched or unbranched, optionally substituted Ci-Cg-alkyl radical and optionally substituted benzyl.
  • the branched or unbranched, optionally substituted CO-Ci-Cg-alkyl, S0 2 -C ⁇ -C 6 alkyl, COO-Ci-Cg-alkyl, CO-NH-C ⁇ -C 6 alkyl, COO- Alkylene-aryl, CO-NH-alkylene-aryl, CO-NH-alkylene-hetaryl or S0-alkylene-aryl radicals or the optionally substituted CO-aryl, S0 2 -aryl, CO-NH-aryl, CO -NH-hetaryl or CO-hetaryl radicals for R A 15 or R A 16 are composed, for example, of the corresponding groups -CO-, -S0 2 -, -CO-O-, -CO-NH- and the corresponding ones described above branched or unbranched, optionally substituted Ci-Cg-alkyl, hetarylalkyl or arylalkyl radicals or the corresponding optionally substituted aryl
  • a radical - (CH 2 ) n - (X A ) jR A 12 for R A 3 or R A 4 is understood independently of one another to be a radical which is composed of the corresponding radicals - (CH 2 ) n -, (X A ) J and R A 12 composed.
  • N can mean 0, 1, 2 or 3 and: 0 or 1.
  • X A represents a double bonded residue selected from the
  • R A 12 means hydrogen
  • Ci-Cg-alkyl radical a branched or unbranched, optionally substituted Ci-Cg-alkyl radical, as described above for RQ 1 ,
  • R A 12 and Rx 1 or Rx 1 * together can form a saturated or unsaturated C 3 ⁇ C 7 heterocycle which may optionally contain up to two further heteroatoms selected from the group 0, S or N.
  • N-pyrrolidinyl N- Piperidinyl, N-hexahydroazepinyl, N-morpholinyl
  • Ci-Cg-alkyl Under a branched or unbranched, optionally substituted Ci-Cg-alkyl, Ci-Cg-alkoxyalkyl, C 2 -Cg alkenyl, C 2 -C 2 alkynyl, CO-C 6 C 6 alkyl, CO 0 -CC 6 alkyl or S0 2 -C-Cg-alkyl radical or an optionally substituted
  • CO-alkylene-aryl, CO-aryl, S0-aryl, hetaryl, CO-hetaryl or S0 2 -alkylene-aryl radical are independently for R ⁇ ⁇ and Rx 1 *, for example, the above for R L 14 and R L 14 * understood residues.
  • R x x and Rx 1 * are independently hydrogen, methyl, cyclopropyl, allyl and propargyl.
  • R A 3 and R A 4 can also together form a 3- to 8-membered, saturated, unsaturated or aromatic N-heterocycle which can additionally contain two further, identical or different heteroatoms 0, N, or S, the cycle optionally substituted or another, optionally substituted, saturated, unsaturated or aromatic cycle may be fused onto this cycle,
  • R A 5 represents a branched or unbranched, optionally substituted Ci-Cg-alkyl, arylalkyl, -C-C 4 alkyl-C 3 -C 7 cycloalkyl or C 3 -C 7 cycloalkyl radical or an optionally substituted Aryl, hetaryl, heterocycloalkyl or heterocycloalkenyl radical, as described for example above for R G 4 , RQ 5 and RQ 6 .
  • R A 6 and R A 6 * independently of one another denote hydrogen, a branched or unbranched, optionally substituted
  • C 1 -C 4 -alkyl radical such as optionally substituted methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl or 1, 1-dimethylethyl,
  • -CO-0-C 4 -alkyl or -CO-C 4 -C 4 -alkyl radical such as composed, for example, of the group -CO-O- or -CO- and the above-described C 1 -C 4 -alkyl radicals,
  • Arylalkyl radical as described above for R G 1 is Arylalkyl radical as described above for R G 1 ,
  • -CO-O-alkylene-aryl or -CO-alkylene-aryl radical such as, for example, composed of the group -CO-O- or -CO- and the arylalkyl radicals described above,
  • both radicals R A 6 and R A 6 * in structural element I A 7 together can form an optionally substituted, saturated, unsaturated or aromatic heterocycle which, in addition to the ring nitrogen, can contain up to two further different or identical heteroatoms 0, N, S .
