Design, synthesis, computational prediction, and biological evaluation of ester soft drugs as inhibitors of dihydrofolate reductase from pneumocystis carinii

Journal of Medicinal Chemistry

Volumn 44, Issue 15, 2001, Pages 2391-2402

  Graffner Nordberg, M ^a   Kolmodin, K ^a   Aqvist J ^a   Queener, S F ^b   Hallberg, A ^a  

^a UPPSALA UNIVERSITY   (Sweden)

^b INDIANA UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIPROTOZOAL AGENT; AROMATIC COMPOUND; DIHYDROFOLATE REDUCTASE INHIBITOR; PIRITREXIM; TRIMETHOPRIM; TRIMETREXATE;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG MECHANISM; DRUG STRUCTURE; ENZYME INHIBITION; ENZYME SPECIFICITY; LIPOPHILICITY; MALE; MOLECULAR DYNAMICS; NONHUMAN; PNEUMOCYSTIS CARINII; RAT;

ANIMALS; ESTERS; FOLIC ACID ANTAGONISTS; HUMANS; LIGANDS; LIVER; MALE; MODELS, MOLECULAR; PNEUMOCYSTIS; PYRIMIDINES; RATS; RATS, SPRAGUE-DAWLEY; STRUCTURE-ACTIVITY RELATIONSHIP; TETRAHYDROFOLATE DEHYDROGENASE; TRIMETREXATE;

EID: 0035913056     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm010856u     Document Type: Article

References (102)

