75884-68-3Relevant academic research and scientific papers
[4,5]-fused-3,6-disubstituted-pyridazines with sulfur-containing substituents in position three for the treatment of neoplasia
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, (2008/06/13)
[4,5]-Fused-3,6 disubstituted-pydidazines of Formula I are useful for inducing or promoting apoptosis and for arresting uncontrolled neoplastic cell proliferation, and are specifically useful in the arresting and treatment of neoplasia: wherein Y1and Y2are independently selected from the group consisting of (CH2)n,—C(X)—NH—,—(CH2)n—C(X)—O—, and X is O or S; R1is selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, and substituted or unsubstituted phenyl, pyridinyl, and the like; R2is selected from the group consisting of substituted or unsubstituted phenyl, benzyl, pyridinyl, and the like; “A” is a benzene ring fused with the pyridazine ring; and R3is independently selected in each instance form the group consisting of halogen, lower alkyl, and the like.
Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. 1. 2-[2-(1-imidazolyl)alkyl]- 1(2H)-phthalazinones
Yamaguchi,Kamei,Koga,Akima,Kuroki,Ohi
, p. 4052 - 4060 (2007/10/02)
A number of 4-substituted 2-[ω-(1-imidazolyl)alkyl]-1(2H)-phthalazinones were synthesized in order to develop agents possessing both thromboxane A2 synthetase inhibitory and bronchodilatory activities. The pharmacological evaluation of these compounds disclosed that they have both activities to various extents. Both activities were slightly dependent on the length of the 2-substituents and largely affected by the nature of the 4-substituents. Compounds bearing phenyl and thienyl groups exhibited relatively high and well-rounded activities. Among these compounds, 12j and 15f were found to be the most effective agents having well-rounded activities in vitro and in vivo. Introduction of a carboxyl group reduced both activities contrary to our expectation. 4-(3-Pyridyl)phthalazinone 18b was of particular interest because of unexpectedly high in vivo activities in spite of an absence of significant in vitro activities.
Novel Antiasthmatic Agents with Dual Activities of Thromboxane A2 Synthetase Inhibition and Bronchodilation. 2. 4-(3-Pyridyl)-1(2H)-phthalazinones
Yamaguchi, Masahisa,Kamei, Kenshi,Koga, Takaki,Akima, Michitaka,Maruyama, Akinori,et al.
, p. 4061 - 4068 (2007/10/02)
A series of novel 4-(3-pyridyl)-1(2H)-phthalazinone derivatives which possess dual activities of thromboxane A2 (TXA2) synthetase inhibition and bronchodilation was synthesized, and their pharmacological activities were evaluated.While the length and the bulk of 2-alkyl substituents had no influence on either activity, the 2-substituents with polar groups reduced bronchodilatory activity.Furthermore, we introduced heteroaromatic nuclei into the 4-position of the phthalazinone and found that 1-imidazolyl (13a) and 5-thiazolyl (16b and 16c) derivatives were as active as the parent 3-pyridyl compound 5b.These findings suggest that heteroaromatic nuclei at the 4-position of phthalazinones play a critical role in TXA2 synthetase inhibition.Additionally, the hydrophobicity of the compounds was found to exert a marked influence on bronchodilatory activity.These observations led to the selection of 2-ethyl-4-(3-pyridyl)-1(2H)-phthalazinone (5b) (KK-505) and 2-methyl-4-(5-thiazolyl)-1(2H)-phthalazinone (16b) (KK-562) for further studies.Although their precise mechanism of action remains unclear, this series of novel phthalazinone derivatives represents a new class of antiasthma agents with dual activities.
