Solid-phase synthesis of a nonpeptide RGD mimetic library: New selective αvβ3 integrin antagonists

Journal of Medicinal Chemistry

Volumn 44, Issue 12, 2001, Pages 1938-1950

  Sulyok, G A G ^a   Gibson, C ^a   Goodman, S L ^b   Holzemann G ^b   Wiesner, M ^b   Kessler, H ^a  

^a TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^b MERCK KGAA   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AMIDE; ARGINYLGLYCYLASPARTIC ACID; ASPARTIC ACID; FIBRINOGEN; GLYCINE; GUANIDINE DERIVATIVE; HETEROCYCLIC COMPOUND; INTEGRIN; INTEGRIN ANTAGONIST; LEAD; LIGAND; UNCLASSIFIED DRUG; VITRONECTIN;

ARTICLE; ASSAY; BIOAVAILABILITY; METABOLISM; MOLECULAR WEIGHT; PROTEIN IMMOBILIZATION; PROTEIN INTERACTION; SCREENING; SOLID STATE; SYNTHESIS;

AMIDINES; AMINO ACID SEQUENCE; DATABASES; FIBRINOGEN; GUANIDINES; HUMANS; LIGANDS; MOLECULAR CONFORMATION; OLIGOPEPTIDES; PEPTIDES, CYCLIC; PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX; PYRIDINES; RECEPTORS, VITRONECTIN; VITRONECTIN;

EID: 0035821594     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0004953     Document Type: Article

References (85)