  • R A 7 means hydrogen, -OH, -CN, -CONH / a branched or unbranched, optionally substituted C 1 -C 4 -alkyl radical, for example as described above for R A 6 , C 1 -C 4 -alkoxy-, arylalkyl- or C.
  • 3 -C-Cycloalkylrest for example as described above for R L 14 , a branched or unbranched, optionally substituted -0-CO-C ⁇ -C 4 alkyl residue, which is from the group -O-CO- and for example from those mentioned above -C-C 4 -alkyl radicals or an optionally substituted -O-alkylene-aryl, -O-CO-aryl, -O-CO-alkylene-aryl or -O-CO-allyl radical which consists of the groups -0 - or -O-CO- and composed for example of the corresponding radicals described above for R G 1 .
  • both radicals R A 6 and R A 7 together can form an optionally substituted, unsaturated or aromatic heterocycle which, in addition to the ring nitrogen, can contain up to two further different or identical heteroatoms 0, N, S.
  • Ci-Cg-alkyl radical or an optionally substituted aryl, arylalkyl, hetaryl or C 3 -C 7 cycloalkyl radical are each independently of one another, for example , radicals described above for R A 14 are understood, preferably methyl or trifluoromethyl.
  • radicals described above for R A 14 are understood, preferably methyl or trifluoromethyl.
  • a remainder CO-0-R A 14 , 0-R A 14 , SR A 14 , S0 2 -NR A 15 RA 16 , NR A 15 RA 16 or CO-NR A 15 R A 16 are each for R A 9 or R A 10 independently of one another, for example, the corresponding radicals described above for R A 13 understood.
  • both radicals R A 9 and R A 10 together in structural element I A 14 can be a 5- to 7-membered saturated, unsaturated or aromatic carbocycle or heterocycle which can contain up to three different or identical heteroatoms 0, N, S and, if appropriate is substituted with up to three identical or different radicals.
  • Ci-Cg-alkyl radical or an optionally substituted aryl, arylalkyl, hetaryl, C 3 -C 7 cycloalkyl radical or a radical CO-O-RA 14 , 0-R A 14 , SR A 14 , NRA 15 R A 16 , S0 2 -NR A 15 RA 16 or CO-NR A 15 R A 16 are understood for R A 11, for example, the corresponding radicals described above for R A 9 .
  • both radicals R A 9 and R A 17 together can form a 5- to 7-membered saturated, unsaturated or aromatic heterocycle which, in addition to the ring nitrogen, contain up to three different or identical heteroatoms 0, N, S can and optionally substituted with up to three identical or different radicals.
  • Ci-Cg-alkyl Under a branched or unbranched, optionally substituted Ci-Cg-alkyl, C 2 -Cg-alkenyl, C 2 -Cg-alkynyl, -C-C 3 alkylene -CC-C 4 alkoxy, mono- and bis -Alkylaminoalkylene or acylaminoalkylene or an optionally substituted aryl, heterocycloalkyl, heterocycloalkenyl, hetaryl, C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene C 3 -C 7 cycloalkyl, arylalkyl, C ⁇ -C alkylene heterocycloalkyl, -C-C 4 alkylene heterocycloalkenyl or hetarylalkyl, or a residue -S0 2 -R G 4 , -CO-ORG 4 , -C0-NR G RQ 4 * or -CO-
  • C-halogen such as C-F, C-Cl, C-Br or C-I or a branched or unbranched, optionally substitute
  • C 1 -C 4 -alkyl radical which is composed of a carbon radical and, for example, a C 1 -C 4 -alkyl radical described above for R A 6 , or a branched or unbranched, optionally substituted C 1 -C 4 -alkoxy radical , which consists of a carbon residue and, for example, one for
  • Z 5 means oxygen, sulfur or a radical NR A 8 .
  • Preferred structural elements A are composed of at least one preferred radical of the radicals belonging to structural element A, while the remaining radicals are widely variable.
  • Particularly preferred structural elements A are composed of the preferred residues of structural element A.
  • spacer structural element E understood a structural element that 2 -C 3 radical of a branched or unbranched, optionally substituted and heteroatom-containing aliphatic C o ⁇ hydrocarbons and / or membered 20-a 4- to optionally substituted and containing heteroatoms, aliphatic or aromatic mono- or polycyclic hydrocarbon radical.
