- Synthesis and antitumor activity of novel pyridazinone derivatives containing 1,3,4-thiadiazole moiety
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A series of novel pyridazinone derivatives containing the 1,3,4-thiadiazole moiety were synthesized and characterized by 1H NMR, 13C NMR, spectroscopies HRMS and IR. Among them, the structure of compound 5c (2-(Tert-butyl)?4-chloro-5-((5-((2-ethylphenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One) was unambiguously confirmed via single crystal X-ray diffraction analysis. The inhibitory activity of all the target compounds against MGC-803 and Bcap-37 was determined by MTT assay, with doxorubicin (the inhibition rates were 95.5 ± 0.4% and 95.7 ± 1.0% respectively) as a control. The preliminary results showed that the inhibitory activity of compound 5n (2-(Tert-butyl)?4-chloro-5-((5-((3-fluorophenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One) was superior to the others. The inhibition rates of MGC-803 and Bcap-37 cells were 86.3 ± 2.2% and 92.3 ± 0.6% at a concentration of 10 μmol/L, respectively. The preliminary structure-activity relationship showed that when the 2-position of the benzene ring was substituted by a methyl group, such as compound 5j (2-(Tert-butyl)?4-chloro-5-((5-((2,3-dimethylphenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), it exhibited good anticancer activity on MGC-803 cells. Besides, introducing fluorine, chlorine, or trifluoromethyl group onto the benzene ring, such as compound 5 m (2-(Tert-butyl)?4-chloro-5-((5-((4-(trifluoromethoxy)phenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), displayed good anticancer activity on MGC-803 and Bcap-37 cells.
- Qin, Junhu,Zhu, Mei,Zhu, Hongmei,Zhang, Liqiong,Fu, Yihong,Liu, Jiamin,Wang, Zhenchao,OuYang, Guiping
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p. 592 - 599
(2020/03/16)
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- Design, synthesis, and bioactivities of novel pyridazinone derivatives containing 2-phenylthiazole or oxazole skeletons
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A series of novel pyridazinone derivatives were designed and synthesized by replacing 4-(tert-butyl)phenyl moiety of pyridaben with 2-phenylthiazole or oxazole fragments via activity substructure connecting approach. The structures of all target compounds were characterized through NMR, MS, and elemental analysis. Bioassay results exhibit that most compounds showed potent bioactivities against Aphis fabae, Tetranychus urticae, Erysiphe graminis, and/or Puccinia polysora. Among the newly synthesized compounds, 2-(tert-butyl)-4-chloro-5-(((2-phenylthiazol-4-yl)methyl)thio)pyridazin-3(2H)-one (12b) displays remarkable insecticidal activity against A fabae. Its LC50 value (2.73 mg/L) is better than that of pyridaben (5.46 mg/L), although inferior to that of imidacloprid (0.51 mg/L). In addition to its extraordinary insecticidal activity, compound 12b also exerts 96.9% fungicidal activities against P polysora at 500 mg/L in vivo, significantly superior to that of pyridaben (50.0%), while slightly lower than that of tebuconazole (100%). This article discusses the synthesis, bioassay results, and structure-activity relationship of this series of novel pyridazinone derivatives.
- Dang, Mingming,Liu, Minhua,Huang, Lu,Ou, Xiaoming,Long, Chuyun,Liu, Xingping,Ren, Yeguo,Zhang, Ping,Huang, Mingzhi,Liu, Aiping
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p. 4088 - 4098
(2020/10/02)
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- DIAGNOSTIC AGENT FOR THERAPEUTIC EFFECT ON CANCER
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The present invention provides a diagnostic agent for a therapeutic effect on cancer, containing a compound represented by formula (1-0). (In formula (1-0), R represents —O(CH2)n—, —O(CH2)nOC2H4—, —CH2O(CH2)n—, or —CH2O(CH2)nOC2H4—, n represents an integer of 1 to 5, and Q1 represents F or —OCH3.)
