Pyridazi nones

A somewhat similar method for the preparation of l,3-oxazolo[4,5-d]pyridazi-nones has been described by Ivachtchenko and coworkers (Scheme 6.214) [385]. Here, the key intermediate 5-amino-4-hydroxy-3(2H)-pyridazinone was treated with... 

The most potent among the compounds tested were the pyridazi-nones (28, R1 = Ph, R2, R3, R4, R5 = H, n = 2-5) [101]. Structure-activity relationships have been investigated in detail with this type of compound. Also, thio-analogues of compounds (28) (3-pyridazinethione derivatives) as well as 2-aminoalky]-6-aryl-3(2//)-pyridazinones were claimed in patents as gastric secretion inhibitors or anti-ulcer agents [100, 102, 103]. 

Moreover, some German patents claiming A-unsubstituted 6-arvi-3(2//)-pyridazinones and 4,5-dihydro congeners as stomach secretion inhibitors and ulcer inhibitors have to be cited [ 110-113], Several cardiotonic 6-aryl-pyridazi-nones, recently prepared in Japan, also have been reported to inhibit secretion... 

Figure 5.15 shows the parallel degradation of cadralazine to triazolone, pyridazi-none, and pyridazine at pH 7.4 and 80°C. 

Reaction of 216 with ethoxycarbonylmethylidene triphenylphosphorane gave 233, which was successfully cyclized to 238 (81MI2 87H2101) (Scheme 49). This reaction is a general method for synthesizing pyridazi-nones. The stereochemical outcome of the reaction of 216 with the phosphorane was found to afford the trans isomer 233, as anticipated from a Wittig reaction. Inspection of models indicated this isomer could not be cyclized. Its cyclization could be achieved experimentally as a consequence of the thermal preisomerization of 233 into the cis isomer 236, which led to its facile cyclization to 238. 

Although not used to make phthalazines, fused phthalazines have been prepared from pyridazine substrates by completing the C6-C7 bond of the phthalazine system therein for example, 2-benzyl-5-o-bromophenyl-6-phenyl-l(27/)-pyridazi-none (155) gave 2-benzyldibenzo[/,/i]phthalazin-l(2/l)-one (155a) [AcNMe2, AcONa, Pd(PPh3)2Cl2, N2, 130°C, 64 h 56%]. Such a reaction should also be useful to make unfused phthalazines. 

The uracils [27] bromacil (Du Pont, 1952), lenacil (Du Pont, 1974) and terbacil (Du Pont, 1966) were invented in the Du Pont laboratories, whereas the pyridazi-nones [28, 29], pyrazon (BASF, 1962) came out from research investigations in BASF and Sandoz laboratories. The phenylcarbamates [32] desmedipham and phenmedipham invented by Sobering AG are also included in the Cl group (HRAC classification) (Fig. 10.1). 

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