  • the spacer structural element E is a structural element of the formula I E
  • R E 2 is independently hydrogen, a branched or unbranched, optionally substituted C ⁇ -C6 alkyl, C ⁇ -C 6 alkoxyalkyl, C 2 -C 6 alkenyl,
  • RE 3 , RE 4 , R E 5, R E 6, RE , R E 8 f R -, 9, R-.10 independently of one another hydrogen, halogen, a hydroxy group, a branched or unbranched, optionally substituted Ci-Cg-alkyl -, C 2 -Cg-alkenyl, C 2 -C 6 ⁇ alkynyl or alkylene-cycloalkyl radical, a radical - (CH 2 ) x - (Y E ) z R E 1: 1 , an optionally substituted C 3 -C 7 cycloalkyl, aryl, arylalkyl, hetaryl or hetarylalkyl radical or, independently of one another, two radicals R E 3 and R E 4 or R E 5 and R E 6 or R E 7 and R E 8 or R E 9 and R E 10 together form a 3- to 7-membered, optionally substituted, saturated or unsaturated carbo- or heterocycle which can contain up
  • R y 2 'R y 2 * independently of one another are hydrogen, a branched or unbranched, optionally substituted Ci-Cg-alkyl-, C 2 -Cg-alkynyl, C 2 -Cg-alkenyl, CO-C 6 -alkyl, CO-0-C 1 -C 6 -alkyl or S0-C 1 -C 6 -alkyl radical or an optionally substituted hetaryl, hetarylalkyl, arylalkyl, C 3 -C 7 -cycloalkyl-, CO -O-alkylene-aryl, CO-alkylene-aryl, CO-aryl, S0 2 -aryl, CO-hetaryl or S0 2 -alkylene-aryl radical,
  • RE 11 is hydrogen, a hydroxyl group, CN, halogen, a branched or unbranched, optionally substituted C 1 -C 6 -alkyl radical, an optionally substituted C 3 -C 7 cycloalkyl, aryl, heteroaryl or arylalkyl radical, one optionally with C 1 -C 4 -Alkyl or aryl-substituted C 2 -Cg-alkynyl or C-Cg-alkenyl radical, an optionally substituted Cg-C ⁇ 2 bicycloalkyl, Ci-Cg alkylene-Cg-C ⁇ -bicycloalkyl-, C 7 -C 2 o- Tricycloalkyl- or -CC-alkylene-C7-co-tricycloalkyl radical, or a 3- to 8-membered, saturated or unsaturated heterocycle substituted with up to three identical or different radicals, which has up to three different or identical heteroatoms 0, ⁇ ,
  • R E 12 is hydrogen, a branched or unbranched, optionally substituted Ci-Cg-alkyl, C 2 -Cg alkenyl, C 2 -Cg alkynyl, an optionally substituted C 3 -C 7 cycloalkyl, hetaryl -, Arylalkyl- or hetarylalkyl radical or a radical CO-R E 16 , COOR E 16 or S0 2 -R E 16 ,
  • R E 13 , R E 14 independently of one another hydrogen, a hydroxyl group, a branched or unbranched, if appropriate substituted Ci-Cg-alkyl, C ⁇ ⁇ C 4 alkoxy, C 2 -Cg -alkenyl, C 2 -Cg-alkynyl or alkylene-cycloalkyl or an optionally substituted C 3 -C 7 cycloalkyl, Aryl, arylalkyl, hetaryl or hetarylalkyl radical,
  • R E 15 is hydrogen, a branched or unbranched, optionally substituted Ci-Cg-alkyl, C 2 -Cg-alkenyl, C 2 -Cg-alkynyl or alkylene-cycloalkyl radical or an optionally substituted CC 7 -cycloalkyl, aryl- , Arylalkyl, hetaryl or hetarylalkyl radical,
  • R E 16 is hydrogen, a hydroxy group, a branched or unbranched, optionally substituted Ci-Cg-alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or -C-C 5 alkylene -CC 4 -alkoxy, or an optionally substituted aryl, heterocycloalkyl, heterocycloalkenyl, hetaryl, C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, arylalkyl, C ⁇ - C 4 alkylene-C 3 -C 7 heterocycloalkyl-, -C-C 4 alkylene-CC 7 heterocycloalkenyl or hetarylalkyl radical and
  • Q E is an optionally substituted 4- to 11-membered mono- or polycyclic, aliphatic or aromatic hydrocarbon which can contain up to 6 double bonds and up to 6 identical or different heteroatoms selected from the group N, 0 or S, the ring carbons or ring nitrogen may optionally be substituted,
  • U E in structural element E means oxygen, sulfur or NR E 2 , with sulfur or NR E 2 being preferred and NR E 2 being particularly preferred.