1. Arg-Gly-Asp: A versatile cell recognition signal
2. Integrins: A family of cell surface receptors
3. New perspectives in cell adhesion: RGD and integrins
4. Adhesion receptors of the immune system
5. Integrins: Versatility, modulation, and signaling in cell adhesion
6. Platelet GPIIb/IIIa antagonists: The first anti-integrin receptor therapeutics
7. Combinatorial chemistry techniques applied to nonpeptide integrin antagonists
8. Structure-activity relationships of β-amino acid-containing integrin antagonists
9. Antithrombotic agents: From RGD to peptide mimetics
10. GPIIb/IIIa antagonists
11. Stereoisomeric peptide libraries and peptidomimetics for designing selective inhibitors of the αvβ3 integrin for a new cancer therapy
12. Vascular indications for integrin αv antagonists
13. The αvβ3 integrin "vitronectin receptor"
14. Molecular mimicry of integrin ligation: Therapeutic potential of arginine-glycine-aspartic acid (RGD) peptides
15. Approach to discovering novel therapeutic agents for osteoporosis based on integrin receptor blockade
16. A peptidomimetic antagonist of the alpha-v beta-3 integrin inhibits bone resorption in vitro and prevents osteoporosis in vivo
17. A peptidomimetic antagonist of the integrin alpha-v beta-3 inhibits leyding cell tumor growth and the development of hypercalcemia of malignancy
18. Inhibition of integrin function by a cyclic RGD-containing peptide prevents neointima formation
19. Inhibition of neointimal hyperplasia by blocking αvβ3 integrin with a small peptide antagonist GpenGRGDSPCA
20. Cyclic RGD peptides ameliorate ischemic acute renal failure in rats
21. Subcutaneous injection of a cyclic peptide antagonist of vitronectin receptor-type integrins inhibits retinal neovascularization
22. Involvement of integrines αvβ3 in ocular neovascular diseases
23. Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels
24. Integrins, angiogenesis and vascular cell survival
25. Involvement of integrin αvβ3 in cell adhesion, motility, and liver metastasis of murine RAW117 large cell lymphoma
26. The pharmacology of the integrins
27. Arg-Gly-Asp constrained within cyclic pentapeptides. Strong and selective inhibitors of cell adhesion to vitronectin and laminin fragment P1
28. Development of a small RGD peptide fibrinogen receptor antagonist with potent antiaggregatory activity in vitro
29. Cyclic RGD analogues as antiplatelet antithrombotics
30. Design and synthesis of sulfur-free cyclic hexapeptides which contain the RGD sequence and bind to the fibrinogen GP IIb/IIIa receptor. A conformation-based correlation between propensity for imide formation and receptor affinity
31. Design and synthesis of novel cyclic RGD-containing peptides in highly potent and selective integrin αIIbβ3 antagonists
32. Selective recognition of cyclic RGD peptides of NMR defined conformation by αIIbβ3, αvβ3, and α5β1 integrins
33. Conformationally constrained peptides and semipeptides derived from RGD as potent inhibitors of the platelet fibrinogen receptor and platelet aggregation
34. Template-constrained cyclic peptides: Design of high-affinity ligands for GPIIb/IIIa
35. Dynamic forcing, a method for evaluating activity and selectivity profiles of RGD (Arg-Gly-Asp) peptides
36. Structural and functional aspects of RGD-containing cyclic pentapeptides as highly potent and selective integrin αvβ3 antagonists
37. Synthesis and conformational studies of N-methylated cyclic RGD-peptides
38. N-methylated cyclic RGD peptides as highly active and selective αvβ3 integrin antagonists
39. Synergy between an antiangiogenic integrin alpha-v antagonist and an antibody-cytokine fusion protein eradicates spontaneous tumor metastases
40. Novel solid-phase synthesis of azapeptides and azapeptoides via fmoc-strategy and its application in the synthesis of RGD-mimetics
41. Solid-phase synthesis of a selective αvβ3 integrin antagonist library
42. A peptidomimetic antagonist of the αvβ3 integrin inhibits bone resorption in vitro and prevents osteoporosis in vivo
43. A peptidomimetic antagonist of the integrin αvβ3 inhibits leyding cell tumor growth and the development of hypercalcemia of malignancy
44. Discovery of potent nonpeptide vitronectin receptor antagonists
45. Benzimidazole derivatives as arginine mimetics in 1,4-benzodiazepine nonpeptide vitronectin receptor (αvβ3) antagonists
46. Discovery of an imidazopyridinecontaining 1,4-benzodiazepine nonpeptide vitronectin receptor (αvβ3) antagonist with efficacy in a restenosis model
47. Design, synthesis and biological evaluation of nonpeptide integrin antagonists
48. Orally bioavailable nonpeptide vitronectin receptor antagonists containing 2-aminopyridine arginine mimetics
49. Orally bioavailable nonpeptide vitronectin receptor antagonists with efficacy in an osteoporosis model
50. Rapid synthesis of RGD mimetics with isoxazoline scaffolds on solid phase: Identification of αvβ3 antagonists lead compounds
51. αvβ3 integrin binding affinity and specificity of SM256 in various species
52. Discovery of orally active nonpeptide vitronectin receptor antagonists based on a 2-benzazepine Gly-Asp mimetic
53. Isoxazolines as potent antagonists of the integrin αvβ3
54. Disubstituted indazoles as potent antagonists of the integrin αvβ3
55. RGD mimetics containing a central hydantoin scaffold: αvβ3 vs αIIbβ3 selectivity requirements
56. Azapeptides
57. Peptidomimetics-tailored enzyme inhibitors
58. Solid-phase synthesis of N, N′-unsymmetrically substituted ureas: Application to the synthesis of carbaza peptides
59. Combinatorial synthesis of small organic molecules
60. Strategy and tactics in combinatorial organic synthesis. Application to drug discovery
61. Design, synthesis, and evaluation of small-molecule libraries
62. Mixture-based synthetic combinatorial libraries
63. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings
64. Novel non-peptide fibrinogen receptor antagonists. 1. Synthesis and glycoprotein IIb-IIIa antagonistic activities of 1,3,4-trisubstituted 2-oxopiperazine derivatives incorporation side-chain functions of the RGD peptide
65. Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids
66. Solid-phase peptide synthesis
67. Synthesis of azapeptides by the Fmoc/tert-butyl/polyamide technique
68. Triphosgene: An efficient carbonylating agent for liquid and solid-phase aza-peptide synthesis
69. A solid-phase synthesis of three aza-, iminoaza- and reduced aza-peptides from the same precursor
70. The 9-fluorenylmethoxycarbonyl amino-protecting group
71. S-2-naphthylmethyl thioacetimidate hydrobromide: A new odorless reagent for the mild synthesis of substituted acetamidines
72. Solvent effects and nuclear magnetic resonance
73. Atomic physicochemical parameters for three-dimensional-structure-directed quantitative structure-activity relationships. 2. Modeling dispersive and hydrophobic interactions
74. Novel purification of vitronectin from human-plasma by heparin affinity-chromatography
75. The Arg-Gly-Asp binding domain of the vitronectin receptor
76. Platelet membrane glycoprotein IIb/IIIa - Member of a family of Arg-Gly-Asp specific adhesion receptors
77. v-integrin antibody that blocks integrin function inhibits the development of a human-melanoma in nude mice