• Biomolecules & Therapeutics
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• 제8권1호
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• pp.1-12
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• 2000

Although the first pyridazine was obtained in 1886, this heterocycle was not thoroughly investigated such isomers as pyrimidine and pyrazine especially in the field of drug development because pyridazine derivatives do not occur as natural products. Recently medicinal chemists have an growing interest in the pyridazine derivatives, since many Pyridazine derivatives were found to possess various potential therapeutic activities. In this paper sixty-eight pyridazine derivatives, which are already introduced as medicines or are being developed as drugs were classified according to their pharmacological activities, reviewed since 1955 and the relationship of structure-activities was discussed.

• Bulletin of the Korean Chemical Society
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• 제23권12호
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• pp.1715-1718
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• 2002

Treatment of ethyl 5-hydroxy-3,4-diphenylthieno[2,3-c]pyridazine-6-carboxylate (1a) with hydrazine hydrate in ethanol gave the carbohydrazide 2,. Some derivatives of the latter compound have been synthesized. Also, 6-acetyl-3,4-diphenyl-5-hydroxythieno[2.3-c]pyridazine (1b) was subjected to some reactions to produce other new thienopyridazine derivatives.

• Archives of Pharmacal Research
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• 제15권3호
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• pp.224-228
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• 1992

Arylhydrazones of diethylacetondicarboxylate 3 was treated with formaldehyde to give 1 aryl-4, 5, 6-trihydropyridaine derivatives 4a-f Cyclization of compound 4a-f by hydroxylamine afforded [3, 4d] 1, 3, 4, 5-tetrahydropyridazine derivatives 5a-f. Also cyclization of compound 4c with semicarbazide gave 1-amidopyrazolo-5-one-1-aryl-3-carboxypyridazine 6. On the other hand compounds 3 reacted with ethylorthoformate to give diethyl-1, 4-dihydro-1-arylpyridazine-4one-2.5 dicarboxylate 7, which on treatment with hydrazine. Semicarbazide and thiosemicarbazide gave pyridazine, amido and thioamido derivatives. The spectral and antimicrobial data of these compounds 1-8 were studied.

• Archives of Pharmacal Research
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• 제16권2호
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• pp.164-167
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• 1993

Arylhydrazones of diethyl acetonedicarboxylate 3 was treated with fomaldehyde to 1-aryl-1, 4, 5, 6-tetrahyeheypyridazine derivatives 4a-f Cyclization of compound 4a-f by hydroxy-lamine afforded [3, 4-d] 1, 4, 5, 6-tetrahydropyridazine derivative 5a-f. Also, cyclization of compound 4c with semicarbazide gave pyrazolote [4, 3-c] pyridazine 6. On the other hand compound 3 reacted with ethylothofomate to give diethyl-1, 4-dihydro-1-arypyridazine-4-one-3, 5 dicaboxylate 7, which on treatment with hydrazine, semicarbazide and thiosemicarbazide gave pyridazine, amido and thioamido derivatives. The spectrl and antimicrobial data of these compounds 1-8 were studied.

• 약학회지
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• 제46권2호
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• pp.89-92
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• 2002

Allylthio group of the sulfur compounds of garlic oil plays an important role for prevention and treatment of hepatic diseases induced by toxic substances or carbon tetrachloride. Thus allylthio group as pharmacologically active group was introduced into pyridazine heterocycle ring. Aryloxyallylthiopyridazine derivatives were synthesized and their hepatoprotective activities were screened in rat. The activities of these compounds were weaker than alkoxyallylthiopyridazine derivatives, which exhibit a superior hepatoprotective effect.

• Archives of Pharmacal Research
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• 제14권4호
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• pp.379-384
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• 1991

The Knoevenagal reaction of malononitrile and acetylacetone gave the acyclic product 3 which was separated in a good yield and identified. The reactivity of 3 towards some chemical reagents is studied. Thus, the reaction of 3 with aromatic aldehydes, hydrazines and cyanomethylene derivatives gave products 6-12. Reaction of 3 with benzenediazonium chloride gave the primidine derivative 14.