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Paragraph 0071; 0072; 0073; 0074
(2016/09/26)
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- COMPOUND SUITABLE FOR DETECTION OF MITOCHONDRIAL COMPLEX-1
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Provided is a compound represented by formula (1-0): wherein in formula (1-0), R represents —O(CH2)n—, —O(CH2)nOC2H4—, —CH2O(CH2)n— or —CH2O(CHs
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Paragraph 0059; 0060; 0062
(2015/09/22)
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- METHODS AND APPARATUS FOR SYNTHESIZING IMAGING AGENTS, AND INTERMEDIATES THEREOF
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The present invention generally relates to methods and system for the synthesis of imaging agents, and precursors thereof. The methods may exhibit improved yields and may allow for the large-scale synthesis of imaging agents, including imaging agents comp
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Page/Page column 151
(2011/09/14)
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- Preparation and biodistribution of [18F]FP2OP as myocardial perfusion imaging agent for positron emission tomography
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Myocardial extractions of pyridaben, a mitochondrial complex I (MC-I) inhibitor, is well correlated with blood flow. Based on the synthesis and characterization of pyridaben analogue 2-tert-butyl-5-[2-(2-[18F]fluroethoxy)ethoxy]benzyloxy]-4-chloro-2H-pyridazin-3-one ([18F]FP2OP), this study assessed its potential to be developed as myocardial perfusion imaging (MPI) agent. Methods: The tosylate labeling precursor 2-(2-(4-(tert-butyl-5-chloro-6-oxo-1,6-dihydro-pyridazin-4-yloxymethyl)benzyloxy)ethoxy)ethyl ester (OTs-P2OP) and the nonradioactive 2-tert-butyl-5-[2-(2-[19F]fluroethoxy)ethoxy]benzyloxy]-4-chloro-2H-pyridazin-3-one ([19F]FP2OP) were synthesized and characterized by IR, 1H NMR, 13C NMR and MS analysis. By substituting tosyl of precursor OTs-P2OP with 18F, the radiolabeled complex [18F]FP2OP was prepared and further evaluated for its in vitro physicochemical properties, in vivo biodistribution, the metabolic stability in mice, ex vivo autoradiography and cardiac PET/CT imaging. Results: Starting with [18F]F- Kryptofix 2.2.2./K2CO3 solution, the total reaction time for [18F]FP2OP was about 100 min, with final high-performance liquid chromatography purification included. Typical decay-corrected radiochemical yield stayed at 41 ± 5.3%, the radiochemical purity, 98% or more. Biodistribution in mice showed that the heart uptake of [18F]FP2OP was 41.90 ± 4.52%ID/g at 2 min post-injection time, when the ratio of heart/liver, heart/lung and heart/blood reached 6.83, 9.49 and 35.74, respectively. Lipophilic molecule was further produced by metabolized [18F]FP2OP in blood and urine at 30 min. Ex vivo autoradiography demonstrates that [18F]FP2OP may have high affinity with MC-I and that can be blocked by [19F]FP2OP or rotenone (a known MC-I inhibitor). Cardiac PET images were obtained in a Chinese mini-swine at 5, 15, 30 and 60 min post-injection time with high quality. Conclusion: [18F]FP2OP was synthesized with high radiochemical yield. The promising biological properties of [18F]FP2OP suggest high potential as MPI agent for positron emission tomography in the future.
- Mou, Tiantian,Jing, Huihui,Yang, Wenjiang,Fang, Wei,Peng, Cheng,Guo, Feng,Zhang, Xianzhong,Pang, Yan,Ma, Yunchuan
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experimental part
p. 1312 - 1320
(2010/05/02)
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- Contrast agents for myocardial perfusion imaging
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The present disclosure is directed, in part, to compounds and methods for imaging myocardial perfusion, comprising administering to a patient a contrast agent which comprises a compound that binds MC-1, and an imaging moiety, and scanning the patient using diagnostic imaging.
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Page/Page column 50
(2010/02/13)
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- Prostaglandin endoperoxide H synthase biosynthesis inhibitors
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The present invention describes pyridazinone compounds of formula I which are cyclooxygenase (COX) inhibitors, and in particular, are selective inhibitors of cyclooxygenase-2 (COX-2). COX-2 is the inducible isoform associated with inflammation, as opposed to the constitutive isoform, cyclooxygenase-1 (COX-1) which is an important “housekeeping” enzyme in many tissues, including the gastrointestinal (GI) tract and the kidneys. The selectivity of these compounds for COX-2 minimizes the unwanted GI and renal side-effects seen with currently marketed non-steroidal anti-inflammatory drugs (NSAIDs).
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- Photoaffinity radioligand for NADH:ubiquinone oxidoreductase: [S- C3H2] (Trifluoromethyl)diazirinyl-pyridaben
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Pyridaben is a new and very potent insecticide and miticide that acts by inhibiting the activity of NADH:ubiquinone oxidoreductase (the most complex of all the respiratory enzymes). The binding site, presumed to be the same as that of rotenone and fenazaq
- Latli, Bachir,Morimoto, Hiromi,Williams, Philip G.,Casida, John E.
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p. 191 - 199
(2007/10/03)
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