Pyridazines biological activity

B. Testa, Inhibition of monoamine oxidase-B by 5H-indeno[1,2-c]pyridazines Biological activities, quantitative structure-activity relationships (QSARs) and 3D-QSARs, J. Med. Chem. 38 (1995) 3874-3883. 

No natural products or their analogues are included among the pyridopyridazines, but several interesting biologically active compounds have emerged. Some l-chloro-4-hydrazino- and 4-chloro-l-hydrazino-pyrido[2,3-d]pyridazines (460) are very active hypotensives, whilst related dialkoxy compounds have anticonvulsant activity (65CPB586). 

Pyrido[2,3-d]pyridazine, 1 -chloro-4-hydrazino-biological activity, 3, 261 Pyrido[2,3-(i]pyridazine, 4-chloro-l-hydrazino-biological activity, 3, 261 Pyrido[2,3-(i]pyridazine, 5,8-dichloro-nucleophilic substitution, 3, 242 Pyrido[2,3-(i]pyridazine, polyhalo- H NMR, 3, 234... 

Pyridazines continued to play a central role in the construction of new biologically active compounds. 2,7-Dihydro-3//-pyridazino 5,4,3-17 acridin-3-ones were synthesized as cytotoxic agents <05BMC1969> and 6-(5-chloro-3-methylbenzofuran-2-sulfonyl)-2//-... 

In Poland, various 5-cycloaminornetbyl-6-(p-chlorophenyl)-4,5-dihydro-3(2//)-pyridazinones (89, R1 = pyrrolidino, piperidino, morpholino, etc. R2 = H, substituted alkyl, aryl) have been prepared in search of biologically active pyridazines some of these compounds have been reported to exhibit immunosuppressive activity [180, 284, 285]. 

Over 50 different pyridazin-3-ones were evaluated for biological activity in a wheat (Triticum aestivum L.) test system described previously (1). Briefly, seeds were germinated in 9-cm petri dishes on three layers of filter paper. Pyridazinones were dissolved in acetone and the filter papers were impregnated with 1 ml of acetone solution. After the soluent evaporated, 10 ml of distilled water were added to form an inhibitor concentration of 100 yM. Seeds were planted directly on the moist papers and germinated for 4 days in a controlled environment chamber on a 16-hr photoperiod with 27+lC day temperature and 21+lC night temperature. Light intensity from both fluorescent and incandescent bulbs was 28 klux at dish level. Lipids were extracted and recovered from 1 g of lyophilized shoot tissue, separated into membrane and non-membrane lipids, and analyzed by gas chromatography as described (1). 

Pyridazine (1,2-diazine) (1) and its benzo analogs cinnoline (1,2-diazanaphthalene) or benzo[c]pyridazine (2) and phthalazine (benzo[rf]pyridazine) (3) have been known since the nineteenth century. Although the basic synthetic principles and reactivity were investigated in the early years, interest in these compounds was not very intense, compared with pyrimidines and their bicyclic analogs, as they were not found in nature. However, during the last three decades intensive research has been stimulated because many derivatives have found application as a result of their biological activity. 

Biologically active pyridazines and benzo-fused derivatives were still avidly sought. For example, pyridazines were prepared as inhibitors of a protein tyrosine phosphatase <02BMC3197>, trisubstituted pyridazines as inhibitors of p38 MAPK <02BMCL689>, and phthalazines as... 

Structures of many pyridazines were determined by X-ray analysis, particularly those compounds that exhibit biological activity. X-Ray structural analysis has been applied to many compounds resulting from syntheses or transformations of pyridazines, such as structures 38 (87JOC2026), 41 (as erythro) (84JHC305), 49, and 50 (82CC1003). 

Pyrido[3,4-d]pyridazine, 1,4-dimorpholino-biological activity, 3, 261 Pyrldo[4,3-c]pyridazine, dihydro-NMR, 3, 234 UV spectra, 3, 236... 

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