Alexandre P. Wentz

Haloacetylated enol ethers: 12 [18]. Regiospecific synthesis and structural determination of stable 5-hydroxy-1H-pyrazolines

Abstract The regiospecific synthesis and structural elucidation by NMR spectroscopy, AM1 semiempirical MO calculations and X-ray diffraction of a novel series of twelve 3-aryl[alkyl]-5-hydroxy-5-trichloromethyl-4, 5-dihydro-1H-pyrazole-1-carboxyamides and analogous 1-thiocarboxy-amides, is reported.

A convenient method for the synthesis of 2-trichloromethyl-4-p-substituted-phenyl-3H-1,5-benzodiazepines

Abstract A convenient method to obtain a new series of 2-trichloromethyl-4-aryl-3H-1,5-benzodiazepines from the reaction of β-methoxyvinyl trichloromethyl ketones derived from acetals and o-phenylenediamine is reported.

Antinociceptive effect of 3-(4-fluorophenyl)-5-trifluoromethyl-1H-1-tosylpyrazole. A Celecoxib structural analog in models of pathological pain

Pain is the most common complaint in the medical field and the identification of novel compounds that can effectively treat painful states without causing side effects remains a major challenge in biomedical research. The aim of the present study is to investigate the antinociceptive effect of 3-(4-fluorophenyl)-5-trifluoromethyl-1H-1-tosylpyrazole (FTosPz) in models of pathological pain in mice and compare these effects with those produced by Celecoxib. FTosPz (100-500 μmol/kg) or Celecoxib (26-260 μmol/kg) was administrated orally. The administration of either FTosPz or Celecoxib reduced the hyperalgesia but not the edema or leukocyte infiltration that was caused by Complete Freunds Adjuvant (CFA), used as an arthritis model. Oral administration of both FTosPz and Celecoxib also attenuated the postoperative hyperalgesia as well as the hyperalgesia caused by partial sciatic nerve ligation, used as a neuropathic pain model. FTosPz and Celecoxib produced antinociceptive effects without altering the locomotor activity of animals. Furthermore, FTosPz neither altered AST/ALT enzyme activity nor the urea/creatinine levels. Still, the FTosPz did not alter the COX-1 and COX-2 enzyme activities. Thus, FTosPz is an interesting prototype for the development of novel analgesic drugs.

Antinociceptive Effect of a Novel Tosylpyrazole Compound in Mice

Pain is the most common complaint in the medical field and the identification of compounds that can effectively treat painful states without induction of side-effects remains a major challenge in biomedical research. The aim of the present study was to investigate the antinociceptive effect of a novel compound, 3-(4-fluorophenyl)-5-trifluoromethyl-1H-1-tosylpyrazole (compound A) in several models of pain in mice and compare with those produced by the known trifluoromethyl-containing pyrazole compound celecoxib. Compound A or celecoxib were administrated by oral (78-780 micromol/kg), intrathecal (9-22.5 nmol/site) or intracerebroventricular (9-22.5 nmol/site) routes. Oral administration of either compound A or celecoxib abolished the mechanical allodynia, but not the oedema caused by intraplantar injection of carrageenan. Similarly, compound A reduced the overt nociception, but not the oedema, produced by bradykinin or capsaicin. However, compound A (500 micromol/kg, orally) did not alter nociception nor oedema caused by intraplantar injection of prostaglandin E(2 )or glutamate, whereas celecoxib reduced only the nociception induced by the former. Moreover, oral and intrathecal administration of compound A or celecoxib also reduced the nociception induced by acetic acid. However, only celecoxib reduced the acetic acid-induced nociception when it was injected by the intracerebroventricular route. Finally, neither compound A nor celecoxib was able to produce antinociceptive effect in the tail-flick test or to alter the motor performance and the body temperature. Besides, compound A or celecoxib did not induce gastric lesion. Thus, compound A seems to be an interesting prototype for the development of novel analgesic drugs.

SYNTHESIS OF SOME N-[1-ALKYL(ARYL)- 3-OXO-4,4,4-TRICHLORO(TRIFLUORO)- 1-BUTEN-1-YL]-o-AMINOPHENOLS AND o-PHENYLENEDIAMINES AS POTENTIAL ANTICANCER AGENTS

ABSTRACT The synthesis of a novel series of N-[1-alkyl(aryl)-3-oxo-4,4,4-trichloro(trifluoro)-1-buten-1-yl]-o-aminophenols and the analogous o-phenylenediamine derivatives [X3CC(O)CH=CR(o-NHC6H4Y), where X = F, Cl; R = H, Me, Et, aryl; and Y = NH2, OH] is reported.

Molecular Structure of Heterocycles: 4# NMR Spectroscopy, X-Ray Diffraction, and Semiempirical Mo Calculations of 3-Phenyl-5-Hydroxy- 5-Trichloromethyl-4,5-Dihydro-FH-Pyrazole-1-Carboxyamide

Abstract A new series of trichloromethylated- 4, 5-dihydro-1H-pyrazoles has been studied. The molecular structure of 5-hydroxy-3-phenyl-5-trichloromethyl-4,5-dihydro-7H-pyrazole-1-carboxyamide (2), synthesized from the reaction of 4-methoxy -4-phenyl-1,1,1-trichloro-3-buten-2-one (1) with semicarbazide hydrochloride, was selected and determined by NMR spectroscopy, X-ray diffraction, and semiempirical MO calculations. Proton and carbon-13 NMR data, as one set of signals, shown that only one pair of the enanfiomers was obtained. The AM1 calculations showed that 2a (1S5S/1R5R) is the more stable enantiomers pair. The x-ray diffraction data confirmed that only the structure 2a (1S5S/1R5R) was obtained. This was explained by the existence of an intramolecular hydrogen bond between the hydroxy group at C(5) and the carbonyl group at N(1), with the formation a stable six-membered ring. Compound 2 (C11H10CI3N3O2, Mr = 320.98) crystallizes in the monoclinic space group P21/c with the unit cell dimensions a = 6.49...