Synthesis and structure-activity relationship study of potent trypanocidal thio semicarbazone inhibitors of the trypanosomal cysteine protease cruzain

Journal of Medicinal Chemistry

Volumn 45, Issue 13, 2002, Pages 2695-2707

  Du, Xiaohui ^a   Guo, Chun ^a   Hansell, Elizabeth ^b   Doyle, Patricia S ^b   Caffrey, Conor R ^b   Holler, Tod P ^c   McKerrow, James H ^a,b   Cohen, Fred E ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 (3 BROMOPHENYL) 4 METHYL 2 PYRAZOLINE 1 THIOCARBOXAMIDE; 3 (3 CHLOROPHENYL) 4 METHYL 2 PYRAZOLINE 1 THIOCARBOXAMIDE; 3 (3 TRIFLUOROMETHYLPHENYL) 4 METHYL 2 PYRAZOLINE 1 THIOCARBOXAMIDE; 3 (3,4 DICHLOROPHENYL) 2 PYRAZOLINE 1 THIOCARBOXAMIDE; 3' BROMOACETOPHENONE THIOSEMICARBAZONE; 3' BROMOPROPIOPHENONE THIOSEMICARBAZONE; 3' CHLOROPROPIOPHENONE THIOSEMICARBAZONE; 3' TRIFLUOROMETHYLPROPIOPHENONE THIOSEMICARBAZONE; 3,4 DICHLOROBENZALDEHYDE THIOSEMICARBAZONE; ANTITRYPANOSOMAL AGENT; CRUZIPAIN; THIOSEMICARBAZONE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL MODEL; ANTIPROTOZOAL ACTIVITY; ARTICLE; CATTLE; CHAGAS DISEASE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOSE TIME EFFECT RELATION; DRUG CYTOTOXICITY; DRUG DESIGN; DRUG MECHANISM; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; ENZYME INHIBITION; ENZYME INHIBITOR INTERACTION; IC 50; MAMMAL CELL; MOLECULAR MODEL; NONHUMAN; STRUCTURE ACTIVITY RELATION; TRYPANOSOMA CRUZI; TRYPANOSOMIASIS;

ANIMALS; CYSTEINE ENDOPEPTIDASES; CYSTEINE PROTEINASE INHIBITORS; MODELS, MOLECULAR; PROTOZOAN PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP; THIOSEMICARBAZONES; TRYPANOCIDAL AGENTS; TRYPANOSOMA CRUZI;

EID: 0037142343     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm010459j     Document Type: Article

References (38)

1. The proteases and pathogenicity of parasitic protozoa
2. Post-cardiac transplant reactivation of Chagas' disease diagnosed by skin biopsy
3. Tropical diseases
4. American trypanosomiasis (Chagas' disease) - A tropical disease now in the United States
5. Assessment of cytogenetic damage in Chagasic children treated with benznidazole
6. Characterization and expression of proteases during trypanosoma cruzi metacyclogenesis
7. Peptide-fluoromethyl ketones arrest intracellular replication and intercellular transmission of T. Cruzi
8. Inhibitors of the major cysteinyl proteinase (GP57/51) impair host cell invasion and arrest the intracellular development of Trypanosoma cruzi in vitro
9. Cysteine protease inhibitors cure an experimental Trypanosoma cruzi infection
10. Cysteine protease inhibitors as chemotherapy for parasitic infections
11. Cysteine proteases and their inhibitors
12. Design, synthesis and evaluation of d-homophenylalanyl epoxysuccinate inhibitors of the trypanosomal cysteine protease cruzain
13. Peptidyl vinyl sulphones: A new class of potent and selective cysteine protease inhibitors
14. Vinyl sulfone as mechanism-based cysteine protease inhibitors
15. Vinyl sulfone esters and vinyl sulfonamides: Potent, irreversible inhibitors of cysteine proteases
16. A target within the target: Probing Cruzain's P1′ site to define structural determinants for the Chagas' disease protease
17. The crystal structure of cruzain: A therapeutic target for Chagas' disease
18. Structural determinants of specificity in the cysteine protease cruzain
19. Structure-based inhibitor design by using protein models for the development of antiparasitic agents
20. Aryl ureas represent a new class of antitrypanosomal agents
21. Structure and design of potent and Selective cathepsin K inhibitors
22. Anticonculsant activity of thioureido derivatives of acetophenone semicarbazone
23. 1-Phenylcarbamoyl-2-pyrazolines: A new class of insecticides. 1. Synthesis and insecticidal properties of 3-phenyl-1-phenylcarbamoyl-2-pyrazolines
24. Critical evaluation of search algorithms for automated molecular docking and database screening
25. 4-Substituted semicarbazones of mono- and dichlorobenzaldehydes as antihypertensive agents
26. Anticonvulsant activities of 4-bromobenzaldehyde semicarbazone
27. Anticonculsant activity of thioureido derivatives of acetophenone semicarbazone
28. Anticonvulsant activities of 4-(4′-fluorophenoxy) benzaldehyde semicarbazone
29. Characterization of the anticonvulsant properties of Co 102862, a novel blocker of voltage-gated sodium channels
30. In vivo metabolism and mass balance of 4-[4-fluorophenoxy]benzaldehyde semicarbazone in rats
31. Synthesis and antitrypanosomal activity of novel 5-nitro-2-furaldehyde and 5-nitrothiophene-2-carboxaldehyde semicarbazone derivatives
32. 1,2,5-Oxadiazole N-oxide derivatives and related compounds as potential antitrypanosomal drugs: Structure-activity relationships
33. Synthesis and antitrypanosomal evaluation of E-isomers of 5-Nitro-2-furaldehyde and 5-nitrothiophene-2-carboxaldehyde semicarbazone derivatives. Structure-activity relationships
34. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings