347-63-7Relevant articles and documents
Synthesis and biological evaluation of new 3(2H)-pyridazinone derivatives as non-toxic anti-proliferative compounds against human colon carcinoma HCT116 cells
?z?elik, Azime Berna,?zdemir, Zeynep,Alag?z, Mehmet Abdullah,Carradori, Simone,Di Simone, Simonetta,Ferrante, Claudio,Mathew, Bijo,Orlando, Giustino,Utku, Semra,Uysal, Mehtap
, p. 1100 - 1109 (2020/04/29)
Novel 3(2H)-pyridazinone derivatives were designed, synthesised in satisfactory yields and evaluated in different experimental assays to assess their preliminary toxicity in vivo and anti-proliferative effects against HCT116 cell lines in vitro. Artemia salina lethality test provided LC50 values >100 μg/mL for all compounds. Successive assays revealed that some compounds were endowed with a promising anti-proliferative effect against HCT116 cells, alone or stimulated by serotonin as a pro-inflammatory factor in order to mimick an inflamed model in vivo of cancer cell microenvironment. Moreover, the kinurenic acid level after treatment with these newly synthesised compounds was monitored as a marker of anti-proliferation in colon carcinoma models. The IC50 values obtained for the best-in-class compounds were comparable to that of daunorubicin as a reference drug. Conversely, these compounds were not able to counteract the spontaneous migration of human cancer HCT116 cell line in the wound healing paradigm.
PYRIDAZINONE DERIVATIVE AND PDE INHIBITOR CONTAINING THE SAME AS ACTIVE INGREDIENT
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Page/Page column 171, (2010/04/25)
It is to provide a novel pyridazinone derivative represented by the following general formula (1), which is useful as a pharmaceutical and has a phosphodiesterase inhibitory action: wherein R1 represents H or C1-6 alkyl, each of R2 and R3 represents H, X, C1-6 alkoxy, Z represents O or S, and A represents AA or BB, wherein AA represents: and BB represents: wherein R4 represents H or C1-6 alkyl, and each of R5 and R6 represents C1-6 alkyl.
Synthesis and Dopaminergic Activity of Some Halogenated Mono- and Dihydroxylated 2-Aminotetralins
Weinstock, Joseph,Gaitanopoulos, Dimitri E.,Oh, Hye-Ja,Pfeiffer, Francis R.,Karash, Carole B.,et al.
, p. 1615 - 1627 (2007/10/02)
In a series of 7,8-dihydroxy-1-phenyltetrahydro-3-benzazepine dopamine receptor agonists introduction of a chloro or fluoro substituent into the 6-position increases dopaminergic potency.Also, in this series replacement of the 7-hydroxyl group with a halogen results in inversion of activity from dopamine receptor agonist to antagonist.The present study was aimed at exploring the possibility that the structure-activity observations in the 3-benzazepine series of dopaminergic agents might be extrapolated to another class of dopamine receptor agonists, the 2-aminotetralins.Thus, a series of chloro- and fluoro-substituted mono- and dihydroxylated 2-aminotetralins was prepared and evaluated for dopaminergic properties in D-1 and D-2 receptor-related tests.Introduction of a chloro substituent into the 8-position of the prototype of this series, i.e. 2-amino-6,7-dihydroxytetralin (ADTN), resulted in a compound with a high degree of selectivity for the D-1 subpopulation of dopamine receptors; it was equally or more potent than ADTN in the D-1 receptor-related tests with greatly decreased effectiveness in the tests involving D-2 receptors.A similar effect was observed with 8-fluoro-ADTN; however, the N-(4-hydroxyphenethyl)-N-propyl derivative 4g of the 8-chloro-substituted ADTN showed markered D-2 binding affinity.Conversely, introduction of a chloro substituent into the 5-position of ADTN markedly decreased D-1 receptor affinity and efficacy.This effect was not seen with the related 5-fluoro derivative, suggesting D-1 receptors are more sensitive to bulk in the 5-position of ADTN than are the D-2 receptors.Replacement of either the 6- or 7-hydroxyl groups of ADTN with a chloro or fluoro substituent, in contrast, did not parallel the response seen in the benzazepine series (i.e., the compounds uniformly demonstrated less receptor affinity and did not have dopamine receptor antagonist activity); however, the decrease in agonist potency was less marked in the case of 2-amino-6-fluoro-7-hydroxytetralins than in the chlorinated monohydroxyaminotetralins.Thus, a parallelism in structure-activity relationships in the benzazepine and aminotetralin series of dopamine receptor agonists was not observed.The differences may reflect altered modes of receptor binding in the two series.
