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At least 325 records · Page 18Linked to original sources
PubMed1996

Synthesis and trazodone-like analgesic activity of 4-phenyl-6-aryl-2-[3-(4-arylpiperazin-1-yl)propyl]pyridazin -3-ones.

A series of 4,6-diaryl pyridazinones, chemically related to trazodone, ws synthesized and evaluated for analgesic activity. With ED50 values ranging from 8.4 to 46.7 mg kg(-1) i.p. in the phenylbenzoquinone-induced writhing test (PBQ test), most compounds were several times more potent than acetaminophen (ED50 = 231.3 mg kg(-1) i.p.) and noramidopyrine (ED50 = 68.5 mg kg(-1) i.p.). A multiple linear regression analysis demonstrated a correlation between antinociceptive activity and lipophilicity, as well as electronic and steric factors. The most active pyridazinones 2c and 2j exhibited minimal sedative and neurotoxic effects at the dose of 25 mg kg(-1) i.p. They were devoid of activity in the hot plate test and their analgesic activity was not significantly reversed by naloxone in the PBQ test. The antinociceptive response induced by morphine (0.15 mg kg(-1) s.c.) in the PBQ test was greatly potentiated by 2c and 2j administered at the low doses of 1 and 2.5 mg kg(-1) i.p., respectively. On the other hand, their analgesic effects were enhanced synergistically by 5-hydroxytryptophan combined with carbidopa. All these data imply that a significant part of the antinociceptive effect induced by 2c and 2j may involve both opioid and serotonergic pathways. In addition, these two pyridazinones did not exhibit any antidepressant properties in the forced swimming test, nor did they potentiate yohimbine-induced toxicity.

5-Hydroxytryptophan↗
PubMed1997

Pyridazines. XIII. Synthesis of 6-aryl-5-oxygenated substituted-3(2H)-pyridazinones and evaluation as platelet aggregation inhibitors.

Several 6-aryl-5-oxygenated substituted pyridazinones have been synthesized and evaluated in vitro for inhibition of platelet aggregation induced by adenosine 5'-diphosphate (ADP), thrombin and collagen. All the tested compounds (except 8 and 9) inhibited platelet aggregation in a dose-dependent manner. The IC50 of the most active substance, compound 2b, was around 60 microM against ADP and collagen as inducers. The inhibition of platelet aggregation caused by test compounds was dependent on the level of oxidation of the function at the 5-position, with the order of IC50 values being R-OH (2a, b, 5) < R-CHO (6, 7) < < R-COOH (8, 9). None of the tested compounds increased the intracellular levels of cAMP, indicating a lack of inhibitory activity on cAMP phosphodiesterase (PDE III) in intact cells. These results suggest that the group present at the 5 position of 6-aryl-5-substituted pyridazinones determines the platelet aggregation-inhibitory activity, and that a mechanism other than PDE inhibition is responsible for this effect.

Adenosine Diphosphate↗
PubMed2002

Synthesis and cytotoxic activities of pyrrole[2,3-d]pyridazin-4-one derivatives.

1-Methyl-2-phenyl (1) and 1,3-dimethyl-2-phenyl (2)-substituted pyrrole[2,3-d]pyridazinones, as well as their tetracyclic analogues 3-6, were synthesized and evaluated in vitro by the National Cancer Institute against 60 human tumor cell lines derived from nine cancer cell types. Biological results showed that the antitumor activities of these compounds were related to the planarity of their ring systems with potency increasing in the order 2<4 congruent with 5<6<3. Among them, the most potent compound 3 showed significant cell line cytotoxicity, particularly against the renal cancer subpanel [GI(50) (microM) 5.07] and displayed significant potency [GI(50) (microM) 3.04-4.32] against MOLT-4, SR (leukemia), NCI-H460 (non-small cell lung), HCT-116 (colon), and SF-295 (CNS) cancer cells, respectively.

Antineoplastic Agents↗
PubMed1990

[Studies on the synthesis of condensed pyridazine derivatives. I. Synthesis and benzodiazepine receptor binding studies of 2-substituted-4,4a,5,6-tetrahydrobenzo[h]cinnolin-3(2H)-ones and related compounds].

A series of 2-substituted-4,4a,5,6-tetrahydrobenzo[h]cinnolin-3(2H)-ones and related compounds were synthesized and tested for their ability to displace [3H]diazepam from rat brain membranes. Among them, compounds bearing 4-methoxyphenyl, 4-chlorophenyl, or 4-methylphenyl group at the position-2 were found to have high affinity to the benzodiazepine receptor. 2-(4-Methoxyphenyl)-9-methyl- and 2-(4-methoxyphenyl)-9-methoxy-4,4a,5,6-tetrahydrobenzo[h]cinnolin- 3(2H)-ones (8b-14 and 8b-15, respectively) showed a potent affinity comparable to that of diazepam. These results suggest that a topographical planarity or pseudoplanarity of these molecules is essential for high affinity to the benzodiazepine receptor. The structure-activity relationships are discussed.

Animals↗