Journal ArticleDOI
Pyrazole derivatives. 5. Synthesis and antineoplastic activity of 3-(2-chloroethyl)-3,4-dihydro-4-oxopyrazolo[5,1-d]-1,2,3, 5-tetrazine-8-carboxamide and related compounds.
TLDR
Biological evaluation of two pyrazolotetrazine derivatives synthesized as the analogous prodrugs of the light-sensitive antineoplastic agents dacarbazine and BIC revealed that the compound containing a 2-chloroethyl function demonstrated good antineopolastic activity in experimental animals, but the one containing a methyl function was inactive.Abstract:
Two pyrazolotetrazine derivatives were synthesized as the analogous prodrugs of the light-sensitive antineoplastic agents dacarbazine and BIC. Both the pyrazole derivatives are stable under ordinary light illumination. Biological evaluation of these pyrazoles revealed that the compound containing a 2-chloroethyl function (6a) demonstrated good antineoplastic activity in experimental animals, but the one containing a methyl function (6b) was inactive. The inactivity of compound 6b may suggest that compound 6a and related imidazotetrazines may simply act as biological alkylating agents per se rather than as prodrugs. The information could also imply that the postulated dealkylation mechanism for the triazene derivatives should be reexamined.read more
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Antitumor imidazotetrazines. 32. Synthesis of novel imidazotetrazinones and related bicyclic heterocycles to probe the mode of action of the antitumor drug temozolomide.
A. S. Clark,B. Deans,Malcolm F. G. Stevens,M. J. Tisdale,Richard T. Wheelhouse,Brian J. Denny,John A. Hartley +6 more
TL;DR: No experimental evidence has been found to support the hypothesis that such regions are involved in catalyzing the ring opening of the imidazotetrazinone prodrugs to their active forms, and these compounds have no inhibitory properties against human GM892A or Raji cell lines in vitro.
Journal ArticleDOI
Antinociceptive effect of novel trihalomethyl-substituted pyrazoline methyl esters in formalin and hot-plate tests in mice.
Julie Milano,Sara Marchesan Oliveira,Mateus Fortes Rossato,Patricia D. Sauzem,Pablo Machado,Paulo Beck,Nilo Zanatta,Marcos A. P. Martins,Carlos Fernando Mello,Maribel Antonello Rubin,Juliano Ferreira,Helio G. Bonacorso +11 more
TL;DR: Results demonstrate that these novel pyrazoline methyl esters tested may be promising prototypes of additional mild analgesics.
Journal ArticleDOI
Recent Progress on Pyrazole Scaffold-Based Antimycobacterial Agents
TL;DR: The possible structure–activity relationship of pyrazole analogs for designing better antituberculosis (anti‐TB) agents has been discussed and is helpful for new thoughts in the quest for rational designs of more active and less toxic pyrazoles‐based anti‐TB drugs.
Journal ArticleDOI
The medicinal chemistry of imidazotetrazine prodrugs.
TL;DR: The somewhat unusual chemical reactivity of the imidazotetrazine class of compounds is explored, probing their mechanisms of reaction, examining which attributes are required for an active drug molecule and reviewing the use of this combined knowledge towards the development of new and improved anti-cancer agents.
Journal ArticleDOI
Antinociceptive effect of 3-(4-fluorophenyl)-5-trifluoromethyl-1H-1-tosylpyrazole. A Celecoxib structural analog in models of pathological pain.
Sara Marchesan Oliveira,Cássia Regina Silva,Alexandre P. Wentz,Gisele R. Paim,Michele S. Correa,Helio G. Bonacorso,Arthur da Silveira Prudente,Michel Fleith Otuki,Juliano Ferreira +8 more
TL;DR: FTosPz is an interesting prototype for the development of novel analgesic drugs because it produced antinociceptive effects without altering the locomotor activity of animals and altered AST/ALT enzyme activity nor the urea/creatinine levels.