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Synthesis, biological evaluation, and structure-activity relationship of clonazepam, meclonazepam, and 1,4-benzodiazepine compounds with schistosomicidal activity.
- Source :
-
Chemical biology & drug design [Chem Biol Drug Des] 2012 Jun; Vol. 79 (6), pp. 943-9. Date of Electronic Publication: 2012 Mar 19. - Publication Year :
- 2012
-
Abstract
- The inherent morbidity and mortality caused by schistosomiasis is a serious public health problem in developing countries. Praziquantel is the only drug in therapeutic use, leading to a permanent risk of parasite resistance. In search for new schistosomicidal drugs, meclonazepam, the 3-methyl-derivative of clonazepam, is still considered an interesting lead-candidate because it has a proven schistosomicidal effect in humans but adverse effects on the central nervous system did not allow its clinical use. Herein, the synthesis, in vitro biological evaluation, and molecular modeling of clonazepam, meclonazepam, and analogues are reported to establish the first structure-activity relationship for schistosomicidal benzodiazepines. Our findings indicate that the amide moiety [N(1) H-C(2) (=O)] is the principal pharmacophoric unit of 1,4-benzodiazepine schistosomicidal compounds and that substitution on the amide nitrogen atom (N(1) position) is not tolerated.<br /> (© 2012 John Wiley & Sons A/S.)
- Subjects :
- Animals
Benzodiazepines chemical synthesis
Benzodiazepines pharmacology
Benzodiazepinones chemical synthesis
Benzodiazepinones pharmacology
Clonazepam chemical synthesis
Clonazepam pharmacology
Humans
Models, Molecular
Schistosoma drug effects
Schistosomiasis parasitology
Schistosomiasis pathology
Schistosomicides chemistry
Schistosomicides pharmacology
Structure-Activity Relationship
Benzodiazepines chemistry
Benzodiazepinones chemistry
Clonazepam chemistry
Schistosomicides chemical synthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1747-0285
- Volume :
- 79
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Chemical biology & drug design
- Publication Type :
- Academic Journal
- Accession number :
- 22321778
- Full Text :
- https://doi.org/10.1111/j.1747-0285.2012.01354.x