  • the coefficients h and i are independently 0 or 1.
  • the coefficient i is 1.
  • Ci-Cg-alkyl, Ci-Cg-alkoxyalkyl, C 2 -Cg alkenyl, C 2 -C ⁇ 2 alkynyl or arylalkyl radical or an optionally substituted aryl, hetaryl or C 3 -C 7 cycloalkyl for R ⁇ and R E 2 in structural element E are understood independently of one another, for example, the corresponding radicals described above for R L 14 .
  • S0-alkylene-aryl, S0-hetaryl or S0 2 -alkylene-hetaryl for R E 1 and R E 2 are composed independently of one another, for example, from the corresponding groups CO, COO, CONH or S0 and the corresponding radicals mentioned above.
  • Preferred radicals for R B 1 or R E 2 are independently hydrogen, a branched or unbranched, optionally substituted Ci-Cg-alkyl, Ci-Cg-alkoxy, C -Cg-alkenyl, C-C ⁇ -alkynyl or Arylalkyl radical, or an optionally substituted hetaryl or C 3 -C 7 cycloalkyl radical.
  • radicals for R E or R E 2 are hydrogen, methyl, cyclopropyl, allyl or propargyl.
  • k2, k4 or k6 can be 0 or 1 and kl, k3, k5 or k7 can be 0, 1 or 2.
  • Ci-Cg-alkyl under a branched or unbranched, optionally substituted Ci-Cg-alkyl, C 2 -Cg-alkenyl, C 2 -Cg-alkynyl or alkylene-cycloalkyl radical or an optionally substituted C 3 -C 7 -cycloalkyl, aryl, Arylalkyl, hetaryl or hetarylalkyl radicals for R E 3 , R E 4 , R E 5 , R E 6 , R E 7 , R E 8 , R E 9 or R E 10 independently of one another are, for example, the corresponding ones, above for L 1 understood residues mentioned.
  • each independently of one another two radicals R E 3 and R E 4 or R E 5 and R E 6 or R E 7 and R E 8 or R E 9 and R E 10 together form a 3- to 7-membered, optionally substituted, saturated or unsaturated carbo- or heterocycle, which can contain up to three heteroatoms from the group 0, N or S, form.
  • the rest - (CH 2 ) X - (Y E ) ⁇ -R E 11 is composed of a Co-C4-alkylene radical, optionally a binding element Y E selected from the group -CO-, -CO-N (R y 2 ) -, -N (R y 2 ) -CO-, -N (R y 2 ) -CO-N (R y 2 *) -, -N (R y 2 ) -CO-O-,
  • R y 2 and R y 2 * independently of one another are hydrogen, a branched or unbranched, optionally substituted Ci-Cg-alkyl, C 2 -Cg-alkenyl, C-Cg-alkynyl, CO-Ci-Cg-alkyl, CO-0-C 6 -alkyl or S0 2 -C-Cg-alkyl radical or an optionally substituted hetaryl, hetarylalkyl, arylalkyl, C 3 -C 7 -cycloalkyl-, CO-O-alkylene- aryl-, CO- Alkylene-aryl, CO-aryl, S0 2 -aryl, CO-hetaryl or S0 2 -alkylene-aryl radical, preferably independently of one another hydrogen, methyl, cyclopropyl, allyl, propargyl, and
  • Hydrogen a hydroxyl group, CN, halogen, a branched or unbranched, optionally substituted Ci-Cg-alkyl radical, an optionally substituted C 3 -C 7 cycloalkyl, aryl, heteroaryl or arylalkyl radical, one optionally with C 1 -C 4 alkyl or aryl substituted C 2 -Cg alkynyl or C 2 -Cg alkenyl, an optionally substituted Cg-C ⁇ -bi- cycloalkyl-, C ⁇ -Cg-alkylene-Cg-C ⁇ 2 -Bicycloalkyl-, C 7 -C 2 o -Tricycloalkyl- or -CC-alkylene-C 7 -C 2 o-tricycloalkyl radical, or a substituted with up to three identical or different radicals, 3- to 8-membered, saturated or unsaturated heterocycle, which is up to three different or can contain the same heteroatoms 0,
  • R E n and R y 2 or R y 2 * together can form a saturated or unsaturated C 3 ⁇ C 7 heterocycle which can optionally contain up to two further heteroatoms selected from the group 0, S or N.
  • N-pyrrolidinyl N- Piperidinyl, N-hexahydroazepinyl, N-morpholinyl or N-pipe
  • R E 3 , R E 4 , R E 5 , R E 6 , R E 7 , R E 8 , R E 9 or R E 10 are independently hydrogen, a branched or unbranched, optionally substituted Ci-Cg- Alkyl radical, optionally substituted aryl or the radical - (CH) X - (Y E ) Z -R E 11 -
  • a radical of R E 3 and R E 4 or R E 5 and R E 6 or R E 7 and R E 8 or R E 9 and R E ⁇ ° denotes hydrogen or methyl.
  • R E 9 or R E 10 independently of one another are hydrogen or methyl.
  • R E 12 denotes hydrogen, a branched or unbranched, optionally substituted Ci-Cg-alkyl, C 2 -Cg alkenyl or C 2 -Cg alkynyl radical or an optionally substituted C 3 -C 7 cycloalkyl, hetaryl, Arylalkyl or hetarylalkyl radical, such as described above for R 1 or a radical CO-R E 16 , COOR E 16 or S0 2 -R E 16 , preferably hydrogen, methyl, allyl, propargyl and cyclopropyl.
  • Ci-Cg-alkyl, C 2 -Cg-alkenyl or C 2 -Cg-alkynyl radical or an optionally substituted C 3 -C 7 cycloalkyl, aryl, Arylalkyl, hetaryl or hetarlyalkyl radical, for R E 13 , R E 14 or R E 15 , are understood independently of one another, for example, the corresponding radicals described above for R L 1 .
  • a branched or unbranched, optionally substituted C 1 -C 4 -alkoxy radical for R E 13 or R E 14 is understood independently of one another, for example, the C 1 -C 4 -alkoxy radicals described above for R A 14 .
  • Preferred alkylene-cycloalkyl radicals for R E 13 , R E 14 or R E i5 independently of one another are, for example, the C 1 -C 4 -alkylene-CC 7 cycloalkyl radicals described above for R L 1 .
  • Ci-Cg-alkyl C 2 -Cg alkenyl, C 2 -Cg alkynyl or
  • the ring carbons or Ring nitrogen may optionally be substituted for Q E, preferably optionally substituted arylene, such as, for example, optionally substituted phenylene or naphthylene, optionally substituted hetarylene such as, for example, the radicals
  • the remnants can be installed in both orientations.
  • Z 6 and Z 7 independently of one another represent CH or nitrogen.
  • Z 8 means oxygen, sulfur or NH
  • Z 9 means oxygen, sulfur or NR E 19 .
  • rl, r2, r3 and t are independently 0, 1, 2 or 3
  • s and u are independently 0, 1 or 2.
  • Q E particularly preferably denotes optionally substituted phenylene, a radical
  • R E 17 and R E 18 independently of one another are hydrogen, -N0 2, -NH 2 , -CN, -COOH, a hydroxyl group, halogen is a branched or unbranched, optionally substituted Ci-Cg-alkyl, -C-C 4 alkoxy -, C 2 -Cg alkenyl, C 2 -Cg alkynyl or alkylene cycloalkyl or an optionally substituted C 3 -C 7 cycloalkyl, aryl, arylalkyl, hetaryl or hetarylalkyl, as in each case above described.
  • R E 19 independently of one another is hydrogen, a branched or unbranched, optionally substituted Ci-Cg-alkyl, Ci-Cg-alkoxyalkyl, C 3 -C ⁇ 2 alkynyl, CO-C ⁇ -C 6 alkyl, CO-O -Ci-Cg-alkyl or S0 2 -C ⁇ -Cg-alkyl radical or an optionally substituted C 3 -C 7 cycloalkyl, aryl, arylalkyl, CO-O-alkylene-aryl, CO-alkylene-aryl, CO-aryl, S0 2 -aryl, hetaryl, CO-hetaryl or S0-alkylene-aryl radical, preferably hydrogen or a branched or unbranched, optionally substituted Ci-Cg-alkyl radical.
