2166-00-9Relevant academic research and scientific papers
Annulation Reaction of in Situ Generated Azoalkenes with Azlactones: Access to 4,5-Dihydropyridazin-3(2 H)-Ones
Yuan, Wei-Cheng,Quan, Bao-Xue,Zhao, Jian-Qiang,You, Yong,Wang, Zhen-Hua,Zhou, Ming-Qiang
, p. 11812 - 11821 (2020)
An unprecedented [4 + 2] annulation reaction between in situ formed azoalkenes and azlactones has been developed. This reaction provides a facile access to an array of 4,5-dihydropyridazin-3(2H)-one derivatives, which are very promising in medicinal applications as potential biologically active candidates. Notably, these dihydropyridazinones could also be synthesized via a one-pot reaction protocol by using the in situ formed azlactones from N-Acyl amino acids and in situ generated azoalkenes from α-halogeno hydrazones. The potential applications of the methodology were also demonstrated by gram-scale experiments and the versatile conversions of the products into other nitrogen-containing compounds.
Design, synthesis and investigation of new diphenyl substituted pyridazinone derivatives as both cholinesterase and Aβ-aggregation inhibitors
Kilic, Burcu,Erdogan, Merve,Gulcan, Hayrettin O.,Aksakal, Fatma,Oruklu, Nihan,Bagriacik, Emin U.,Dogruer, Deniz S.
, p. 59 - 76 (2019/06/11)
Background: With respect to the increase in the average life expectancy, Alzheimer Disease (AD), the most common form of age-related dementia, has become a major threat to the population over the age of 65 during the past several decades. The majority of AD treatments are focused on cholinergic and amyloid hypotheses. Objective: In this study, three series of diphenyl-2-(2-(4-substitutedpiperazin-1-yl)ethyl)pyridazin- 3(2H)-one derivatives were designed, synthesized and investigated for their ability to inhibit both cholinesterase enzymes and amyloid-β aggregation. Method: The inhibitory activities of the synthesized compounds on AChE (from electric eel) and BChE (from equine serum) were determined by the modified Ellman’s method. The reported thioflavin T-based fluorometric assay was performed to investigate the effect of the selected compounds on the aggregation of Aβ1-42. The cytotoxic effect of the compounds (4g, 11g and 18g) was monitored in 3T3 cell lines to gain insight into therapeutic potential of the compounds by using MTT assay. The crystal structures of the AChE (1EVE) and BChE (1P0I) enzymes were retrieved from the RCSB Protein Data Bank and Molecular Operating Environment (MOE) software was used for molecular docking of the ligands. Results: Among the tested compounds, 5,6-diphenyl derivative 18g was identified as the most potent and selective AChE inhibitor (IC50 = 1.75 μM, Selectivity Index for AChE > 22.857). 4,6- Diphenyl derivative 11g showed the highest and the most selectivity for BChE (IC50= 4.97 μM, SI for AChE 0.124). Interestingly, 4,5-diphenyl derivative 4g presented dual cholinesterase inhibition (AChE IC50= 5.11 μM; BChE IC50= 14.16 μM, SI for AChE = 2.771). Conclusion: Based on biological activity results and low toxicity of the compounds, it can be said that diphenyl substituted pyridazinone core is a valuable scaffold. Especially, dual inhibitory potencies of 4,5-diphenylpyridazin-3(2H)-one core for the cholinesterase enzymes and Aβ- aggregation makes this core a promising disease-modifying agent.
Organocatalyzed Formal [4+2] Cycloaddition of in situ Generated Azoalkenes with Arylacetic Acids: An Efficient Approach to the Synthesis of 4,5-Dihydropyridazin-3(2H)-ones
Li, Xuanyi,Gai, Kuo,Yuan, Zhenbo,Wu, Jie,Lin, Aijun,Yao, Hequan
, p. 3479 - 3484 (2016/01/25)
An unprecedented [4+2] cycloaddition of in situ generated azoalkenes with arylacetic acids has been developed under the catalysis of isothiourea. The reaction provided an efficient approach to the synthesis of 4,5-dihydropyridazin-3(2H)-one derivatives in moderate to good yields (up to 95%).