• Archives of Pharmacal Research
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• 제13권2호
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• pp.198-200
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• 1990

3, 4-Diphenyl-5-cyanopyridazin-6-one 3 was prepared from the reaction of cyano acetamide 2 with benzihydrazone in dry pyridine. A series of its derivatives was prepard. Tolyl and benene sulphonyl derivatives 6a and 6b are also prepared. 3, 4-Diphenyl-5-cyanopyridazin-6-thione 5 was obtained from 3 by the action of $P_2S_5$ while 3, 4 diphenyl-5-cyano 6-chloropyridazine 4 was obtained from 3 by the action POCl$_3$. The reaction of 4 with hydrazine hydrate directly afforded the pyrazolopyridazine derivative 7. Compound 4 also reacted with phenylhydrazine, aniline, thiophenol and anthranilic acid to yield pyridazine derivatives 8, 9, 10 and 11, respectively. On treatment of compound 11 with acetic anhydride it cyclised to afford pyridazino pyrimidine derivatives 12.

• Bulletin of the Korean Chemical Society
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• 제32권7호
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• pp.2428-2432
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• 2011

A series of new 4-aryl-6,8-dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-diones have been synthesized via three component reaction of 1,3-dimethylbarbituric acid with arylglyoxals in the presence of hydrazinium dihydrochloride in ethanol. All of these derivatives may act as potential monoamine oxidase inhibitors.

• Archives of Pharmacal Research
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• 제28권4호
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• pp.391-394
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• 2005

The allylthio group of allicin and other organosulfur compounds, isolated from garlic, is considered a pharmacophore, and a key structure component of the molecule, which affords biological activities. In the foregoing studies, various 3-alkoxy-6-allylthiopyridazine derivatives (K­compounds) were synthesized, and their biological activities tested in animals. As expected, the various derivatives showed good hepatoprotective activities on carbon tetrachloride-treated mice and aflatoxin B1-treated rats, and chemopreventive activities on hepatocarcinoma cells in rats. Other new pyridazine derivatives, with the oxygen atom at the 3-position of the 3-alkoxy­6-allylthiopyridazine displaced by sulfur (S), were synthesized, and their activities tested in vitro. Thio-K6, one of the sulfur-substituted compounds, showed better chemopreventive activity toward hepatocarcinoma cells.

• Bulletin of the Korean Chemical Society
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• 제24권8호
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• pp.1181-1187
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• 2003

Condensation of 4-cyano-5,6-dimethyl-3-pyridazinone 1 with aromatic aldehydes gave the novel styryl derivatives 2a-c. Refluxing of compound 2a with phosphorus oxychloride furnished 3-chloropyridazine derivative 3. Compound 3 was reacted with thiourea and produced pyridazine-3(2H)thione 4. Thieno[2,3-c]- pyridazines 5a-e were achieved by cycloalkylation of compound 4 with halocompounds in methanol under reflux and in the presence of sodium methoxide. Also, refluxing of compound 4 with N-substituted chloroacetamide in the presence of potassium carbonate afforded thienopyridazines 6a-e. Cyclization of compound 6 with some electrophilic reagents as carbon disulfide and triethyl orthoformate furnished the novel pyrimido[4',5':4,5]thieno[2,3-c]pyridazines 12 and 13a-c, respectively. Diazotisation of compound 6 with sodium nitrite in acetic acid produced the pyridazino[4',3':4,5]thieno[3,2-d][1,2,3]triazines 14a-c. Ternary condensation of compound 1, aromatic aldehydes and malononitrile in ethanol containing piperidine under reflux afforded the novel phthalazines 16a-c. Compound 3 was subjected to some nucleophilic substitution reactions with amines and sodium azide and formed the aminopyridazines 17a, b and tetrazolo[1,5-b]-pyridazine 19, respectively. The structures of the synthesized compounds were established by elemental and spectral analyses.