  • Preferred structural elements E are composed of at least one preferred radical of the radicals belonging to structural element E, while the remaining radicals are widely variable.
  • Particularly preferred structural elements E are composed of the preferred residues of structural element E.
  • Preferred structural elements B are composed either of the preferred structural element A, while E is widely variable, or of the preferred structural element E, while A is widely variable.
  • the compounds of the formula I and also the intermediates for their preparation can have one or more asymmetrically substituted carbon atoms.
  • the compounds can exist as pure enantiomers or pure diastereomers or as a mixture thereof.
  • the use of an enantiomerically pure compound as the active ingredient is preferred.
  • the compounds of the formula I can also be in the form of physiologically tolerable salts.
  • the compounds of formula I can also be used as prodrugs in one
  • one of the three structural elements B, G or L has the preferred range, while the remaining structural elements are widely variable.
  • two of the three structural elements B, G or L each have the preferred range, while the remaining structural elements are widely variable.
  • Preferred compounds of the formula I have, for example, the preferred structural element G, while the structural elements B and L are widely variable.
  • npip-pyma2-eoco-anger 619 n2py-dimephmem-ocho-zdapee 620 2py-am3-oem-np ⁇ dap 671 bras-25thiz-men-glyzdap

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Abstract

L'invention concerne de nouveaux composés qui se lient à des récepteurs d'intégrine, leur préparation, leur utilisation comme ligands de récepteurs d'intégrine et pour traiter des affections. L'invention concerne également des compositions médicamenteuses contenant lesdits composés, ainsi que des compositions médicamenteuses contenant au moins un autre composé actif.
EP00920612A 1999-04-13 2000-03-29 Pyrimidine-2-one derives comme ligands de recepteurs d'integrine Withdrawn EP1171435A2 (fr)

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DE19916719 1999-04-13
DE19916719A DE19916719A1 (de) 1999-04-13 1999-04-13 Neue ECE-Inhibitoren, ihre Herstellung und Verwendung
DE1999162998 DE19962998A1 (de) 1999-12-24 1999-12-24 Integrinrezeptorliganden
DE19962998 1999-12-24
PCT/EP2000/002746 WO2000061551A2 (fr) 1999-04-13 2000-03-29 Ligands de recepteurs d'integrine

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DE10108995A1 (de) * 2001-02-23 2002-09-05 Abbott Gmbh & Co Kg Substituierte Pyrimidinon-Derivate als Liganden von Integrinrezeptoren
WO2002068409A1 (fr) 2001-02-23 2002-09-06 Merck & Co., Inc. Antagonistes nmda/nr2b nonaryl-heterocycliques n-substitues
US20030171368A1 (en) * 2002-02-06 2003-09-11 Werner Seitz Pyrimidinonesulfamoylureas`
GB0322552D0 (en) 2003-09-26 2003-10-29 Astrazeneca Uk Ltd Therapeutic treatment
KR100759130B1 (ko) * 2005-02-12 2007-09-19 휴메드 주식회사 항 인테그린 항체 코팅스텐트 및 그의 제조방법
ZA200805192B (en) 2005-12-29 2009-11-25 Lexicon Pharmaceuticals Inc Multicyclic amino acid derivatives and methods of their use
UY30892A1 (es) * 2007-02-07 2008-09-02 Smithkline Beckman Corp Inhibidores de la actividad akt
JP2012516344A (ja) * 2009-01-30 2012-07-19 グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー 結晶質ｎ−｛（１ｓ）−２−アミノ−１−［（３−フルオロフェニル）メチル］エチル｝−５−クロロ−４−（４−クロロ−１−メチル−１ｈ−ピラゾール−５−イル）−２−チオフェンカルボキサミド塩酸塩
US10285998B1 (en) 2018-04-04 2019-05-14 The Menopause Method, Inc. Composition and method to aid in hormone replacement therapy
US11925643B2 (en) 2018-05-23 2024-03-12 Mor Research Applications Ltd. Toll-like receptor 4 (TLR4) inhibitors and use thereof
CN111493034B (zh) * 2020-05-08 2021-12-21 安徽宏飞钓具有限公司 一种耐油污的发光型仿生鱼饵

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996040685A1 (fr) * 1995-06-07 1996-12-19 Perseptive Biosystems, Inc. Synthons ameliores pour la synthese et la deprotection d'acides nucleiques peptidiques dans des conditions douces
EP0761681A2 (fr) * 1995-09-04 1997-03-12 Hoechst Aktiengesellschaft Procédé de préparation de dérivés de substitués de N-éthylglycine
EP0863150A1 (fr) * 1997-02-08 1998-09-09 Boehringer Mannheim Gmbh Procédé pour la préparation d'une substance liant des acides nucléiques
US5849893A (en) * 1993-09-13 1998-12-15 Bayer Aktiengesellschaft Nucleic acid-binding oligomers possessing C-branching for therapy and diagnostics

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK0710657T3 (da) 1994-11-02 1999-05-25 Merck Patent Gmbh Adhæsionsreceptor-antagonister
DE19516483A1 (de) 1995-05-05 1996-11-07 Merck Patent Gmbh Adhäsionsrezeptor-Antagonisten
DE19548709A1 (de) 1995-12-23 1997-07-03 Merck Patent Gmbh Tyrosinderivate
ES2185009T3 (es) 1996-04-10 2003-04-16 Merck & Co Inc Antagonistas de alfa y beta 3'.