1. Problems in the management of opportunistic infections in patients infected with human immunodeficiency virus
2. Infection in the organ transplant recipient. An overview
3. Infection prophylaxis and antiretroviral therapy in patients with HIV infection and malignancy
4. Pneumocystis carinii pneumonia: A comparison between patients with the acquired immunodeficiency syndrome and patients with other immunodeficiencies
5. Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients
6. The causes of death in patients with human immunodeficiency virus infections: A clinical and pathological study with emphasis on the role of pulmonary diseases
7. AIDS and the lung. Update 1995: 1 pneumocystis carinii pneumonia
8. Pneumocystis carinii and toxoplasma gondii infections in patients with AIDS
9. Pneumocystis carinii pneumonia
10. Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy
11. A new preadmission staging system for predicting inpatient mortality from HIV associated pneumocystis carinii pneumonia in the early ighly active antiretroviral therapy (HAART) era
12. Safety and efficiency of sulfamethoxazole and trimethoprim chemoprophylaxis for pneumocystis carinii pneumonia in AIDS
13. Adverse reactions to trimethoprim-sulfamethoxazole in patients with the aquired immunodeficiency syndrome
14. Prevention and treatment of pneumocystis pneumonia
15. Adverse cutanous reactions to trimethoprim-sulfamethoxazole in patients with the acquired immunodeficiency syndrome and pneumocystis carinii pneumonia
16. Aerosolised pentamidine as sole therapy for pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome
17. Prevention of pneumocystis carinii by inhaled pentamidine
18. Inhaled pentamidine. An overview of its pharmacological properties and a review of its therapeutic use in pneumocystis carinii pneumonia
19. Aerosolized pentamidine for prophylaxis against pneumocystis carinii pneumonia
20. A controlled study of inhaled pentamidine for primary prevention of pneumocystis carinii pneumonia
21. Pentamidine for the treatment of pneumocystis carinii pneumonia and other protozoal diseases
22. Folate antagonists. 20. Synthesis, antitumor, and antimalarial properties of trimetrexate and related 6-[(Phenylamino)methyl]-2,4-quinazolindiamines
23. Synthesis and antitumor activity of 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d]pyrimidine
24. 2,4-Diamino-5-methyl-6-[(2,4,5-trimethoxyanilino)methyl]quinazoline (TMQ), a potent non-classical folate antagonist inhibitor-I
25. Pharmacology and toxicity of a potent "Nonclassical" 2,4-diamino quinazoline folate antagonist, trimetrexate, in normal dogs
26. Biochemical and chemotherapeutic studies on 2,4-diamino6-(2,5-dimethoxybenzyl)-5-methylpyrido [2,3-d]pyrimidine (BW301U), a novel lipid-soluble inhibitor of dihydrofolate reductase
27. Phase I studies with trimetrexate: Clinical pharmacology, analytical methodology, and pharmacokinetics
28. Potent antipneumocystis and antitoxoplasma activities of piritrexim, a lipid-soluble antifolate
29. FDA approves trimetrexate as a second line therapy for pneumocystis carinii pneumonia
30. Activity of antifolates against pneumocystis carinii dihydrofolate reductase and identification of a potent new agent
31. Pneumocystis carinii dihydrofolate reductase used to screen potential antipneumocystis drugs
32. Trimetrexate for the treatment of pneumocystis carinii pneumonia in patients with the acquired immunodeficeincy syndrome
33. Trimetrexate-leucoverin dosage evaluation study for the treatment of pneumocystis carinii pneumonia
34. Salvage trial of trimetrexate-leucovorin for the treatment of cerebral toxoplasmosis
35. Piritrexim with leucovorin for the treatment of pneumocystis pneumonia (PCP) in AIDS patients
36. Soft drug design: General principles and recent applications
37. Budesonide. A preliminary review of its pharmacodynamic properties and therapeutic efficacy in asthma and rhinitis
38. Topical and systemic glucocorticoid potencies of budesonide and beclomethasone dipropionate in man
39. Synthesis and enzymatic hydrolysis of esters, constituting simple models of soft drugs
40. Preparation of carboxylic acids from aldehydes (including hydroxylated benzaldehydes) by oxidation with chlorite
41. Synthetic studies toward verrucarol. 2. Synthesis of the AB ring system
42. Model studies for the synthesis of quassinoids. 1. Construction of the BCE ring system
43. Protection and deprotection of fused 2-amino-4(3h)-pyrimidinones. Conversion of pterins and 5-deazapterins to 2,4-diamino derivatives
44. Quinazoline analogues of folic acid
45. Synthesis and antifolate activity of 5-methyl-5-deaza-analogues of aminopterin. Methotrexate, folic acid, and N-10 methyl folic acid
46. 6-substituted 2,4-diamino-5-methylpyrido[2,3-d]pyrimidines as inhibitors of dihydrofolate reductases from pneumocystis carinii and toxoplasma gondii and as antitumor agents
47. Synthesis and antifolate activity of 5-methyl-5,10-dideaza analogues of aminopterin and folic acid and an alternative synthesis of 5,10-dideazatetrahydrofolic acid, a potent inhibitor of glycinamide ribonucleotide formyltransferase
48. Synthesis of 5,10-dideazaaminopterin