FORMULATIONS CONTAINING PYRIDAZINE COMPOUNDS
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Page/Page column 29, (2010/01/31)
The invention relates to chemical compounds, compositions and methods of making and using the same. In particular, the invention provides selected pyridazine compounds of the formula I are independently hydrogen, hydroxyl, alkyl, alkenyl, alkynyl, alkylene, alkenylene, alkoxy, alkenyloxy, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkoxy, aryl, aryloxy, arylalkoxy, aroyl, heteroaryl, heterocyclic, acyl, acyloxy, amino, imino, azido, thiol, thioalkyl, thioalkoxy, thioaryl, nitro, cyano, halo, sulfate, sulfenyl, sulfinyl, sulfonyl, sulfonate, sulfoxide, silyl, silyloxy, silylalkyl, silylthio, ═O, ═S, phosphonate, ureido, carboxyl, carbonyl, carbamoyl, or carboxamide; and X is optionally substituted pyrimidinyl or pyridazinyl, an isomer, a pharmaceutically acceptable salt, or derivative thereof. The invention additional relates to compositions comprising the compounds, and methods of using the compounds and compositions for modulation of cellular pathways, for treatment or prevention of inflammatory diseases, for research, drug screening, and therapeutic applications.
COMPOSITIONS AND TREATMENTS USING PYRIDAZINE COMPOUNDS AND SECRETASES
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, (2010/11/29)
The invention relates to compositions, conjugates and methods comprising pyridazine compounds and secretase inhibitors for modulation of cellular pathways (e.g., signal transduction pathways), for treatment or prevention of inflammatory diseases (e.g., Alzheimer's disease), for research, drug screening, and therapeutic applications.
COMPOSITIONS AND TREATMENTS USING PYRIDAZINE COMPOUNDS AND CHOLINESTERASE INHIBITORS
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Page/Page column 93; 7/13, (2008/06/13)
The invention relates to compositions, conjugates and methods comprising pyridazine compounds and cholinesterase inhibitors for modulation of cellular pathways (e.g., signal transduction pathways), for treatment or prevention of inflammatory diseases (e.g., Alzheimer's disease), for research, drug screening, and therapeutic applications.
COMPOSITIONS AND TREATMENTS FOR DEMYELINATING DISEASES AND PAIN DISORDERS
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Page/Page column 73-74; 7/13, (2008/06/13)
The invention relates to compositions and methods for treating patients with Demyelinating Diseases and Conditions including Multiple Sclerosis, Spinal Cord Injury, Traumatic Brain Injury and Stroke. The compositions and methods may also be used for Stroke Rehabilitation and the treatment of pain disorders including Neuropathic Pain and Chemokine-Induced Pain. The compositions comprise one or more pyridazine compounds having a pyridazinyl radical pendant with an aryl or substituted aryl, a heteroaryl or substituted heteroaryl.
3,4,6-Substituted pyridazines for treating neuropathic pain and associated syndromes
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Page/Page column 17, (2008/06/13)
The present invention is directed to the use of 3,4,6-substituted pyridazines such as those characterized by structure I for treating conditions such as neuropathic pain among others.
Microwave assisted synthesis of 4,6-diarylpyridazin-3(2H)-ones in solid state
Meenakshi,Ramamoorthy,Muthusubramanian,Sivasubramanian
, p. 645 - 651 (2007/10/03)
Microwave assisted synthesis of dihydropyridazin-3(2H)-ones and the subsequent dehydrogenation using selenium dioxide are described.
A New Synthetic Route to 4,6-Diarylpyridazinones and Some of their Derivatives
Coudert, P.,Couquelet, J.,Tronche, P.
, p. 799 - 802 (2007/10/02)
A novel approach to the titled ring system starting from conveniently available chalcones 1 is proposed.It involves a catalysed exchange of hydrogen cyanide between acetone cyanohydrin and 1.The resulting γ-ketonitriles 2 give the expected 4,6-diarylpyrid