JP2000516575A (ja) 1996-06-28 2000-12-12 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング インテグリンインヒビターとしてのフェニルアラニン誘導体
WO1998008840A1 (fr) 1996-08-29 1998-03-05 Merck & Co., Inc. Antagonistes de l'integrine
AU717283B2 (en) * 1996-10-30 2000-03-23 Merck & Co., Inc. Integrin antagonists
DE19705450A1 (de) 1997-02-13 1998-08-20 Merck Patent Gmbh Bicyclische aromatische Aminosäuren
IT1290447B1 (it) * 1997-03-28 1998-12-03 Zambon Spa Derivati 1,3-ossatiolanici ad attivita' antivirale
ATE299023T1 (de) 1997-12-17 2005-07-15 Merck & Co Inc Integrinrezeptor antagonisten
SI1040111T1 (en) 1997-12-17 2005-10-31 Merck & Co., Inc. Integrin receptor antagonists
EP1105377B1 (fr) 1998-08-21 2003-10-08 SmithKline Beecham plc Derives de pyrimidinone destines au traitement de l'atherosclerose

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5849893A (en) * 1993-09-13 1998-12-15 Bayer Aktiengesellschaft Nucleic acid-binding oligomers possessing C-branching for therapy and diagnostics
WO1996040685A1 (fr) * 1995-06-07 1996-12-19 Perseptive Biosystems, Inc. Synthons ameliores pour la synthese et la deprotection d'acides nucleiques peptidiques dans des conditions douces
EP0761681A2 (fr) * 1995-09-04 1997-03-12 Hoechst Aktiengesellschaft Procédé de préparation de dérivés de substitués de N-éthylglycine
EP0863150A1 (fr) * 1997-02-08 1998-09-09 Boehringer Mannheim Gmbh Procédé pour la préparation d'une substance liant des acides nucléiques

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, vol. 82, 1975, Columbus, Ohio, US; abstract no. 327 *
CHEMICAL ABSTRACTS, vol. 90, 1979, Columbus, Ohio, US; abstract no. 147604 *
DOEL ET AL., TETRAHEDRON, vol. 30, - 1974, pages 2755 - 2759 *
ZECHEL ET AL., BIOORG.MED.CHEM.LETT., no. 12, 2002, pages 165 - 169 *

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SK14102001A3 (sk) 2002-07-02
CA2368049A1 (fr) 2000-10-19
AU4112900A (en) 2000-11-14
BR0009739A (pt) 2002-04-09
PL351279A1 (en) 2003-04-07
JP3936844B2 (ja) 2007-06-27
IL145773A0 (en) 2002-07-25
HUP0203338A2 (hu) 2003-03-28
BG105979A (bg) 2002-06-28
KR20010108499A (ko) 2001-12-07
WO2000061551A2 (fr) 2000-10-19
NO20014961L (no) 2001-11-07
US7125883B1 (en) 2006-10-24
CN1353706A (zh) 2002-06-12
WO2000061551A3 (fr) 2000-12-28
MXPA01010232A (es) 2002-03-27
JP2002541243A (ja) 2002-12-03
NO20014961D0 (no) 2001-10-12
TR200102944T2 (tr) 2002-08-21
CZ20013678A3 (cs) 2002-07-17

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