49. Synthesis and antifolate evaluation of the 10-propargyl derivatives of 5-deazafolic acid, 5-deazaaminopterin, and 5-methyl-5-deazaaminopterin
50. New pathways from pteridines. Design and synthesis of a new class of potent and selective antitumor agents
51. Preparation of 6-(bromomethyl)2,4-pteridinediamine hydrobromide and its use in improved syntheses of methotrexate and related compounds
52. Synthesis and biological activites of 5-deaza analogues of aminopterin and folic acid
53. Pyridopyrimidines. 12. Synthesis of 8-deaza analogues of aminopterin and folic acid
54. Studies on analogues of classical antifolates bearing the naphthoyl group in place of the benzoyl in the side chain
55. Computational predictions of binding affinities to dihydrofolate reductase: Synthesis and biological evaluation of methotrexate analogues
56. A simple synthesis of 5,8,10-trideazaminopterin analogues
57. Antifolate and antibacterial activities of 6-substituted 2,4-diaminoquinazolines
58. Palladium-catalyzed vinylation of organic halides
59. The heck reaction as a sharpening stone of palladium catalysis
60. 10-methylfolic acid
61. Identification of highly potent and selective inhibitors of toxoplasma gondii dihydrofolate reductase
62. Structure-activity relationships of dihydrofolate reductase inhibitors
63. 2,4-diamino-5-deaza-6-substituted pyrido[2,3-d]pyrimidine antifolates as potent and selective nonclassical inhibitors of dihydrofolate reductases
64. Synthesis and evaluation of 2,4-diamino quinazoline antifolates with activity against methotrexate resistan human tumor cells
65. Chemistry and antitumor evaluation of selected classical 2,4-diaminoquinazoline analogues of folic acid
66. Ligand binding affinity prediction by linear binding free energies
67. Purification and characterization of dihydrofolate reductase form walker 256 carcinosarcoma
68. Purification and characterization of dihydrofolate reductase from methotrexate-resistant human lymphoblastoid cells
69. Inhibitors binding analysis of dihydrofolate reductases from various species
70. The mammalian carboxylesterases: From molecules to functions
71. ((Arylcarbonyl)oxy)propanolamines. 1. Novel β-blockers with ultrashort duration of action
72. Multiple forms of esterase in vertebrate blood plasma
73. Species differences in the stereoselective hydrolysis of esmolol by blood esterases
74. Species differences in hydrolysis of isocarbacyclin methyl ester (TEI-9090) by blood esterases
75. A controlled trial of aerosolized pentamidine or trimethoprimsulfamethoxazole as primary prophylaxis against pneumocystis carinii pneumonia in patients with human immunodeficiency virus infection
76. A controlled trial of trimethoprim-sulfamethoxazole or aerosolized pentamidine for secondary prophylaxis of pneumocystis carinii pneumonia in patients with the aquired immunodeficiency syndrome
77. Lipophlic antifolates as agents against opportunistic infections. 1. Agents superior to trimetrexate and piritrexim against toxoplasma gondii and pneumocystis carinii in in vitro evaluations
78. Isolation and expression of the pneumocystis carinii dihydrofolate reductase gene
79. New drug developments for opportunistic infections in immunosuppressed patients: Pneumocystis carinii
80. Specificity in structure-based drug design: Identification of a novel, selective inhibitor of pneumocystis carinii dihydrofolate reductase
81. Structure-based deisgn of selective inhibitors of dihydrofolate reductase: Synthesis and antiparasitic activity of 2,4-diaminopteridine analogues with a bridged diarylamine side
82. Structural studies on bioactive compounds. 30. Crystal structure and molecular modeling studies on the pneumocystis carinii dihydrofolate reductase cofactor complex with TAB, a highly selective antifolate
83. Activity of lipid-soluble inhibitors of dihydrofolate reductase against pneumocystis carinii in culture and in a rat model of infection
84. A fast flexible docking method using an incremental construction algorithm
85. Syntheses with nitriles. Part 46. Synthesis of alkoxymethylenemalononitriles, tetracyanoproperides, and highly substituted α-aminopyridines
86. The synthesis of 2,4,6-trisubstituted pyrido[2,3-d]pyrimidines from 2-amino-3,5dicyanopyridine
87. Reductions with raney alloy in acid solution
88. A new method for predicting binding affinity in computer-aided drug design
89. Ligand binding affinity prediction by linear interaction energy methods
90. Computational modelling of inhibitor binding to human thrombin
91. An MD program for free energy calculations and empirical valence bond simulations in biomolecular systems
92. Computation of affinity and selectivity: Binding of 2,4-diaminopteridine and 2,4-diaminoquinazoline inhibitors to dihydrofolate reductases
93. The structure of pneumocystis carinii dihydrofolate reductase to 1.9 Å resolution
94. Methotrexate-resistant variants of human dihydrofolate reductase with substitutions of leucine 22: Kinetics, crystallography, and potential as selectable markers
95. A local reaction field method for fast evaluation of long-range electrostatic interactions in molecular simulations