GRID/CPCA: A new computational tool to design selective ligands

Journal of Medicinal Chemistry

Volumn 43, Issue 16, 2000, Pages 3033-3044

  Kastenholz, M A ^a   Pastor, M ^b   Cruciani, G ^b   Haaksma, E E J ^a   Fox, T ^a  

^a BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

^b UNIVERSITY OF PERUGIA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

2 [4 [(1 ACETIMIDOYL 3 PYRROLIDINYL)OXY]PHENYL] 3 (7 AMIDINO 2 NAPHTHYL)PROPIONIC ACID; BENZAMIDINE; BLOOD CLOTTING FACTOR 10A; BLOOD CLOTTING FACTOR 10A INHIBITOR; FX 2212A; PARACETAMOL; PIPERIDINE DERIVATIVE; THROMBIN; TRYPSIN; UNCLASSIFIED DRUG;

ARTICLE; CHEMOMETRICS; DRUG STRUCTURE; PRINCIPAL COMPONENT ANALYSIS; PROTEIN STRUCTURE; STRUCTURE ACTIVITY RELATION; THREE DIMENSIONAL IMAGING;

ALGORITHMS; BINDING SITES; DRUG DESIGN; FACTOR XA; LIGANDS; MODELS, MOLECULAR; STRUCTURE-ACTIVITY RELATIONSHIP; THROMBIN; TRYPSIN;

EID: 0034632795     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm000934y     Document Type: Article

References (60)

1. A critical review of recent CoMFA applications
2. A search for specificity in DNA-drug interactions
3. A novel strategy for improving ligand selectivity in receptor-based drug design
4. Affinity and selectivity of matrix metalloproteinase inhibitors: A chemometrical study from the perspective of ligands and proteins
5. Chemometric rationalization of the structural and physico-chemical basis for selective cyclooxygenase-2 inhibition: Toward more specific ligands
6. A computational procedure for determining energetically favorable binding sites on biologically important macromolecules
7. New hydrogen-bond potentials for use in determining energetically favorable binding sites on molecules of known structure
8. Further development of hydrogen bond functions for use in determining energetically favorable binding sites on molecules of known structure. 1. Ligand probe groups with the ability to form two hydrogen bonds
9. Principal component analysis
10. The coagulation cascade: Initiation, maintenance, and regulation
11. Thrombin and factor Xa inhibitors
12. Small-molecule direct thrombin inhibitors
13. Synthetic low-molecular weight thrombin inhibitors: Molecular design and pharmacological profile
14. Synthetic inhibitors of thrombin and factor Xa: From bench to bedside
15. Molecular recognition of protein-ligand complexes: Applications to drug design
16. Highly selective mechanism-based thrombin inhibitors: Structures of thrombin and trypsin inhibited with rigid peptidyl aldehydes
17. A player of many parts: The spotlight falls on thrombin's structure
18. Synthesis and structure-activity relationships of potent thrombin inhibitors: Piperazides of 3-amidinophenylalanine
19. Comparative molecular field analysis and energy interaction studies of thrombin-inhibitor complexes
20. Crystal structures of factor Xa specific inhibitors in complex with trypsin: Structural grounds for inhibition of factor Xa and selectivity against thrombin
21. Design and structure-activity relationships of potent and selective inhibitors of blood coagulation factor Xa
22. Rational design and synthesis of novel, potent bis-phenylamidine carboxylate factor Xa inhibitors
23. Structural basis for chemical inhibition of human blood coagulation factor Xa
24. DX 9065A, a novel, synthetic, selective and orally active inhibitor of factor Xa: In vitro and in vivo studies
25. Dibasic (amidinoaryl)propanoic acid derivatives as novel blood coagulation factor Xa inhibitors
26. Design and synthesis of potent and highly selective thrombin inhibitors
27. X-ray structure of active site-inhibited clotting factor Xa. Implications for drug design and substrate recognition
28. Three-dimensional quantitative structure-activity relationship analyses using comparative molecular field analysis and comparative molecular similarity indices analysis to elucidate selectivity differences of inhibitors binding to trypsin, thrombin, and factor Xa
29. Hierarchical multiblock PLS and PC models for easier model interpretation and as an alternative to variable selection
30. Analysis of multiblock and hierarchical PCA and PLS models
31. Discovery of a novel, selective, and orally bioavailable class of thrombin inhibitors incorporating aminopyridyl moieties at the P1 position
32. L-374,087, an efficacious, orally bioavailable, pyridinone acetamide thrombin inhibitor
33. Molecular design and characterization of an a-thrombin inhibitor containing a novel P1 moiety
34. 1-Aminoisoquinoline as benzamidine isostere in the design and synthesis of orally active thrombin inhibitors
35. Selective inhibition of thrombin by (2R,4R)-4-methyl-1-[N2-[1,2,3,4-tetrahydro-8-quinolinyl)sulfonyl] -L-arginyl]-2-piperidinecarboxylic acid
36. Structural and functional analyses of benzamidine-based inhibitors in complex with trypsin: Implications for the inhibition of factor Xa, tPA, and urokinase
37. Structural analysis of thrombin complexed with potent inhibitors incorporating a phenyl group as a peptide mimetic and aminopyridines as guanidine substitutes
38. Rational design, synthesis, and X-ray structure of selective noncovalent thrombin inhibitors
39. Structure of human Des(1-45) factor Xa at 2.2 Å resolution
40. Factor Xa inhibitors by classical and combinatorial chemistry
41. Design, synthesis, and activity of 2,6-diphenoxypyridine-derived factor Xa inhibitors
42. Design of benzamidine-type inhibitors of factor Xa
43. Synthesis, SAR and in vivo activity of novel thienopyridine sulfonamide pyrrolidinones as factor Xa inhibitors
44. Sulfonamidopyrrolidinone factor Xa inhibitors: Potency and selectivity enhancements via P-1 and P-4 optimization
45. Structure-based design of potent, amidine-derived inhibitors of factor Xa: Evaluation of selectivity, anticoagulant activity, and antithrombotic activity
46. A novel factor Xa inhibitor: Structure-activity relationships and selectivity between factor Xa and thrombin
47. Synthesis, characterization, and structure-activity relationships of amidine-substituted (bis)benzylidene-cycloketone olefin isomers as potent and selective factor Xa inhibitors
48. Proposed cation-π mediated binding by factor Xa: A novel enzymatic mechanism for molecular recognition
49. Contribution of lysine 60f to S1' specificity of thrombin
50. Bound structures of novel P3-P1' β-strand mimetic inhibitors of thrombin
51. Bovine thrombin complexed with an uncleavable analogue of residues 7-19 of fibrinogen Aα: Geometry of the catalytic triad and interactions of the P1', P2', and P3' substrate residues